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Date: 2023-11-02  ·  Issue: 2023  ·  Volume: 1530
An integrated review of music cognition and rhythmic stimuli in sensorimotor neurocognition and neurorehabilitation
Contributors: Laura Emmery| Madeleine E. Hackney| Trisha Kesar| J. Lucas McKay| Michael C. Rosenberg|
Abstract: This work reviews the growing body of interdisciplinary research on music cognition, using biomechanical, kinesiological, clinical, psychosocial, and sociological methods. The review primarily examines the relationship between temporal elements in music and motor responses under varying contexts, with considerable relevance for clinical rehabilitation. After providing an overview of the terminology and approaches pertinent to theories of rhythm and meter from the musical‐theoretical and cognitive fields, this review focuses on studies on the effects of rhythmic sensory stimulation on gait, rhythmic cues’ effect on the motor system, reactions to rhythmic stimuli attempting to synchronize mobility (i.e., musical embodiment), and the application of rhythm for motor rehabilitation for individuals with Parkinson's disease, stroke, mild cognitive impairment, Alzheimer's disease, and other neurodegenerative or neurotraumatic diseases. This work ultimately bridges the gap between the musical‐theoretical and cognitive science fields to facilitate innovative research in which each discipline informs the other.
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Date: 2023-10-30  · 
Cardiac complications in thalassemia throughout the lifespan: Victories and challenges
Contributors: John C. Wood|
Abstract: Thalassemias are among the most common hereditary diseases in the world because heterozygosity offers protection against malarial infection. Affected individuals have variable expression of alpha or beta chains that lead to their unbalanced utilization during hemoglobin formation, oxidative stress, and apoptosis of red cell precursors prior to maturation. Some individuals produce sufficient hemoglobin to survive but suffer the vascular stress imposed by chronic anemia and ineffective erythropoiesis. In other patients, mature red cell formation is insufficient, and chronic transfusions are required—suppressing anemia and ineffective erythropoiesis but at the expense of iron overload. The cardiovascular consequences of thalassemia have changed dramatically over the previous five decades because of evolving treatment practices. This review summarizes this evolution, focusing on complications and management pertinent to modern patient cohorts.
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Date: 2023-10-28  · 
Being in the room together
Contributors: Lorraine Daston|
Abstract: As historians have shown and political theorists have acknowledged: no viable collective is ever just the result of cool cost‐benefit calculations. Rather, it is a shared vision of what it would mean to be part of a collective that surmounts hesitation and commands allegiance. What that collective vision should be for science already has a 350‐odd‐year history, and the work of the imagination is still ongoing.
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Date: 2023-10-19  · 
Shaping the development of complex social behavior
Contributors: James P. Curley| Frances A. Champagne|
Abstract: Early life experiences can have an enduring impact on the brain and behavior, with implications for stress reactivity, cognition, and social behavior. In particular, the neural systems that contribute to the expression of social behavior are altered by early life social environments. However, paradigms that have been used to alter the social environment during development have typically focused on exposure to stress, adversity, and deprivation of species‐typical social stimulation. Here, we explore whether complex social environments can shape the development of complex social behavior. We describe lab‐based paradigms for studying early life social complexity in rodents that are generally focused on enriching the social and sensory experiences of the neonatal and juvenile periods of development. The impact of these experiences on social behavior and neuroplasticity is highlighted. Finally, we discuss the degree to which our current approaches for studying social behavior outcomes give insight into “complex” social behavior and how social complexity can be better integrated into lab‐based methodologies.
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Date: 2023-10-13  ·  Issue: 2023  · 
Corticosteroid‐induced chromatin loop dynamics at the FKBP5 gene
Contributors: Cheng Wang| Freek Manders| Laszlo Groh| Roel Oldenkamp| Colin Logie|
Abstract: FKBP5 is a 115‐kb‐long glucocorticoid‐inducible gene implicated in psychiatric disorders. To investigate the complexities of chromatin interaction frequencies at the FKBP5 topologically associated domain (TAD), we deployed 15 one‐to‐all chromatin capture viewpoints near gene promoters, enhancers, introns, and CTCF‐loop anchors. This revealed a “one‐TAD‐one‐gene” structure encompassing the FKBP5 promoter and its enhancers. The FKBP5 promoter and its two glucocorticoid‐stimulated enhancers roam the entire TAD while displaying subtle cell type–specific interactomes. The FKBP5 TAD consists of two nested CTCF loops that are coordinated by one CTCF site in the eight intron of FKBP5 and another beyond its polyadenylation site, 61 kb further. Loop extension correlates with transcription increases through the intronic CTCF site. This is efficiently compensated for, since the short loop is restored even under high transcription regimes. The boundaries of the FKBP5 TAD consist of divergent CTCF site patterns, harbor multiple smaller genes, and are resilient to glucocorticoid stimulation. Interestingly, both FKBP5 TAD boundaries harbor H3K27me3‐marked heterochromatin blocks that may reinforce them. We propose that cis‐acting genetic and epigenetic polymorphisms underlying FKBP5 expression variation are likely to reside within a 240‐kb region that consists of the FKBP5 TAD, its left sub‐TAD, and both its boundaries.
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Date: 2023-10-13  ·  Issue: 2023  · 
Viruses as archaeological tools for uncovering ancient molecular relationships
Contributors: Ascensión Ariza‐Mateos| Carlos Briones| Celia Perales| María Teresa Bayo‐Jiménez| Esteban Domingo| Jordi Gómez|
Abstract: The entry of a virus into the host cell always implies the alteration of certain intracellular molecular relationships, some of which may involve the recovery of ancient cellular activities. In this sense, viruses are archaeological tools for identifying unexpressed activities in noninfected cells. Among these, activities that hinder virus propagation may represent cellular defense mechanisms, for example, activities that mutagenize the viral genome such as ADAR‐1 or APOBEC activities. Instead, those that facilitate virus propagation can be interpreted as the result of viral adaptation to—or mimicking—cellular structures, enabling the virus to perform anthropomorphic activities, including hijacking, manipulating, and reorganizing cellular factors for their own benefit. The alternative we consider here is that some of these second set of cellular activities were already in the uninfected cell but silenced, under the negative control of the cell or lineage, and that they represent a necessary precondition for viral infection. For example, specifically loading an amino acid at the 3'‐end of the mRNA of some plant viruses by aminoacyl‐tRNA synthetases has proved essential for virus infection despite this reaction not occurring with cellular mRNAs. Other activities of this type are discussed here, together with the biological context in which they acquire a coherent meaning, that is, genetic latency and molecular conflict.
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Date: 2023-10-13  ·  Issue: 2023  · 
Gene addition for beta thalassemia
Contributors: Janet L. Kwiatkowski|
Abstract: Individuals with transfusion‐dependent beta thalassemia require a high burden of care and experience significant morbidity from the underlying disease and its treatment, which negatively impact the quality of life. Allogeneic hematopoietic stem cell transplantation offers the chance for a cure, but donor availability and transplant‐related risks, especially in older patients, limit its use. Gene addition utilizing autologous CD34+ cells is an alternative, potentially curative, treatment option. Several clinical trials have investigated the use of lentiviral vectors containing a functional beta globin gene, including Lentiglobin BB305, GLOBE, and TNS9.3.55. The efficacy and safety data from these ongoing trials are discussed in this review.
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Date: 2023-10-13  ·  Issue: 2023  ·  Volume: 1528
Issue Information
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Abstract:
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Date: 2023-10-13  · 
Gene addition for beta thalassemia
Contributors: Janet L. Kwiatkowski|
Abstract: Individuals with transfusion‐dependent beta thalassemia require a high burden of care and experience significant morbidity from the underlying disease and its treatment, which negatively impact the quality of life. Allogeneic hematopoietic stem cell transplantation offers the chance for a cure, but donor availability and transplant‐related risks, especially in older patients, limit its use. Gene addition utilizing autologous CD34+ cells is an alternative, potentially curative, treatment option. Several clinical trials have investigated the use of lentiviral vectors containing a functional beta globin gene, including Lentiglobin BB305, GLOBE, and TNS9.3.55. The efficacy and safety data from these ongoing trials are discussed in this review.
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Date: 2023-10-13  ·  Issue: 2023  · 
Distinct patterns of activity within columns of the periaqueductal gray are associated with functionally distinct birdsongs
Contributors: Chinweike N. Asogwa| Changjiu Zhao| Brandon J. Polzin| Alyse N. Maksimoski| Sarah A. Heimovics| Lauren V. Riters|
Abstract: Male songbirds produce female‐directed songs in spring that convey a state of sexual motivation. Many songbirds also sing in fall flocks in affiliative/gregarious contexts in which song is linked to an intrinsic positive affective state. The periaqueductal gray (PAG) in mammals, which is organized into functional columns, integrates information from multiple brain regions and relays this information to vocal motor areas so that an animal emits a vocal signal reflective of its affective state. Here, we test the hypothesis that distinct columns in the songbird PAG play roles in the distinct affective states communicated by sexually motivated and gregarious song. We quantified the numbers of immediate early gene ZENK‐positive cells in 16 PAG subregions in male European starlings (Sturnus vulgaris) after singing gregarious or sexually motivated song. Results suggest that distinct PAG columns in songbirds context‐specifically regulate song, agonistic, and courtship behaviors. A second exploratory, functional tract‐tracing study also demonstrated that inputs to the PAG from specific subregions of the medial preoptic nucleus may contribute to gregarious song and behaviors indicative of social dominance. Together, findings suggest that conserved PAG columns and inputs from the preoptic nucleus may play a role in context‐specific vocal and other social behaviors.
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Date: 2023-10-12  · 
Dynamics in interbrain synchronization while playing a piano duet
Contributors: Anja Lender| Dionysios Perdikis| Walter Gruber| Ulman Lindenberger| Viktor Müller|
Abstract: Humans interact with each other through actions that are implemented by sensory and motor processes. To investigate the role of interbrain synchronization emerging during interpersonal action coordination, electroencephalography data from 13 pairs of pianists were recorded simultaneously while they performed a duet together. The study aimed to investigate whether interbrain phase couplings can be reduced to similar bottom‐up driven processes during synchronous play, or rather represent cognitive top‐down control required during periods of higher coordination demands. To induce such periods, one of the musicians acted as a confederate who deliberately desynchronized the play. As intended, on the behavioral level, the perturbation caused a breakdown in the synchronization of the musicians’ play and in its stability across trials. On the brain level, interbrain synchrony, as measured by the interbrain phase coherence (IPC), increased in the delta and theta frequency bands during perturbation as compared to non‐perturbed trials. Interestingly, this increase in IPC in the delta band was accompanied by the shift of the phase difference angle from in‐phase toward anti‐phase synchrony. In conclusion, the current study demonstrates that interbrain synchronization is based on the interpersonal temporal alignment of different brain mechanisms and is not simply reducible to similar sensory or motor responses.
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Date: 2023-10-12  · 
Temporal deployment of attention in musicians: Evidence from an attentional blink paradigm
Contributors: Dawei Shen| Bernhard Ross| Claude Alain|
Abstract: The generalization of music training to unrelated nonmusical domains is well established and may reflect musicians’ superior ability to regulate attention. We investigated the temporal deployment of attention in musicians and nonmusicians using scalp‐recording of event‐related potentials in an attentional blink (AB) paradigm. Participants listened to rapid sequences of stimuli and identified target and probe sounds. The AB was defined as a probe identification deficit when the probe closely follows the target. The sequence of stimuli was preceded by a neutral or informative cue about the probe position within the sequence. Musicians outperformed nonmusicians in identifying the target and probe. In both groups, cueing improved target and probe identification and reduced the AB. The informative cue elicited a sustained potential, which was more prominent in musicians than nonmusicians over left temporal areas and yielded a larger N1 amplitude elicited by the target. The N1 was larger in musicians than nonmusicians, and its amplitude over the left frontocentral cortex of musicians correlated with accuracy. Together, these results reveal musicians’ superior ability to regulate attention, allowing them to prepare for incoming stimuli, thereby improving sound object identification. This capacity to manage attentional resources to optimize task performance may generalize to nonmusical activities.
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Date: 2023-10-11  · 
Role of the rostral dorsomedial column of the periaqueductal gray during social defeat in rats
Contributors: Alisson Pinto Almeida| Alicia Moraes Tamais| Carolina Zerbini| Fernando Falkenburger Melleu| Newton Sabino Canteras| Simone Cristina Motta|
Abstract: Previous studies showed that the dorsal premammillary nucleus of the hypothalamus (PMD) is involved in social passive defensive behaviors likely to be meditated by descending projections to the periaqueductal gray (PAG). We focused on the rostral dorsomedial PAG (rPAGdm) to reveal its putative neural mechanisms involved in mediating social defensive responses. By combining retrograde tracing and FOS expression analysis, we showed that in addition to the PMD, the rPAGdm is influenced by several brain sites active during social defeat. Next, we found that cytotoxic lesions of the rPAGdm drastically reduced passive defense and did not affect active defensive responses. We then examined the rPAGdm's projection pattern and found that the PAGdm projections are mostly restricted to midbrain sites, including the precommissural nucleus, different columns of the PAG, and the cuneiform nucleus (CUN). Also, we found decreased FOS expression in the caudal PAGdm, CUN, and PMD after the rPAGdm was lesioned. The results support that the rPAGdm mediates passive social defensive responses through ascending paths to prosencephalic circuits likely mediated by the CUN. This study provides further support for the role of the PAG in the modulation of behavioral responses by working as a unique hub for influencing prosencephalic sites during the mediation of aversive responses.
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Date: 2023-10-07  · 
African bovid tribe classification using transfer learning and computer vision
Contributors: Manuel Domínguez‐Rodrigo| Juliet Brophy| Gregory J. Mathews| Marcos Pizarro‐Monzo| Enrique Baquedano|
Abstract: Objective analytical identification methods are still a minority in the praxis of paleobiological sciences. Subjective interpretation of fossils and their modifications remains a nonreplicable expert endeavor. Identification of African bovids is a crucial element in the reconstruction of paleo‐landscapes, ungulate paleoecology, and, eventually, hominin adaptation and ecosystemic reconstruction. Recent analytical efforts drawing on Fourier functional analysis and discrimination methods applied to occlusal surfaces of teeth have provided a highly accurate framework to correctly classify African bovid tribes and taxa. Artificial intelligence tools, like computer vision, have also shown their potential to be objectively more accurate in the identification of taphonomic agency than human experts. For this reason, here we implement some of the most successful computer vision methods, using transfer learning and ensemble analysis, to classify bidimensional images of African bovid teeth and show that 92% of the large testing set of images of African bovid tribes analyzed could be correctly classified. This brings an objective tool to paleoecological interpretation, where bovid identification and paleoecological interpretation can be more confidently carried out.
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Date: 2023-10-06  · 
Viruses as archaeological tools for uncovering ancient molecular relationships
Contributors: Ascensión Ariza‐Mateos| Carlos Briones| Celia Perales| María Teresa Bayo‐Jiménez| Esteban Domingo| Jordi Gómez|
Abstract: The entry of a virus into the host cell always implies the alteration of certain intracellular molecular relationships, some of which may involve the recovery of ancient cellular activities. In this sense, viruses are archaeological tools for identifying unexpressed activities in noninfected cells. Among these, activities that hinder virus propagation may represent cellular defense mechanisms, for example, activities that mutagenize the viral genome such as ADAR‐1 or APOBEC activities. Instead, those that facilitate virus propagation can be interpreted as the result of viral adaptation to—or mimicking—cellular structures, enabling the virus to perform anthropomorphic activities, including hijacking, manipulating, and reorganizing cellular factors for their own benefit. The alternative we consider here is that some of these second set of cellular activities were already in the uninfected cell but silenced, under the negative control of the cell or lineage, and that they represent a necessary precondition for viral infection. For example, specifically loading an amino acid at the 3'‐end of the mRNA of some plant viruses by aminoacyl‐tRNA synthetases has proved essential for virus infection despite this reaction not occurring with cellular mRNAs. Other activities of this type are discussed here, together with the biological context in which they acquire a coherent meaning, that is, genetic latency and molecular conflict.
Read More  

Date: 2023-10-06  · 
Distinct patterns of activity within columns of the periaqueductal gray are associated with functionally distinct birdsongs
Contributors: Chinweike N. Asogwa| Changjiu Zhao| Brandon J. Polzin| Alyse N. Maksimoski| Sarah A. Heimovics| Lauren V. Riters|
Abstract: Male songbirds produce female‐directed songs in spring that convey a state of sexual motivation. Many songbirds also sing in fall flocks in affiliative/gregarious contexts in which song is linked to an intrinsic positive affective state. The periaqueductal gray (PAG) in mammals, which is organized into functional columns, integrates information from multiple brain regions and relays this information to vocal motor areas so that an animal emits a vocal signal reflective of its affective state. Here, we test the hypothesis that distinct columns in the songbird PAG play roles in the distinct affective states communicated by sexually motivated and gregarious song. We quantified the numbers of immediate early gene ZENK‐positive cells in 16 PAG subregions in male European starlings (Sturnus vulgaris) after singing gregarious or sexually motivated song. Results suggest that distinct PAG columns in songbirds context‐specifically regulate song, agonistic, and courtship behaviors. A second exploratory, functional tract‐tracing study also demonstrated that inputs to the PAG from specific subregions of the medial preoptic nucleus may contribute to gregarious song and behaviors indicative of social dominance. Together, findings suggest that conserved PAG columns and inputs from the preoptic nucleus may play a role in context‐specific vocal and other social behaviors.
Read More  

Date: 2023-10-05  · 
Corticosteroid‐induced chromatin loop dynamics at the FKBP5 gene
Contributors: Cheng Wang| Freek Manders| Laszlo Groh| Roel Oldenkamp| Colin Logie|
Abstract: FKBP5 is a 115‐kb‐long glucocorticoid‐inducible gene implicated in psychiatric disorders. To investigate the complexities of chromatin interaction frequencies at the FKBP5 topologically associated domain (TAD), we deployed 15 one‐to‐all chromatin capture viewpoints near gene promoters, enhancers, introns, and CTCF‐loop anchors. This revealed a “one‐TAD‐one‐gene” structure encompassing the FKBP5 promoter and its enhancers. The FKBP5 promoter and its two glucocorticoid‐stimulated enhancers roam the entire TAD while displaying subtle cell type–specific interactomes. The FKBP5 TAD consists of two nested CTCF loops that are coordinated by one CTCF site in the eight intron of FKBP5 and another beyond its polyadenylation site, 61 kb further. Loop extension correlates with transcription increases through the intronic CTCF site. This is efficiently compensated for, since the short loop is restored even under high transcription regimes. The boundaries of the FKBP5 TAD consist of divergent CTCF site patterns, harbor multiple smaller genes, and are resilient to glucocorticoid stimulation. Interestingly, both FKBP5 TAD boundaries harbor H3K27me3‐marked heterochromatin blocks that may reinforce them. We propose that cis‐acting genetic and epigenetic polymorphisms underlying FKBP5 expression variation are likely to reside within a 240‐kb region that consists of the FKBP5 TAD, its left sub‐TAD, and both its boundaries.
Read More  

Date: 2023-10-02  ·  Issue: 2023  · 
On the evolution of epigenetics via exaptation: A developmental systems perspective
Contributors: David S. Moore|
Abstract: Evolution and development are interrelated processes influenced by genomic, epigenetic, and environmental factors. Epigenetic processes serve critical roles in development and operate as intermediaries that connect the genome to the rest of the world. Therefore, it is of interest to consider the evolution of epigenetic processes. The developmental systems perspective offers a distinctive, coherent, integrative way to understand the relationships between evolution, epigenetics, development, and the effects of experienced contexts. By adopting this perspective, this paper draws attention to the role of exaptation in the evolution of epigenetics in the RNA world and addresses the role of epigenetics in the later evolution of developmental processes such as cellular differentiation, learning, and memory. In so doing, the paper considers the appearance and functions of epigenetics in evolutionary history—sketching a pathway by which epigenetic processes might have evolved via exaptation and then contributed to the later development and evolution of phenotypes.
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Date: 2023-09-29  ·  Issue: 2023  ·  Volume: 1528
Effect of an action‐research nutrition intervention on the Global Diet Quality Score of Colombian adolescents
Contributors: Sandra L. Restrepo‐Mesa| Nathalia Correa Guzmán| Víctor Calvo| María Cristina Giraldo Quijano| Carolina Hernández Álvarez| Gilles Bergeron|
Abstract: Strategies to address the nutritional needs of adolescent girls and young women often focus on supplementation. In this study, an action‐research approach involving a nutrition education and entrepreneurship intervention was carried out among adolescent girls and young women in poor neighborhoods of Medellín, Colombia. The intervention group significantly increased its intake of several nutrients, including energy, protein, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, dietary fiber, calcium, zinc, and vitamins A, B2, B3, B9, and C. A significant increase was observed in the intake of the Global Diet Quality Score (GDQS) healthy food groups (other fruits, other vegetables, legumes, high‐fat dairy products), accompanied by a decrease in the consumption of some unhealthy food groups (sweets and ice creams). A multivariate regression controlling for age, socioeconomic status, occupation, Household Hunger Scale, mean probability of adequacy, physical activity, and body self‐perception showed that the nutrition intervention improved the total GDQS by 33% in the intervention group—a substantial improvement notwithstanding the study group's precarious social and economic conditions. We conclude that nutrition education and entrepreneurship models based on this approach may improve the dietary profile of this population and reduce future pressures from nutrition‐related chronic diseases.
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Date: 2023-09-29  ·  Issue: 2023  · 
Effect of an action‐research nutrition intervention on the Global Diet Quality Score of Colombian adolescents
Contributors: Sandra L. Restrepo‐Mesa| Nathalia Correa Guzmán| Víctor Calvo| María Cristina Giraldo Quijano| Carolina Hernández Álvarez| Gilles Bergeron|
Abstract: Strategies to address the nutritional needs of adolescent girls and young women often focus on supplementation. In this study, an action‐research approach involving a nutrition education and entrepreneurship intervention was carried out among adolescent girls and young women in poor neighborhoods of Medellín, Colombia. The intervention group significantly increased its intake of several nutrients, including energy, protein, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, dietary fiber, calcium, zinc, and vitamins A, B2, B3, B9, and C. A significant increase was observed in the intake of the Global Diet Quality Score (GDQS) healthy food groups (other fruits, other vegetables, legumes, high‐fat dairy products), accompanied by a decrease in the consumption of some unhealthy food groups (sweets and ice creams). A multivariate regression controlling for age, socioeconomic status, occupation, Household Hunger Scale, mean probability of adequacy, physical activity, and body self‐perception showed that the nutrition intervention improved the total GDQS by 33% in the intervention group—a substantial improvement notwithstanding the study group's precarious social and economic conditions. We conclude that nutrition education and entrepreneurship models based on this approach may improve the dietary profile of this population and reduce future pressures from nutrition‐related chronic diseases.
Read More  

Date: 2023-09-26  · 
On the evolution of epigenetics via exaptation: A developmental systems perspective
Contributors: David S. Moore|
Abstract: Evolution and development are interrelated processes influenced by genomic, epigenetic, and environmental factors. Epigenetic processes serve critical roles in development and operate as intermediaries that connect the genome to the rest of the world. Therefore, it is of interest to consider the evolution of epigenetic processes. The developmental systems perspective offers a distinctive, coherent, integrative way to understand the relationships between evolution, epigenetics, development, and the effects of experienced contexts. By adopting this perspective, this paper draws attention to the role of exaptation in the evolution of epigenetics in the RNA world and addresses the role of epigenetics in the later evolution of developmental processes such as cellular differentiation, learning, and memory. In so doing, the paper considers the appearance and functions of epigenetics in evolutionary history—sketching a pathway by which epigenetic processes might have evolved via exaptation and then contributed to the later development and evolution of phenotypes.
Read More  

Date: 2023-09-26  ·  Issue: 2023  ·  Volume: 1529
On the evolution of epigenetics via exaptation: A developmental systems perspective
Contributors: David S. Moore|
Abstract: Evolution and development are interrelated processes influenced by genomic, epigenetic, and environmental factors. Epigenetic processes serve critical roles in development and operate as intermediaries that connect the genome to the rest of the world. Therefore, it is of interest to consider the evolution of epigenetic processes. The developmental systems perspective offers a distinctive, coherent, integrative way to understand the relationships between evolution, epigenetics, development, and the effects of experienced contexts. By adopting this perspective, this paper draws attention to the role of exaptation in the evolution of epigenetics in the RNA world and addresses the role of epigenetics in the later evolution of developmental processes such as cellular differentiation, learning, and memory. In so doing, the paper considers the appearance and functions of epigenetics in evolutionary history—sketching a pathway by which epigenetic processes might have evolved via exaptation and then contributed to the later development and evolution of phenotypes.
Read More  

Date: 2023-09-22  ·  Issue: 2022  · 
Uncertainty in surface wind speed projections over the Iberian Peninsula: CMIP6 GCMs versus a WRF‐RCM
Contributors: Miguel Andres‐Martin| Cesar Azorin‐Molina| Cheng Shen| José C. Fernández‐Alvarez| Luis Gimeno| Sergio M. Vicente‐Serrano| Jinlin Zha|
Abstract: This study assessed the projected near‐surface wind speed (SWS) changes and variability over the Iberian Peninsula for the 21st century. Here, we compared Coupled Model Intercomparison Project Phase 6 global climate models (GCMs) with a higher spatial resolution regional climate model (RCM; ∼20 km), known as WRF‐CESM2, which was created by a dynamic downscaling of the Community Earth System Model version 2 (CESM2) using the Weather Research and Forecasting (WRF) model. Our analysis found that the GCMs tended to overestimate observed SWS for 1985–2014, while the higher spatial resolution of the WRF‐CESM2 did not improve the accuracy and underestimated the SWS magnitude. GCMs project a decline of SWS under high shared socioeconomic pathways (SSPs) greenhouse concentrations, such as SSP370 and SSP585, while an interdecadal oscillation appears in SSP126 and SSP245 for the end of the century. The WRF‐CESM2 under SSP585 predicts the opposite increasing SWS. Our results suggest that 21st‐century projections of SWS are uncertain even for regionalized products and should be taken with caution.
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Date: 2023-09-21  ·  Issue: 2023  · 
Thalassemia and malignancies: Updates from the literature
Contributors: Mohammad Hassan Hodroj| Ali Taher|
Abstract: Thalassemia management has undergone significant development with the advancement in iron chelation therapy, which has led to a prolonged life expectancy. This has been accompanied by the emergence of several new morbidities and chronic diseases, including cancer. Over the years, multiple cases of solid and hematologic malignancies in thalassemia patients have been reported in the literature, with no clear mechanism for the development of cancer in these patients despite a number of potential mechanisms. However, the results of many studies have been contradictory regarding the risk of development of malignancies in thalassemia. The present review aims to discuss the available data on cancer and thalassemia in the literature, with the latest updates regarding possible malignancy development mechanisms, risks, and the most commonly reported types.
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Date: 2023-09-21  ·  Issue: 2023  · 
Review of intervention products for use in the prevention and control of anemia
Contributors: Daniel Lopez de Romaña| Alison Mildon| Jenna Golan| Maria Elena D. Jefferds| Lisa M. Rogers| Mandana Arabi|
Abstract: Anemia remains a major public health problem, especially in low‐ and middle‐income countries. The World Health Organization recommends several interventions to prevent and manage anemia in vulnerable population groups, including young children, menstruating adolescent girls and women, and pregnant and postpartum women. Daily iron supplementation reduces the risk of anemia in infants, children, and pregnant women, and intermittent iron supplementation reduces anemia risk in menstruating girls and women. Micronutrient powders reduce the risk of anemia in children. Fortifying wheat flour with iron reduces the risk of anemia in the overall population, whereas the effect of fortifying maize flour and rice is still uncertain. Regarding non‐nutrition‐related interventions, malaria treatment and deworming have been reported to decrease anemia prevalence. Promising interventions to prevent anemia include vitamin A supplementation, multiple micronutrient supplementation for pregnant women, small‐quantity lipid‐based supplements, and fortification of salt with iodine and iron. Future research could address the efficacy and safety of different iron supplementation formulations, identify the most bioavailable form of iron for fortification, examine adherence to supplementation regimens and fortification standards, and investigate the effectiveness of integrating micronutrient, helminth, and malaria control programs.
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Date: 2023-09-20  ·  Issue: 2023  ·  Volume: 1527
Issue Information
Contributors:
Abstract:
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Date: 2023-09-18  ·  Issue: 2023  · 
Food and nutrient intake of adolescent women in Medellín, Colombia
Contributors: Sandra L. Restrepo‐Mesa| Nathalia Correa Guzmán| Luz M. Manjarrés Correa| Luz Duque Franco| Gilles Bergeron|
Abstract: Nutritional imbalance in adolescent girls causes alterations in health, reproductive cycles, and fetal outcomes of future generations. To evaluate the dietary pattern and prevalence of inadequate nutrient intake, a 24‐hour multi‐step food recall was carried out among 793 adolescent women (14–20 years old) from Medellin, Colombia. Their dietary pattern was characterized by lower than recommended intakes of fruits and vegetables (CRI 0.4, AMD 0.2), dairy (CRI 0.5, AMD 0.2), and proteins (CRI 0.8, AMD 0.3), while starches (CRI 1.2, AMD 0.4), fats (CRI 1.1, AMD 0.6), and sugars (CRI 1.0, AMD 0.5) were at similar or higher levels than recommendations. A high risk of deficiency was found in the usual intake of energy (53.0%), protein (39.8%), calcium (98.9%), folates (85.7%), iron (74.4%), thiamine (44.3%), vitamin C (31.3%), zinc (28.3%), vitamin A (23.4%), cyanocobalamin (17.3%), and pyridoxine (10.9%). A low risk of deficiency was noted in usual fiber intake (0.5%), and a higher than recommended intake was noted in saturated fat (100.0%) and simple carbohydrates (68.8%). Anecdotally, a large proportion of respondents saw decreases in their food consumption during the COVID‐19 pandemic. These results suggest an urgent need for nutrition education programs to emphasize the importance of adequate nutrition among adolescent women.
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Date: 2023-09-16  · 
Uncertainty in surface wind speed projections over the Iberian Peninsula: CMIP6 GCMs versus a WRF‐RCM
Contributors: Miguel Andres‐Martin| Cesar Azorin‐Molina| Cheng Shen| José C. Fernández‐Alvarez| Luis Gimeno| Sergio M. Vicente‐Serrano| Jinlin Zha|
Abstract: This study assessed the projected near‐surface wind speed (SWS) changes and variability over the Iberian Peninsula for the 21st century. Here, we compared Coupled Model Intercomparison Project Phase 6 global climate models (GCMs) with a higher spatial resolution regional climate model (RCM; ∼20 km), known as WRF‐CESM2, which was created by a dynamic downscaling of the Community Earth System Model version 2 (CESM2) using the Weather Research and Forecasting (WRF) model. Our analysis found that the GCMs tended to overestimate observed SWS for 1985–2014, while the higher spatial resolution of the WRF‐CESM2 did not improve the accuracy and underestimated the SWS magnitude. GCMs project a decline of SWS under high shared socioeconomic pathways (SSPs) greenhouse concentrations, such as SSP370 and SSP585, while an interdecadal oscillation appears in SSP126 and SSP245 for the end of the century. The WRF‐CESM2 under SSP585 predicts the opposite increasing SWS. Our results suggest that 21st‐century projections of SWS are uncertain even for regionalized products and should be taken with caution.
Read More  

Date: 2023-09-08  · 
Review of intervention products for use in the prevention and control of anemia
Contributors: Daniel Lopez de Romaña| Alison Mildon| Jenna Golan| Maria Elena D. Jefferds| Lisa M. Rogers| Mandana Arabi|
Abstract: Anemia remains a major public health problem, especially in low‐ and middle‐income countries. The World Health Organization recommends several interventions to prevent and manage anemia in vulnerable population groups, including young children, menstruating adolescent girls and women, and pregnant and postpartum women. Daily iron supplementation reduces the risk of anemia in infants, children, and pregnant women, and intermittent iron supplementation reduces anemia risk in menstruating girls and women. Micronutrient powders reduce the risk of anemia in children. Fortifying wheat flour with iron reduces the risk of anemia in the overall population, whereas the effect of fortifying maize flour and rice is still uncertain. Regarding non‐nutrition‐related interventions, malaria treatment and deworming have been reported to decrease anemia prevalence. Promising interventions to prevent anemia include vitamin A supplementation, multiple micronutrient supplementation for pregnant women, small‐quantity lipid‐based supplements, and fortification of salt with iodine and iron. Future research could address the efficacy and safety of different iron supplementation formulations, identify the most bioavailable form of iron for fortification, examine adherence to supplementation regimens and fortification standards, and investigate the effectiveness of integrating micronutrient, helminth, and malaria control programs.
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Date: 2023-09-07  · 
Thalassemia and malignancies: Updates from the literature
Contributors: Mohammad Hassan Hodroj| Ali Taher|
Abstract: Thalassemia management has undergone significant development with the advancement in iron chelation therapy, which has led to a prolonged life expectancy. This has been accompanied by the emergence of several new morbidities and chronic diseases, including cancer. Over the years, multiple cases of solid and hematologic malignancies in thalassemia patients have been reported in the literature, with no clear mechanism for the development of cancer in these patients despite a number of potential mechanisms. However, the results of many studies have been contradictory regarding the risk of development of malignancies in thalassemia. The present review aims to discuss the available data on cancer and thalassemia in the literature, with the latest updates regarding possible malignancy development mechanisms, risks, and the most commonly reported types.
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Date: 2023-09-02  · 
Clostridium butyricum MIYAIRI 588 alleviates periodontal bone loss in mice with diabetes mellitus
Contributors: Yanan Zhang| Miao Lu| Yang Zhang| Xulei Yuan| Mengjiao Zhou| Xiaohui Xu| Tingwei Zhang| Jinlin Song|
Abstract: The gut microbiota is a bridge linking periodontitis and systemic diseases, such as diabetes mellitus (DM). The probiotic Clostridium butyricum MIYAIRI 588 (CBM588) is reportedly an effective therapeutic approach for gut dysbiosis. Here, in a mouse model, we explored the therapeutic effect of CBM588 on periodontal bone destruction in DM and DM‐associated periodontitis (DMP), as well as the underlying mechanism. Micro‐computed tomography revealed that DM and DMP both aggravated periodontal bone destruction, which was alleviated by intragastric supplementation with CBM588. Moreover, 16S rRNA sequencing and untargeted metabolite analysis indicated that CBM588 ameliorated DMP‐triggered dysbiosis and led to reduced oxidative stress associated with elevated 4‐hydroxybenzenemethanol (4‐HBA) in serum. Furthermore, in vitro and in vivo experiments found that the metabolite 4‐HBA promoted nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling activation and modulated the polarization of macrophages, thus ameliorating inflammatory bone destruction in DMP. Our study demonstrates the protective effects of CBM588 in DM‐induced mice, with and without ligature‐induced periodontitis. The mechanism involves regulation of the gut microbiota and restoration of the integrity of the gut barrier to alleviate oxidative damage by elevating serum 4‐HBA. This study suggests the possibility of CBM588 as a therapeutic adjuvant for periodontal treatment in diabetes patients.
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Date: 2023-08-29  · 
A novel approach to egg and math: Improved geometrical standardization of any avian egg profile
Contributors: Valeriy G. Narushin| Stefan T. Orszulik| Michael N. Romanov| Darren K. Griffin|
Abstract: Developing a geometric formulation of any biological object has a number of justifications and applications. Recently, we developed a universal geometric figure for describing a bird's egg in any of the possible basic shapes: spherical, ellipsoidal, ovoid, and pyriform. The formulation proved widely applicable but had a number of drawbacks, including a very obvious join between two parts of the egg. To correct this, we developed the Main Axiom of the universal mathematical formula. This essentially involved making the ordinate of the extremum of the function correspond to half the maximum egg breadth (B), and the abscissa to the reciprocal of the parameter w that reflects the shift of the vertical axis to its coincidence with B. This, in turn, helped us develop a new, simplified mathematical model without a nonbiological join. Experimental verification was performed to confirm the adequacy of the new geometric figure. It accurately described actual avian eggs of various shapes more closely than our previous model. To the best of our knowledge, our new, simplified equation can be applied as a standard for any bird egg that exists in nature. As a rather simple equation, it can be used in a broad range of applications.
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Date: 2023-08-25  ·  Issue: 2023  · 
Combination chelation therapy
Contributors: Yesim Aydinok|
Abstract: Combination chelation therapies are considered in transfusion‐dependent thalassemia patients for whom monotherapy regimens have failed to achieve iron balance or intensification of iron chelation therapy is required for the rapid reduction of excess iron to avoid permanent organ damage. Combination chelation may provide a more flexible approach for individualizing chelation therapy, thereby improving tolerability, adherence, and quality of life. In principle, iron chelators can be combined with an infinite number of dosing regimens; these involve simultaneous or sequential exposure to the chelators on the same day or alternating the drugs on different days. Clinical studies have established the safety and efficacy of chelation combinations. However, real‐life data with combination therapies indicate the significance of compliance for a meaningful reduction in iron overload compared to monotherapies.
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Date: 2023-08-24  ·  Issue: 2023  ·  Volume: 1528
The neurobiology of vocal communication in marmosets
Contributors: Dori M. Grijseels| Brendan J. Prendergast| Julia C. Gorman| Cory T. Miller|
Abstract: An increasingly popular animal model for studying the neural basis of social behavior, cognition, and communication is the common marmoset (Callithrix jacchus). Interest in this New World primate across neuroscience is now being driven by their proclivity for prosociality across their repertoire, high volubility, and rapid development, as well as their amenability to naturalistic testing paradigms and freely moving neural recording and imaging technologies. The complement of these characteristics set marmosets up to be a powerful model of the primate social brain in the years to come. Here, we focus on vocal communication because it is the area that has both made the most progress and illustrates the prodigious potential of this species. We review the current state of the field with a focus on the various brain areas and networks involved in vocal perception and production, comparing the findings from marmosets to other animals, including humans.
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Date: 2023-08-24  ·  Issue: 2023  · 
The neurobiology of vocal communication in marmosets
Contributors: Dori M. Grijseels| Brendan J. Prendergast| Julia C. Gorman| Cory T. Miller|
Abstract: An increasingly popular animal model for studying the neural basis of social behavior, cognition, and communication is the common marmoset (Callithrix jacchus). Interest in this New World primate across neuroscience is now being driven by their proclivity for prosociality across their repertoire, high volubility, and rapid development, as well as their amenability to naturalistic testing paradigms and freely moving neural recording and imaging technologies. The complement of these characteristics set marmosets up to be a powerful model of the primate social brain in the years to come. Here, we focus on vocal communication because it is the area that has both made the most progress and illustrates the prodigious potential of this species. We review the current state of the field with a focus on the various brain areas and networks involved in vocal perception and production, comparing the findings from marmosets to other animals, including humans.
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Date: 2023-08-19  ·  Issue: 2023  ·  Volume: 1528
Characterizing affiliative touch in humans and its role in advancing haptic design
Contributors: James H. Kryklywy| Preeti Vyas| Karon E. Maclean| Rebecca M. Todd|
Abstract: An emerging view in cognitive neuroscience holds that the extraction of emotional relevance from sensory experience extends beyond the centralized appraisal of sensation in associative brain regions, including frontal and medial‐temporal cortices. This view holds that sensory information can be emotionally valenced from the point of contact with the world. This view is supported by recent research characterizing the human affiliative touch system, which carries signals of soft, stroking touch to the central nervous system and is mediated by dedicated C‐tactile afferent receptors. This basic scientific research on the human affiliative touch system is informed by, and informs, technology design for communicating and regulating emotion through touch. Here, we review recent research on the basic biology and cognitive neuroscience of affiliative touch, its regulatory effects across the lifespan, and the factors that modulate it. We further review recent work on the design of haptic technologies, devices that stimulate the affiliative touch system, such as wearable technologies that apply the sensation of soft stroking or other skin‐to‐skin contact, to promote physiological regulation. We then point to future directions in interdisciplinary research aimed at both furthering scientific understanding and application of haptic technology for health and wellbeing.
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Date: 2023-08-19  ·  Issue: 2022  · 
Characterizing affiliative touch in humans and its role in advancing haptic design
Contributors: James H. Kryklywy| Preeti Vyas| Karon E. Maclean| Rebecca M. Todd|
Abstract: An emerging view in cognitive neuroscience holds that the extraction of emotional relevance from sensory experience extends beyond the centralized appraisal of sensation in associative brain regions, including frontal and medial‐temporal cortices. This view holds that sensory information can be emotionally valenced from the point of contact with the world. This view is supported by recent research characterizing the human affiliative touch system, which carries signals of soft, stroking touch to the central nervous system and is mediated by dedicated C‐tactile afferent receptors. This basic scientific research on the human affiliative touch system is informed by, and informs, technology design for communicating and regulating emotion through touch. Here, we review recent research on the basic biology and cognitive neuroscience of affiliative touch, its regulatory effects across the lifespan, and the factors that modulate it. We further review recent work on the design of haptic technologies, devices that stimulate the affiliative touch system, such as wearable technologies that apply the sensation of soft stroking or other skin‐to‐skin contact, to promote physiological regulation. We then point to future directions in interdisciplinary research aimed at both furthering scientific understanding and application of haptic technology for health and wellbeing.
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Date: 2023-08-18  · 
Combination chelation therapy
Contributors: Yesim Aydinok|
Abstract: Combination chelation therapies are considered in transfusion‐dependent thalassemia patients for whom monotherapy regimens have failed to achieve iron balance or intensification of iron chelation therapy is required for the rapid reduction of excess iron to avoid permanent organ damage. Combination chelation may provide a more flexible approach for individualizing chelation therapy, thereby improving tolerability, adherence, and quality of life. In principle, iron chelators can be combined with an infinite number of dosing regimens; these involve simultaneous or sequential exposure to the chelators on the same day or alternating the drugs on different days. Clinical studies have established the safety and efficacy of chelation combinations. However, real‐life data with combination therapies indicate the significance of compliance for a meaningful reduction in iron overload compared to monotherapies.
Read More  

Date: 2023-08-18  ·  Issue: 2023  · 
Combination chelation therapy
Contributors: Yesim Aydinok|
Abstract: Combination chelation therapies are considered in transfusion‐dependent thalassemia patients for whom monotherapy regimens have failed to achieve iron balance or intensification of iron chelation therapy is required for the rapid reduction of excess iron to avoid permanent organ damage. Combination chelation may provide a more flexible approach for individualizing chelation therapy, thereby improving tolerability, adherence, and quality of life. In principle, iron chelators can be combined with an infinite number of dosing regimens; these involve simultaneous or sequential exposure to the chelators on the same day or alternating the drugs on different days. Clinical studies have established the safety and efficacy of chelation combinations. However, real‐life data with combination therapies indicate the significance of compliance for a meaningful reduction in iron overload compared to monotherapies.
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Date: 2023-08-17  ·  Issue: 2023  ·  Volume: 1528
Validation of the NOVA score for the consumption of ultra‐processed foods by young women of Medellín, Colombia
Contributors: María Camila Correa‐Madrid| Nathalia Correa Guzmán| Gilles Bergeron| Sandra L. Restrepo‐Mesa| Gustavo Cediel|
Abstract: Ultra‐processed foods (UPFs) are associated with deterioration in dietary quality and the development of chronic diseases. The NOVA score, developed in Brazil to assess UPF consumption quickly and inexpensively, is adapted and validated here using a sample of 203 young women from Medellín, Colombia. Food consumption was evaluated using 24‐hour dietary recall and with the NOVA‐UPF score. Food items were classified using the NOVA categories. The energy consumed from UPFs and its percentage of the total energy consumed was estimated. The association between the NOVA‐UPF score and the percentage of energy from UPF (%UPF/E) was evaluated. Both variables were categorized into quintiles and concordance was estimated using prevalence and bias‐adjusted kappa (PABAK). A regression model was used to assess the association between the NOVA‐UPF score and critical nutrients. The mean NOVA‐UPF score among study participants was 4.5, with 27% of the total energy they consumed coming from UPFs. There was a positive, linear association between the NOVA‐UPF score and %UPF/E (p < 0.001) and substantial agreement (PABAK = 0.75) in the classification of participants between UPF energy quintiles and NOVA‐UPF score quintiles. The NOVA‐UPF score was positively and significantly associated with sodium, total fat, and saturated fat intake. We conclude that the adapted NOVA‐UPF score may help monitor the consumption of UPFs among young women in Medellín.
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Date: 2023-08-17  ·  Issue: 2023  ·  Volume: 1528
Exploring the potential of meeting adolescent girls’ nutrient needs in urban Colombia using food‐based recommendations
Contributors: Frances Knight| Sabrina Kuri| Claudia Damu| Carla Mejia| Nathalia Correa Guzmán| Gilles Bergeron| Sandra L. Restrepo‐Mesa|
Abstract: During adolescence, many young people gain greater food choice agency but also become increasingly exposed and susceptible to environmental pressures that influence their food choices. This coincides with increased nutritional needs, especially for girls. In urban Colombia, adolescent diets are often high in undesirable foods and low in nutritious foods, contributing to overweight and micronutrient deficiencies. This study aimed to explore the potential of improving diet quality using food‐based recommendations (FBRs) within the parameters of local food systems and adolescents’ existing dietary patterns to inform context‐specific programmatic responses to malnutrition. We applied linear programming analysis to dietary data from 13‐ to 20‐year‐old girls in Medellin to identify problem nutrients, local micronutrient sources, and promising FBRs. Iron and, to a lesser extent, calcium targets were difficult to meet using optimized diets based on local foods, especially for 13‐ to 17‐year‐olds. High habitual consumption of foods with excessive salt, fat, or sugar provided >5% of micronutrients in optimized diets. Otherwise, significant micronutrient sources included legumes, meat, dairy, bread, potatoes, and fruit. FBRs met targets for 10 micronutrients but only 32%–39% recommended nutrient intake for iron. FBRs, including occasionally consumed foods and supplements, met all intake targets for less cost, indicating a need to increase access to nutrient‐dense products.
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Date: 2023-08-16  ·  Issue: 2023  ·  Volume: 1526
Issue Information
Contributors:
Abstract:
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Date: 2023-08-15  ·  Issue: 2023  · 
Neuromodulators and neuroepigenetics of social behavior in ants
Contributors: Matan Sorek| Shelley L. Berger|
Abstract: Eusocial insects exemplify a remarkable system of division of labor within the same colony. This behavioral range, which is sometimes accompanied by morphological or physiological differences, provides an opportunity to study the relationship between complex behaviors and their underlying molecular mechanisms. This is especially true in ants because certain genera have an elaborate caste system and can dramatically change their stereotypical behavior over their lifetime. Recent studies experimentally alter ant behavior over short times, thus opening the study of underlying plasticity pathways. The molecular underpinnings of these behaviors are neuromodulators as well as the regulation of chromatin. Here, we concisely review the current understanding of the relationship between neuromodulators, epigenetics, and social behavior in ants. We discuss future directions in light of experimental limitations of the ant system.
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Date: 2023-08-15  ·  Issue: 2023  ·  Volume: 1528
Neuromodulators and neuroepigenetics of social behavior in ants
Contributors: Matan Sorek| Shelley L. Berger|
Abstract: Eusocial insects exemplify a remarkable system of division of labor within the same colony. This behavioral range, which is sometimes accompanied by morphological or physiological differences, provides an opportunity to study the relationship between complex behaviors and their underlying molecular mechanisms. This is especially true in ants because certain genera have an elaborate caste system and can dramatically change their stereotypical behavior over their lifetime. Recent studies experimentally alter ant behavior over short times, thus opening the study of underlying plasticity pathways. The molecular underpinnings of these behaviors are neuromodulators as well as the regulation of chromatin. Here, we concisely review the current understanding of the relationship between neuromodulators, epigenetics, and social behavior in ants. We discuss future directions in light of experimental limitations of the ant system.
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Date: 2023-08-12  ·  Issue: 2023  ·  Volume: 1528
Neurovascular segregation of the retinal nerve fiber layer in glaucoma
Contributors: Ai Ping Yow| Jacqueline Chua| Bingyao Tan| Rachel Chong| Monisha E. Nongpiur| Preeti Gupta| Ecosse Lamoureux| Rahat Husain| Leopold Schmetterer| Damon Wong|
Abstract: The imaging data of one eye from 154 healthy and 143 glaucoma participants were acquired to evaluate the contributions of the neuronal and vascular components within the retinal nerve fiber layer (RNFL) for detecting glaucoma and modeling visual field loss through the use of optical coherence tomography (OCT) and OCT angiography. The neuronal and vascular components within the circumpapillary RNFL were independently evaluated. In healthy eyes, the neuronal component showed a stronger association with age (r = −0.52, p < 0.001) compared to measured RNFL thickness (r = −0.46, p < 0.001). Using the neuronal component alone improved detection of glaucoma (AUC: 0.890 ± 0.020) compared to measured RNFL thickness (AUC: 0.877 ± 0.021; χ2 = 5.54, p = 0.019). Inclusion of the capillary components with the sectoral neuronal component resulted in a significant improvement in glaucoma detection (AUC: 0.927 ± 0.015; χ2 = 15.34, p < 0.001). After adjusting for potential confounders, AUC increased to 0.952 ± 0.011. Results from modeling visual field loss in glaucoma eyes suggest that visual field losses associated with neuronal thinning were moderated in eyes with a larger capillary component. These findings suggest that segregation of the neurovascular components could help improve understanding of disease pathophysiology and affect disease management in glaucoma.
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Date: 2023-08-11  ·  Issue: 2023  · 
The Global Diet Quality Score is associated with nutrient adequacy and depression among Vietnamese youths
Contributors: Phuong Hong Nguyen| Lan Mai Tran| Nga Thu Hoang| Megan Deitchler| Mourad Moursi| Gilles Bergeron|
Abstract: The Global Diet Quality Score (GDQS) has been recommended as a simple diet quality metric that is reflective of both nutrient adequacy and noncommunicable disease outcomes. It has been validated among women of reproductive age (15–49 years) in diverse settings but not specifically among younger women. This paper examines the relationship between the GDQS and nutrient adequacy, anthropometric outcomes, and depressive symptoms among 1001 Vietnamese young women aged 16–22 years. In energy‐adjusted models, the GDQS was significantly (p < 0.05) and positively correlated with intakes of protein (ρ = 0.23), total fat (ρ = 0.06), nine micronutrients (calcium, iron, zinc, vitamin C, riboflavin, niacin, vitamin B6, folate, and vitamin A) (ρ = 0.12–0.35), and the mean probability of adequacy of micronutrients (ρ = 0.28). Compared to young women with optimal GDQS, those with low and very low GDQS were two to five times more likely to have a mean probability of nutrient adequacy less than 50% and showed two to three times higher odds for depression. No association was observed for GDQS and anthropometric outcomes. In conclusion, the GDQS performed well in capturing nutrient adequacy and depressive symptoms among Vietnamese young women. Further research is warranted to explore the relationship between diet quality and depression in other settings.
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Date: 2023-08-11  ·  Issue: 2023  ·  Volume: 1528
The Global Diet Quality Score is associated with nutrient adequacy and depression among Vietnamese youths
Contributors: Phuong Hong Nguyen| Lan Mai Tran| Nga Thu Hoang| Megan Deitchler| Mourad Moursi| Gilles Bergeron|
Abstract: The Global Diet Quality Score (GDQS) has been recommended as a simple diet quality metric that is reflective of both nutrient adequacy and noncommunicable disease outcomes. It has been validated among women of reproductive age (15–49 years) in diverse settings but not specifically among younger women. This paper examines the relationship between the GDQS and nutrient adequacy, anthropometric outcomes, and depressive symptoms among 1001 Vietnamese young women aged 16–22 years. In energy‐adjusted models, the GDQS was significantly (p < 0.05) and positively correlated with intakes of protein (ρ = 0.23), total fat (ρ = 0.06), nine micronutrients (calcium, iron, zinc, vitamin C, riboflavin, niacin, vitamin B6, folate, and vitamin A) (ρ = 0.12–0.35), and the mean probability of adequacy of micronutrients (ρ = 0.28). Compared to young women with optimal GDQS, those with low and very low GDQS were two to five times more likely to have a mean probability of nutrient adequacy less than 50% and showed two to three times higher odds for depression. No association was observed for GDQS and anthropometric outcomes. In conclusion, the GDQS performed well in capturing nutrient adequacy and depressive symptoms among Vietnamese young women. Further research is warranted to explore the relationship between diet quality and depression in other settings.
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Date: 2023-08-10  ·  Issue: 2023  ·  Volume: 1527
Corrigendum for Ann. N.Y. Acad. Sci. (2022), 1515, 143‐154.
Contributors:
Abstract:
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Date: 2023-08-10  ·  Issue: 2023  ·  Volume: 1528
Mobilizing adolescents and young women to promote healthy diets in urban settings of Colombia and Vietnam: Lessons from two action‐research programs
Contributors: Gilles Bergeron| Phuong Hong Nguyen| Nathalia Correa Guzman| Lan Mai Tran| Nga Thu Hoang| Sandra L. Restrepo‐Mesa|
Abstract: Adolescent and young women face grave nutrition challenges, but limited evidence exists on solutions to improve their diets. Action‐research was done over 3 years (2020–2022) in secondary cities of Colombia (Medellin) and Vietnam (Thai Nguyen) to identify nutrient deficits in adolescent and young women diets; elaborate food‐based recommendations to improve their nutritional status using Optifood linear programming; and engage respondents in incorporating suggested recommendations to their diet using a Social Innovation Challenge approach. A total of 1001 respondents were interviewed in Vietnam, 793 in Colombia. The probability of nutrient inadequacy in both locations was highest for iron and calcium, followed by the risk of deficiency for several other vitamins and minerals. Social Innovation Challenge teams (11 in Vietnam, 9 in Colombia) were created and supported in developing solutions to improve diets and tackle those deficiencies. Awards and resources were transferred to the most promising solutions to enable their implementation. Pre/post measurements of the interventions’ impact using the Global Diet Quality Score as outcome metric showed significant improvement in the diets of Challenge participants. After introducing a series of companion articles that offer detailed results on those various steps, this paper draws strategic lessons from an action‐research perspective.
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Date: 2023-08-03  ·  Issue: 2023  ·  Volume: 1527
Reimagining scientific conferences—a Keystone Symposia report
Contributors: Shannon Weiman| Jennifer Cable| Walter Greenleaf| Felix Rundel| Kate E. Whitfield| Lory Wingate| Richard Gallagher| Jennifer Pesanelli| Dereck Orr| Thale C. Jarvis| Raluca Cadar| Matthew D' Uva| Dylan Ruediger| Robert Vaez| Adam Frisby| Sami Ahmed| Dorit Donoviel| Judith Klinman| Debbie Johnson|
Abstract: Scientific conferences play an important role in advancing research, scholarship, and the careers of emerging scientists. The COVID‐19 pandemic offered meeting organizers and researchers alike an opportunity to reimagine what scientific conferences could look like. Virtual conferences can increase inclusivity and accessibility while decreasing costs and carbon emissions. However, it is generally perceived that the digital world fails to adequately recapitulate many of the benefits of in‐person face‐to‐face interactions; these include socializing, and collaborative environments that can forge new research directions and provide critical career development opportunities. On November 15 and 16, 2022, researchers, representatives from diverse scientific conference organizations, leaders in virtual platform technologies, and innovators in conference design gathered online for the Open Access Keystone eSymposium “Reimagining Scientific Conferences.” The meeting focused on how conference organizers can leverage lessons from the pandemic and emerging virtual platforms to engage new audiences, rethink strategies for scientific exchange, and decrease the carbon footprint of in‐person events.
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Date: 2023-08-02  ·  Issue: 2023  ·  Volume: 1527
Transfusion management in thalassemia
Contributors: Jeanne Boudreaux|
Abstract: This review describes the current challenges and recommendations in the transfusion management of thalassemia patients. In addition, it reviews the components of blood safety and blood product modification in special populations. Adverse transfusion reactions are described as are some of the newer technologies being utilized to reduce potential transfusion‐associated pathogens. Lastly, research in blood storage and in manufactured blood is briefly described.
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Date: 2023-08-02  ·  Issue: 2023  ·  Volume: 1527
REG1A protects retinal photoreceptors from blue light damage
Contributors: Ze‐Hua Xu| Hang Zhang| Chang‐Jun Zhang| Si‐Jian Yu| Jing Yuan| Kangxin Jin| Zi‐Bing Jin|
Abstract: With the increased use of artificial light and the prolonged use of optoelectronic products, light damage (LD) to the human retina has been identified as a global vision‐threatening problem. While there is evidence of a significant correlation between light‐induced retinal damage and age‐related vision impairment in age‐related macular degeneration, it is unclear how light‐induced retinal degeneration manifests itself and whether there are agents capable of preventing the development of LD in the retina. This study investigated a mechanism by which blue light leads to photoreceptor death. By observing blue light exposure in retinal organoids and photoreceptor cells, we concluded that there could be significant apoptosis of the photoreceptors. We demonstrate that regenerating islet‐derived 1 alpha (REG1A) prevents photoreceptors from undergoing this LD‐induced apoptosis by increasing expression of the anti‐apoptotic gene Bcl2 and downregulating expression of the pro‐apoptotic gene Bax, resulting in reduced mitochondrial damage and improved aerobic capacity in photoreceptor cells. For the first time, REG1A has been shown to restore mitochondrial function and cell apoptosis after LD‐induced damage, suggesting its potential application in the prevention and treatment of retinal vision loss.
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Date: 2023-08-02  ·  Issue: 2023  · 
Transfusion management in thalassemia
Contributors: Jeanne Boudreaux|
Abstract: This review describes the current challenges and recommendations in the transfusion management of thalassemia patients. In addition, it reviews the components of blood safety and blood product modification in special populations. Adverse transfusion reactions are described as are some of the newer technologies being utilized to reduce potential transfusion‐associated pathogens. Lastly, research in blood storage and in manufactured blood is briefly described.
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Date: 2023-08-01  ·  Issue: 2023  ·  Volume: 1527
The melanocortin receptor signaling system and its role in neuroprotection against neurodegeneration: Therapeutic insights
Contributors: Alemu Gebrie|
Abstract: The melanocortin signaling system consists of the melanocortin peptides, their distinctive receptors, accessory proteins, and endogenous antagonists. Melanocortin peptides are small peptide hormones that have been studied in a variety of physiological and pathological conditions. There are five types of melanocortin receptors, and they are distributed within the central nervous system and in several tissues of the periphery. The G protein–coupled melanocortin receptors typically signal through adenylyl cyclase and other downstream signaling pathways. Depending on the ligand, surface expression of melanocortin receptor, receptor occupancy period, related proteins, the type of cell, and other parameters, the signaling pathways are complicated and pleiotropic. While it is known that all five melanocortin receptors are coupled to Gs, they can also occasionally couple to Gq or Gi. Both direct and indirect neuroprotection are induced by the melanocortin signaling system. Targeting several of the components of the melanocortin signaling system (ligands, receptors, accessory proteins, signaling effectors, and regulators) may provide therapeutic opportunities. Activation of the melanocortin system improves different functional traits in neurodegenerative diseases. There is a potential for additional melanocortin system interventions by interfering with dimerization or dissociation. This review aims to discuss the melanocortin receptor signaling system and its role in neuroprotection, as well as its therapeutic potential.
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Date: 2023-07-31  ·  Issue: 2023  ·  Volume: 1527
Will social scientists’ never‐ending disputes over words ever end?
Contributors: Gabriel Abend|
Abstract: Social science literatures are rife with disputes over their key words. I show that they tend to conflate two activities. One of them I call “word goes first!” It concerns word uses and how to appraise them. The other I call “distinction goes first!” It concerns distinctions and classifications and how to appraise them. For each activity, social science communities should get clear on what to do, what to circumvent, and what's at stake. I argue that both are practical reason activities. They should be partly driven by the common good, justice, and equality.
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Date: 2023-07-31  ·  Issue: 2023  · 
Will social scientists’ never‐ending disputes over words ever end?
Contributors: Gabriel Abend|
Abstract: Social science literatures are rife with disputes over their key words. I show that they tend to conflate two activities. One of them I call “word goes first!” It concerns word uses and how to appraise them. The other I call “distinction goes first!” It concerns distinctions and classifications and how to appraise them. For each activity, social science communities should get clear on what to do, what to circumvent, and what's at stake. I argue that both are practical reason activities. They should be partly driven by the common good, justice, and equality.
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Date: 2023-07-28  ·  Issue: 2023  · 
Dietary intake and occupational status among female youths of Thai Nguyen, Vietnam
Contributors: Lan Mai Tran| Phuong Hong Nguyen| Nga Thu Hoang| Duong Thuy Thi Truong| Trang Huyen Thi Tran| Diep Ngoc Bui| Hanh Thi Hong Hoa| Diem Thi Hua| Gilles Bergeron|
Abstract: Adolescence is a sensitive transition time that affects rights, roles, and responsibilities in food choice, yet limited evidence exists on dietary intakes during this critical period. This study assessed the food consumption pattern and the adequacy of energy, macronutrient, and micronutrient intakes among female youth belonging to three occupational groups in Vietnam. Dietary intakes were measured for 1001 participants aged 16–22 years using INDDEX24's 24‐h recall method. Multivariate regression analyses were conducted to examine differences in diet outcomes among the three occupational groups. Dietary diversity was similar across groups but workers, compared to high school and college students, consumed less baked/grain‐based sweets and fast foods, and more soft drinks, other sweets, and processed meat. Two‐thirds of the sample showed energy intake lower than the estimated energy requirement, while a substantial percentage had insufficient or excessive intake of carbohydrate and fat. The mean probability of adequacy of nutrient intakes was low (0.33) and not different across all three occupational groups except for folate, which favored workers. Our study provides novel evidence supporting the development and implementation of interventions to achieve national targets, with emphasis on female youths who undergo special transitions in education, occupation, and lifestyle.
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Date: 2023-07-27  ·  Issue: 2023  · 
Automated behavioral scoring: Do we even need humans?
Contributors: Will Kenkel|
Abstract: The development of automated behavior scoring technology has been a tremendous boon to the study of social behavior. However, completely outsourcing behavioral analysis to a computer runs the risk of overlooking important nuances, and researchers risk distancing themselves from their very object of study. Here, I make the case that while automating analysis has been valuable, and overautomating analysis is risky, more effort should be spent automating the collection of behavioral data. Continuous automated behavioral observations conducted in situ have the promise to reduce confounding elements of social behavior research, such as handling stress, novel environments, one‐time “snapshot” measures, and experimenter presence. Now that we have the capability to automatically process behavioral observations thanks to machine vision and machine learning, we would do well to leverage the same open‐source ethos to increase the throughput of behavioral observation and collection. Fortunately, several such platforms have recently been developed. Repeated testing in the home environment will produce higher qualities and quantities of data, bringing us closer to realizing the ethological goals of studying animal behavior in a naturalistic context.
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Date: 2023-07-27  ·  Issue: 2023  ·  Volume: 1527
Automated behavioral scoring: Do we even need humans?
Contributors: Will Kenkel|
Abstract: The development of automated behavior scoring technology has been a tremendous boon to the study of social behavior. However, completely outsourcing behavioral analysis to a computer runs the risk of overlooking important nuances, and researchers risk distancing themselves from their very object of study. Here, I make the case that while automating analysis has been valuable, and overautomating analysis is risky, more effort should be spent automating the collection of behavioral data. Continuous automated behavioral observations conducted in situ have the promise to reduce confounding elements of social behavior research, such as handling stress, novel environments, one‐time “snapshot” measures, and experimenter presence. Now that we have the capability to automatically process behavioral observations thanks to machine vision and machine learning, we would do well to leverage the same open‐source ethos to increase the throughput of behavioral observation and collection. Fortunately, several such platforms have recently been developed. Repeated testing in the home environment will produce higher qualities and quantities of data, bringing us closer to realizing the ethological goals of studying animal behavior in a naturalistic context.
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Date: 2023-07-24  ·  Issue: 2023  ·  Volume: 1525
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Abstract:
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Date: 2023-07-21  ·  Issue: 2023  · 
Rethinking education, rethinking society
Contributors: Philip Kitcher|
Abstract: What should education aim to accomplish? What are its goals and how should it attempt to achieve them? Much excellent work, by philosophers and by policymakers, takes for granted the institutions and practices devised in the past. Yet, from time to time, it is important to stand back and to think more generally, to pose larger questions. My book, The Main Enterprise of the World, is written in that spirit.
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Date: 2023-07-21  ·  Issue: 2023  ·  Volume: 1527
Rethinking education, rethinking society
Contributors: Philip Kitcher|
Abstract: What should education aim to accomplish? What are its goals and how should it attempt to achieve them? Much excellent work, by philosophers and by policymakers, takes for granted the institutions and practices devised in the past. Yet, from time to time, it is important to stand back and to think more generally, to pose larger questions. My book, The Main Enterprise of the World, is written in that spirit.
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Date: 2023-07-19  ·  Issue: 2023  ·  Volume: 1527
The patient perspective: The struggles of living with thalassemia as an adult
Contributors: Radhika N. Sawh|
Abstract: Today it has become the norm for individuals diagnosed with severe forms of thalassemia who have access to hypertransfusion regimens, chelation therapy, and annual surveillance to survive well beyond childhood. However, with this improvement in prognosis and subsequent transition to adult care, it has become apparent that most adult healthcare providers, including many adult hematologists and primary care providers, are ill‐prepared to care for these patients and the complications that accompany their survival into adulthood. Collaborative efforts are needed to develop comprehensive approaches to contend with the challenges faced by adult patients to ensure they are properly managed and supported.
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Date: 2023-07-19  ·  Issue: 2023  · 
The patient perspective: The struggles of living with thalassemia as an adult
Contributors: Radhika N. Sawh|
Abstract: Today it has become the norm for individuals diagnosed with severe forms of thalassemia who have access to hypertransfusion regimens, chelation therapy, and annual surveillance to survive well beyond childhood. However, with this improvement in prognosis and subsequent transition to adult care, it has become apparent that most adult healthcare providers, including many adult hematologists and primary care providers, are ill‐prepared to care for these patients and the complications that accompany their survival into adulthood. Collaborative efforts are needed to develop comprehensive approaches to contend with the challenges faced by adult patients to ensure they are properly managed and supported.
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Date: 2023-07-19  ·  Issue: 2023  · 
The role of insider knowledge in the trajectories of highly accomplished scientists
Contributors: Rena F. Subotnik| Paula Olszewski‐Kubilius| Frank C. Worrell|
Abstract: Insider knowledge is critical information about how to achieve success that is not available to the general public but is relatively well‐known to individuals within the domain and to those who have access to those individuals. The goal of this study was to examine the perceived role of insider knowledge in a sample of highly accomplished American professionals in science, technology, engineering, and mathematics (STEM). We asked participants explicitly if insider knowledge had played a role in their talent development trajectory from K–12 education to their current creative work, with questions related to experiences at the undergraduate and graduate level and during their careers. The study was exploratory, so no formal hypotheses were put forward. Given the lack of research on the topic of insider knowledge as defined in this paper, we conducted semi‐structured interviews with a select group of individuals who had successful careers in STEM fields, both to see if insider knowledge was something that they considered important and to see if they felt that insider knowledge had played a role in their educational and career trajectories. Our hope is that the results of this paper will inform future in‐depth studies on the topic of insider knowledge.
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Date: 2023-07-19  ·  Issue: 2023  ·  Volume: 1527
The role of insider knowledge in the trajectories of highly accomplished scientists
Contributors: Rena F. Subotnik| Paula Olszewski‐Kubilius| Frank C. Worrell|
Abstract: Insider knowledge is critical information about how to achieve success that is not available to the general public but is relatively well‐known to individuals within the domain and to those who have access to those individuals. The goal of this study was to examine the perceived role of insider knowledge in a sample of highly accomplished American professionals in science, technology, engineering, and mathematics (STEM). We asked participants explicitly if insider knowledge had played a role in their talent development trajectory from K–12 education to their current creative work, with questions related to experiences at the undergraduate and graduate level and during their careers. The study was exploratory, so no formal hypotheses were put forward. Given the lack of research on the topic of insider knowledge as defined in this paper, we conducted semi‐structured interviews with a select group of individuals who had successful careers in STEM fields, both to see if insider knowledge was something that they considered important and to see if they felt that insider knowledge had played a role in their educational and career trajectories. Our hope is that the results of this paper will inform future in‐depth studies on the topic of insider knowledge.
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Date: 2023-07-10  ·  Issue: 2023  ·  Volume: 1527
Affordances and curvature preference: The case of real objects and spaces
Contributors: Zakaria Djebbara| Saleh Kalantari|
Abstract: Chuquichambi and colleagues recently questioned the prevailing belief that a universal human visual preference exists for curved shapes and lines. Their comprehensive meta‐analysis demonstrated that while curvature preference is widespread, it is not universally constant or invariant. By revisiting their dataset, we made an intriguing discovery: a negative relationship between curvature preference and an object's “affordances.” Taking an embodiment perspective into account, we propose an explanation for this phenomenon, suggesting that the diminished curvature preference in objects with abundant affordances can be understood through the lens of embodied cognition.
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Date: 2023-07-06  ·  Issue: 2023  ·  Volume: 1527
Locally relevant food‐based recommendations could increase iron and calcium intake for adolescent girls in Vietnam
Contributors: Simone Michelle Gie| Phuong Hong Nguyen| Gilles Bergeron| Lan Mai Tran| Nga Thu Hoang| Frances Knight|
Abstract: Unhealthy eating habits are common among adolescents in Vietnam, where transitioning food environments increasingly offer energy‐dense micronutrient‐poor foods. Successful behavior change approaches must be feasible and acceptable, promoting local foods that are available, accessible, and preferred. Yet, few studies have investigated the potential of food‐based approaches for adolescents. We used linear programming to identify problem nutrients, local nutrient sources, and realistic food‐based recommendations (FBRs) to improve nutrient intake among girls 16–22 years in Thai Nguyen, Vietnam. We then identified a reduced set of FBRs to prioritize the most critical micronutrient gaps. Calcium and iron targets could not be met in any realistic diet modeling scenario. The best set of FBRs included seven recommendations which could meet intake targets for 9 of 11 modeled micronutrients. The best reduced set of three FBRs targeting iron and calcium only—although more feasible for behavior change—was less effective at improving intake of these nutrients since fewer foods were recommended. Given the difficulty of meeting calcium and iron targets using local foods within acceptable dietary patterns, additional interventions, such as supplementation, staple food fortification, or increasing the availability of affordable calcium‐ and iron‐rich foods, may be necessary to promote dietary adequacy for adolescent girls.
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Date: 2023-07-06  ·  Issue: 2023  · 
Locally relevant food‐based recommendations could increase iron and calcium intake for adolescent girls in Vietnam
Contributors: Simone Michelle Gie| Phuong Hong Nguyen| Gilles Bergeron| Lan Mai Tran| Nga Thu Hoang| Frances Knight|
Abstract: Unhealthy eating habits are common among adolescents in Vietnam, where transitioning food environments increasingly offer energy‐dense micronutrient‐poor foods. Successful behavior change approaches must be feasible and acceptable, promoting local foods that are available, accessible, and preferred. Yet, few studies have investigated the potential of food‐based approaches for adolescents. We used linear programming to identify problem nutrients, local nutrient sources, and realistic food‐based recommendations (FBRs) to improve nutrient intake among girls 16–22 years in Thai Nguyen, Vietnam. We then identified a reduced set of FBRs to prioritize the most critical micronutrient gaps. Calcium and iron targets could not be met in any realistic diet modeling scenario. The best set of FBRs included seven recommendations which could meet intake targets for 9 of 11 modeled micronutrients. The best reduced set of three FBRs targeting iron and calcium only—although more feasible for behavior change—was less effective at improving intake of these nutrients since fewer foods were recommended. Given the difficulty of meeting calcium and iron targets using local foods within acceptable dietary patterns, additional interventions, such as supplementation, staple food fortification, or increasing the availability of affordable calcium‐ and iron‐rich foods, may be necessary to promote dietary adequacy for adolescent girls.
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Date: 2023-07-04  ·  Issue: 2023  ·  Volume: 1526
Patterns, predictors, and outcomes of situated expectancy‐value profiles in an introductory chemistry course
Contributors: Tony Perez| Kristy A. Robinson| Stacy J. Priniski| You‐kyung Lee| Delaram A. Totonchi| Lisa Linnenbrink‐Garcia|
Abstract: Using latent profile analysis, we identified profiles of expectancy beliefs, perceived values, and perceived costs among 1433 first‐ and second‐year undergraduates in an introductory chemistry course for STEMM majors. We also investigated demographic differences in profile membership and the relation of profiles to chemistry final exam achievement, science/STEMM credits completed, and graduating with a science/STEMM major. Four motivational profiles were identified: Moderately Confident and Costly (profile 1), Mixed Values‐Costs/Moderate‐High Confidence (profile 2), High Confidence and Values/Moderate‐Low Costs (profile 3), and High All (profile 4). Underrepresented students in STEMM were more likely to be in profile 2 relative to profile 3. First‐generation college students were more likely to be in profile 4 than profile 3. Finally, students likely to be in profile 3 had higher final exam grades than the other profiles and were more likely to graduate with a science major compared to profile 1. There were no differences in graduating science major between profile 3 and the other two profiles. Thus, profile 3 was most adaptive for both proximal (final exam) and distal (graduating with a science major) outcomes. Results suggest that supporting motivation early in college is important for persistence and ultimately the talent development of undergraduate STEMM students.
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Date: 2023-07-03  ·  Issue: 2023  · 
Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies
Contributors: George Agyapong| Farzaneh Dashti| Bubu A. Banini|
Abstract: Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease worldwide and a leading indication for liver transplantation in the United States. NAFLD encompasses a heterogeneous clinicopathologic spectrum, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis, and progressive fibrosis, which can lead to end‐stage liver disease including cirrhosis and hepatocellular cancer. Predictive models suggest that over 100 million adults in the United States will have NAFLD by 2030, representing over a third of the population. In this manuscript, we provide an overview of NAFLD risk factors, natural history (including hepatic and extra‐hepatic outcomes), diagnosis, and current management strategies.
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Date: 2023-07-03  ·  Issue: 2023  ·  Volume: 1526
Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies
Contributors: George Agyapong| Farzaneh Dashti| Bubu A. Banini|
Abstract: Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease worldwide and a leading indication for liver transplantation in the United States. NAFLD encompasses a heterogeneous clinicopathologic spectrum, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis, and progressive fibrosis, which can lead to end‐stage liver disease including cirrhosis and hepatocellular cancer. Predictive models suggest that over 100 million adults in the United States will have NAFLD by 2030, representing over a third of the population. In this manuscript, we provide an overview of NAFLD risk factors, natural history (including hepatic and extra‐hepatic outcomes), diagnosis, and current management strategies.
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Date: 2023-07-01  ·  Issue: 2023  ·  Volume: 1526
Effects of sleep disturbance on trauma‐focused psychotherapy outcomes in posttraumatic stress disorder: A systematic review
Contributors: Sarah A. Bottari| Erin R. Trifilio| David M. Janicke| Eric C. Porges| Ronald A. Cohen| Michael S. Jaffee| John B. Williamson|
Abstract: This study aimed to synthesize existing research on the effects of sleep disturbances on trauma‐focused psychotherapy outcomes in adults with posttraumatic stress disorder (PTSD). A systematic review using PubMed, PsycINFO, Embase, Web of Science, and PTSDpubs was performed up to April 2021. Two independent reviewers screened articles for inclusion, performed data extraction, and assessed risk of bias and certainty of the evidence. Narrative synthesis was conducted based on the type of sleep disorder symptom assessed. Sixteen primary studies were included in this review, the majority of which had a high overall risk of bias. Results suggested that sleep disorder symptoms were associated with higher overall PTSD severity across treatment; however, they did not interfere with treatment effectiveness, with the exception of sleep‐disordered breathing. Improvements in insomnia, sleep duration, and sleep quality during treatment were associated with greater treatment gains. Certainty of the evidence ranged from low to very low. These results suggest that it may not be necessary to address sleep disorder symptoms prior to initiating trauma‐focused psychotherapy. Instead, concurrent treatment of sleep‐ and trauma‐related symptoms may be most beneficial. Continued research is needed to clarify the mechanistic relationship between sleep and treatment outcomes and to guide clinical decision‐making.
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Date: 2023-06-30  ·  Issue: 2023  · 
Inheritance of epigenetic transcriptional memory through read–write replication of a histone modification
Contributors: Jason H. Brickner|
Abstract: Epigenetic transcriptional regulation frequently requires histone modifications. Some, but not all, of these modifications are able to template their own inheritance. Here, I discuss the molecular mechanisms by which histone modifications can be inherited and relate these ideas to new results about epigenetic transcriptional memory, a phenomenon that poises recently repressed genes for faster reactivation and has been observed in diverse organisms. Recently, we found that the histone H3 lysine 4 dimethylation that is associated with this phenomenon plays a critical role in sustaining memory and, when factors critical for the establishment of memory are inactivated, can be stably maintained through multiple mitoses. This chromatin‐mediated inheritance mechanism may involve a physical interaction between an H3K4me2 reader, SET3C, and an H3K4me2 writer, Spp1− COMPASS. This is the first example of a chromatin‐mediated inheritance of a mark that promotes transcription.
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Date: 2023-06-30  ·  Issue: 2023  ·  Volume: 1526
Advancing understanding of discordant mentoring relationships in STEMM: A method and framework
Contributors: Danielle X. Morales| Sara E. Grineski| Timothy W. Collins|
Abstract: Having a diverse workforce in STEMM (science, technology, engineering, mathematics, and medicine) fields is essential for the United States to remain competitive in the global economy and to create a more just society. Faculty‐mentored undergraduate research experiences have been identified as a high‐impact practice for encouraging students from diverse backgrounds to pursue STEMM education and careers. Despite extensive research examining factors influencing the effectiveness of mentor−mentee relationships, there is still limited understanding of how differences or similarities in the social identities of mentors and mentees, which we term mentor−mentee discordance, impact undergraduates’ research experiences and outcomes. In this perspective, we propose that mentor−mentee discordance should be conceptualized as a multidimensional, continuous construct and suggest a global index to measure varying degrees of discordance in mentoring relationships. We also offer a conceptual model that incorporates the Discordance Index to systematize the understanding of the effects of discordant mentoring relationships on student development across social contexts and over time. Finally, we provide recommendations for future researchers, STEMM educators, and program directors who are interested in using the Discordance Index.
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Date: 2023-06-30  ·  Issue: 2022  · 
Including calcium‐fortified water or flour in modeled diets based on local foods could improve calcium intake for women, adolescent girls, and young children in Bangladesh, Uganda, and Guatemala
Contributors: Frances Knight| Elaine L. Ferguson| Ziaul H. Rana| José Belizan| Filomena Gomes| Megan W. Bourassa| Katherine L. Dickin| Connie M. Weaver| Gabriela Cormick|
Abstract: Adequate calcium intake is essential for health, especially for infants, children, adolescents, and women, yet is difficult to achieve with local foods in many low‐ and middle‐income countries. Previous analysis found it was not always possible to identify food‐based recommendations (FBRs) that reached the calcium population recommended intake (PRI) for these groups in Bangladesh, Guatemala, and Uganda. We have modeled the potential contribution of calcium‐fortified drinking water or wheat flour to FBR sets, to fill the remaining intake gaps. Optimized diets containing fortified products, with calcium‐rich local foods, achieved the calcium PRI for all target groups. Combining fortified water or flour with FBRs met dietary intake targets for adolescent girls in all geographies and allowed a reduction from 3–4 to the more feasible 1–2 FBRs. Water with a calcium concentration of 100 mg/L with FBRs was sufficient to meet calcium targets in Uganda, but higher concentrations (400–500 mg/L) were mostly required in Guatemala and Bangladesh. Combining calcium‐fortified wheat flour at 400 mg/100 g of flour and the FBR for small fish resulted in diets meeting the calcium PRI in Bangladesh. Calcium‐fortified water or flour could improve calcium intake for vulnerable populations, especially when combined with FBRs based on locally available foods.
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Date: 2023-06-30  ·  Issue: 2023  · 
Advancing understanding of discordant mentoring relationships in STEMM: A method and framework
Contributors: Danielle X. Morales| Sara E. Grineski| Timothy W. Collins|
Abstract: Having a diverse workforce in STEMM (science, technology, engineering, mathematics, and medicine) fields is essential for the United States to remain competitive in the global economy and to create a more just society. Faculty‐mentored undergraduate research experiences have been identified as a high‐impact practice for encouraging students from diverse backgrounds to pursue STEMM education and careers. Despite extensive research examining factors influencing the effectiveness of mentor−mentee relationships, there is still limited understanding of how differences or similarities in the social identities of mentors and mentees, which we term mentor−mentee discordance, impact undergraduates’ research experiences and outcomes. In this perspective, we propose that mentor−mentee discordance should be conceptualized as a multidimensional, continuous construct and suggest a global index to measure varying degrees of discordance in mentoring relationships. We also offer a conceptual model that incorporates the Discordance Index to systematize the understanding of the effects of discordant mentoring relationships on student development across social contexts and over time. Finally, we provide recommendations for future researchers, STEMM educators, and program directors who are interested in using the Discordance Index.
Read More  

Date: 2023-06-30  ·  Issue: 2023  ·  Volume: 1526
Inheritance of epigenetic transcriptional memory through read–write replication of a histone modification
Contributors: Jason H. Brickner|
Abstract: Epigenetic transcriptional regulation frequently requires histone modifications. Some, but not all, of these modifications are able to template their own inheritance. Here, I discuss the molecular mechanisms by which histone modifications can be inherited and relate these ideas to new results about epigenetic transcriptional memory, a phenomenon that poises recently repressed genes for faster reactivation and has been observed in diverse organisms. Recently, we found that the histone H3 lysine 4 dimethylation that is associated with this phenomenon plays a critical role in sustaining memory and, when factors critical for the establishment of memory are inactivated, can be stably maintained through multiple mitoses. This chromatin‐mediated inheritance mechanism may involve a physical interaction between an H3K4me2 reader, SET3C, and an H3K4me2 writer, Spp1− COMPASS. This is the first example of a chromatin‐mediated inheritance of a mark that promotes transcription.
Read More  

Date: 2023-06-23  ·  Issue: 2023  · 
Transcriptomic effects of the foraging gene shed light on pathways of pleiotropy and plasticity
Contributors: Dustin J. Sokolowski| Oscar E. Vasquez| Michael D. Wilson| Marla B. Sokolowski| Ina Anreiter|
Abstract: Genes are often pleiotropic and plastic in their expression, features which increase and diversify the functionality of the genome. The foraging (for) gene in Drosophila melanogaster is highly pleiotropic and a long‐standing model for studying individual differences in behavior and plasticity from ethological, evolutionary, and genetic perspectives. Its pleiotropy is known to be linked to its complex molecular structure; however, the downstream pathways and interactors remain mostly elusive. To uncover these pathways and interactors and gain a better understanding of how pleiotropy and plasticity are achieved at the molecular level, we explore the effects of different for alleles on gene expression at baseline and in response to 4 h of food deprivation, using RNA sequencing analysis in different Drosophila larval tissues. The results show tissue‐specific transcriptomic dynamics influenced by for allelic variation and food deprivation, as well as genotype by treatment interactions. Differentially expressed genes yielded pathways linked to previously described for phenotypes and several potentially novel phenotypes. Together, these findings provide putative genes and pathways through which for might regulate its varied phenotypes in a pleiotropic, plastic, and gene‐structure‐dependent manner.
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Date: 2023-06-23  ·  Issue: 2023  ·  Volume: 1526
Transcriptomic effects of the foraging gene shed light on pathways of pleiotropy and plasticity
Contributors: Dustin J. Sokolowski| Oscar E. Vasquez| Michael D. Wilson| Marla B. Sokolowski| Ina Anreiter|
Abstract: Genes are often pleiotropic and plastic in their expression, features which increase and diversify the functionality of the genome. The foraging (for) gene in Drosophila melanogaster is highly pleiotropic and a long‐standing model for studying individual differences in behavior and plasticity from ethological, evolutionary, and genetic perspectives. Its pleiotropy is known to be linked to its complex molecular structure; however, the downstream pathways and interactors remain mostly elusive. To uncover these pathways and interactors and gain a better understanding of how pleiotropy and plasticity are achieved at the molecular level, we explore the effects of different for alleles on gene expression at baseline and in response to 4 h of food deprivation, using RNA sequencing analysis in different Drosophila larval tissues. The results show tissue‐specific transcriptomic dynamics influenced by for allelic variation and food deprivation, as well as genotype by treatment interactions. Differentially expressed genes yielded pathways linked to previously described for phenotypes and several potentially novel phenotypes. Together, these findings provide putative genes and pathways through which for might regulate its varied phenotypes in a pleiotropic, plastic, and gene‐structure‐dependent manner.
Read More  

Date: 2023-06-22  ·  Issue: 2023  · 
Morality anchored in bedrock—one philosopher's obsession
Contributors: David Edmonds|
Abstract:
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Date: 2023-06-22  ·  Issue: 2023  ·  Volume: 1526
Morality anchored in bedrock—one philosopher's obsession
Contributors: David Edmonds|
Abstract:
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Date: 2023-06-21  ·  Issue: 2023  ·  Volume: 1524
Issue Information
Contributors:
Abstract:
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Date: 2023-06-21  ·  Issue: 2023  ·  Volume: 1526
Emotion in the mind's eye: Imagination for adaptive cognition
Contributors: Chantelle M. Cocquyt| Daniela J. Palombo|
Abstract: In a complex world, we are constantly faced with environmental stimuli that shape our moment‐to‐moment experiences. But just as rich and complex as the external world is the internal milieu—our imagination. Imagination offers a powerful vehicle for playing out hypothetical experiences in the mind's eye. It allows us to mentally time travel to behold what the future might bring, including our greatest desires or fears. Indeed, imagined experiences tend to be emotion‐laden. How and why are humans capable of this remarkable feat? Based on psychological findings, we highlight the importance of imagination for emotional aspects of cognition and behavior, namely in the generation and regulation of emotions. Based on recent cognitive neuroscience work, we identify putative neural networks that are most critical for emotional imagination, with a major focus on the default mode network. Finally, we briefly highlight the possible functional implications of individual differences in imagination. Overall, we hope to address why humans have the capacity to simulate hypothetical emotional experiences and how this ability can be harnessed in adaptive (and sometimes maladaptive) ways. We end by discussing open questions.
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Date: 2023-06-21  ·  Issue: 2022  · 
Claudin‐19 localizes to the thick ascending limb where its expression is required for junctional claudin‐16 localization
Contributors: Henrik Dimke| Camille Griveau| Wung‐Man Evelyne Ling| Gaelle Brideau| Lydie Cheval| Pravina Muthan| Dominik Müller| Amr Al‐Shebel| Pascal Houillier| Caroline Prot‐Bertoye|
Abstract: The kidney is critical for mineral homeostasis. Calcium and magnesium reabsorption in the renal thick ascending limb (TAL) involves claudin‐16 (CLDN16) and claudin‐19 (CLDN19) and pathogenic variants in either gene lead to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) with severe calcium and magnesium wasting. While both CLDN16 and CLDN19 localize to the TAL, varying expression patterns in the renal tubule have been reported using different antibodies. We, therefore, studied the localization of CLDN19 in the kidneys of wild‐type and Cldn19‐deleted mice using three anti‐CLDN19 antibodies and examined the role of Cldn19 deletion on CLDN16 and CLDN10 localization. We find that CLDN19 localizes to basolateral membrane domains of the medullary and cortical TAL but only to the tight junction of TALs in the outer stripe of outer medulla and cortex, where it colocalizes with CLDN16. Furthermore, in TALs from Cldn19‐deleted mice, CLDN16 is expressed in basolateral membrane domains but not at the tight junction. In contrast, Cldn19 ablation does not change CLDN10 localization. These findings directly implicate CLDN19 in regulating permeability in the TAL by allowing junctional insertion of CLDN16 and may explain the shared renal phenotypic characteristics in FHHNC patients.
Read More  

Date: 2023-06-21  ·  Issue: 2022  · 
Emotion in the mind's eye: Imagination for adaptive cognition
Contributors: Chantelle M. Cocquyt| Daniela J. Palombo|
Abstract: In a complex world, we are constantly faced with environmental stimuli that shape our moment‐to‐moment experiences. But just as rich and complex as the external world is the internal milieu—our imagination. Imagination offers a powerful vehicle for playing out hypothetical experiences in the mind's eye. It allows us to mentally time travel to behold what the future might bring, including our greatest desires or fears. Indeed, imagined experiences tend to be emotion‐laden. How and why are humans capable of this remarkable feat? Based on psychological findings, we highlight the importance of imagination for emotional aspects of cognition and behavior, namely in the generation and regulation of emotions. Based on recent cognitive neuroscience work, we identify putative neural networks that are most critical for emotional imagination, with a major focus on the default mode network. Finally, we briefly highlight the possible functional implications of individual differences in imagination. Overall, we hope to address why humans have the capacity to simulate hypothetical emotional experiences and how this ability can be harnessed in adaptive (and sometimes maladaptive) ways. We end by discussing open questions.
Read More  

Date: 2023-06-21  ·  Issue: 2023  ·  Volume: 1526
Claudin‐19 localizes to the thick ascending limb where its expression is required for junctional claudin‐16 localization
Contributors: Henrik Dimke| Camille Griveau| Wung‐Man Evelyne Ling| Gaelle Brideau| Lydie Cheval| Pravina Muthan| Dominik Müller| Amr Al‐Shebel| Pascal Houillier| Caroline Prot‐Bertoye|
Abstract: The kidney is critical for mineral homeostasis. Calcium and magnesium reabsorption in the renal thick ascending limb (TAL) involves claudin‐16 (CLDN16) and claudin‐19 (CLDN19) and pathogenic variants in either gene lead to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) with severe calcium and magnesium wasting. While both CLDN16 and CLDN19 localize to the TAL, varying expression patterns in the renal tubule have been reported using different antibodies. We, therefore, studied the localization of CLDN19 in the kidneys of wild‐type and Cldn19‐deleted mice using three anti‐CLDN19 antibodies and examined the role of Cldn19 deletion on CLDN16 and CLDN10 localization. We find that CLDN19 localizes to basolateral membrane domains of the medullary and cortical TAL but only to the tight junction of TALs in the outer stripe of outer medulla and cortex, where it colocalizes with CLDN16. Furthermore, in TALs from Cldn19‐deleted mice, CLDN16 is expressed in basolateral membrane domains but not at the tight junction. In contrast, Cldn19 ablation does not change CLDN10 localization. These findings directly implicate CLDN19 in regulating permeability in the TAL by allowing junctional insertion of CLDN16 and may explain the shared renal phenotypic characteristics in FHHNC patients.
Read More  

Date: 2023-06-07  ·  Issue: 2023  ·  Volume: 1526
Childhood experiences and undergraduate student interest in STEM disciplines: Attending to setting and activity type
Contributors: Remy Dou| Heidi Cian| Zahra Hazari| Gerhard Sonnert| Philip M. Sadler|
Abstract: Informal STEM learning experiences (ISLEs), such as participating in science, computing, and engineering clubs and camps, have been associated with the development of youth’s science, technology, engineering, and mathematics interests and career aspirations. However, research on ISLEs predominantly focuses on institutional settings such as museums and science centers, which are often discursively inaccessible to youth who identify with minoritized demographic groups. Using latent class analysis, we identify five general profiles (i.e., classes) of childhood participation in ISLEs from data reported by a nationally representative sample of college students (N = 15,579). Results show that childhood participation in specific typologies of ISLEs (i.e., setting and activity type) is associated with youth's disciplinary interests at the end of high school. Participation in outdoor activities that invite observation is more often reported by female respondents and is negatively associated with interest in computing and mathematics. Participation in indoor activities that invite object manipulation is more often reported by male respondents and is positively associated with interest in computing and engineering. However, frequent participation in multiple ISLEs is positively associated with interest in “science.” These results elucidate stereotypical discourses that reinforce the exclusion of minoritized students and expose critical areas needing reform.
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Date: 2023-06-07  ·  Issue: 2023  · 
Childhood experiences and undergraduate student interest in STEM disciplines: Attending to setting and activity type
Contributors: Remy Dou| Heidi Cian| Zahra Hazari| Gerhard Sonnert| Philip M. Sadler|
Abstract: Informal STEM learning experiences (ISLEs), such as participating in science, computing, and engineering clubs and camps, have been associated with the development of youth’s science, technology, engineering, and mathematics interests and career aspirations. However, research on ISLEs predominantly focuses on institutional settings such as museums and science centers, which are often discursively inaccessible to youth who identify with minoritized demographic groups. Using latent class analysis, we identify five general profiles (i.e., classes) of childhood participation in ISLEs from data reported by a nationally representative sample of college students (N = 15,579). Results show that childhood participation in specific typologies of ISLEs (i.e., setting and activity type) is associated with youth's disciplinary interests at the end of high school. Participation in outdoor activities that invite observation is more often reported by female respondents and is negatively associated with interest in computing and mathematics. Participation in indoor activities that invite object manipulation is more often reported by male respondents and is positively associated with interest in computing and engineering. However, frequent participation in multiple ISLEs is positively associated with interest in “science.” These results elucidate stereotypical discourses that reinforce the exclusion of minoritized students and expose critical areas needing reform.
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Date: 2023-06-05  ·  Issue: 2023  · 
Convergent mechanisms of microglia‐mediated synaptic dysfunction contribute to diverse neuropathological conditions
Contributors: Nicole Scott‐Hewitt| Youtong Huang| Beth Stevens|
Abstract: Changes in synaptic function are an early hallmark of neuropathological conditions that often precede symptom onset, with mounting genetic, transcriptional, and epidemiological evidence implicating microglia in this process. The correlation between infection and neurocognitive sequelae further suggests that environmental exposures modulate neuroimmune interactions and contribute to synaptic alterations. Recent studies investigating functional roles of microglia across broad neuropathological contexts including neurodegeneration, aging, neuropsychiatric and neurodevelopmental disorders, and neurotropic infections reveal convergent mechanisms underlying microglial‐mediated synaptic dysfunction. We propose that early microglial changes, driven by genetic alterations coupled with environmental neuroimmune modulation, may be a common denominator that contributes to early synaptic pathologies. Here we review the evidence and discuss how microglia respond, and contribute, to synaptopathies across diverse neurological conditions, spotlighting their importance as broadly relevant therapeutic targets within neurological diseases.
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Date: 2023-06-05  ·  Issue: 2023  ·  Volume: 1525
Convergent mechanisms of microglia‐mediated synaptic dysfunction contribute to diverse neuropathological conditions
Contributors: Nicole Scott‐Hewitt| Youtong Huang| Beth Stevens|
Abstract: Changes in synaptic function are an early hallmark of neuropathological conditions that often precede symptom onset, with mounting genetic, transcriptional, and epidemiological evidence implicating microglia in this process. The correlation between infection and neurocognitive sequelae further suggests that environmental exposures modulate neuroimmune interactions and contribute to synaptic alterations. Recent studies investigating functional roles of microglia across broad neuropathological contexts including neurodegeneration, aging, neuropsychiatric and neurodevelopmental disorders, and neurotropic infections reveal convergent mechanisms underlying microglial‐mediated synaptic dysfunction. We propose that early microglial changes, driven by genetic alterations coupled with environmental neuroimmune modulation, may be a common denominator that contributes to early synaptic pathologies. Here we review the evidence and discuss how microglia respond, and contribute, to synaptopathies across diverse neurological conditions, spotlighting their importance as broadly relevant therapeutic targets within neurological diseases.
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Date: 2023-05-30  ·  Issue: 2023  ·  Volume: 1525
Design and evaluation of an independent 4‐week, exosuit‐assisted, post‐stroke community walking program
Contributors: Richard W. Nuckols| Chih‐Kang Chang| Daekyum Kim| Asa Eckert‐Erdheim| Dorothy Orzel| Lauren Baker| Teresa Baker| Nicholas C. Wendel| Brendan Quinlivan| Patrick Murphy| Jesse Grupper| Jacqueline Villalobos| Louis N. Awad| Terry D. Ellis| Conor J. Walsh|
Abstract: Chronic impairment in the paretic ankle following stroke often requires that individuals use compensatory patterns such as asymmetric propulsion to achieve effective walking speeds needed for community engagement. Ankle exosuit assistance can provide ankle biomechanical benefit in the lab, but such environments inherently limit the amount of practice available. Community walking studies without exosuits can provide massed practice and benefit walking speed but are limited in their ability to assist proper mechanics. In this study, we combined the positive aspects of community training with those of exosuit assistance. We developed and evaluated a community Robotic Exosuit Augmented Locomotion (cREAL) program. Four participants in the chronic stage of stroke independently used our community ankle exosuit for walking in the community 3–5 days/week for 4 weeks. We performed lab evaluations before and after the 4‐week program. Two participants significantly improved their unassisted paretic propulsion by an average of 27% after the program and walked on average 4001 steps/day more in the week following the program. Despite the small number of participants, this study provides preliminary evidence for the potential of exosuits to augment gait training and rehabilitation in the community.
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Date: 2023-05-25  ·  Issue: 2023  ·  Volume: 1525
Could local foods achieve recommended calcium intakes for nutritionally vulnerable populations in Uganda, Guatemala, and Bangladesh?
Contributors: Frances Knight| Ziaul H. Rana| Gabriela Cormick| José Belizan| Filomena Gomes| Megan W. Bourassa| Katherine L. Dickin| Connie M. Weaver| Elaine L. Ferguson|
Abstract: Globally, dietary intake of calcium is often insufficient, and it is unclear if adequacy could be achieved by promoting calcium‐rich local foods. This study used linear programming and household consumption data from Uganda, Bangladesh, and Guatemala to assess whether local foods could meet calcium population reference intakes (Ca PRIs). The most promising food‐based approaches to promote dietary calcium adequacy were identified for 12‐ to 23‐month‐old breastfed children, 4‐ to 6‐year‐old children, 10‐ to 14‐year‐old girls, and nonpregnant and nonbreastfeeding (NPNB) women of reproductive age living in two regions of each country. Calcium‐optimized diets achieved 75–253% of the Ca PRI, depending on the population, and were <100% for 4‐ to 6‐year‐olds in one region of each country and 10‐ to 14‐year‐old girls in Sylhet, Bangladesh. The best food sources of calcium were green leafy vegetables and milk, across geographic locations, and species of small fish, nixtamalized (lime‐treated) maize products, sesame seeds, and bean varieties, where consumed. Food‐based recommendations (FBRs) achieving the minimum calcium threshold were identified for 12‐ to 23‐month‐olds and NPNB women across geographic locations, and for 4‐ to 6‐year‐olds and 10‐to 14‐year‐old girls in Uganda. However, for 4‐ to 6‐year‐olds and 10‐ to 14‐year‐old girls in Bangladesh and Guatemala, calcium‐adequate FBRs could not be identified, indicating a need for alternative calcium sources or increased access to and consumption of local calcium‐rich foods.
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Date: 2023-05-25  ·  Issue: 2023  ·  Volume: 1525
The need for robust critique of arts and health research: Dance‐movement therapy, girls, and depression
Contributors: Katarzyna Grebosz‐Haring| Leonhard Thun‐Hohenstein| Anna K. Schuchter‐Wiegand| Arne C. Bathke| Stephen Clift|
Abstract: We examine a highly cited randomized controlled trial on dance‐movement therapy with adolescent girls with mild depression and examine its treatment in 14 evidence reviews and meta‐analyses of dance research. We demonstrate substantial limitations in the trial which seriously undermine the conclusions reached regarding the effectiveness of dance movement therapy in reducing depression. We also show that the dance research reviews vary substantially in their treatment of the study. Some reviews provide a positive assessment of the study and take its findings at face value without critical commentary. Others are critical of the study, identifying significant limitations, but showing marked differences in Cochrane Risk of Bias assessments. Drawing on recent criticisms of systematic reviewing and meta‐analysis, we consider how reviews can be so variable and discuss what is needed to improve the quality of primary studies, systematic reviews, and meta‐analyses in the field of creative arts and health.
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Date: 2023-05-25  ·  Issue: 2023  · 
Holistic Evaluation of Language Models
Contributors: Rishi Bommasani| Percy Liang| Tony Lee|
Abstract: Language models (LMs) like GPT‐3, PaLM, and ChatGPT are the foundation for almost all major language technologies, but their capabilities, limitations, and risks are not well understood. We present Holistic Evaluation of Language Models (HELM) to improve the transparency of LMs. LMs can serve many purposes and their behavior should satisfy many desiderata. To navigate the vast space of potential scenarios and metrics, we taxonomize the space and select representative subsets. We evaluate models on 16 core scenarios and 7 metrics, exposing important trade‐offs. We supplement our core evaluation with seven targeted evaluations to deeply analyze specific aspects (including world knowledge, reasoning, regurgitation of copyrighted content, and generation of disinformation). We benchmark 30 LMs, from OpenAI, Microsoft, Google, Meta, Cohere, AI21 Labs, and others. Prior to HELM, models were evaluated on just 17.9% of the core HELM scenarios, with some prominent models not sharing a single scenario in common. We improve this to 96.0%: all 30 models are now benchmarked under the same standardized conditions. Our evaluation surfaces 25 top‐level findings. For full transparency, we release all raw model prompts and completions publicly. HELM is a living benchmark for the community, continuously updated with new scenarios, metrics, and models https://crfm.stanford.edu/helm/latest/.
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Date: 2023-05-25  ·  Issue: 2022  · 
Could local foods achieve recommended calcium intakes for nutritionally vulnerable populations in Uganda, Guatemala, and Bangladesh?
Contributors: Frances Knight| Ziaul H. Rana| Gabriela Cormick| José Belizan| Filomena Gomes| Megan W. Bourassa| Katherine L. Dickin| Connie M. Weaver| Elaine L. Ferguson|
Abstract: Globally, dietary intake of calcium is often insufficient, and it is unclear if adequacy could be achieved by promoting calcium‐rich local foods. This study used linear programming and household consumption data from Uganda, Bangladesh, and Guatemala to assess whether local foods could meet calcium population reference intakes (Ca PRIs). The most promising food‐based approaches to promote dietary calcium adequacy were identified for 12‐ to 23‐month‐old breastfed children, 4‐ to 6‐year‐old children, 10‐ to 14‐year‐old girls, and nonpregnant and nonbreastfeeding (NPNB) women of reproductive age living in two regions of each country. Calcium‐optimized diets achieved 75–253% of the Ca PRI, depending on the population, and were <100% for 4‐ to 6‐year‐olds in one region of each country and 10‐ to 14‐year‐old girls in Sylhet, Bangladesh. The best food sources of calcium were green leafy vegetables and milk, across geographic locations, and species of small fish, nixtamalized (lime‐treated) maize products, sesame seeds, and bean varieties, where consumed. Food‐based recommendations (FBRs) achieving the minimum calcium threshold were identified for 12‐ to 23‐month‐olds and NPNB women across geographic locations, and for 4‐ to 6‐year‐olds and 10‐to 14‐year‐old girls in Uganda. However, for 4‐ to 6‐year‐olds and 10‐ to 14‐year‐old girls in Bangladesh and Guatemala, calcium‐adequate FBRs could not be identified, indicating a need for alternative calcium sources or increased access to and consumption of local calcium‐rich foods.
Read More  

Date: 2023-05-25  ·  Issue: 2023  ·  Volume: 1525
Holistic Evaluation of Language Models
Contributors: Rishi Bommasani| Percy Liang| Tony Lee|
Abstract: Language models (LMs) like GPT‐3, PaLM, and ChatGPT are the foundation for almost all major language technologies, but their capabilities, limitations, and risks are not well understood. We present Holistic Evaluation of Language Models (HELM) to improve the transparency of LMs. LMs can serve many purposes and their behavior should satisfy many desiderata. To navigate the vast space of potential scenarios and metrics, we taxonomize the space and select representative subsets. We evaluate models on 16 core scenarios and 7 metrics, exposing important trade‐offs. We supplement our core evaluation with seven targeted evaluations to deeply analyze specific aspects (including world knowledge, reasoning, regurgitation of copyrighted content, and generation of disinformation). We benchmark 30 LMs, from OpenAI, Microsoft, Google, Meta, Cohere, AI21 Labs, and others. Prior to HELM, models were evaluated on just 17.9% of the core HELM scenarios, with some prominent models not sharing a single scenario in common. We improve this to 96.0%: all 30 models are now benchmarked under the same standardized conditions. Our evaluation surfaces 25 top‐level findings. For full transparency, we release all raw model prompts and completions publicly. HELM is a living benchmark for the community, continuously updated with new scenarios, metrics, and models https://crfm.stanford.edu/helm/latest/.
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Date: 2023-05-23  ·  Issue: 2023  · 
Agency in evolution of biomolecular communication
Contributors: Gustavo Caetano‐Anollés|
Abstract: Biomolecular communication demands that interactions between parts of a molecular system act as scaffolds for message transmission. It also requires an organized system of signs—a communicative agency—for creating and transmitting meaning. The emergence of agency, the capacity to act in a given context and generate end‐directed behaviors, has baffled evolutionary biologists for centuries. Here, I explore its emergence with knowledge grounded in over two decades of evolutionary genomic and bioinformatic exploration. Biphasic processes of growth and diversification exist that generate hierarchy and modularity in biological systems at widely ranging time scales. Similarly, a biphasic process exists in communication that constructs a message before it can be transmitted for interpretation. Transmission dissipates matter‐energy and information and involves computation. Agency emerges when molecular machinery generates hierarchical layers of vocabularies in an entangled communication network clustered around the universal Turing machine of the ribosome. Computations canalize biological systems to perform biological functions in a dissipative quest to structure long‐lived occurrents. This occurs within the confines of a “triangle of persistence” that maximizes invariance with trade‐offs between economy, flexibility, and robustness. Thus, learning from previous historical and circumstantial experiences unifies modules in a hierarchy that expands the agency of systems.
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Date: 2023-05-23  ·  Issue: 2023  · 
Astrocytes as master modulators of neural networks: Synaptic functions and disease‐associated dysfunction of astrocytes
Contributors: Jeffrey A. Stogsdill| Corey C. Harwell| Steven A. Goldman|
Abstract: Astrocytes are the most abundant glial cell type in the central nervous system and are essential to the development, plasticity, and maintenance of neural circuits. Astrocytes are heterogeneous, with their diversity rooted in developmental programs modulated by the local brain environment. Astrocytes play integral roles in regulating and coordinating neural activity extending far beyond their metabolic support of neurons and other brain cell phenotypes. Both gray and white matter astrocytes occupy critical functional niches capable of modulating brain physiology on time scales slower than synaptic activity but faster than those adaptive responses requiring a structural change or adaptive myelination. Given their many associations and functional roles, it is not surprising that astrocytic dysfunction has been causally implicated in a broad set of neurodegenerative and neuropsychiatric disorders. In this review, we focus on recent discoveries concerning the contributions of astrocytes to the function of neural networks, with a dual focus on the contribution of astrocytes to synaptic development and maturation, and on their role in supporting myelin integrity, and hence conduction and its regulation. We then address the emerging roles of astrocytic dysfunction in disease pathogenesis and on potential strategies for targeting these cells for therapeutic purposes.
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Date: 2023-05-18  ·  Issue: 2023  ·  Volume: 1525
Emerging roles of brain tanycytes in regulating blood–hypothalamus barrier plasticity and energy homeostasis
Contributors: Hasni Kannangara| Liam Cullen| Sari Miyashita| Funda Korkmaz| Anne Macdonald| Anisa Gumerova| Ronit Witztum| Ofer Moldavski| Steven Sims| Jocoll Burgess| Tal Frolinger| Rauf Latif| Yelena Ginzburg| Daria Lizneva| Ki Goosens| Terry F. Davies| Tony Yuen| Mone Zaidi| Vitaly Ryu|
Abstract: Seasonal changes in food intake and adiposity in many animal species are triggered by changes in the photoperiod. These latter changes are faithfully transduced into a biochemical signal by melatonin secreted by the pineal gland. Seasonal variations, encoded by melatonin, are integrated by third ventricular tanycytes of the mediobasal hypothalamus through the detection of the thyroid‐stimulating hormone (TSH) released from the pars tuberalis. The mediobasal hypothalamus is a critical brain region that maintains energy homeostasis by acting as an interface between the neural networks of the central nervous system and the periphery to control metabolic functions, including ingestive behavior, energy homeostasis, and reproduction. Among the cells involved in the regulation of energy balance and the blood–hypothalamus barrier (BHB) plasticity are tanycytes. Increasing evidence suggests that anterior pituitary hormones, specifically TSH, traditionally considered to have unitary functions in targeting single endocrine sites, display actions on multiple somatic tissues and central neurons. Notably, modulation of tanycytic TSH receptors seems critical for BHB plasticity in relation to energy homeostasis, but this needs to be proven.
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Date: 2023-05-17  ·  Issue: 2023  · 
Integrating and coordinating programs for the management of anemia across the life course
Contributors: Alison Mildon| Daniel Lopez de Romaña| Maria Elena D. Jefferds| Lisa M. Rogers| Jenna M. Golan| Mandana Arabi|
Abstract: Anemia is a major global public health concern with a complex etiology. The main determinants are nutritional factors, infection and inflammation, inherited blood disorders, and women's reproductive biology, but the relative role of each varies between settings. Effective anemia programming, therefore, requires evidence‐based, data‐driven, contextualized multisectoral strategies, with coordinated implementation. Priority population groups are preschool children, adolescent girls, and pregnant and nonpregnant women of reproductive age. Opportunities for comprehensive anemia programming include: (i) bundling interventions through shared delivery platforms, including antenatal care, community‐based platforms, schools, and workplaces; (ii) integrating delivery platforms to extend reach; (iii) integrating anemia and malaria programs in endemic areas; and (iv) integrating anemia programming across the life course. Major barriers to effective anemia programming include weak delivery systems, lack of data or poor use of data, lack of financial and human resources, and poor coordination. Systems strengthening and implementation research approaches are needed to address critical gaps, explore promising platforms, and identify solutions to persistent barriers to high intervention coverage. Immediate priorities are to close the gap between access to service delivery platforms and coverage of anemia interventions, reduce subnational coverage disparities, and improve the collection and use of data to inform anemia strategies and programming.
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Date: 2023-05-17  ·  Issue: 2023  ·  Volume: 1525
Integrating and coordinating programs for the management of anemia across the life course
Contributors: Alison Mildon| Daniel Lopez de Romaña| Maria Elena D. Jefferds| Lisa M. Rogers| Jenna M. Golan| Mandana Arabi|
Abstract: Anemia is a major global public health concern with a complex etiology. The main determinants are nutritional factors, infection and inflammation, inherited blood disorders, and women's reproductive biology, but the relative role of each varies between settings. Effective anemia programming, therefore, requires evidence‐based, data‐driven, contextualized multisectoral strategies, with coordinated implementation. Priority population groups are preschool children, adolescent girls, and pregnant and nonpregnant women of reproductive age. Opportunities for comprehensive anemia programming include: (i) bundling interventions through shared delivery platforms, including antenatal care, community‐based platforms, schools, and workplaces; (ii) integrating delivery platforms to extend reach; (iii) integrating anemia and malaria programs in endemic areas; and (iv) integrating anemia programming across the life course. Major barriers to effective anemia programming include weak delivery systems, lack of data or poor use of data, lack of financial and human resources, and poor coordination. Systems strengthening and implementation research approaches are needed to address critical gaps, explore promising platforms, and identify solutions to persistent barriers to high intervention coverage. Immediate priorities are to close the gap between access to service delivery platforms and coverage of anemia interventions, reduce subnational coverage disparities, and improve the collection and use of data to inform anemia strategies and programming.
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Date: 2023-05-12  ·  Issue: 2023  ·  Volume: 1523
Issue Information
Contributors:
Abstract:
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Date: 2023-05-11  ·  Issue: 2022  · 
A neurocognitive theory of flexible emotion control: The role of the lateral frontal pole in emotion regulation
Contributors: Karin Roelofs| Bob Bramson| Ivan Toni|
Abstract: Emotion regulation is essential to survive in a world full of challenges with rapidly changing contextual demands. The ability to flexibly shift between different emotional control strategies is critical to successfully deal with these demands. Recently, decision neuroscience has shown the importance of monitoring alternative control strategies. However, this insight has not been incorporated into current neurocognitive models of emotional control. Here, we integrate insights from decision and affective sciences into a novel viewpoint on emotion control, the Flexible Emotion Control Theory (FECT). This theory explains how an individual can flexibly change emotion‐regulatory behavior to adapt to varying goals and contextual demands. Crucially, FECT proposes that rapid switching between alternative emotional control strategies requires concurrent evaluation of current as well as alternative (unchosen) options. The neural implementation of FECT relies on the involvement of distinct prefrontal structures, including the lateral frontal pole (FPl) and its connections with other cortical (prefrontal, parietal, motor) and subcortical systems. This novel account of emotion control integrates insights from decision sciences, clinical research, as well as meta‐analytic evidence for the consistent FPl involvement during emotional control when monitoring of alternative emotional control strategies is required. Moreover, it provides novel, neurocognitively grounded starting points for interventions to improve emotion control in affective disorders, such as anxiety and aggression.
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Date: 2023-05-11  ·  Issue: 2023  ·  Volume: 1525
A neurocognitive theory of flexible emotion control: The role of the lateral frontal pole in emotion regulation
Contributors: Karin Roelofs| Bob Bramson| Ivan Toni|
Abstract: Emotion regulation is essential to survive in a world full of challenges with rapidly changing contextual demands. The ability to flexibly shift between different emotional control strategies is critical to successfully deal with these demands. Recently, decision neuroscience has shown the importance of monitoring alternative control strategies. However, this insight has not been incorporated into current neurocognitive models of emotional control. Here, we integrate insights from decision and affective sciences into a novel viewpoint on emotion control, the Flexible Emotion Control Theory (FECT). This theory explains how an individual can flexibly change emotion‐regulatory behavior to adapt to varying goals and contextual demands. Crucially, FECT proposes that rapid switching between alternative emotional control strategies requires concurrent evaluation of current as well as alternative (unchosen) options. The neural implementation of FECT relies on the involvement of distinct prefrontal structures, including the lateral frontal pole (FPl) and its connections with other cortical (prefrontal, parietal, motor) and subcortical systems. This novel account of emotion control integrates insights from decision sciences, clinical research, as well as meta‐analytic evidence for the consistent FPl involvement during emotional control when monitoring of alternative emotional control strategies is required. Moreover, it provides novel, neurocognitively grounded starting points for interventions to improve emotion control in affective disorders, such as anxiety and aggression.
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Date: 2023-05-08  ·  Issue: 2023  · 
On the origin and nature of nongenetic information in eumetazoans
Contributors: Nelson R. Cabej|
Abstract: Nongenetic information implies all the forms of biological information not related to genes and DNA in general. Despite the deep scientific relevance of the concept, we currently lack reliable knowledge about its carriers and origins; hence, we still do not understand its true nature. Given that genes are the targets of nongenetic information, it appears that a parsimonious approach to find the ultimate source of that information is to trace back the sequential steps of the causal chain upstream of the target genes up to the ultimate link as the source of the nongenetic information. From this perspective, I examine seven nongenetically determined phenomena: placement of locus‐specific epigenetic marks on DNA and histones, changes in snRNA expression patterns, neural induction of gene expression, site‐specific alternative gene splicing, predator‐induced morphological changes, and cultural inheritance. Based on the available evidence, I propose a general model of the common neural origin of all these forms of nongenetic information in eumetazoans.
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Date: 2023-05-08  ·  Issue: 2023  ·  Volume: 1525
On the origin and nature of nongenetic information in eumetazoans
Contributors: Nelson R. Cabej|
Abstract: Nongenetic information implies all the forms of biological information not related to genes and DNA in general. Despite the deep scientific relevance of the concept, we currently lack reliable knowledge about its carriers and origins; hence, we still do not understand its true nature. Given that genes are the targets of nongenetic information, it appears that a parsimonious approach to find the ultimate source of that information is to trace back the sequential steps of the causal chain upstream of the target genes up to the ultimate link as the source of the nongenetic information. From this perspective, I examine seven nongenetically determined phenomena: placement of locus‐specific epigenetic marks on DNA and histones, changes in snRNA expression patterns, neural induction of gene expression, site‐specific alternative gene splicing, predator‐induced morphological changes, and cultural inheritance. Based on the available evidence, I propose a general model of the common neural origin of all these forms of nongenetic information in eumetazoans.
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Date: 2023-05-02  ·  Issue: 2022  · 
Anxiety and depression: A top‐down, bottom‐up model of circuit function
Contributors: Deryn O. LeDuke| Matilde Borio| Raymundo Miranda| Kay M. Tye|
Abstract: A functional interplay of bottom‐up and top‐down processing allows an individual to appropriately respond to the dynamic environment around them. These processing modalities can be represented as attractor states using a dynamical systems model of the brain. The transition probability to move from one attractor state to another is dependent on the stability, depth, neuromodulatory tone, and tonic changes in plasticity. However, how does the relationship between these states change in disease states, such as anxiety or depression? We describe bottom‐up and top‐down processing from Marr's computational‐algorithmic‐implementation perspective to understand depressive and anxious disease states. We illustrate examples of bottom‐up processing as basolateral amygdala signaling and projections and top‐down processing as medial prefrontal cortex internal signaling and projections. Understanding these internal processing dynamics can help us better model the multifaceted elements of anxiety and depression.
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Date: 2023-04-27  ·  Issue: 2023  ·  Volume: 1524
A simple way to calculate the volume and surface area of avian eggs
Contributors: Peijian Shi| Long Chen| Brady K. Quinn| Kexin Yu| Qinyue Miao| Xuchen Guo| Meng Lian| Johan Gielis| Karl J. Niklas|
Abstract: Egg geometry can be described using Preston's equation, which has seldom been used to calculate egg volume (V) and surface area (S) to explore S versus V scaling relationships. Herein, we provide an explicit re‐expression of Preston's equation (designated as EPE) to calculate V and S, assuming that an egg is a solid of revolution. The side (longitudinal) profiles of 2221 eggs of six avian species were digitized, and the EPE was used to describe each egg profile. The volumes of 486 eggs from two avian species predicted by the EPE were compared with those obtained using water displacement in graduated cylinders. There was no significant difference in V using the two methods, which verified the utility of the EPE and the hypothesis that eggs are solids of revolution. The data also indicated that V is proportional to the product of egg length (L) and maximum width (W) squared. A 2/3‐power scaling relationship between S and V for each species was observed, that is, S is proportional to (LW2)2/3. These results can be extended to describe the shapes of the eggs of other species to study the evolution of avian (and perhaps reptilian) eggs.
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Date: 2023-04-20  ·  Issue: 2023  ·  Volume: 1524
What experiences constitute failures? High school students’ reflections on their struggles in STEM classes
Contributors: Xiaodong Lin‐Siegler| Benjamin J. Lovett| Yiran Du| Kan Yamane| Keying Wang| Syntia Hadis|
Abstract: Inculcating the capacity to adapt successfully to failures is essential for talent development in science, technology, engineering, and mathematics (STEM) fields. Despite its importance, this capacity to learn from failure is among the least understood processes in the field of talent development. This study aims to investigate how students conceptualize and react to failures and whether there is a correlation between students’ conceptualizations of failure, emotional reactions to it, and academic performance. We invited 150 high‐achieving high school students to share, interpret, and label their most memorable struggles in their STEM classes. Most of their struggles focused on the learning process itself, such as poor understanding of the subject matter, insufficient motivation or effort, or adopting ineffective learning strategies. Poor performance outcomes, such as poor test scores and bad grades, were not mentioned as frequently as the learning process. Students who labeled their struggle experiences as failures tended to focus more on performance outcomes, whereas students who labeled their struggle experiences as neither failures nor successes focused more on the learning process. Higher‐achieving students were also less likely to label their struggles as failures than less‐high achievers. Implications for classroom instruction are discussed with a particular focus on talent development in STEM fields.
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Date: 2023-04-20  ·  Issue: 2023  · 
What experiences constitute failures? High school students’ reflections on their struggles in STEM classes
Contributors: Xiaodong Lin‐Siegler| Benjamin J. Lovett| Yiran Du| Kan Yamane| Keying Wang| Syntia Hadis|
Abstract: Inculcating the capacity to adapt successfully to failures is essential for talent development in science, technology, engineering, and mathematics (STEM) fields. Despite its importance, this capacity to learn from failure is among the least understood processes in the field of talent development. This study aims to investigate how students conceptualize and react to failures and whether there is a correlation between students’ conceptualizations of failure, emotional reactions to it, and academic performance. We invited 150 high‐achieving high school students to share, interpret, and label their most memorable struggles in their STEM classes. Most of their struggles focused on the learning process itself, such as poor understanding of the subject matter, insufficient motivation or effort, or adopting ineffective learning strategies. Poor performance outcomes, such as poor test scores and bad grades, were not mentioned as frequently as the learning process. Students who labeled their struggle experiences as failures tended to focus more on performance outcomes, whereas students who labeled their struggle experiences as neither failures nor successes focused more on the learning process. Higher‐achieving students were also less likely to label their struggles as failures than less‐high achievers. Implications for classroom instruction are discussed with a particular focus on talent development in STEM fields.
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Date: 2023-04-17  ·  Issue: 2023  ·  Volume: 1524
Comprehensive framework for integrated action on the prevention, diagnosis, and management of anemia: An introduction
Contributors: Shelby E. Wilson| Lisa M. Rogers| Maria Nieves Garcia‐Casal| María Barreix| Andrea Bosman| Jane Cunningham| Ameena Goga| Antonio Montresor| Özge Tunçalp|
Abstract: The World Health Organization (WHO) announced in 2021 a commitment to develop a comprehensive framework for integrated action on the prevention, diagnosis, and management of anemia and to establish an Anaemia Action Alliance to support the implementation of the framework. WHO commissioned four background papers to provide reflections about the most pressing issues to be addressed for accelerating reductions in the prevalence of anemia. Here, we provide a complete vision of the framework.
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Date: 2023-04-17  ·  Issue: 2023  · 
Comprehensive framework for integrated action on the prevention, diagnosis, and management of anemia: An introduction
Contributors: Shelby E. Wilson| Lisa M. Rogers| Maria Nieves Garcia‐Casal| María Barreix| Andrea Bosman| Jane Cunningham| Ameena Goga| Antonio Montresor| Özge Tunçalp|
Abstract: The World Health Organization (WHO) announced in 2021 a commitment to develop a comprehensive framework for integrated action on the prevention, diagnosis, and management of anemia and to establish an Anaemia Action Alliance to support the implementation of the framework. WHO commissioned four background papers to provide reflections about the most pressing issues to be addressed for accelerating reductions in the prevalence of anemia. Here, we provide a complete vision of the framework.
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Date: 2023-04-15  ·  Issue: 2023  ·  Volume: 1524
Diagnosing anemia: Challenges selecting methods, addressing underlying causes, and implementing actions at the public health level
Contributors: Maria Nieves Garcia‐Casal| Omar Dary| Maria Elena Jefferds| Sant‐Rayn Pasricha|
Abstract: Accurate and affordable tools for diagnosing anemia and its main determinants are essential for understanding the magnitude and distribution of the problem and the appropriate interventions needed for its timely prevention and treatment. The objective of this review is to address methods, equipment, and sample‐related and quality control aspects of hemoglobin measurement for anemia diagnosis. Also, other iron‐, infectious‐, and genetic‐related causes of anemia are addressed in individuals and populations. The best practice for hemoglobin determination is the use of venous blood, analyzed on automated hematology analyzers, with high‐quality control measures in place. The importance of a correct anemia diagnosis is highlighted by the cost of a misdiagnosis. A false‐negative diagnosis may result in missing out and not treating anemia, its causes, and its adverse effects. On the other hand, a false‐positive diagnosis may result in the provision of unneeded treatment or referral for expensive laboratory tests to determine a cause of anemia, wasting valuable resources and risking causing harm. At the individual level, clinicians must understand the causes of absolute and functional anemia to diagnose and treat anemia at the clinical level. Actions toward anemia diagnosis and control at public health levels require global, regional, and country actions that should cover general and context‐specific characteristics.
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Date: 2023-04-15  ·  Issue: 2023  · 
Diagnosing anemia: Challenges selecting methods, addressing underlying causes, and implementing actions at the public health level
Contributors: Maria Nieves Garcia‐Casal| Omar Dary| Maria Elena Jefferds| Sant‐Rayn Pasricha|
Abstract: Accurate and affordable tools for diagnosing anemia and its main determinants are essential for understanding the magnitude and distribution of the problem and the appropriate interventions needed for its timely prevention and treatment. The objective of this review is to address methods, equipment, and sample‐related and quality control aspects of hemoglobin measurement for anemia diagnosis. Also, other iron‐, infectious‐, and genetic‐related causes of anemia are addressed in individuals and populations. The best practice for hemoglobin determination is the use of venous blood, analyzed on automated hematology analyzers, with high‐quality control measures in place. The importance of a correct anemia diagnosis is highlighted by the cost of a misdiagnosis. A false‐negative diagnosis may result in missing out and not treating anemia, its causes, and its adverse effects. On the other hand, a false‐positive diagnosis may result in the provision of unneeded treatment or referral for expensive laboratory tests to determine a cause of anemia, wasting valuable resources and risking causing harm. At the individual level, clinicians must understand the causes of absolute and functional anemia to diagnose and treat anemia at the clinical level. Actions toward anemia diagnosis and control at public health levels require global, regional, and country actions that should cover general and context‐specific characteristics.
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Date: 2023-04-10  ·  Issue: 2023  ·  Volume: 1522
Issue Information
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Abstract:
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Date: 2023-04-07  ·  Issue: 2023  ·  Volume: 1524
Calcium concentration of drinking water to improve calcium intake: A simulation study
Contributors: Gabriela Cormick| Iris B. Romero| Natalia Matamoros| Miriam Sosa| M. Fernanda GugoleOttaviano| Lorena Garitta| José M. Belizán| Luz Gibbons|
Abstract: The risk of inadequate calcium intake is a worldwide problem. We performed a simulation exercise on the impact, effectiveness, and safety of increasing calcium levels in drinking water using the 2019 Health and Nutrition National Survey of Argentina, which provides water intake and water sources data at the individual level. We simulated the distribution of calcium intake assuming a calcium concentration of 100 mg of calcium per liter of tap water and 400 mg of calcium per liter of bottled water. After the simulation, all population groups had a slightly improved calcium intake. Higher impacts were observed in adults, as reported water intake was higher in adults 19–51 years old. In young adult women, the estimated calcium intake inadequacy decreased from 91.0% to 79.7% when calcium was increased in tap water and to 72.2% when calcium was increased in tap and bottled water. The impact was lower in adolescents and older adults who have higher calcium recommendations and reported lower water intake. Increased calcium concentration of water could improve calcium intake in Argentina, especially in adults as their reported water intake is higher. Combining more than one strategy to improve calcium intake might be required for countries like Argentina with low calcium intake.
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Date: 2023-04-07  ·  Issue: 2023  ·  Volume: 1524
Rethinking human cytomegalovirus latency reservoir
Contributors: Michal Schwartz| Noam Stern‐Ginossar|
Abstract: Human cytomegalovirus (HCMV) is a prevalent herpesvirus, infecting the majority of the human population. Like other herpesviruses, it causes lifelong infection through the establishment of latency. Although reactivation from latency can cause significant morbidity and mortality in immunocompromised hosts, our understanding of HCMV latency and how it is maintained remains limited. Here, we discuss the characterized latency reservoir in hematopoietic cells in the bone marrow and the gaps in our knowledge of mechanisms that facilitate HCMV genome maintenance in dividing cells. We further review clinical evidence that strongly suggests the tissue origin of HCMV reactivation, and we outline similarities to murine cytomegalovirus where latency in tissue‐resident cells has been demonstrated. Overall, we think these observations call for a rethinking of HCMV latency reservoirs and point to potential sources of HCMV latency that reside in tissues.
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Date: 2023-04-07  ·  Issue: 2022  · 
Rethinking human cytomegalovirus latency reservoir
Contributors: Michal Schwartz| Noam Stern‐Ginossar|
Abstract: Human cytomegalovirus (HCMV) is a prevalent herpesvirus, infecting the majority of the human population. Like other herpesviruses, it causes lifelong infection through the establishment of latency. Although reactivation from latency can cause significant morbidity and mortality in immunocompromised hosts, our understanding of HCMV latency and how it is maintained remains limited. Here, we discuss the characterized latency reservoir in hematopoietic cells in the bone marrow and the gaps in our knowledge of mechanisms that facilitate HCMV genome maintenance in dividing cells. We further review clinical evidence that strongly suggests the tissue origin of HCMV reactivation, and we outline similarities to murine cytomegalovirus where latency in tissue‐resident cells has been demonstrated. Overall, we think these observations call for a rethinking of HCMV latency reservoirs and point to potential sources of HCMV latency that reside in tissues.
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Date: 2023-04-07  ·  Issue: 2022  · 
Calcium concentration of drinking water to improve calcium intake: A simulation study
Contributors: Gabriela Cormick| Iris B. Romero| Natalia Matamoros| Miriam Sosa| M. Fernanda GugoleOttaviano| Lorena Garitta| José M. Belizán| Luz Gibbons|
Abstract: The risk of inadequate calcium intake is a worldwide problem. We performed a simulation exercise on the impact, effectiveness, and safety of increasing calcium levels in drinking water using the 2019 Health and Nutrition National Survey of Argentina, which provides water intake and water sources data at the individual level. We simulated the distribution of calcium intake assuming a calcium concentration of 100 mg of calcium per liter of tap water and 400 mg of calcium per liter of bottled water. After the simulation, all population groups had a slightly improved calcium intake. Higher impacts were observed in adults, as reported water intake was higher in adults 19–51 years old. In young adult women, the estimated calcium intake inadequacy decreased from 91.0% to 79.7% when calcium was increased in tap water and to 72.2% when calcium was increased in tap and bottled water. The impact was lower in adolescents and older adults who have higher calcium recommendations and reported lower water intake. Increased calcium concentration of water could improve calcium intake in Argentina, especially in adults as their reported water intake is higher. Combining more than one strategy to improve calcium intake might be required for countries like Argentina with low calcium intake.
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Date: 2023-04-05  ·  Issue: 2022  · 
Toward understanding links between the microbiome and neurotransmitters
Contributors: Jonathan B. Lynch| Elaine Y. Hsiao|
Abstract: The gut microbiota modulates neurobiological activity in various animal lineages. This is often proposed to occur through interactions with neurotransmitters and other neuromodulatory molecules in the host. Our commentary will discuss recent research that establishes microbiota–neurotransmitter connections, gaps in current understanding, and outstanding questions that may guide future advances in the field of microbiota–nervous system interactions.
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Date: 2023-04-05  ·  Issue: 2023  ·  Volume: 1524
Progress in vaccine development for infectious diseases—a Keystone Symposia report
Contributors: Jennifer Cable| Barney S. Graham| Richard A. Koup| Robert A. Seder| Katalin Karikó| Norbert Pardi| Dan H. Barouch| Bhawna Sharma| Susanne Rauch| Raffael Nachbagauer| Mattias N. E. Forsell| Michael Schotsaert| Ali H. Ellebedy| Karin Loré| Darrell J. Irvine| Emily Pilkington| Siri Tahtinen| Elizabeth A. Thompson| Yanis Feraoun| Neil P. King| Kevin Saunders| Galit Alter| Syed M. Moin| Kwinten Sliepen| Gunilla B. Karlsson Hedestam| Hedda Wardemann| Bali Pulendran| Nicole A. Doria‐Rose| Wan‐Ting He| Jennifer A. Juno| Sila Ataca| Adam K. Wheatley| Jason S. McLellan| Laura M. Walker| Julia Lederhofer| Lisa C. Lindesmith| Holger Wille| Peter J. Hotez| Linda‐Gail Bekker|
Abstract: The COVID‐19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies’ preparedness for future pandemics. On June 1–4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium “Progress in Vaccine Development for Infectious Diseases” to discuss state‐of‐the‐art technologies, recent advancements in understanding vaccine‐mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
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Date: 2023-04-05  ·  Issue: 2023  · 
Progress in vaccine development for infectious diseases—a Keystone Symposia report
Contributors: Jennifer Cable| Barney S. Graham| Richard A. Koup| Robert A. Seder| Katalin Karikó| Norbert Pardi| Dan H. Barouch| Bhawna Sharma| Susanne Rauch| Raffael Nachbagauer| Mattias N. E. Forsell| Michael Schotsaert| Ali H. Ellebedy| Karin Loré| Darrell J. Irvine| Emily Pilkington| Siri Tahtinen| Elizabeth A. Thompson| Yanis Feraoun| Neil P. King| Kevin Saunders| Galit Alter| Syed M. Moin| Kwinten Sliepen| Gunilla B. Karlsson Hedestam| Hedda Wardemann| Bali Pulendran| Nicole A. Doria‐Rose| Wan‐Ting He| Jennifer A. Juno| Sila Ataca| Adam K. Wheatley| Jason S. McLellan| Laura M. Walker| Julia Lederhofer| Lisa C. Lindesmith| Holger Wille| Peter J. Hotez| Linda‐Gail Bekker|
Abstract: The COVID‐19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies’ preparedness for future pandemics. On June 1–4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium “Progress in Vaccine Development for Infectious Diseases” to discuss state‐of‐the‐art technologies, recent advancements in understanding vaccine‐mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
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Date: 2023-04-04  ·  Issue: 2023  ·  Volume: 1524
Abstraction and analogy in AI
Contributors: Melanie Mitchell|
Abstract: The abilities to form concepts and abstractions, and to make analogies, are key to human intelligence, but AI systems have a long way to go before they can match the abilities of humans in these areas. To develop machines that can abstract and analogize, researchers typically focus on idealized problem domains that are meant to capture the essence of human abstraction abilities without having to deal with the complexity of real‐world situations. This commentary describes why solving problems in these domains remains difficult for AI systems, and discusses how AI researches can make progress on imbuing machines with these essential abilities.
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Date: 2023-04-04  ·  Issue: 2023  · 
Abstraction and analogy in AI
Contributors: Melanie Mitchell|
Abstract: The abilities to form concepts and abstractions, and to make analogies, are key to human intelligence, but AI systems have a long way to go before they can match the abilities of humans in these areas. To develop machines that can abstract and analogize, researchers typically focus on idealized problem domains that are meant to capture the essence of human abstraction abilities without having to deal with the complexity of real‐world situations. This commentary describes why solving problems in these domains remains difficult for AI systems, and discusses how AI researches can make progress on imbuing machines with these essential abilities.
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Date: 2023-04-02  ·  Issue: 2023  ·  Volume: 1524
PAX9 mutations and genetic synergism in familial tooth agenesis
Contributors: Kuan‐Yu Chu| Yin‐Lin Wang| Jung‐Tsu Chen| Chia‐Hui Lin| Chung‐Chen Jane Yao| Yi‐Jane Chen| Huan‐Wen Chen| James P. Simmer| Jan C.‐C. Hu| Shih‐Kai Wang|
Abstract: Familial tooth agenesis (FTA) is one of the most common craniofacial anomalies in humans. Loss‐of‐function mutations in PAX9 and WNT10A have been known to cause FTA with various expressivity. In this study, we identified five FTA kindreds with novel PAX9 disease‐causing mutations: p.(Glu7Lys), p.(Val83Leu), p.(Pro118Ser), p.(Ser197Argfs*23), and c.771+4A>G. Concomitant PAX9 and WNT10A pathogenic variants found in two probands with severe phenotypes suggested an effect of mutational synergism. All overexpressed PAX9s showed proper nuclear localization, excepting the p.(Pro118Ser) mutant. Various missense mutations caused differential loss of PAX9 transcriptional ability. PAX9 overexpression in dental pulp cells upregulated LEF1 and AXIN2 expression, indicating a positive regulatory role for PAX9 in canonical Wnt signaling. Analyzing 176 cases with 63 different mutations, we observed a distinct pattern of tooth agenesis for PAX9‐associated FTA: Maxillary teeth are in general more frequently affected than mandibular ones. Along with all second molars, maxillary bicuspids and first molars are mostly involved, while maxillary lateral incisors and mandibular bicuspids are relatively less affected. Genotypically, missense mutations are associated with fewer missing teeth than frameshift and nonsense variants. This study significantly expands the phenotypic and genotypic spectrums of PAX9‐associated disorders and reveals a molecular mechanism of genetic synergism underlying FTA variable expressivity.
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Date: 2023-04-02  ·  Issue: 2023  · 
Food for thought: Opportunities to target carbon metabolism in antibacterial drug discovery
Contributors: Madeline Tong| Eric D. Brown|
Abstract: Antimicrobial resistance is at an all‐time high and new drugs are required to overcome this crisis. Traditional approaches to drug discovery have failed to produce novel classes of antibiotics, with only a few currently in development. It is thought that novel classes will come from antibacterial drug discovery efforts that focus on unconventional targets. One such collection of antibacterial targets are those that comprise central carbon metabolism. Targets of this kind have been largely overlooked because conventional antibacterial testing media are ill‐suited for exploring carbon source utilization. Nevertheless, as a consequence of infection, bacteria must find a carbon source in order to survive. Here, we review what is known about the carbon sources available and used by bacteria in different host infection sites. We also look at discovery efforts targeting central carbon metabolism and evaluate how these processes can influence antibiotic efficacy.
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Date: 2023-04-02  ·  Issue: 2023  ·  Volume: 1524
Food for thought: Opportunities to target carbon metabolism in antibacterial drug discovery
Contributors: Madeline Tong| Eric D. Brown|
Abstract: Antimicrobial resistance is at an all‐time high and new drugs are required to overcome this crisis. Traditional approaches to drug discovery have failed to produce novel classes of antibiotics, with only a few currently in development. It is thought that novel classes will come from antibacterial drug discovery efforts that focus on unconventional targets. One such collection of antibacterial targets are those that comprise central carbon metabolism. Targets of this kind have been largely overlooked because conventional antibacterial testing media are ill‐suited for exploring carbon source utilization. Nevertheless, as a consequence of infection, bacteria must find a carbon source in order to survive. Here, we review what is known about the carbon sources available and used by bacteria in different host infection sites. We also look at discovery efforts targeting central carbon metabolism and evaluate how these processes can influence antibiotic efficacy.
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Date: 2023-03-31  ·  Issue: 2023  ·  Volume: 1523
Double mutation of claudin‐1 and claudin‐3 causes alopecia in infant mice
Contributors: Koya Suzuki| Kosuke Yamaga| Reitaro Tokumasu| Tatsuya Katsuno| Hiroo Tanaka| Shuhei Chiba| Takeshi Yagi| Ichiro Katayama| Atsushi Tamura| Hiroyuki Murota| Sachiko Tsukita|
Abstract: Hair follicles (HFs) undergo cyclic phases of growth, regression, and rest in association with hair shafts to maintain the hair coat. Nonsense mutations in the tight junction protein claudin (CLDN)‐1 cause hair loss in humans. Therefore, we evaluated the roles of CLDNs in hair retention. Among the 27 CLDN family members, CLDN1, CLDN3, CLDN4, CLDN6, and CLDN7 were expressed in the inner bulge layer, isthmus, and sebaceous gland of murine HFs. Hair phenotypes were observed in Cldn1 weaker knockdown and Cldn3‐knockout (Cldn1Δ/ΔCldn3−/−) mice. Although hair growth was normal, Cldn1Δ/ΔCldn3−/− mice showed striking hair loss in the first telogen. Simultaneous deficiencies in CLDN1 and CLDN3 caused abnormalities in telogen HFs, such as an aberrantly layered architecture of epithelial cell sheets in bulges with multiple cell layers, mislocalization of bulges adjacent to sebaceous glands, and dilated hair canals. Along with the telogen HF abnormalities, which shortened the hair retention period, there was an enhanced proliferation of the epithelium surrounding HFs in Cldn1Δ/ΔCldn3−/− mice, causing accelerated hair regrowth in adults. Our findings suggested that CLDN1 and CLDN3 may regulate hair retention in infant mice by maintaining the appropriate layered architecture of HFs, a deficiency of which can lead to alopecia.
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Date: 2023-03-31  ·  Issue: 2023  · 
Epigenetic inheritance in adaptive evolution
Contributors: Gonzalo Sabarís| Maximilian H. Fitz‐James| Giacomo Cavalli|
Abstract: Since the Modern Synthesis, our ideas of evolution have mostly centered on the information encoded in the DNA molecule and their mechanisms of heredity. Increasing evidence, however, suggests that epigenetic mechanisms have the potential to perpetuate gene activity states in the context of the same DNA sequence. Here, we discuss recent compelling evidence showing that epigenetic signals triggered by environmental stress can persist over very long timeframes, contributing to phenotypic changes in relevant traits upon which selection could act. We argue that epigenetic inheritance plays an important role in fast phenotypic adaptation to fluctuating environments, ensuring the survival of the organisms of a population under environmental stress in the short term while maintaining a “bet‐hedging” strategy of reverting to the original state if the environment returns to standard conditions. These examples call for a reevaluation of the role of nongenetic information in adaptive evolution, raising questions about its broader relevance in nature.
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Date: 2023-03-31  ·  Issue: 2023  ·  Volume: 1524
Epigenetic inheritance in adaptive evolution
Contributors: Gonzalo Sabarís| Maximilian H. Fitz‐James| Giacomo Cavalli|
Abstract: Since the Modern Synthesis, our ideas of evolution have mostly centered on the information encoded in the DNA molecule and their mechanisms of heredity. Increasing evidence, however, suggests that epigenetic mechanisms have the potential to perpetuate gene activity states in the context of the same DNA sequence. Here, we discuss recent compelling evidence showing that epigenetic signals triggered by environmental stress can persist over very long timeframes, contributing to phenotypic changes in relevant traits upon which selection could act. We argue that epigenetic inheritance plays an important role in fast phenotypic adaptation to fluctuating environments, ensuring the survival of the organisms of a population under environmental stress in the short term while maintaining a “bet‐hedging” strategy of reverting to the original state if the environment returns to standard conditions. These examples call for a reevaluation of the role of nongenetic information in adaptive evolution, raising questions about its broader relevance in nature.
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Date: 2023-03-31  ·  Issue: 2022  · 
Double mutation of claudin‐1 and claudin‐3 causes alopecia in infant mice
Contributors: Koya Suzuki| Kosuke Yamaga| Reitaro Tokumasu| Tatsuya Katsuno| Hiroo Tanaka| Shuhei Chiba| Takeshi Yagi| Ichiro Katayama| Atsushi Tamura| Hiroyuki Murota| Sachiko Tsukita|
Abstract: Hair follicles (HFs) undergo cyclic phases of growth, regression, and rest in association with hair shafts to maintain the hair coat. Nonsense mutations in the tight junction protein claudin (CLDN)‐1 cause hair loss in humans. Therefore, we evaluated the roles of CLDNs in hair retention. Among the 27 CLDN family members, CLDN1, CLDN3, CLDN4, CLDN6, and CLDN7 were expressed in the inner bulge layer, isthmus, and sebaceous gland of murine HFs. Hair phenotypes were observed in Cldn1 weaker knockdown and Cldn3‐knockout (Cldn1Δ/ΔCldn3−/−) mice. Although hair growth was normal, Cldn1Δ/ΔCldn3−/− mice showed striking hair loss in the first telogen. Simultaneous deficiencies in CLDN1 and CLDN3 caused abnormalities in telogen HFs, such as an aberrantly layered architecture of epithelial cell sheets in bulges with multiple cell layers, mislocalization of bulges adjacent to sebaceous glands, and dilated hair canals. Along with the telogen HF abnormalities, which shortened the hair retention period, there was an enhanced proliferation of the epithelium surrounding HFs in Cldn1Δ/ΔCldn3−/− mice, causing accelerated hair regrowth in adults. Our findings suggested that CLDN1 and CLDN3 may regulate hair retention in infant mice by maintaining the appropriate layered architecture of HFs, a deficiency of which can lead to alopecia.
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Date: 2023-03-29  ·  Issue: 2023  · 
Accelerating action to reduce anemia: Review of causes and risk factors and related data needs
Contributors: Sonja Y. Hess| Aatekah Owais| Maria Elena D. Jefferds| Melissa F. Young| Andrew Cahill| Lisa M. Rogers|
Abstract: Anemia is a major public health concern. Young children, menstruating adolescent girls and women, and pregnant women are among the most vulnerable. Anemia is the consequence of a wide range of causes, including biological, socioeconomic, and ecological risk factors. Primary causes include: iron deficiency; inherited red blood cell disorders; infections, such as soil‐transmitted helminthiasis, schistosomiasis, and malaria; gynecological and obstetric conditions; and other chronic diseases that lead to blood loss, decreased erythropoiesis, or destruction of erythrocytes. The most vulnerable population groups in low‐ and middle‐income countries are often at the greatest risk to suffer from several of these causes simultaneously as low socioeconomic status is linked with an increased risk of anemia through multiple pathways. Targeted and effective action is needed to prevent anemia. Understanding the causes and risk factors of anemia for different population subgroups within a country guides the design and implementation of effective strategies to prevent and treat anemia. A coordinated approach across various expert groups and programs could make the best use of existing data or could help to determine when newer and more relevant data may need to be collected, especially in countries with a high anemia burden and limited information on the etiology of anemia.
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Date: 2023-03-29  ·  Issue: 2023  ·  Volume: 1523
Online mentoring for girls in secondary education to increase participation rates of women in STEM: A long‐term follow‐up study on later university major and career choices
Contributors: Heidrun Stoeger| Tobias Debatin| Michael Heilemann| Sigrun Schirner| Albert Ziegler|
Abstract: An important first step in talent development in science, technology, engineering, and mathematics (STEM) is getting individuals excited about STEM. Females, in particular, are underrepresented in many STEM fields. Since girls’ interest in STEM declines in adolescence, interventions should begin in secondary education at the latest. One appropriate intervention is (online) mentoring. Although its short‐term effectiveness has been demonstrated for proximal outcomes during secondary education (e.g., positive changes in elective intentions in STEM), studies of the long‐term effectiveness of STEM mentoring provided during secondary education—especially for real‐life choices of university STEM majors and professions—are lacking. In our study, we examine females’ real‐life decisions about university majors and entering professions made years after they had participated in an online mentoring program (CyberMentor) during secondary education. The program's proximal positive influence on girls’ elective intentions in STEM and certainty about career plans during secondary education had previously been demonstrated in several studies with pre–post‐test waitlist control group designs. Specifically, we compared the choices that former mentees (n = 410) made about university majors and entering professions several years after program participation with (1) females of their age cohort and (2) females of a group of girls comparably interested in STEM who had signed up for the program but then not participated (n = 71). Further, we examined the explanatory contribution to these later career‐path‐relevant, real‐life choices based on (1) mentees’ baseline conditions prior to entering the program (e.g., elective intentions in STEM), (2) successful 1‐year program participation, and (3) multiyear program participation. Findings indicate positive long‐term effects of the program in all areas investigated.
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Date: 2023-03-29  ·  Issue: 2023  · 
Online mentoring for girls in secondary education to increase participation rates of women in STEM: A long‐term follow‐up study on later university major and career choices
Contributors: Heidrun Stoeger| Tobias Debatin| Michael Heilemann| Sigrun Schirner| Albert Ziegler|
Abstract: An important first step in talent development in science, technology, engineering, and mathematics (STEM) is getting individuals excited about STEM. Females, in particular, are underrepresented in many STEM fields. Since girls’ interest in STEM declines in adolescence, interventions should begin in secondary education at the latest. One appropriate intervention is (online) mentoring. Although its short‐term effectiveness has been demonstrated for proximal outcomes during secondary education (e.g., positive changes in elective intentions in STEM), studies of the long‐term effectiveness of STEM mentoring provided during secondary education—especially for real‐life choices of university STEM majors and professions—are lacking. In our study, we examine females’ real‐life decisions about university majors and entering professions made years after they had participated in an online mentoring program (CyberMentor) during secondary education. The program's proximal positive influence on girls’ elective intentions in STEM and certainty about career plans during secondary education had previously been demonstrated in several studies with pre–post‐test waitlist control group designs. Specifically, we compared the choices that former mentees (n = 410) made about university majors and entering professions several years after program participation with (1) females of their age cohort and (2) females of a group of girls comparably interested in STEM who had signed up for the program but then not participated (n = 71). Further, we examined the explanatory contribution to these later career‐path‐relevant, real‐life choices based on (1) mentees’ baseline conditions prior to entering the program (e.g., elective intentions in STEM), (2) successful 1‐year program participation, and (3) multiyear program participation. Findings indicate positive long‐term effects of the program in all areas investigated.
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Date: 2023-03-27  ·  Issue: 2023  ·  Volume: 1523
Intra‐ and interbrain synchrony and hyperbrain network dynamics of a guitarist quartet and its audience during a concert
Contributors: Viktor Müller| Ulman Lindenberger|
Abstract: Playing music in a concert represents a multilevel interaction between musicians and the audience, where interbrain synchronization might play an essential role. Here, we simultaneously recorded electroencephalographs (EEGs) from the brains of eight people during a concert: a quartet of professional guitarists and four participants in the audience. Using phase synchronization analyses between EEG signals within and between brains, we constructed hyperbrain networks, comprising synchronized brain activity across the eight brains, and analyzed them using a graph‐theoretical approach. We found that strengths within and between brains in the delta band were higher in the quartet than in the public. Within‐brain strengths were higher and between‐brain strengths were lower in the music than in the applause condition, both particularly in the quartet group. These changes in coupling strength were accompanied by corresponding changes in the hyperbrain network topology, which were also frequency‐specific. Moreover, the network topology and the dynamical structure of guitar sounds showed specific guitar–brain, guitar–guitar, and brain–brain directional associations, indicating multilevel dynamics with upward and downward causation. Finally, the hyperbrain networks exhibit modular structures that were more stable during music performance than during applause. Our findings illustrate complex hyperbrain network interactions in a quartet and its audience during a concert.
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Date: 2023-03-25  ·  Issue: 2023  ·  Volume: 1523
Multidimensional components of (state) mathematics anxiety: Behavioral, cognitive, emotional, and psychophysiological consequences
Contributors: Irene C. Mammarella| Sara Caviola| Serena Rossi| Elisabetta Patron| Daniela Palomba|
Abstract: The present study aimed to analyze the different components of state mathematics anxiety that students experienced while solving calculation problems by manipulating their stress levels. A computerized mathematical task was administered to 165 fifth‐graders randomly assigned to three different groups: positive, negative, and control conditions, in which positive, negative, or no feedback during the task was given, respectively. Behavioral (task performance), emotional (negative feelings), cognitive (worrisome thoughts and perceived competence), and psychophysiological responses (skin conductance and vagal withdrawal) were analyzed. Behavioral responses did not differ in the positive and negative conditions, while the latter was associated with children's reportedly negative emotional states, worries, and perceived lack of competence. The stress induced in the negative condition led to an increase in skin conductance and cardiac vagal withdrawal in children. Our data suggest the importance of considering students’ interpretation of mathematics‐related experiences, which might affect their emotional, cognitive, and psychophysiological responses.
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Date: 2023-03-25  ·  Issue: 2022  · 
Multidimensional components of (state) mathematics anxiety: Behavioral, cognitive, emotional, and psychophysiological consequences
Contributors: Irene C. Mammarella| Sara Caviola| Serena Rossi| Elisabetta Patron| Daniela Palomba|
Abstract: The present study aimed to analyze the different components of state mathematics anxiety that students experienced while solving calculation problems by manipulating their stress levels. A computerized mathematical task was administered to 165 fifth‐graders randomly assigned to three different groups: positive, negative, and control conditions, in which positive, negative, or no feedback during the task was given, respectively. Behavioral (task performance), emotional (negative feelings), cognitive (worrisome thoughts and perceived competence), and psychophysiological responses (skin conductance and vagal withdrawal) were analyzed. Behavioral responses did not differ in the positive and negative conditions, while the latter was associated with children's reportedly negative emotional states, worries, and perceived lack of competence. The stress induced in the negative condition led to an increase in skin conductance and cardiac vagal withdrawal in children. Our data suggest the importance of considering students’ interpretation of mathematics‐related experiences, which might affect their emotional, cognitive, and psychophysiological responses.
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Date: 2023-03-25  ·  Issue: 2023  ·  Volume: 1523
Social conformity is associated with inter‐trial electroencephalogram variability
Contributors: Haoming Zhang| Kunkun Zhang| Ziqi Zhang| Mingqi Zhao| Quanying Liu| Wenbo Luo| Haiyan Wu|
Abstract: Human society encompasses diverse social influences, and people experience events differently and may behave differently under such influence, including in forming an impression of others. However, little is known about the underlying neural relevance of individual differences in following others’ opinions or social norms. In the present study, we designed a series of tasks centered on social influence to investigate the underlying relevance between an individual's degree of social conformity and their neural variability. We found that individual differences under the social influence are associated with the amount of inter‐trial electroencephalogram (EEG) variability over multiple stages in a conformity task (making face judgments and receiving social influence). This association was robust in the alpha band over the frontal and occipital electrodes for negative social influence. We also found that inter‐trial EEG variability is a very stable, participant‐driven internal state measurement and could be interpreted as mindset instability. Overall, these findings support the hypothesis that higher inter‐trial EEG variability may be related to higher mindset instability, which makes participants more vulnerable to exposed external social influence. The present study provides a novel approach that considers the stability of one's endogenous neural signal during tasks and links it to human social behaviors.
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Date: 2023-03-24  ·  Issue: 2023  · 
Immunometabolism at the crossroads of obesity and cancer—a Keystone Symposia report
Contributors: Jennifer Cable| Jeffrey C. Rathmell| Erika L. Pearce| Ping‐Chih Ho| Marcia C. Haigis| Murad R. Mamedov| Meng‐Ju Wu| Susan M. Kaech| Lydia Lynch| Mark A. Febbraio| Sagar P. Bapat| Hanna S. Hong| Weiping Zou| Yasmine Belkaid| Zuri A. Sullivan| Andrea Keller| Stefanie K. Wculek| Douglas R. Green| Catherine Postic| Ido Amit| Salvador Aznar Benitah| Russell G. Jones| Miguel Reina‐Campos| Santiago Valle Torres| Semir Beyaz| Donal Brennan| Luke A. J. O'Neill| Rachel J. Perry| Dirk Brenner|
Abstract: Immunometabolism considers the relationship between metabolism and immunity. Typically, researchers focus on either the metabolic pathways within immune cells that affect their function or the impact of immune cells on systemic metabolism. A more holistic approach that considers both these viewpoints is needed. On September 5–8, 2022, experts in the field of immunometabolism met for the Keystone symposium “Immunometabolism at the Crossroads of Obesity and Cancer” to present recent research across the field of immunometabolism, with the setting of obesity and cancer as an ideal example of the complex interplay between metabolism, immunity, and cancer. Speakers highlighted new insights on the metabolic links between tumor cells and immune cells, with a focus on leveraging unique metabolic vulnerabilities of different cell types in the tumor microenvironment as therapeutic targets and demonstrated the effects of diet, the microbiome, and obesity on immune system function and cancer pathogenesis and therapy. Finally, speakers presented new technologies to interrogate the immune system and uncover novel metabolic pathways important for immunity.
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Date: 2023-03-24  ·  Issue: 2023  ·  Volume: 1521
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Date: 2023-03-24  ·  Issue: 2023  ·  Volume: 1523
Immunometabolism at the crossroads of obesity and cancer—a Keystone Symposia report
Contributors: Jennifer Cable| Jeffrey C. Rathmell| Erika L. Pearce| Ping‐Chih Ho| Marcia C. Haigis| Murad R. Mamedov| Meng‐Ju Wu| Susan M. Kaech| Lydia Lynch| Mark A. Febbraio| Sagar P. Bapat| Hanna S. Hong| Weiping Zou| Yasmine Belkaid| Zuri A. Sullivan| Andrea Keller| Stefanie K. Wculek| Douglas R. Green| Catherine Postic| Ido Amit| Salvador Aznar Benitah| Russell G. Jones| Miguel Reina‐Campos| Santiago Valle Torres| Semir Beyaz| Donal Brennan| Luke A. J. O'Neill| Rachel J. Perry| Dirk Brenner|
Abstract: Immunometabolism considers the relationship between metabolism and immunity. Typically, researchers focus on either the metabolic pathways within immune cells that affect their function or the impact of immune cells on systemic metabolism. A more holistic approach that considers both these viewpoints is needed. On September 5–8, 2022, experts in the field of immunometabolism met for the Keystone symposium “Immunometabolism at the Crossroads of Obesity and Cancer” to present recent research across the field of immunometabolism, with the setting of obesity and cancer as an ideal example of the complex interplay between metabolism, immunity, and cancer. Speakers highlighted new insights on the metabolic links between tumor cells and immune cells, with a focus on leveraging unique metabolic vulnerabilities of different cell types in the tumor microenvironment as therapeutic targets and demonstrated the effects of diet, the microbiome, and obesity on immune system function and cancer pathogenesis and therapy. Finally, speakers presented new technologies to interrogate the immune system and uncover novel metabolic pathways important for immunity.
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Date: 2023-03-21  ·  Issue: 2023  · 
Epistemic communities and their situated practices: Perspectival realism—a primer
Contributors: Michela Massimi|
Abstract: The epistemic feat that we call science is not an aseptic outcome of reasoning from an eternal viewpoint but the product of myriad epistemic communities with intersecting and interlacing scientific perspectives.
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Date: 2023-03-21  ·  Issue: 2023  ·  Volume: 1523
Epistemic communities and their situated practices: Perspectival realism—a primer
Contributors: Michela Massimi|
Abstract: The epistemic feat that we call science is not an aseptic outcome of reasoning from an eternal viewpoint but the product of myriad epistemic communities with intersecting and interlacing scientific perspectives.
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Date: 2023-03-18  ·  Issue: 2023  ·  Volume: 1523
Tet methylcytosine dioxygenase 1 modulates Porphyromonas gingivalis–triggered pyroptosis by regulating glycolysis in cementoblasts
Contributors: Yan Peng| Huiyi Wang| Xin Huang| Heyu Liu| Junhong Xiao| Chuan Wang| Li Ma| Xiaoxuan Wang| Zhengguo Cao|
Abstract: Porphyromonas gingivalis is involved in the pathogenesis of multiple polymicrobial biofilm–induced inflammatory diseases, including apical periodontitis, and it triggers pyroptosis accompanied by robust inflammatory responses. Tet methylcytosine dioxygenase 1 (TET1), an epigenetic modifier enzyme, has been is correlated with inflammation, though an association of TET1 and P. gingivalis–related pyroptosis in cementoblasts and the molecular mechanisms has not been shown. Our study here demonstrated that P. gingivalis downregulated Tet1 expression and elicited CASP11‐ and GSDMD‐dependent pyroptosis. Additionally, Tet1 mRNA silencing in cementoblasts appeared to result in a more severe pyroptotic phenotype, where levels of CASP11 and GSDMD cleavage, lactate dehydrogenase release, and IL‐1β and IL‐18 production were significantly increased. Moreover, Tet1 overexpression resulted in blockade of pyroptosis activation accompanied by inflammation moderation. Further analyses revealed that TET1 modulated glycolysis, confirmed by the application of the specific inhibitor 2‐deoxy‐d‐glucose (2‐DG). The pyroptosis phenotype enhanced by Tet1 silencing was moderated by 2‐DG upon P. gingivalis invasion. Taken together, these data show the effects and underlying mechanisms of TET1 on pyroptosis and inflammatory phenotype induced by P. gingivalis in cementoblasts, and provides insight into the involvement of P. gingivalis in apical periodontitis and, possibly, other inflammatory diseases.
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Date: 2023-03-18  ·  Issue: 2023  · 
Exosomes, microvesicles, and other extracellular vesicles—a Keystone Symposia report
Contributors: Jennifer Cable| Kenneth W. Witwer| Robert J. Coffey| Aleksandar Milosavljevic| Ariana K. Lersner| Lizandra Jimenez| Ferdinando Pucci| Maureen M. Barr| Niek Dekker| Bahnisikha Barman| Daniel Humphrys| Justin Williams| Michele Palma| Wei Guo| Nuno Bastos| Andrew F. Hill| Efrat Levy| Michael P. Hantak| Clair Crewe| Elena Aikawa| Alan M. Adamczyk| Tamires M. Zanotto| Matias Ostrowski| Tanina Arab| Daniel C. Rabe| Aadil Sheikh| Danilo Rodrigues da Silva| Jennifer C. Jones| Chioma Okeoma| Thomas Gaborski| Qin Zhang| Olesia Gololobova|
Abstract: Extracellular vesicles (EVs) are small, lipid‐bilayer‐bound particles released by cells that can contain important bioactive molecules, including lipids, RNAs, and proteins. Once released in the extracellular environment, EVs can act as messengers locally as well as to distant tissues to coordinate tissue homeostasis and systemic responses. There is a growing interest in not only understanding the physiology of EVs as signaling particles but also leveraging them as minimally invasive diagnostic and prognostic biomarkers (e.g., they can be found in biofluids) and drug‐delivery vehicles. On October 30–November 2, 2022, researchers in the EV field convened for the Keystone symposium “Exosomes, Microvesicles, and Other Extracellular Vesicles” to discuss developing standardized language and methodology, new data on the basic biology of EVs and potential clinical utility, as well as novel technologies to isolate and characterize EVs.
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Date: 2023-03-18  ·  Issue: 2023  ·  Volume: 1523
Exosomes, microvesicles, and other extracellular vesicles—a Keystone Symposia report
Contributors: Jennifer Cable| Kenneth W. Witwer| Robert J. Coffey| Aleksandar Milosavljevic| Ariana K. Lersner| Lizandra Jimenez| Ferdinando Pucci| Maureen M. Barr| Niek Dekker| Bahnisikha Barman| Daniel Humphrys| Justin Williams| Michele Palma| Wei Guo| Nuno Bastos| Andrew F. Hill| Efrat Levy| Michael P. Hantak| Clair Crewe| Elena Aikawa| Alan M. Adamczyk| Tamires M. Zanotto| Matias Ostrowski| Tanina Arab| Daniel C. Rabe| Aadil Sheikh| Danilo Rodrigues da Silva| Jennifer C. Jones| Chioma Okeoma| Thomas Gaborski| Qin Zhang| Olesia Gololobova|
Abstract: Extracellular vesicles (EVs) are small, lipid‐bilayer‐bound particles released by cells that can contain important bioactive molecules, including lipids, RNAs, and proteins. Once released in the extracellular environment, EVs can act as messengers locally as well as to distant tissues to coordinate tissue homeostasis and systemic responses. There is a growing interest in not only understanding the physiology of EVs as signaling particles but also leveraging them as minimally invasive diagnostic and prognostic biomarkers (e.g., they can be found in biofluids) and drug‐delivery vehicles. On October 30–November 2, 2022, researchers in the EV field convened for the Keystone symposium “Exosomes, Microvesicles, and Other Extracellular Vesicles” to discuss developing standardized language and methodology, new data on the basic biology of EVs and potential clinical utility, as well as novel technologies to isolate and characterize EVs.
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Date: 2023-03-15  ·  Issue: 2023  ·  Volume: 1522
Growth failure among children of adolescent mothers at ages 0–5 and 6–12 years in India
Contributors: Arindam Nandi| Fatima Zahra| Karen Austrian| Nicole Haberland| Thoại D. Ngô|
Abstract: Adolescent motherhood has been linked with poor health outcomes at birth for children, including high neonatal mortality, low birthweight, and small‐for‐gestational‐age rates. However, longer‐term growth outcomes in the children of adolescent mothers in low‐resource settings remain inadequately studied. We used longitudinal data from the India Human Development Surveys, 2004–2005 and 2011–2012 (n = 12,182) and employed regression and propensity score matching analysis to compare the following growth indicators of children born to adolescent mothers (ages 19 years or below) with those born to older mothers. Growth indicators included height and weight during ages 0–5 years and 6–12 years and change in height and weight between the two periods. In regression‐based estimates, children born to adolescent mothers were 0.01 m shorter and weighed 0.2 kg less than children of older mothers at ages 0–5 years. At ages 6–12 years, those born to adolescent mothers were 0.02 m shorter and weighed 0.97 kg less. The height difference between the two groups increased by 0.01 m and the weight difference grew by 0.77 kg over time. Height and weight difference between the two groups worsened among boys over time, while for girls, only the weight gap worsened. The results were similar when using propensity score matching methods. Public policies for reducing child marriage, combined with targeted health, nutrition, and well‐being programs for adolescent mothers, are essential for both preventing adolescent childbearing and reducing its impact on growth failure among children in India.
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Date: 2023-03-12  ·  Issue: 2023  · 
A theoretically based STEM talent development program that bridges excellence gaps
Contributors: Susan G. Assouline| Duhita Mahatmya| Lori M. Ihrig| Stephanie Lynch| Nesibe Karakis|
Abstract: The pipeline of highly trained STEM (science, technology, engineering, and mathematics) professionals has narrowed in recent decades, forcing society to re‐examine how schools are discovering and developing STEM talent. Of particular concern is the finding that rural students attend post‐secondary schools at lower rates than their urban counterparts, and when they do attend, they are less likely to graduate from STEM programs. One reason may be that they are not prepared for advanced STEM coursework because they lack access to essential STEM talent‐development programs in middle or high school. This creates excellence gaps, which exacerbate the narrowing STEM pipeline to the workforce. To address this, we formed a university–school partnership to develop an outside‐of‐school STEM talent development program, called STEM Excellence, for rural middle‐school students who attend under‐resourced schools. The aim of STEM Excellence was to increase students’ achievement and aspirations while empowering their teachers to develop local STEM programs grounded in developmental psychology theories. STEM Excellence integrated the Talent Development Megamodel Principles of ability, domains of talent, opportunity, and psychosocial variables. STEM Excellence also recognized the interplay of multiple person–environment systems as presented in the Bioecological Systems Model.
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Date: 2023-03-12  ·  Issue: 2023  ·  Volume: 1522
A theoretically based STEM talent development program that bridges excellence gaps
Contributors: Susan G. Assouline| Duhita Mahatmya| Lori M. Ihrig| Stephanie Lynch| Nesibe Karakis|
Abstract: The pipeline of highly trained STEM (science, technology, engineering, and mathematics) professionals has narrowed in recent decades, forcing society to re‐examine how schools are discovering and developing STEM talent. Of particular concern is the finding that rural students attend post‐secondary schools at lower rates than their urban counterparts, and when they do attend, they are less likely to graduate from STEM programs. One reason may be that they are not prepared for advanced STEM coursework because they lack access to essential STEM talent‐development programs in middle or high school. This creates excellence gaps, which exacerbate the narrowing STEM pipeline to the workforce. To address this, we formed a university–school partnership to develop an outside‐of‐school STEM talent development program, called STEM Excellence, for rural middle‐school students who attend under‐resourced schools. The aim of STEM Excellence was to increase students’ achievement and aspirations while empowering their teachers to develop local STEM programs grounded in developmental psychology theories. STEM Excellence integrated the Talent Development Megamodel Principles of ability, domains of talent, opportunity, and psychosocial variables. STEM Excellence also recognized the interplay of multiple person–environment systems as presented in the Bioecological Systems Model.
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Date: 2023-03-02  ·  Issue: 2023  ·  Volume: 1522
Astrocytic contributions to Huntington's disease pathophysiology
Contributors: Baljit S. Khakh| Steven A. Goldman|
Abstract: Huntington's disease (HD) is a fatal, monogenic, autosomal dominant neurodegenerative disease caused by a polyglutamine‐encoding CAG expansion in the huntingtin (HTT) gene that results in mutant huntingtin proteins (mHTT) in cells throughout the body. Although large parts of the central nervous system (CNS) are affected, the striatum is especially vulnerable and undergoes marked atrophy. Astrocytes are abundant within the striatum and contain mHTT in HD, as well as in mouse models of the disease. We focus on striatal astrocytes and summarize how they participate in, and contribute to, molecular pathophysiology and disease‐related phenotypes in HD model mice. Where possible, reference is made to pertinent astrocyte alterations in human HD. Astrocytic dysfunctions related to cellular morphology, extracellular ion and neurotransmitter homeostasis, and metabolic support all accompany the development and progression of HD, in both transgenic mouse and human cellular and chimeric models of HD. These findings reveal the potential for the therapeutic targeting of astrocytes so as to restore synaptic as well as tissue homeostasis in HD. Elucidation of the mechanisms by which astrocytes contribute to HD pathogenesis may inform a broader understanding of the role of glial pathology in neurodegenerative disorders and, by so doing, enable new strategies of glial‐directed therapeutics.
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Date: 2023-02-27  ·  Issue: 2022  · 
Confronting ethical and social issues related to the genetics of musicality
Contributors: Reyna L. Gordon| Daphne O. Martschenko| Srishti Nayak| Maria Niarchou| Matthew D. Morrison| Eamonn Bell| Nori Jacoby| Lea K. Davis|
Abstract: New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh the potential risks and benefits of these studies and the use of their outcomes. Here, we bring together diverse disciplinary expertise (complex trait genetics, music cognition, musicology, bioethics, developmental psychology, and neuroscience) to interpret and guide the ethical use of findings from recent and future studies. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication.
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Date: 2023-02-27  ·  Issue: 2023  ·  Volume: 1522
Confronting ethical and social issues related to the genetics of musicality
Contributors: Reyna L. Gordon| Daphne O. Martschenko| Srishti Nayak| Maria Niarchou| Matthew D. Morrison| Eamonn Bell| Nori Jacoby| Lea K. Davis|
Abstract: New interdisciplinary research into genetic influences on musicality raises a number of ethical and social issues for future avenues of research and public engagement. The historical intersection of music cognition and eugenics heightens the need to vigilantly weigh the potential risks and benefits of these studies and the use of their outcomes. Here, we bring together diverse disciplinary expertise (complex trait genetics, music cognition, musicology, bioethics, developmental psychology, and neuroscience) to interpret and guide the ethical use of findings from recent and future studies. We discuss a framework for incorporating principles of ethically and socially responsible conduct of musicality genetics research into each stage of the research lifecycle: study design, study implementation, potential applications, and communication.
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Date: 2023-02-25  ·  Issue: 2023  ·  Volume: 1522
Achieving net‐zero emissions targets: An analysis of long‐term scenarios using an integrated assessment model
Contributors: Ioannis Dafnomilis| Michel den Elzen| Detlef P. Vuuren|
Abstract: More than 100 countries have communicated or adopted new Nationally Determined Contributions (NDCs) and net‐zero target pledges. We investigate the impact on global, national, sectoral, and individual greenhouse gas emissions projections under different scenarios based on the announced NDCs and net‐zero pledges using the IMAGE integrated assessment model. Our results show that while the net‐zero pledges, if implemented, could be an important step forward, they are still not enough to achieve the Paris Agreement goals of well below 2°C and preferably 1.5°C by the end of the century. Still, our net‐zero scenarios project significant all‐sector decarbonization, in particular, electricity; however, certain sectors like industry and transport prove hard to completely abate.
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Date: 2023-02-25  ·  Issue: 2022  · 
Achieving net‐zero emissions targets: An analysis of long‐term scenarios using an integrated assessment model
Contributors: Ioannis Dafnomilis| Michel den Elzen| Detlef P. Vuuren|
Abstract: More than 100 countries have communicated or adopted new Nationally Determined Contributions (NDCs) and net‐zero target pledges. We investigate the impact on global, national, sectoral, and individual greenhouse gas emissions projections under different scenarios based on the announced NDCs and net‐zero pledges using the IMAGE integrated assessment model. Our results show that while the net‐zero pledges, if implemented, could be an important step forward, they are still not enough to achieve the Paris Agreement goals of well below 2°C and preferably 1.5°C by the end of the century. Still, our net‐zero scenarios project significant all‐sector decarbonization, in particular, electricity; however, certain sectors like industry and transport prove hard to completely abate.
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Date: 2023-02-25  ·  Issue: 2022  · 
Calculation of the contribution of water to calcium intake in low‐ and middle‐income countries
Contributors: Gabriela Cormick| Eugenia Settecase| Michaella L. Wu| Paulina M. Nichols| Mara Devia| Alisha Dziarski| Natalia Matamoros| María B. Puchulu| José M. Belizán| Luz Gibbons|
Abstract: Dietary calcium intake is low in many countries, particularly in low‐ and middle‐income countries (LMICs). Water is often overlooked as a source of dietary calcium despite it being universally consumed and providing good calcium bioavailability. Our objective was to assess water distribution systems in LMICs and to develop a formula to simulate the contribution of different water sources to calcium availability. We calculated the contribution of drinking water considering different calcium concentration levels to estimate total calcium availability. We consider a country's households’ access to drinking water sources and the distribution of the country's population by age and gender. Calcium availability could be increased by an average of 49 mg of calcium per person per day in the 62 countries assessed if calcium in drinking water was considered. In 22 (31%) of the countries studied, 80% of households are supplied by water sources that could increase calcium availability. Improving calcium concentration in water could be considered as a strategy in LMICs to slightly improve calcium availability.
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Date: 2023-02-22  ·  Issue: 2023  ·  Volume: 1520
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Date: 2023-02-17  ·  Issue: 2023  ·  Volume: 1522
Cortical thickness of the left parahippocampal cortex links central hearing and cognitive performance in aging
Contributors: Rui Li| Xiaoyan Miao| Buxin Han| Juan Li|
Abstract: Hearing impairment is considered a leading modifiable risk factor of cognitive decline and dementia. While most evidence has been established on clinical assessment of peripheral hearing loss, understanding of how central hearing in real‐world conditions is associated with cognitive aging is limited. This study analyzed the data of 473 unrelated healthy adults aged 36–100 years old from the Lifespan Human Connectome Project in Aging. Central hearing was evaluated using the Words‐in‐Noise decibel threshold. Cognitive functions were evaluated by the performance on cognitive tests, and cortical thickness was estimated from magnetic resonance imaging (MRI) data. Here, we show that a higher hearing threshold was associated with a lower performance on immediate and delayed episodic memory retrieval, switching aspect of executive function, working memory, reading decoding, and vocabulary comprehension. Cortical thickness in the left parahippocampal cortex (lPHC) was negatively associated with the hearing threshold and acted as a significant partial mediator in the association of central hearing with immediate recall, switching, reading decoding, and vocabulary comprehension. These findings suggest that cortical thickness in the lPHC, an early target of dementia, partially links central hearing and performance in multiple cognitive domains in aging.
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Date: 2023-02-05  ·  Issue: 2023  ·  Volume: 1522
The epigenetic landscape of oligodendrocyte lineage cells
Contributors: Ipek Selcen| Emily Prentice| Patrizia Casaccia|
Abstract: The epigenetic landscape of oligodendrocyte lineage cells refers to the cell‐specific modifications of DNA, chromatin, and RNA that define a unique gene expression pattern of functionally specialized cells. Here, we focus on the epigenetic changes occurring as progenitors differentiate into myelin‐forming cells and respond to the local environment. First, modifications of DNA, RNA, nucleosomal histones, key principles of chromatin organization, topologically associating domains, and local remodeling will be reviewed. Then, the relationship between epigenetic modulators and RNA processing will be explored. Finally, the reciprocal relationship between the epigenome as a determinant of the mechanical properties of cell nuclei and the target of mechanotransduction will be discussed. The overall goal is to provide an interpretative key on how epigenetic changes may account for the heterogeneity of the transcriptional profiles identified in this lineage.
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Date: 2023-02-05  ·  Issue: 2023  ·  Volume: 1522
Influence of cognitive reserve on cognitive and motor function in α‐synucleinopathies: A systematic review protocol
Contributors: Isaac Saywell| Brittany Child| Lauren Foreman| Lyndsey Collins‐Praino| Irina Baetu|
Abstract: Cognitive reserve has been used to justify neuropathologically unexplainable mismatches in Alzheimer's disease outcomes. Recent evidence has suggested this effect may be replicable across other conditions. However, it is still unclear whether cognitive reserve applies to α‐synucleinopathies or to motor outcomes, or if medication confounds effects. This review protocol follows PRISMA‐P guidelines and aims to investigate whether cognitive reserve can predict both cognitive and motor outcomes for α‐synucleinopathy patients. MEDLINE (via PubMed), Scopus, psycINFO (via Ovid), CINAHL (via EBSCO), and Web of Science have been searched. Cross‐sectional, cohort, case‐control, and longitudinal studies investigating the association between cognitive reserve and cognitive and/or motor outcomes for Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy will be included. Reviewers will independently perform screening, while also extracting data, assessing the risk of bias (using a version of the Quality in Prognostic Studies tool), and rating evidence quality (using GRADE). If possible, random‐effects meta‐analyses will be conducted for each unique outcome variable and α‐synucleinopathy; otherwise, a narrative synthesis will be performed. Depending on the number of studies, exploratory analyses may involve meta‐regression to assess potential confounding effects. Understanding the broader protective effect of cognitive reserve has significant implications for preventive interventions in the wider population.
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Date: 2023-02-05  ·  Issue: 2023  · 
The epigenetic landscape of oligodendrocyte lineage cells
Contributors: Ipek Selcen| Emily Prentice| Patrizia Casaccia|
Abstract: The epigenetic landscape of oligodendrocyte lineage cells refers to the cell‐specific modifications of DNA, chromatin, and RNA that define a unique gene expression pattern of functionally specialized cells. Here, we focus on the epigenetic changes occurring as progenitors differentiate into myelin‐forming cells and respond to the local environment. First, modifications of DNA, RNA, nucleosomal histones, key principles of chromatin organization, topologically associating domains, and local remodeling will be reviewed. Then, the relationship between epigenetic modulators and RNA processing will be explored. Finally, the reciprocal relationship between the epigenome as a determinant of the mechanical properties of cell nuclei and the target of mechanotransduction will be discussed. The overall goal is to provide an interpretative key on how epigenetic changes may account for the heterogeneity of the transcriptional profiles identified in this lineage.
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Date: 2023-02-01  ·  Issue: 2022  · 
Advancing understanding of land–atmosphere interactions by breaking discipline and scale barriers
Contributors: Jordi Vilà‐Guerau de Arellano| Oscar Hartogensis| Imme Benedict| Hugo de Boer| Peter J. M. Bosman| Santiago Botía| Micael Amore Cecchini| Kim A. P. Faassen| Raquel González‐Armas| Kevin van Diepen| Bert G. Heusinkveld| Martin Janssens| Felipe Lobos‐Roco| Ingrid T. Luijkx| Luiz A. T. Machado| Mary Rose Mangan| Arnold F. Moene| Wouter B. Mol| Michiel van der Molen| Robbert Moonen| H. G. Ouwersloot| So‐Won Park| Xabier Pedruzo‐Bagazgoitia| Thomas Röckmann| Getachew Agmuas Adnew| Reinder Ronda| Martin Sikma| Ruben Schulte| Bart J. H. van Stratum| Menno A. Veerman| Margreet C. van Zanten| Chiel C. van Heerwaarden|
Abstract: Vegetation and atmosphere processes are coupled through a myriad of interactions linking plant transpiration, carbon dioxide assimilation, turbulent transport of moisture, heat and atmospheric constituents, aerosol formation, moist convection, and precipitation. Advances in our understanding are hampered by discipline barriers and challenges in understanding the role of small spatiotemporal scales. In this perspective, we propose to study the atmosphere–ecosystem interaction as a continuum by integrating leaf to regional scales (multiscale) and integrating biochemical and physical processes (multiprocesses). The challenges ahead are (1) How do clouds and canopies affect the transferring and in‐canopy penetration of radiation, thereby impacting photosynthesis and biogenic chemical transformations? (2) How is the radiative energy spatially distributed and converted into turbulent fluxes of heat, moisture, carbon, and reactive compounds? (3) How do local (leaf‐canopy‐clouds, 1 m to kilometers) biochemical and physical processes interact with regional meteorology and atmospheric composition (kilometers to 100 km)? (4) How can we integrate the feedbacks between cloud radiative effects and plant physiology to reduce uncertainties in our climate projections driven by regional warming and enhanced carbon dioxide levels? Our methodology integrates fine‐scale explicit simulations with new observational techniques to determine the role of unresolved small‐scale spatiotemporal processes in weather and climate models.
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Date: 2023-02-01  ·  Issue: 2023  ·  Volume: 1521
Developing eminence in STEMM: An interview study with talent development and STEMM experts
Contributors: Linlin Luo| Heidrun Stoeger|
Abstract: In the present day, we need outstanding scientists, engineers, mathematicians, and medical science researchers more than ever to solve the world's most pressing issues, such as climate change, water contamination, and cyber security. Naturally, we ask the question: What does it take to develop eminence in science, technology, engineering, mathematics, and medical science (STEMM)? To answer this question, we interviewed two relevant groups of experts: 14 talent development researchers and 14 STEMM experts. The interview questions were developed based on the theoretical framework of the Actiotope Model of Giftedness and the related educational and learning capital approach that differentiates five types of exogenous resources (educational capital) and five types of endogenous resources (learning capital) that feed into talent development toward eminence. The results show that all types of capital were regarded as important by the experts for developing eminence in STEMM. However, there were also differences. We describe the educational and learning capital that talent development researchers and STEMM experts considered to be important for talent development in STEMM, as well as the similarities and differences between the two groups.
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Date: 2023-01-31  ·  Issue: 2023  ·  Volume: 1521
Protocol and application of basal erythrocyte transketolase activity to improve assessment of thiamine status
Contributors: Kerry S. Jones| Damon A. Parkington| Megan W. Bourassa| Carla Cerami| Albert Koulman|
Abstract: Thiamine (vitamin B1) is an essential micronutrient required as a cofactor in many metabolic processes. Clinical symptoms of thiamine deficiency are poorly defined, hence biomarkers of thiamine status are important. The erythrocyte transketolase activity coefficient (ETKac) is a sensitive measure of thiamine status, but its interpretation may be confounded where the availability of the transketolase enzyme is limited. Basal ETK activity per gram of hemoglobin provides a complementary biomarker of thiamine status; however, its measurement and calculation are poorly described. Here, we describe in detail the assessment of basal ETK activity, including the calculation of path length in microplates and the molar absorption coefficient of NADH specific to the assay, and the measurement of hemoglobin in sample hemolysates. To illustrate the application of the methods, we present ETKac and basal ETK activity from women in The Gambia and UK. In conclusion, we present a clear protocol for the measurement of basal ETK activity that will permit the harmonization of methods to improve replication between laboratories.
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Date: 2023-01-31  ·  Issue: 2023  ·  Volume: 1521
Polymeric carbon nitride as a platform for photoelectrochemical water‐splitting cells
Contributors: Michael Volokh| Menny Shalom|
Abstract: Polymeric carbon nitride (CN) materials are promising low‐cost photocatalysts that exhibit a combination of chemical and physical properties suitable for converting light into redox activity on their surface. In this perspective, we describe our experience with this family of materials as light absorbers that serve as an anode in photoelectrochemical cells toward water‐splitting. We describe some of the CN deposition techniques and procedures established in our lab. The knowledge gained from powder‐based photocatalysis is implemented in photoelectrochemical scenarios and is used to determine the merits and shortcomings of resulting layers. We show how the preparation methods are oriented based on these factors and how high photoelectrochemical water‐splitting activity develops in photoanodes we developed where CN(s) act as photoabsorbers. Lastly, we present our view on the future prospects of this field.
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Date: 2023-01-31  ·  Issue: 2022  · 
Polymeric carbon nitride as a platform for photoelectrochemical water‐splitting cells
Contributors: Michael Volokh| Menny Shalom|
Abstract: Polymeric carbon nitride (CN) materials are promising low‐cost photocatalysts that exhibit a combination of chemical and physical properties suitable for converting light into redox activity on their surface. In this perspective, we describe our experience with this family of materials as light absorbers that serve as an anode in photoelectrochemical cells toward water‐splitting. We describe some of the CN deposition techniques and procedures established in our lab. The knowledge gained from powder‐based photocatalysis is implemented in photoelectrochemical scenarios and is used to determine the merits and shortcomings of resulting layers. We show how the preparation methods are oriented based on these factors and how high photoelectrochemical water‐splitting activity develops in photoanodes we developed where CN(s) act as photoabsorbers. Lastly, we present our view on the future prospects of this field.
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Date: 2023-01-30  ·  Issue: 2023  · 
Viral immunity: Basic mechanisms and therapeutic applications—a Keystone Symposia report
Contributors: Jennifer Cable| Siddharth Balachandran| Lisa P. Daley‐Bauer| Arjun Rustagi| Ferrin Antony| Justin J. Frere| Jamie Strampe| Katherine Kedzierska| Judy L. Cannon| Maureen A. McGargill| Daniela Weiskopf| Robert C. Mettelman| Julia Niessl| Paul G. Thomas| Bryan Briney| Sophie A. Valkenburg| Jesse D. Bloom| Pamela J. Bjorkman| Sho Iketani| C. Garrett Rappazzo| Chelsea M. Crooks| Kali F. Crofts| Stefan Pöhlmann| Florian Krammer| Andrea J. Sant| Gary J. Nabel| Stacey Schultz‐Cherry|
Abstract: Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in‐depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium “Viral Immunity: Basic Mechanisms and Therapeutic Applications.” This report presents concise summaries from several of the symposium presenters.
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Date: 2023-01-30  ·  Issue: 2022  · 
Exploring the genetics of rhythmic perception and musical engagement in the Vanderbilt Online Musicality Study
Contributors: Daniel E. Gustavson| Peyton L. Coleman| Youjia Wang| Rachana Nitin| Lauren E. Petty| Catherine T. Bush| Miriam A. Mosing| Laura W. Wesseldijk| Fredrik Ullén| 23 and Me Research Team| Jennifer E. Below| Nancy J. Cox| Reyna L. Gordon|
Abstract: Uncovering the genetic underpinnings of musical ability and engagement is a foundational step for exploring their wide‐ranging associations with cognition, health, and neurodevelopment. Prior studies have focused on using twin and family designs, demonstrating moderate heritability of musical phenotypes. The current study used genome‐wide complex trait analysis and polygenic score (PGS) approaches utilizing genotype data to examine genetic influences on two musicality traits (rhythmic perception and music engagement) in N = 1792 unrelated adults in the Vanderbilt Online Musicality Study. Meta‐analyzed heritability estimates (including a replication sample of Swedish individuals) were 31% for rhythmic perception and 12% for self‐reported music engagement. A PGS derived from a recent study on beat synchronization ability predicted both rhythmic perception (β = 0.11) and music engagement (β = 0.19) in our sample, suggesting that genetic influences underlying self‐reported beat synchronization ability also influence individuals’ rhythmic discrimination aptitude and the degree to which they engage in music. Cross‐trait analyses revealed a modest contribution of PGSs from several nonmusical traits (from the cognitive, personality, and circadian chronotype domains) to individual differences in musicality (β = −0.06 to 0.07). This work sheds light on the complex relationship between the genetic architecture of musical rhythm processing, beat synchronization, music engagement, and other nonmusical traits.
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Date: 2023-01-30  ·  Issue: 2023  ·  Volume: 1521
Postgraduate perspectives on mentoring undergraduate researchers for talent development
Contributors: Muhammad Zaka Asif| Arthur S Edison| Erin L Dolan|
Abstract: Undergraduate research experiences are critical for the talent development of the STEM research workforce, and research mentors play an influential role in this process. Given the many life science majors seeking research experiences at universities, graduate and postdoctoral researchers (i.e., postgraduates) provide much of the daily mentoring of undergraduate researchers. Yet, there remains little research on how postgraduates contribute to talent development among undergraduate researchers. To begin to address this knowledge gap, we conducted an exploratory study of the experiences of 32 postgraduates who mentored life science undergraduate researchers. We identified four factors that they perceived as enabling undergraduate researcher talent development: undergraduate researcher characteristics, research project characteristics, and mentoring implementation as well as outcomes for both the postgraduate and undergraduate. We then describe a team‐based approach to postgraduate mentoring of undergraduate researchers that attends to these factors to provide an example that practitioners can adapt or adopt for their own research groups.
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Date: 2023-01-30  ·  Issue: 2023  ·  Volume: 1521
Viral immunity: Basic mechanisms and therapeutic applications—a Keystone Symposia report
Contributors: Jennifer Cable| Siddharth Balachandran| Lisa P. Daley‐Bauer| Arjun Rustagi| Ferrin Antony| Justin J. Frere| Jamie Strampe| Katherine Kedzierska| Judy L. Cannon| Maureen A. McGargill| Daniela Weiskopf| Robert C. Mettelman| Julia Niessl| Paul G. Thomas| Bryan Briney| Sophie A. Valkenburg| Jesse D. Bloom| Pamela J. Bjorkman| Sho Iketani| C. Garrett Rappazzo| Chelsea M. Crooks| Kali F. Crofts| Stefan Pöhlmann| Florian Krammer| Andrea J. Sant| Gary J. Nabel| Stacey Schultz‐Cherry|
Abstract: Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in‐depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium “Viral Immunity: Basic Mechanisms and Therapeutic Applications.” This report presents concise summaries from several of the symposium presenters.
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Date: 2023-01-30  ·  Issue: 2023  ·  Volume: 1521
Exploring the genetics of rhythmic perception and musical engagement in the Vanderbilt Online Musicality Study
Contributors: Daniel E. Gustavson| Peyton L. Coleman| Youjia Wang| Rachana Nitin| Lauren E. Petty| Catherine T. Bush| Miriam A. Mosing| Laura W. Wesseldijk| Fredrik Ullén| 23 and Me Research Team| Jennifer E. Below| Nancy J. Cox| Reyna L. Gordon|
Abstract: Uncovering the genetic underpinnings of musical ability and engagement is a foundational step for exploring their wide‐ranging associations with cognition, health, and neurodevelopment. Prior studies have focused on using twin and family designs, demonstrating moderate heritability of musical phenotypes. The current study used genome‐wide complex trait analysis and polygenic score (PGS) approaches utilizing genotype data to examine genetic influences on two musicality traits (rhythmic perception and music engagement) in N = 1792 unrelated adults in the Vanderbilt Online Musicality Study. Meta‐analyzed heritability estimates (including a replication sample of Swedish individuals) were 31% for rhythmic perception and 12% for self‐reported music engagement. A PGS derived from a recent study on beat synchronization ability predicted both rhythmic perception (β = 0.11) and music engagement (β = 0.19) in our sample, suggesting that genetic influences underlying self‐reported beat synchronization ability also influence individuals’ rhythmic discrimination aptitude and the degree to which they engage in music. Cross‐trait analyses revealed a modest contribution of PGSs from several nonmusical traits (from the cognitive, personality, and circadian chronotype domains) to individual differences in musicality (β = −0.06 to 0.07). This work sheds light on the complex relationship between the genetic architecture of musical rhythm processing, beat synchronization, music engagement, and other nonmusical traits.
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Date: 2023-01-25  ·  Issue: 2023  · 
Positive‐strand RNA viruses—a Keystone Symposia report
Contributors: Jennifer Cable| Mark R. Denison| Margaret Kielian| William T. Jackson| Ralf Bartenschlager| Tero Ahola| Suchetana Mukhopadhyay| Daved H. Fremont| Richard J. Kuhn| Ashleigh Shannon| Meredith N. Frazier| Kwok‐Yung Yuen| Carolyn B. Coyne| Katja C. Wolthers| Guo‐Li Ming| Camy S. Guenther| Jasmine Moshiri| Sonja M. Best| John W. Schoggins| Kellie Ann Jurado| Gregory D. Ebel| Alexandra Schäfer| Lisa F. P. Ng| Marjolein Kikkert| Alessandro Sette| Eva Harris| Peter A. C. Wing| Julie Eggenberger| Siddharth R. Krishnamurthy| Marcus G. Mah| Rita M. Meganck| Donghoon Chung| Sebastian Maurer‐Stroh| Raul Andino| Bette Korber| Stanley Perlman| Pei‐Yong Shi| Montserrat Bárcena| Sophie‐Marie Aicher| Michelle N. Vu| Devin J. Kenney| Brett D. Lindenbach| Yukiko Nishida| Laurent Rénia| Evan P. Williams|
Abstract: Positive‐strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS‐CoV‐2 pandemic. On June 18–22, 2022, researchers focusing on positive‐strand RNA viruses met for the Keystone Symposium “Positive‐Strand RNA Viruses” to share the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report presents concise summaries of the scientific discussions at the symposium.
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Date: 2023-01-25  ·  Issue: 2023  ·  Volume: 1521
Positive‐strand RNA viruses—a Keystone Symposia report
Contributors: Jennifer Cable| Mark R. Denison| Margaret Kielian| William T. Jackson| Ralf Bartenschlager| Tero Ahola| Suchetana Mukhopadhyay| Daved H. Fremont| Richard J. Kuhn| Ashleigh Shannon| Meredith N. Frazier| Kwok‐Yung Yuen| Carolyn B. Coyne| Katja C. Wolthers| Guo‐Li Ming| Camy S. Guenther| Jasmine Moshiri| Sonja M. Best| John W. Schoggins| Kellie Ann Jurado| Gregory D. Ebel| Alexandra Schäfer| Lisa F. P. Ng| Marjolein Kikkert| Alessandro Sette| Eva Harris| Peter A. C. Wing| Julie Eggenberger| Siddharth R. Krishnamurthy| Marcus G. Mah| Rita M. Meganck| Donghoon Chung| Sebastian Maurer‐Stroh| Raul Andino| Bette Korber| Stanley Perlman| Pei‐Yong Shi| Montserrat Bárcena| Sophie‐Marie Aicher| Michelle N. Vu| Devin J. Kenney| Brett D. Lindenbach| Yukiko Nishida| Laurent Rénia| Evan P. Williams|
Abstract: Positive‐strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS‐CoV‐2 pandemic. On June 18–22, 2022, researchers focusing on positive‐strand RNA viruses met for the Keystone Symposium “Positive‐Strand RNA Viruses” to share the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report presents concise summaries of the scientific discussions at the symposium.
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Date: 2023-01-18  ·  Issue: 2023  ·  Volume: 1521
Relative importance of students’ expectancy–value beliefs as predictors of academic success in gateway math courses
Contributors: Daria K. Benden| Fani Lauermann|
Abstract: Math‐intensive fields in postsecondary education, such as physics and math, often struggle with high student dropout rates. Motivational declines after the transition to postsecondary education are a key factor underlying students’ achievement difficulties and decisions to leave these fields. A better understanding of which motivational factors play a particularly central role in predicting achievement difficulties and dropout decisions is needed to inform potential interventions. Thus, drawing on Eccles’ expectancy–value theory, we examined changes in the relative importance of students’ expected success and different task values as unique or joint predictors of students’ academic success and course dropout across three time points within a semester. Data were collected in gatekeeper math courses for physics and math majors (N = 811). Commonality analyses showed an increasing overlap in the predictive effects of students’ expectancies and values on later academic outcomes, which indicates convergence in these motivational beliefs, as they likely influence each other over time. A significant shift in the relative importance of students’ expectancies and values occurred after the transition to postsecondary education, highlighting a sensitive time point for interventions. Pre‐existing achievement, socioeconomic, and gender differences lost some of their unique predictive power toward the midpoint of the semester.
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Date: 2023-01-18  ·  Issue: 2023  · 
Relative importance of students’ expectancy–value beliefs as predictors of academic success in gateway math courses
Contributors: Daria K. Benden| Fani Lauermann|
Abstract: Math‐intensive fields in postsecondary education, such as physics and math, often struggle with high student dropout rates. Motivational declines after the transition to postsecondary education are a key factor underlying students’ achievement difficulties and decisions to leave these fields. A better understanding of which motivational factors play a particularly central role in predicting achievement difficulties and dropout decisions is needed to inform potential interventions. Thus, drawing on Eccles’ expectancy–value theory, we examined changes in the relative importance of students’ expected success and different task values as unique or joint predictors of students’ academic success and course dropout across three time points within a semester. Data were collected in gatekeeper math courses for physics and math majors (N = 811). Commonality analyses showed an increasing overlap in the predictive effects of students’ expectancies and values on later academic outcomes, which indicates convergence in these motivational beliefs, as they likely influence each other over time. A significant shift in the relative importance of students’ expectancies and values occurred after the transition to postsecondary education, highlighting a sensitive time point for interventions. Pre‐existing achievement, socioeconomic, and gender differences lost some of their unique predictive power toward the midpoint of the semester.
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Date: 2023-01-11  ·  Issue: 2023  ·  Volume: 1521
Optimizing a therapeutic humanized follicle‐stimulating hormone–blocking antibody formulation by protein thermal shift assay
Contributors: Damini Sant| Satish Rojekar| Sakshi Gera| Anusha R. Pallapati| Judit Gimenez‐Roig| Tan‐Chun Kuo| Ashley Padilla| Funda Korkmaz| Liam Cullen| Jiya Chatterjee| Eleanor Shelly| Marcia Meseck| Sari Miyashita| Anne Macdonald| Farhath Sultana| Orly Barak| Vitaly Ryu| Se‐Min Kim| Cemre Robinson| Clifford J. Rosen| John Caminis| Daria Lizneva| Shozeb Haider| Tony Yuen| Mone Zaidi|
Abstract: Biopharmaceutical products are formulated using several Food and Drug Administration (FDA) approved excipients within the inactive ingredient limit to maintain their storage stability and shelf life. Here, we have screened and optimized different sets of excipient combinations to yield a thermally stable formulation for the humanized follicle‐stimulating hormone (FSH)–blocking antibody, MS‐Hu6. We used a protein thermal shift assay in which rising temperatures resulted in the maximal unfolding of the protein at the melting temperature (Tm). To determine the buffer and pH for a stable solution, four different buffers with a pH range from 3 to 8 were screened. This resulted in maximal Tms at pH 5.62 for Fab in phosphate buffer and at pH 6.85 for Fc in histidine buffer. Upon testing a range of salt concentrations, MS‐Hu6 was found to be more stable at lower concentrations, likely due to reduced hydrophobic effects. Molecular dynamics simulations revealed a higher root‐mean‐square deviation with 1 mM than with 100 mM salt, indicating enhanced stability, as noted experimentally. Among the stabilizers tested, Tween 20 was found to yield the highest Tm and reversed the salt effect. Among several polyols/sugars, trehalose and sucrose were found to produce higher thermal stabilities. Finally, binding of recombinant human FSH to MS‐Hu6 in a final formulation (20 mM phosphate buffer, 1 mM NaCl, 0.001% w/v Tween 20, and 260 mM trehalose) resulted in a thermal shift (increase in Tm) for the Fab, but expectedly not in the Fc domain. Given that we used a low dose of MS‐Hu6 (1 μM), the next challenge would be to determine whether 100‐fold higher, industry‐standard concentrations are equally stable.
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Date: 2023-01-10  ·  Issue: 2023  ·  Volume: 1519
Issue Information
Contributors:
Abstract:
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Date: 2023-01-09  ·  Issue: 2023  ·  Volume: 1521
Mechanisms of paracellular transport of magnesium in intestinal and renal epithelia
Contributors: Pascal Houillier| Loïc Lievre| Marguerite Hureaux| Caroline Prot‐Bertoye|
Abstract: Magnesium is the fourth most abundant cation in the body. It plays a critical role in many biological processes, including the process of energy release. Paracellular transport of magnesium is mandatory for magnesium homeostasis. In addition to intestinal absorption that occurs in part across the paracellular pathway, magnesium is reabsorbed by the kidney tubule. The bulk of magnesium is reabsorbed through the paracellular pathway in the proximal tubule and the thick ascending limb of the loop of Henle. The finding that rare genetic diseases due to pathogenic variants in genes encoding specific claudins (CLDNs), proteins located at the tight junction that determine the selectivity and the permeability of the paracellular pathway, led to an awareness of their importance in magnesium homeostasis. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is caused by a loss of function of CLDN16 or CLDN19. Pathogenic CLDN10 variants cause HELIX syndrome, which is associated with a severe renal loss of sodium chloride and hypermagnesemia. The present review summarizes the current knowledge of the mechanisms and factors involved in paracellular magnesium permeability. The review also highlights some of the unresolved questions that need to be addressed.
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Date: 2023-01-09  ·  Issue: 2022  · 
Mechanisms of paracellular transport of magnesium in intestinal and renal epithelia
Contributors: Pascal Houillier| Loïc Lievre| Marguerite Hureaux| Caroline Prot‐Bertoye|
Abstract: Magnesium is the fourth most abundant cation in the body. It plays a critical role in many biological processes, including the process of energy release. Paracellular transport of magnesium is mandatory for magnesium homeostasis. In addition to intestinal absorption that occurs in part across the paracellular pathway, magnesium is reabsorbed by the kidney tubule. The bulk of magnesium is reabsorbed through the paracellular pathway in the proximal tubule and the thick ascending limb of the loop of Henle. The finding that rare genetic diseases due to pathogenic variants in genes encoding specific claudins (CLDNs), proteins located at the tight junction that determine the selectivity and the permeability of the paracellular pathway, led to an awareness of their importance in magnesium homeostasis. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is caused by a loss of function of CLDN16 or CLDN19. Pathogenic CLDN10 variants cause HELIX syndrome, which is associated with a severe renal loss of sodium chloride and hypermagnesemia. The present review summarizes the current knowledge of the mechanisms and factors involved in paracellular magnesium permeability. The review also highlights some of the unresolved questions that need to be addressed.
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Date: 2023-01-06  ·  Issue: 2023  ·  Volume: 1521
Anatomical and functional study of the cuneiform nucleus: A critical site to organize innate defensive behaviors
Contributors: Ricardo P. Bindi| Cibele C. Guimarães| Amanda R. Oliveira| Fernando F. Melleu| Miguel A. X. Lima| Marcus V. C. Baldo| Simone C. Motta| Newton S. Canteras|
Abstract: The cuneiform nucleus (CUN) is a midbrain structure located lateral to the caudal part of the periaqueductal gray. In the present investigation, we first performed a systematic analysis of the afferent and efferent projections of the CUN using FluoroGold and Phaseolus vulgaris leucoagglutinin as retrograde and anterograde neuronal tracers, respectively. Next, we examined the behavioral responses to optogenetic activation of the CUN and evaluated the impact of pharmacological inactivation of the CUN in both innate and contextual fear responses to a predatory threat (i.e., a live cat). The present hodologic evidence indicates that the CUN might be viewed as a caudal component of the periaqueductal gray. The CUN has strong bidirectional links with the dorsolateral periaqueductal gray (PAGdl). Our hodological findings revealed that the CUN and PAGdl share a similar source of inputs involved in integrating information related to life‐threatening events and that the CUN provides particularly strong projections to brain sites influencing antipredatory defensive behaviors. Our functional studies revealed that the CUN mediates innate freezing and flight antipredatory responses but does not seem to influence the acquisition and expression of learned fear responses.
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Date: 2022-12-30  ·  Issue: 2023  ·  Volume: 1519
Retraction: CircRNA_103948 inhibits autophagy in colorectal cancer in a ceRNA manner
Contributors:
Abstract: The following article,1 published online on 3 Sept 2021 in Wiley Online Library (https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/nyas.14679), has been retracted by agreement between the authors, the journal Editor‐in‐Chief and Wiley Periodicals LLC. The article is being retracted at the authors' request after the journal was contacted by the authors. The authors notified the journal that they were unable to verify or replicate the experimental results of the transmission electron microscopy examination and autophagosome detection presented in Figure 6. As a result, the article's conclusions are not considered reliable.
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Date: 2022-12-28  ·  Issue: 2022  · 
Un‐yielding: Evidence for the agriculture transformation we need
Contributors: Rebecca Chaplin‐Kramer| M. Jahi Chappell| Elena M. Bennett|
Abstract: There has been a seismic shift in the center of gravity of scientific writing and thinking about agriculture over the past decades, from a prevailing focus on maximizing yields toward a goal of balancing trade‐offs and ensuring the delivery of multiple ecosystem services. Maximizing crop yields often results in a system where most benefits accrue to very few (in the form of profits), alongside irreparable environmental harm to agricultural ecosystems, landscapes, and people. Here, we present evidence that an un‐yielding, which we define as de‐emphasizing the importance of yields alone, is necessary to achieve the goal of a more Food secure, Agrobiodiverse, Regenerative, Equitable and just (FARE) agriculture. Focusing on yields places the emphasis on one particular outcome of agriculture, which is only an intermediate means to the true endpoint of human well‐being. Using yields as a placeholder for this outcome ignores the many other benefits of agriculture that people also care about, like health, livelihoods, and a sense of place. Shifting the emphasis to these multiple benefits rather than merely yields, and to their equitable delivery to all people, we find clear scientific evidence of win‐wins for people and nature through four strategies that foster FARE agriculture: reduced disturbance, systems reintegration, diversity, and justice (in the form of securing rights to land and other resources). Through a broad review of the current state of agriculture, desired futures, and the possible pathways to reach them, we argue that while trade‐offs between some ecosystem services in agriculture are unavoidable, the same need not be true of the end benefits we desire from them.
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Date: 2022-12-28  ·  Issue: 2023  ·  Volume: 1520
Un‐yielding: Evidence for the agriculture transformation we need
Contributors: Rebecca Chaplin‐Kramer| M. Jahi Chappell| Elena M. Bennett|
Abstract: There has been a seismic shift in the center of gravity of scientific writing and thinking about agriculture over the past decades, from a prevailing focus on maximizing yields toward a goal of balancing trade‐offs and ensuring the delivery of multiple ecosystem services. Maximizing crop yields often results in a system where most benefits accrue to very few (in the form of profits), alongside irreparable environmental harm to agricultural ecosystems, landscapes, and people. Here, we present evidence that an un‐yielding, which we define as de‐emphasizing the importance of yields alone, is necessary to achieve the goal of a more Food secure, Agrobiodiverse, Regenerative, Equitable and just (FARE) agriculture. Focusing on yields places the emphasis on one particular outcome of agriculture, which is only an intermediate means to the true endpoint of human well‐being. Using yields as a placeholder for this outcome ignores the many other benefits of agriculture that people also care about, like health, livelihoods, and a sense of place. Shifting the emphasis to these multiple benefits rather than merely yields, and to their equitable delivery to all people, we find clear scientific evidence of win‐wins for people and nature through four strategies that foster FARE agriculture: reduced disturbance, systems reintegration, diversity, and justice (in the form of securing rights to land and other resources). Through a broad review of the current state of agriculture, desired futures, and the possible pathways to reach them, we argue that while trade‐offs between some ecosystem services in agriculture are unavoidable, the same need not be true of the end benefits we desire from them.
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Date: 2022-12-27  ·  Issue: 2023  ·  Volume: 1520
Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests
Contributors: Skylar L. Martin| Tatum D. Mortimer| Yonatan H. Grad|
Abstract: Neisseria gonorrhoeae is an urgent public health threat due to the emergence of antibiotic resistance. As most isolates in the United States are susceptible to at least one antibiotic, rapid molecular antimicrobial susceptibility tests (ASTs) would offer the opportunity to tailor antibiotic therapy, thereby expanding treatment options. With genome sequence and antibiotic resistance phenotype data for nearly 20,000 clinical N. gonorrhoeae isolates now available, there is an opportunity to use statistical methods to develop sequence‐based diagnostics that predict antibiotic susceptibility from genotype. N. gonorrhoeae, therefore, provides a useful example illustrating how to apply machine learning models to aid in the design of sequence‐based ASTs. We present an overview of this framework, which begins with establishing the assay technology, the performance criteria, the population in which the diagnostic will be used, and the clinical goals, and extends to the choices that must be made to arrive at a set of features with the desired properties for predicting susceptibility phenotype from genotype. While we focus on the example of N. gonorrhoeae, the framework generalizes to other organisms for which large‐scale genotype and antibiotic resistance data can be combined to aid in diagnostics development.
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Date: 2022-12-27  ·  Issue: 2023  · 
Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests
Contributors: Skylar L. Martin| Tatum D. Mortimer| Yonatan H. Grad|
Abstract: Neisseria gonorrhoeae is an urgent public health threat due to the emergence of antibiotic resistance. As most isolates in the United States are susceptible to at least one antibiotic, rapid molecular antimicrobial susceptibility tests (ASTs) would offer the opportunity to tailor antibiotic therapy, thereby expanding treatment options. With genome sequence and antibiotic resistance phenotype data for nearly 20,000 clinical N. gonorrhoeae isolates now available, there is an opportunity to use statistical methods to develop sequence‐based diagnostics that predict antibiotic susceptibility from genotype. N. gonorrhoeae, therefore, provides a useful example illustrating how to apply machine learning models to aid in the design of sequence‐based ASTs. We present an overview of this framework, which begins with establishing the assay technology, the performance criteria, the population in which the diagnostic will be used, and the clinical goals, and extends to the choices that must be made to arrive at a set of features with the desired properties for predicting susceptibility phenotype from genotype. While we focus on the example of N. gonorrhoeae, the framework generalizes to other organisms for which large‐scale genotype and antibiotic resistance data can be combined to aid in diagnostics development.
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Date: 2022-12-20  ·  Issue: 2023  ·  Volume: 1520
Front‐loading STEM enrichment to prepare learners for STEM pathways
Contributors: Paula Olszewski‐Kubilius|
Abstract: In this article, we describe a collaboration between a university and school district aimed at preparing more students who are typically underidentified and underserved in gifted programs for advanced STEM coursework in high school. Features of the collaboration included early intervention, significant outside‐of‐school programming and coursework in STEM through elementary and middle school (over 400 h), tutoring, and support for families. Data included scores on two standardized achievement tests for 14 cohorts of students who self‐identified as African American and/or Hispanic (361 total students) as they progressed from Grade 3 to Grade 8, placement in accelerated mathematics courses in Grade 9, and college matriculation. Comparisons were made to data for comparable demographic groups within the school district. Results showed greater growth in reading and mathematics compared to demographic peers in the district reaching achievement levels comparable to the highest‐scoring students in the district. There were significant increases in the percentage of students entering high school with advanced placement in mathematics as well as improvement over multiple cohorts in matriculation at more selective institutions of higher education. Results are discussed with respect to best practices for the identification of students with potential STEM talent, effective university–school partnerships, and STEM‐talent development pathways.
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Date: 2022-12-20  ·  Issue: 2023  ·  Volume: 1520
How are different math knowledge presentations associated with math anxiety?
Contributors: Tian Li| Chuansheng Chen| Xinlin Zhou|
Abstract: A close relationship between math performance and math anxiety has been demonstrated, but how different presentations of mathematics are associated with math anxiety has not been investigated. This study recruited 826 elementary school students in grades 5 and 6. All students were given math trait and state anxiety questionnaires; a nonverbal matrix reasoning task; and verbalized, symbolic, and situational fraction problem‐solving tasks. After data cleaning, 475 boys and 323 girls (798 in total) were included in the analysis (mean age = 11.79, SD = 0.82). Partial correlation analysis showed that students’ math traits and state anxiety were more closely related to symbolic fraction problem‐solving than to verbalized and situational fraction problem‐solving. Mixed linear model analysis showed that math state anxiety for symbolic problem‐solving was significantly greater than that for verbalized and situational problem‐solving. Based on these findings, we concluded that the presentation of symbolic math is more likely to induce math anxiety than verbalized or situational math. This finding has potential practical applications in math anxiety interventions and education.
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Date: 2022-12-20  ·  Issue: 2023  · 
Front‐loading STEM enrichment to prepare learners for STEM pathways
Contributors: Paula Olszewski‐Kubilius|
Abstract: In this article, we describe a collaboration between a university and school district aimed at preparing more students who are typically underidentified and underserved in gifted programs for advanced STEM coursework in high school. Features of the collaboration included early intervention, significant outside‐of‐school programming and coursework in STEM through elementary and middle school (over 400 h), tutoring, and support for families. Data included scores on two standardized achievement tests for 14 cohorts of students who self‐identified as African American and/or Hispanic (361 total students) as they progressed from Grade 3 to Grade 8, placement in accelerated mathematics courses in Grade 9, and college matriculation. Comparisons were made to data for comparable demographic groups within the school district. Results showed greater growth in reading and mathematics compared to demographic peers in the district reaching achievement levels comparable to the highest‐scoring students in the district. There were significant increases in the percentage of students entering high school with advanced placement in mathematics as well as improvement over multiple cohorts in matriculation at more selective institutions of higher education. Results are discussed with respect to best practices for the identification of students with potential STEM talent, effective university–school partnerships, and STEM‐talent development pathways.
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Date: 2022-12-14  ·  Issue: 2022  ·  Volume: 1518
Issue Information
Contributors:
Abstract:
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Date: 2022-12-08  ·  Issue: 2023  ·  Volume: 1520
Spatial neglect encompasses impaired verticality representation after right hemisphere stroke
Contributors: Rémi Lafitte| Marie Jeager| Céline Piscicelli| Shenhao Dai| Camille Lemaire| Anne Chrispin| Patrice Davoine| Eve Dupierrix| Dominic Pérennou|
Abstract: Spatial neglect after right hemisphere stroke (RHS) was recently found to encompass lateropulsion, a deficit in body orientation with respect to gravity caused by altered brain processing of graviception. By analogy, we hypothesized that spatial neglect after RHS might encompass an altered representation of verticality. We also assumed a strong relation between body neglect and impaired postural vertical, both referring to the body. To tackle these issues, we performed contingency and correlation analyses between two domains of spatial neglect (body, extra‐body) and two modalities of verticality perception (postural, visual) in 77 individuals (median age = 67) with a first‐ever subacute RHS (1–3 months). All individuals with a transmodal (postural and visual) tilt in verticality perception (n = 26) had spatial neglect, but the reverse was not found. Correlation and multivariate analyses revealed that spatial neglect (and notably body neglect) was associated more with postural than visual vertical tilts. These findings indicate that after RHS, an impaired verticality representation results from a kind of graviceptive neglect, bearing first on somaesthetic graviception and second on vestibular graviception. They also suggest that the human brain uses not only a mosaic of 2D representations but also 3D maps involving a transmodal representation of verticality.
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Date: 2022-12-07  ·  Issue: 2023  ·  Volume: 1520
Quality standards and recommendations for research in music and neuroplasticity
Contributors: Efthymios Papatzikis| Maria Agapaki| Rosari Naveena Selvan| Varun Pandey| Fathima Zeba|
Abstract: Research on how music influences brain plasticity has gained momentum in recent years. Considering, however, the nonuniform methodological standards implemented, the findings end up being nonreplicable and less generalizable. To address the need for a standardized baseline of research quality, we gathered all the studies in the music and neuroplasticity field in 2019 and appraised their methodological rigor systematically and critically. The aim was to provide a preliminary and, at the minimum, acceptable quality threshold—and, ipso facto, suggested recommendations—whereupon further discussion and development may take place. Quality appraisal was performed on 89 articles by three independent raters, following a standardized scoring system. The raters’ scoring was cross‐referenced following an inter‐rater reliability measure, and further studied by performing multiple ratings comparisons and matrix analyses. The results for methodological quality were at a quite good level (quantitative articles: mean = 0.737, SD = 0.084; qualitative articles: mean = 0.677, SD = 0.144), following a moderate but statistically significant level of agreement between the raters (W = 0.44, χ2 = 117.249, p = 0.020). We conclude that the standards for implementation and reporting are of high quality; however, certain improvements are needed to reach the stringent levels presumed for such an influential interdisciplinary scientific field.
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Date: 2022-12-07  ·  Issue: 2023  ·  Volume: 1520
Breeding and adoption of biofortified crops and their nutritional impact on human health
Contributors: Sachin Kumar| Ron M. DePauw| Sudhir Kumar| Jitendra Kumar| Sourabh Kumar| Madhav P. Pandey|
Abstract: Micronutrient malnutrition has affected over two billion people worldwide and continues to be a health risk. A growing human population, poverty, and the prevalence of low dietary diversity are jointly responsible for malnutrition, particularly in developing nations. Inadequate bioavailability of key micronutrients, such as iron (Fe), zinc (Zn), and vitamin A, can be improved through agronomic and/or genetic interventions. The Consultative Group on International Agricultural Research prioritizes developing biofortified food crops that are rich in minerals and vitamins through the HarvestPlus initiative on biofortification. The objective of this review is to provide an overview of biofortified food crops along with evidence supporting their acceptability and adoption. Between 2004 and 2019, 242 biofortified varieties belonging to 11 major crops were released in 30 countries across Asia, Africa, and Latin America. These conventionally bred biofortified crops include Fe‐enriched beans, pearl millet, and cowpea; Zn‐enriched rice, wheat, and maize; both Fe‐ and Zn‐enriched lentil and sorghum; and varieties with improved vitamin A in orange‐fleshed sweet potato, maize, cassava, and banana/plantain. In addition to ongoing efforts, breeding innovations, such as speed breeding and CRISPR‐based gene editing technologies, will be necessary for the next decade to reach two billion people with biofortified crops.
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Date: 2022-12-07  ·  Issue: 2023  ·  Volume: 1520
Lp‐pPG‐611.1‐LPS as an immune enhancer provides effective protection against Aeromonas veronii infection in Carassius auratus
Contributors: Tong Zhao| Bintong Yang| Hongjin Li| Zhipeng Hao| Wei Cong| Yuanhuan Kang|
Abstract: Aeromonas veronii (A. veronii) is an important zoonotic pathogen that causes substantial economic losses in aquaculture. In this study, we aimed to develop a safe and effective immune enhancer to protect Carassius auratus (C. auratus) from A. veronii infections. With recognized safety, lactic acid bacteria are used as antigen delivery vehicles to present antigens. Lipopolysaccharide (LPS), a protective antigen, induces immune responses in animals. Therefore, we created recombinant Lactobacillus plantarum (L. plantarum) with surface‐displayed LPS of A. veronii TH0426 and tested its effects on immune responses in C. auratus. The results showed that recombinant L. plantarum Lp‐pPG‐611.1‐LPS, as an immune enhancer, could improve the innate and adaptive immune responses of C. auratus when it was added to the diet of C. auratus. The challenge test showed that the survival rate of C. auratus fed with L. plantarum Lp‐pPG‐611.1‐LPS was higher than that of the control groups, indicating that the recombinant L. plantarum Lp‐pPG‐611.1‐LPS increased the resistance of C. auratus to A. veronii infection. The present results provide a theoretical basis for the development of recombinant L. plantarum Lp‐pPG‐611.1‐LPS as an immune enhancer in aquaculture.
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Date: 2022-12-07  ·  Issue: 2023  ·  Volume: 1520
Differences in brain functional networks for audiovisual integration during reading between children and adults
Contributors: Junjun Li| Yang Yang| Nestor Viñas‐Guasch| Yinghui Yang| Hong‐Yan Bi|
Abstract: Building robust letter‐to‐sound correspondences is a prerequisite for developing reading capacity. However, the neural mechanisms underlying the development of audiovisual integration for reading are largely unknown. This study used functional magnetic resonance imaging in a lexical decision task to investigate functional brain networks that support audiovisual integration during reading in developing child readers (10–12 years old) and skilled adult readers (20–28 years old). The results revealed enhanced connectivity in a prefrontal–superior temporal network (including the right medial frontal gyrus, right superior frontal gyrus, and left superior temporal gyrus) in adults relative to children, reflecting the development of attentional modulation of audiovisual integration involved in reading processing. Furthermore, the connectivity strength of this brain network was correlated with reading accuracy. Collectively, this study, for the first time, elucidates the differences in brain networks of audiovisual integration for reading between children and adults, promoting the understanding of the neurodevelopment of multisensory integration in high‐level human cognition.
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Date: 2022-12-07  ·  Issue: 2022  · 
Quality standards and recommendations for research in music and neuroplasticity
Contributors: Efthymios Papatzikis| Maria Agapaki| Rosari Naveena Selvan| Varun Pandey| Fathima Zeba|
Abstract: Research on how music influences brain plasticity has gained momentum in recent years. Considering, however, the nonuniform methodological standards implemented, the findings end up being nonreplicable and less generalizable. To address the need for a standardized baseline of research quality, we gathered all the studies in the music and neuroplasticity field in 2019 and appraised their methodological rigor systematically and critically. The aim was to provide a preliminary and, at the minimum, acceptable quality threshold—and, ipso facto, suggested recommendations—whereupon further discussion and development may take place. Quality appraisal was performed on 89 articles by three independent raters, following a standardized scoring system. The raters’ scoring was cross‐referenced following an inter‐rater reliability measure, and further studied by performing multiple ratings comparisons and matrix analyses. The results for methodological quality were at a quite good level (quantitative articles: mean = 0.737, SD = 0.084; qualitative articles: mean = 0.677, SD = 0.144), following a moderate but statistically significant level of agreement between the raters (W = 0.44, χ2 = 117.249, p = 0.020). We conclude that the standards for implementation and reporting are of high quality; however, certain improvements are needed to reach the stringent levels presumed for such an influential interdisciplinary scientific field.
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Date: 2022-12-05  ·  Issue: 2023  ·  Volume: 1519
Impacts of micronutrient intervention programs on effective coverage and lives saved: Modeled evidence from Cameroon
Contributors: Stephen A. Vosti| Katherine P. Adams| Aleksandr Michuda| Karen Ortiz‐Becerra| Hanqi Luo| Demewoz Haile| Victoria B. Chou| Adrienne Clermont| Ismael Teta| Alex Ndjebayi| Justin Kagin| Jules Guintang| Reina Engle‐Stone|
Abstract: Policymakers are committed to improving nutritional status and to saving lives. Some micronutrient intervention programs (MIPs) can do both, but not to the same degrees. We apply the Micronutrient Intervention Modeling tool to compare sets of MIPs for (1) achieving dietary adequacy separately for zinc, vitamin A (VA), and folate for children and women of reproductive age (WRA), and (2) saving children's lives via combinations of MIPs. We used 24‐h dietary recall data from Cameroon to estimate usual intake distributions of zinc and VA for children 6–59 months and of folate for WRA. We simulated the effects on dietary inadequacy and lives saved of four fortified foods and two VA supplementation (VAS) platforms. We estimated program costs over 10 years. To promote micronutrient‐specific dietary adequacy, the economic optimization model (EOM) selected zinc‐ and folic acid–fortified wheat flour, VA‐fortified edible oils, and bouillon cubes, and VAS via Child Health Days in the North macroregion. A different set of cost‐effective MIPs emerged for reducing child mortality, shifting away from VA and toward more zinc for children and more folic acid for WRA. The EOM identified more efficient sets of MIPs than the business‐as‐usual MIPs, especially among programs aiming to save lives.
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Date: 2022-12-05  ·  Issue: 2022  · 
Impacts of micronutrient intervention programs on effective coverage and lives saved: Modeled evidence from Cameroon
Contributors: Stephen A. Vosti| Katherine P. Adams| Aleksandr Michuda| Karen Ortiz‐Becerra| Hanqi Luo| Demewoz Haile| Victoria B. Chou| Adrienne Clermont| Ismael Teta| Alex Ndjebayi| Justin Kagin| Jules Guintang| Reina Engle‐Stone|
Abstract: Policymakers are committed to improving nutritional status and to saving lives. Some micronutrient intervention programs (MIPs) can do both, but not to the same degrees. We apply the Micronutrient Intervention Modeling tool to compare sets of MIPs for (1) achieving dietary adequacy separately for zinc, vitamin A (VA), and folate for children and women of reproductive age (WRA), and (2) saving children's lives via combinations of MIPs. We used 24‐h dietary recall data from Cameroon to estimate usual intake distributions of zinc and VA for children 6–59 months and of folate for WRA. We simulated the effects on dietary inadequacy and lives saved of four fortified foods and two VA supplementation (VAS) platforms. We estimated program costs over 10 years. To promote micronutrient‐specific dietary adequacy, the economic optimization model (EOM) selected zinc‐ and folic acid–fortified wheat flour, VA‐fortified edible oils, and bouillon cubes, and VAS via Child Health Days in the North macroregion. A different set of cost‐effective MIPs emerged for reducing child mortality, shifting away from VA and toward more zinc for children and more folic acid for WRA. The EOM identified more efficient sets of MIPs than the business‐as‐usual MIPs, especially among programs aiming to save lives.
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Date: 2022-12-02  ·  Issue: 2023  ·  Volume: 1519
Transdisciplinarity: Science for the public good
Contributors: Roderick J. Lawrence|
Abstract:
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Date: 2022-11-29  ·  Issue: 2023  · 
Antibiotic discovery in the artificial intelligence era
Contributors: Telmah Lluka| Jonathan M. Stokes|
Abstract: As the global burden of antibiotic resistance continues to grow, creative approaches to antibiotic discovery are needed to accelerate the development of novel medicines. A rapidly progressing computational revolution—artificial intelligence—offers an optimistic path forward due to its ability to alleviate bottlenecks in the antibiotic discovery pipeline. In this review, we discuss how advancements in artificial intelligence are reinvigorating the adoption of past antibiotic discovery models—namely natural product exploration and small molecule screening. We then explore the application of contemporary machine learning approaches to emerging areas of antibiotic discovery, including antibacterial systems biology, drug combination development, antimicrobial peptide discovery, and mechanism of action prediction. Lastly, we propose a call to action for open access of high‐quality screening datasets and interdisciplinary collaboration to accelerate the rate at which machine learning models can be trained and new antibiotic drugs can be developed.
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Date: 2022-11-22  ·  Issue: 2023  ·  Volume: 1519
The role of bacterial membrane vesicles in antibiotic resistance
Contributors: Craig R. MacNair| Man‐Wah Tan|
Abstract: Bacterial survival during antibiotic exposure is a complex and multifaceted phenomenon. On top of antibiotic resistance genes, biofilm formation, and persister tolerance, bacterial membrane vesicles (MVs) provide a layer of protection that has been largely overlooked. MVs are spherical nanoparticles composed of lipid membranes and are common to Gram‐positive and Gram‐negative bacteria. Although the importance of MVs in bacterial pathogenesis and virulence factor transport has been firmly established, a growing body of work now identifies MVs as key contributors to bacterial survival during antibiotic exposure. Herein, we highlight the ability of MVs to reduce antibiotic efficacy and transmit resistance elements. We also discuss the potential of targeting MV production as an unconventional therapeutic approach.
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Date: 2022-11-22  ·  Issue: 2022  ·  Volume: 1516
Cover Image, Volume 1516, Issue 1
Contributors:
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Date: 2022-11-22  ·  Issue: 2023  · 
The role of bacterial membrane vesicles in antibiotic resistance
Contributors: Craig R. MacNair| Man‐Wah Tan|
Abstract: Bacterial survival during antibiotic exposure is a complex and multifaceted phenomenon. On top of antibiotic resistance genes, biofilm formation, and persister tolerance, bacterial membrane vesicles (MVs) provide a layer of protection that has been largely overlooked. MVs are spherical nanoparticles composed of lipid membranes and are common to Gram‐positive and Gram‐negative bacteria. Although the importance of MVs in bacterial pathogenesis and virulence factor transport has been firmly established, a growing body of work now identifies MVs as key contributors to bacterial survival during antibiotic exposure. Herein, we highlight the ability of MVs to reduce antibiotic efficacy and transmit resistance elements. We also discuss the potential of targeting MV production as an unconventional therapeutic approach.
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Date: 2022-11-19  ·  Issue: 2023  ·  Volume: 1519
Music engagement is negatively correlated with depressive symptoms during the COVID‐19 pandemic via reward‐related mechanisms
Contributors: Ernest Mas‐Herrero| Neomi Singer| Laura Ferreri| Michael McPhee| Robert J. Zatorre| Pablo Ripollés|
Abstract: The COVID‐19 pandemic has deeply affected the mental health of millions of people. We assessed which of many leisure activities correlated with positive mental health outputs, with particular attention to music, which has been reported to be important for coping with the psychological burden of the pandemic. Questionnaire data from about 1000 individuals primarily from Italy, Spain, and the United States during May–June 2020 show that people picked music activities (listening to, playing, singing, etc.) most often as the leisure experiences that helped them the most to cope with psychological distress related with the pandemic. During the pandemic, hours of engagement in music and food‐related activities were associated with lower depressive symptoms. The negative correlation between music and depression was mediated by individual differences in sensitivity to reward, whereas the correlation between food‐related activities and improved mental health outputs was explained by differences in emotion suppression strategies. Our results, while correlational, suggest that engaging in music activities could be related to improved well‐being with the underlying mechanism being related to reward, consistent with neuroscience findings. Our data have practical significance in pointing to effective strategies to cope with mental health issues beyond those related to the COVID‐19 pandemic.
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Date: 2022-11-19  ·  Issue: 2022  · 
Music engagement is negatively correlated with depressive symptoms during the COVID‐19 pandemic via reward‐related mechanisms
Contributors: Ernest Mas‐Herrero| Neomi Singer| Laura Ferreri| Michael McPhee| Robert J. Zatorre| Pablo Ripollés|
Abstract: The COVID‐19 pandemic has deeply affected the mental health of millions of people. We assessed which of many leisure activities correlated with positive mental health outputs, with particular attention to music, which has been reported to be important for coping with the psychological burden of the pandemic. Questionnaire data from about 1000 individuals primarily from Italy, Spain, and the United States during May–June 2020 show that people picked music activities (listening to, playing, singing, etc.) most often as the leisure experiences that helped them the most to cope with psychological distress related with the pandemic. During the pandemic, hours of engagement in music and food‐related activities were associated with lower depressive symptoms. The negative correlation between music and depression was mediated by individual differences in sensitivity to reward, whereas the correlation between food‐related activities and improved mental health outputs was explained by differences in emotion suppression strategies. Our results, while correlational, suggest that engaging in music activities could be related to improved well‐being with the underlying mechanism being related to reward, consistent with neuroscience findings. Our data have practical significance in pointing to effective strategies to cope with mental health issues beyond those related to the COVID‐19 pandemic.
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Date: 2022-11-18  ·  Issue: 2023  ·  Volume: 1519
Passive somatosensory training enhances piano skill in adolescent and adult pianists: A preliminary study
Contributors: Shinichi Furuya| Ryuya Tanibuchi| Hayato Nishioka| Yudai Kimoto| Masato Hirano| Takanori Oku|
Abstract: Sensory afferent information, such as auditory and somatosensory feedback while moving, plays a crucial role in both control and learning of motor performance across the lifespan. Music performance requires skillful integration of multimodal sensory information for the production of dexterous movements. However, it has not been understood what roles somatosensory afferent information plays in the acquisition and sophistication of specialized motor skills of musicians across different stages of development. In the present preliminary study, we addressed this issue by using a novel technique with a hand exoskeleton robot that can externally move the fingers of pianists. Short‐term exposure to fast and complex finger movements generated by the exoskeleton (i.e., passive movements) increased the maximum rate of repetitive piano keystrokes by the pianists. This indicates that somatosensory inputs derived from the externally generated motions enhanced the quickness of the sequential finger movements in piano performance, even though the pianists did not voluntarily move the fingers. The enhancement of motor skill through passive somatosensory training using the exoskeleton was more pronounced in adolescent pianists than adult pianists. These preliminary results implicate a sensitive period of neuroplasticity of the somatosensory‐motor system of trained pianists, which emphasizes the importance of somatosensory‐motor training in professional music education during adolescence.
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Date: 2022-11-18  ·  Issue: 2023  ·  Volume: 1519
Glial aging and its impact on central nervous system myelin regeneration
Contributors: Khalil S. Rawji| Björn Neumann| Robin J. M. Franklin|
Abstract: Aging is a major risk factor for several neurodegenerative diseases and is associated with cognitive decline. In addition to affecting neuronal function, the aging process significantly affects the functional phenotype of the glial cell compartment, comprising oligodendrocyte lineage cells, astrocytes, and microglia. These changes result in a more inflammatory microenvironment, resulting in a condition that is favorable for neuron and synapse loss. In addition to facilitating neurodegeneration, the aging glial cell population has negative implications for central nervous system remyelination, a regenerative process that is of particular importance to the chronic demyelinating disease multiple sclerosis. This review will discuss the changes that occur with aging in the three main glial populations and provide an overview of the studies documenting the impact these changes have on remyelination.
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Date: 2022-11-18  ·  Issue: 2023  · 
Glial aging and its impact on central nervous system myelin regeneration
Contributors: Khalil S. Rawji| Björn Neumann| Robin J. M. Franklin|
Abstract: Aging is a major risk factor for several neurodegenerative diseases and is associated with cognitive decline. In addition to affecting neuronal function, the aging process significantly affects the functional phenotype of the glial cell compartment, comprising oligodendrocyte lineage cells, astrocytes, and microglia. These changes result in a more inflammatory microenvironment, resulting in a condition that is favorable for neuron and synapse loss. In addition to facilitating neurodegeneration, the aging glial cell population has negative implications for central nervous system remyelination, a regenerative process that is of particular importance to the chronic demyelinating disease multiple sclerosis. This review will discuss the changes that occur with aging in the three main glial populations and provide an overview of the studies documenting the impact these changes have on remyelination.
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Date: 2022-11-18  ·  Issue: 2022  · 
Passive somatosensory training enhances piano skill in adolescent and adult pianists: A preliminary study
Contributors: Shinichi Furuya| Ryuya Tanibuchi| Hayato Nishioka| Yudai Kimoto| Masato Hirano| Takanori Oku|
Abstract: Sensory afferent information, such as auditory and somatosensory feedback while moving, plays a crucial role in both control and learning of motor performance across the lifespan. Music performance requires skillful integration of multimodal sensory information for the production of dexterous movements. However, it has not been understood what roles somatosensory afferent information plays in the acquisition and sophistication of specialized motor skills of musicians across different stages of development. In the present preliminary study, we addressed this issue by using a novel technique with a hand exoskeleton robot that can externally move the fingers of pianists. Short‐term exposure to fast and complex finger movements generated by the exoskeleton (i.e., passive movements) increased the maximum rate of repetitive piano keystrokes by the pianists. This indicates that somatosensory inputs derived from the externally generated motions enhanced the quickness of the sequential finger movements in piano performance, even though the pianists did not voluntarily move the fingers. The enhancement of motor skill through passive somatosensory training using the exoskeleton was more pronounced in adolescent pianists than adult pianists. These preliminary results implicate a sensitive period of neuroplasticity of the somatosensory‐motor system of trained pianists, which emphasizes the importance of somatosensory‐motor training in professional music education during adolescence.
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Date: 2022-11-17  ·  Issue: 2022  ·  Volume: 1517
Cover Image, Volume 1517, Issue 1
Contributors:
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Date: 2022-11-17  ·  Issue: 2022  · 
Translational models of addiction phenotypes to advance addiction pharmacotherapy
Contributors: Lara A. Ray| Steven J. Nieto| Erica N. Grodin|
Abstract: Alcohol and substance use disorders are heterogeneous conditions with limited effective treatment options. While there have been prior attempts to classify addiction subtypes, they have not been translated into clinical practice. In an effort to better understand heterogeneity in psychiatric disorders, the National Institute for Mental Health Research Domain Criteria (RDoC) has challenged scientists to think beyond diagnostic symptoms and to consider the underlying features of psychopathology from a neuroscience‐based framework. The field of addiction has grappled with this approach by considering several key constructs with the potential to capture RDoC domains. This critical review will focus on the efforts to apply translational models of addiction phenomenology in human clinical samples, including their relative strengths and weaknesses. Opportunities for forward and reverse translation are also discussed. Deep behavioral phenotyping using neuroscience‐informed batteries shows promise for a better understanding of the clinical neuroscience of addiction and advancing precision medicine for alcohol and substance use disorders.
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Date: 2022-11-17  ·  Issue: 2022  ·  Volume: 1517
Cover Image, Volume 1517, Issue 1
Contributors:
Abstract:
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Date: 2022-11-17  ·  Issue: 2023  ·  Volume: 1519
Translational models of addiction phenotypes to advance addiction pharmacotherapy
Contributors: Lara A. Ray| Steven J. Nieto| Erica N. Grodin|
Abstract: Alcohol and substance use disorders are heterogeneous conditions with limited effective treatment options. While there have been prior attempts to classify addiction subtypes, they have not been translated into clinical practice. In an effort to better understand heterogeneity in psychiatric disorders, the National Institute for Mental Health Research Domain Criteria (RDoC) has challenged scientists to think beyond diagnostic symptoms and to consider the underlying features of psychopathology from a neuroscience‐based framework. The field of addiction has grappled with this approach by considering several key constructs with the potential to capture RDoC domains. This critical review will focus on the efforts to apply translational models of addiction phenomenology in human clinical samples, including their relative strengths and weaknesses. Opportunities for forward and reverse translation are also discussed. Deep behavioral phenotyping using neuroscience‐informed batteries shows promise for a better understanding of the clinical neuroscience of addiction and advancing precision medicine for alcohol and substance use disorders.
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Date: 2022-11-17  ·  Issue: 2023  ·  Volume: 1519
Punitive school discipline as a mechanism of structural marginalization with implications for health inequity: A systematic review of quantitative studies in the health and social sciences literature
Contributors: Catherine dP. Duarte| Candice Moses| Melissa Brown| Sandhya Kajeepeta| Seth J. Prins| Janelle Scott| Mahasin S. Mujahid|
Abstract: Punitive school discipline deploys surveillance, exclusion, and corporal punishment to deter or account for perceived student misbehavior. Yet, education and legal scholarship suggests it fails to achieve stated goals and exacerbates harm. Furthermore, it is disproportionately imposed upon Black, Latinx, Native/Indigenous, LGBTQIA, and disabled students, concentrating its harms among marginalized young people. Its implications for health, however, are less clear. Using public health theories of sociostructural embodiment, we propose a framework characterizing pathways linking societal ideologies (e.g., racism) to punitive discipline with implications for health and health inequity and then present our systematic review of the punitive school discipline–health literature (N = 19 studies) conducted in accordance with PRISMA guidelines. Data were extracted on guiding theories, study characteristics, measurement, methods, and findings. This literature links punitive school discipline to greater risk for numerous health outcomes, including persistent depressive symptoms, depression, drug use disorder in adulthood, borderline personality disorder, antisocial behavior, death by suicide, injuries, trichomoniasis, pregnancy in adolescence, tobacco use, and smoking, with documented implications for racial health inequity. Using our adapted framework, we contextualize results and recommend avenues for future research. Our findings support demands to move away from punitive school discipline toward health‐affirming interventions to promote school connectedness, safety, and wellbeing.
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Date: 2022-11-17  ·  Issue: 2022  ·  Volume: 1517
Issue Information
Contributors:
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Date: 2022-11-16  ·  Issue: 2023  ·  Volume: 1519
Antibodies as drugs—a Keystone Symposia report
Contributors: Jennifer Cable| Erica Ollmann Saphire| Adrian C. Hayday| Timothy D. Wiltshire| Jarrod J. Mousa| David P. Humphreys| Esther C. W. Breij| Pierre Bruhns| Matteo Broketa| Genta Furuya| Blake M. Hauser| Matthieu Mahévas| Andrea Carfi| Tineke Cantaert| Peter D. Kwong| Prabhanshu Tripathi| Jonathan H. Davis| Neil Brewis| Bruce A. Keyt| Felix L. Fennemann| Vincent Dussupt| Arvind Sivasubramanian| Philip M. Kim| Reda Rawi| Eve Richardson| Daniel Leventhal| Rachael M. Wolters| Cecile A. W. Geuijen| Matthew A. Sleeman| Niccolo Pengo| Francesca Rose Donnellan|
Abstract: Therapeutic antibodies have broad indications across diverse disease states, such as oncology, autoimmune diseases, and infectious diseases. New research continues to identify antibodies with therapeutic potential as well as methods to improve upon endogenous antibodies and to design antibodies de novo. On April 27–30, 2022, experts in antibody research across academia and industry met for the Keystone symposium “Antibodies as Drugs” to present the state‐of‐the‐art in antibody therapeutics, repertoires and deep learning, bispecific antibodies, and engineering.
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Date: 2022-11-16  ·  Issue: 2023  · 
Antibodies as drugs—a Keystone Symposia report
Contributors: Jennifer Cable| Erica Ollmann Saphire| Adrian C. Hayday| Timothy D. Wiltshire| Jarrod J. Mousa| David P. Humphreys| Esther C. W. Breij| Pierre Bruhns| Matteo Broketa| Genta Furuya| Blake M. Hauser| Matthieu Mahévas| Andrea Carfi| Tineke Cantaert| Peter D. Kwong| Prabhanshu Tripathi| Jonathan H. Davis| Neil Brewis| Bruce A. Keyt| Felix L. Fennemann| Vincent Dussupt| Arvind Sivasubramanian| Philip M. Kim| Reda Rawi| Eve Richardson| Daniel Leventhal| Rachael M. Wolters| Cecile A. W. Geuijen| Matthew A. Sleeman| Niccolo Pengo| Francesca Rose Donnellan|
Abstract: Therapeutic antibodies have broad indications across diverse disease states, such as oncology, autoimmune diseases, and infectious diseases. New research continues to identify antibodies with therapeutic potential as well as methods to improve upon endogenous antibodies and to design antibodies de novo. On April 27–30, 2022, experts in antibody research across academia and industry met for the Keystone symposium “Antibodies as Drugs” to present the state‐of‐the‐art in antibody therapeutics, repertoires and deep learning, bispecific antibodies, and engineering.
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Date: 2022-11-15  ·  Issue: 2023  ·  Volume: 1519
The impacts of sport emissions on climate: Measurement, mitigation, and making a difference
Contributors: Robert L. Wilby| Madeleine Orr| Duncan Depledge| Richard Giulianotti| George Havenith| Jamie A. Kenyon| Tom K. R. Matthews| Stephen A. Mears| Donal J. Mullan| Lee Taylor|
Abstract: As a global industry, sport makes potentially significant contributions to climate change through both carbon emissions and influence over sustainability practices. Yet, evidence regarding impacts is uneven and spread across many disciplines. This paper investigates the impacts of sport emissions on climate and identifies knowledge gaps. We undertook a systematic and iterative meta‐analysis of relevant literature (1992–2022) on organized and individual sports. Using a defined search protocol, 116 sources were identified that map to four sport‐related themes: (1) carbon emissions and their measurement; (2) emissions control and decarbonization; (3) carbon sinks and offsets; and (4) behavior change. We find that mega sport events, elite sport, soccer, skiing, and golf have received most attention, whereas grass‐roots and women's sport, activity in Africa and South America, cricket, tennis, and volleyball are understudied. Other knowledge gaps include carbon accounting tools and indicators for smaller sports clubs and active participants; cobenefits and tradeoffs between mitigation‐adaptation efforts in sport, such as around logistics, venues, sports equipment, and facilities; geopolitical influence; and scope for climate change litigation against hosts and/or sponsors of carbon‐intensive events. Among these, researchers should target cobenefits given their scope to deliver wins for both climate mitigation and risk management of sport.
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Date: 2022-11-13  ·  Issue: 2023  ·  Volume: 1519
Connecting insufficient sleep and insomnia with metabolic dysfunction
Contributors: Daisy Duan| Lenise J. Kim| Jonathan C. Jun| Vsevolod Y. Polotsky|
Abstract: The global epidemic of obesity and type 2 diabetes parallels the rampant state of sleep deprivation in our society. Epidemiological studies consistently show an association between insufficient sleep and metabolic dysfunction. Mechanistically, sleep and circadian rhythm exert considerable influences on hormones involved in appetite regulation and energy metabolism. As such, data from experimental sleep deprivation in humans demonstrate that insufficient sleep induces a positive energy balance with resultant weight gain, due to increased energy intake that far exceeds the additional energy expenditure of nocturnal wakefulness, and adversely impacts glucose metabolism. Conversely, animal models have found that sleep loss–induced energy expenditure exceeds caloric intake resulting in net weight loss. However, animal models have significant limitations, which may diminish the clinical relevance of their metabolic findings. Clinically, insomnia disorder and insomnia symptoms are associated with adverse glucose outcomes, though it remains challenging to isolate the effects of insomnia on metabolic outcomes independent of comorbidities and insufficient sleep durations. Furthermore, both pharmacological and behavioral interventions for insomnia may have direct metabolic effects. The goal of this review is to establish an updated framework for the causal links between insufficient sleep and insomnia and risks for type 2 diabetes and obesity.
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Date: 2022-11-09  ·  Issue: 2022  · 
Effects of melodic intonation therapy in patients with chronic nonfluent aphasia
Contributors: Sarah Marchina| Andrea Norton| Gottfried Schlaug|
Abstract: Patients with large left‐hemisphere lesions and post‐stroke aphasia often remain nonfluent. Melodic intonation therapy (MIT) may be an effective alternative to traditional speech therapy for facilitating recovery of fluency in those patients. In an open‐label, proof‐of‐concept study, 14 subjects with nonfluent aphasia with large left‐hemisphere lesions (171 ± 76 cc) underwent two speech/language assessments before, one at the midpoint, and two after the end of 75 sessions (1.5 h/session) of MIT. Functional MR imaging was done before and after therapy asking subjects to vocalize the same set of 10 bi‐syllabic words. We found significant improvements in speech output after a period of intensive MIT (75 sessions for a total of 112.5 h) compared to two pre‐therapy assessments. Therapy‐induced gains were maintained 4 weeks post‐treatment. Imaging changes were seen in a right‐hemisphere network that included the posterior superior temporal and inferior frontal gyri, inferior pre‐ and postcentral gyri, pre‐supplementary motor area, and supramarginal gyrus. Functional changes in the posterior right inferior frontal gyri significantly correlated with changes in a measure of fluency. Intense training of intonation‐supported auditory‐motor coupling and engaging feedforward/feedback control regions in the unaffected hemisphere improves speech‐motor functions in subjects with nonfluent aphasia and large left‐hemisphere lesions.
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Date: 2022-11-09  ·  Issue: 2023  ·  Volume: 1519
Effects of melodic intonation therapy in patients with chronic nonfluent aphasia
Contributors: Sarah Marchina| Andrea Norton| Gottfried Schlaug|
Abstract: Patients with large left‐hemisphere lesions and post‐stroke aphasia often remain nonfluent. Melodic intonation therapy (MIT) may be an effective alternative to traditional speech therapy for facilitating recovery of fluency in those patients. In an open‐label, proof‐of‐concept study, 14 subjects with nonfluent aphasia with large left‐hemisphere lesions (171 ± 76 cc) underwent two speech/language assessments before, one at the midpoint, and two after the end of 75 sessions (1.5 h/session) of MIT. Functional MR imaging was done before and after therapy asking subjects to vocalize the same set of 10 bi‐syllabic words. We found significant improvements in speech output after a period of intensive MIT (75 sessions for a total of 112.5 h) compared to two pre‐therapy assessments. Therapy‐induced gains were maintained 4 weeks post‐treatment. Imaging changes were seen in a right‐hemisphere network that included the posterior superior temporal and inferior frontal gyri, inferior pre‐ and postcentral gyri, pre‐supplementary motor area, and supramarginal gyrus. Functional changes in the posterior right inferior frontal gyri significantly correlated with changes in a measure of fluency. Intense training of intonation‐supported auditory‐motor coupling and engaging feedforward/feedback control regions in the unaffected hemisphere improves speech‐motor functions in subjects with nonfluent aphasia and large left‐hemisphere lesions.
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Date: 2022-11-07  ·  Issue: 2023  ·  Volume: 1519
New understanding of multidrug efflux and permeation in antibiotic resistance, persistence, and heteroresistance
Contributors: Pedro D. Manrique| Cesar A. López| S. Gnanakaran| Valentin V. Rybenkov| Helen I. Zgurskaya|
Abstract: Antibiotics effective against Gram‐negative ESKAPE pathogens are a critical area of unmet need. Infections caused by these pathogens are not only difficult to treat but finding new therapies to overcome Gram‐negative resistance is also a challenge. There are not enough antibiotics in development that target the most dangerous pathogens and there are not enough novel drugs in the pipeline. The major obstacle in the antibiotic discovery pipeline is the lack of understanding of how to breach antibiotic permeability barriers of Gram‐negative pathogens. These barriers are created by active efflux pumps acting across both the inner and the outer membranes. Overproduction of efflux pumps alone or together with either modification of the outer membrane or antibiotic‐inactivating enzymes and target mutations contribute to clinical levels of antibiotics resistance. Recent efforts have generated significant advances in the rationalization of compound efflux and permeation across the cell envelopes of Gram‐negative pathogens. Combined with earlier studies and novel mathematical models, these efforts have led to a multilevel understanding of how antibiotics permeate these barriers and how multidrug efflux and permeation contribute to the development of antibiotic resistance and heteroresistance. Here, we discuss the new developments in this area.
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Date: 2022-11-03  ·  Issue: 2022  · 
The Phanerozoic climate
Contributors: Nir J. Shaviv| Henrik Svensmark| Ján Veizer|
Abstract: We review the long‐term climate variations during the last 540 million years (Phanerozoic Eon). We begin with a short summary of the relevant geological and geochemical datasets available for the reconstruction of long‐term climate variations. We then explore the main drivers of climate that appear to explain a large fraction of these climatic oscillations. The first is the long‐term trend in atmospheric CO2 due to geological processes, while the second is the atmospheric ionization due to the changing galactic environment. Other drivers, such as albedo and geographic effects, are of secondary importance. In this review, we pay particular attention to problems that may affect the measurements of temperature obtained from oxygen isotopes, such as the long‐term changes in the concentration of δ18O seawater.
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Date: 2022-11-03  ·  Issue: 2022  ·  Volume: 1518
miR‐141‐3p affects β‐catenin signaling and apoptosis by targeting Ubtd2 in rats with anorectal malformations
Contributors: Chen Yi Wang| Si Ying Li| Yun Xia Xiao| Lin Zhen| Xiao Gao Wei| Xiao Bing Tang| Zheng Wei Yuan| Yu Zuo Bai|
Abstract: Anorectal malformations (ARMs) are the most common gastrointestinal malformations. miR‐141‐3p was obtained from whole‐transcriptome sequencing, and Ub domain‐containing protein 2 (Ubtd2) was predicted as the target gene. An ARM rat model was induced using ethylenethiourea. Fluorescence in situ hybridization and immunofluorescence were used to detect the spatiotemporal expression of miR‐141‐3p and Ubtd2, respectively. A dual‐luciferase reporter assay confirmed their targeting relationship, and cell proliferation and apoptosis were investigated after transfection in the intestinal epithelium (IEC‐6). Additionally, western blotting and co‐immunoprecipitation were used to examine the protein levels and the endogenous binding relationship. miR‐141‐3p was downregulated in the ARM group, whereas Ubtd2 increased and colocalized with TUNEL‐positive cells. After miR‐141‐3p inhibition, protein expression of USP5 and β‐catenin was affected via Ubtd2, and USP5 could bind to both Ubtd2 and β‐catenin. Flow cytometry analysis and caspase 3/7 staining demonstrated that downregulated miR‐141‐3p promoted cell apoptosis through Ubtd2. In summary, targeting Ubtd2 decreased in miR‐141‐3p and promoted apoptosis of intestinal epithelium and regulated β‐catenin expression. This may cause aberrant apoptosis during hindgut development and mediate the imbalance of β‐catenin signaling in the cloaca, further affecting the occurrence of ARMs.
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Date: 2022-11-03  ·  Issue: 2023  ·  Volume: 1519
The Phanerozoic climate
Contributors: Nir J. Shaviv| Henrik Svensmark| Ján Veizer|
Abstract: We review the long‐term climate variations during the last 540 million years (Phanerozoic Eon). We begin with a short summary of the relevant geological and geochemical datasets available for the reconstruction of long‐term climate variations. We then explore the main drivers of climate that appear to explain a large fraction of these climatic oscillations. The first is the long‐term trend in atmospheric CO2 due to geological processes, while the second is the atmospheric ionization due to the changing galactic environment. Other drivers, such as albedo and geographic effects, are of secondary importance. In this review, we pay particular attention to problems that may affect the measurements of temperature obtained from oxygen isotopes, such as the long‐term changes in the concentration of δ18O seawater.
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Date: 2022-11-02  ·  Issue: 2022  · 
The effect of the severity of neurocognitive disorders on emotional and motor responses to music
Contributors: Lise Hobeika| Matthieu Ghilain| Loris Schiaratura| Micheline Lesaffre| François Puisieux| Dominique Huvent‐Grelle| Séverine Samson|
Abstract: The successful design of musical interventions for dementia patients requires knowledge of how rhythmic abilities change with disease severity. In this study, we tested the impact of the severity of the neurocognitive disorders (NCD) on the socioemotional and motor responses to music in three groups of patients with Major NCD, Mild NCD, or No NCD. Patients were asked to tap to a metronomic or musical rhythm while facing a live musician or through a video. We recorded their emotional facial reactions and their sensorimotor synchronization (SMS) abilities. Patients with No NCD or Mild NCD expressed positive socioemotional reactions to music, but patients with Major NCD did not, indicating a decrease in the positive emotional impact of music at this stage of the disease. SMS to a metronome was less regular and less precise in patients with a Major NCD than in patients with No NCD or Mild NCD, which was not the case when tapping with music, particularly in the presence of a live musician, suggesting the relevance of live performance for patients with Major NCD. These findings suggest that the socioemotional and motor reactions to music are negatively affected by the progression of the NCD.
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Date: 2022-10-31  ·  Issue: 2022  ·  Volume: 1517
Corrigendum for Ann. N. Y. Acad. Sci. (2020), 1462, 65–78.
Contributors:
Abstract:
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Date: 2022-10-31  ·  Issue: 2022  ·  Volume: 1518
Mobile genetic elements in Acinetobacter antibiotic‐resistance acquisition and dissemination
Contributors: Hannah R. Noel| Jessica R. Petrey| Lauren D. Palmer|
Abstract: Pathogenic Acinetobacter species, most notably Acinetobacter baumannii, are a significant cause of healthcare‐associated infections worldwide. Acinetobacter infections are of particular concern to global health due to the high rates of multidrug resistance and extensive drug resistance. Widespread genome sequencing and analysis has determined that bacterial antibiotic resistance is often acquired and disseminated through the movement of mobile genetic elements, including insertion sequences (IS), transposons, integrons, and conjugative plasmids. In Acinetobacter specifically, resistance to carbapenems and cephalosporins is highly correlated with IS, as many ISAba elements encode strong outwardly facing promoters that are required for sufficient expression of β‐lactamases to confer clinical resistance. Here, we review the role of mobile genetic elements in antibiotic resistance in Acinetobacter species through the framework of the mechanism of resistance acquisition and with a focus on experimentally validated mechanisms.
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Date: 2022-10-31  ·  Issue: 2023  · 
Mobile genetic elements in Acinetobacter antibiotic‐resistance acquisition and dissemination
Contributors: Hannah R. Noel| Jessica R. Petrey| Lauren D. Palmer|
Abstract: Pathogenic Acinetobacter species, most notably Acinetobacter baumannii, are a significant cause of healthcare‐associated infections worldwide. Acinetobacter infections are of particular concern to global health due to the high rates of multidrug resistance and extensive drug resistance. Widespread genome sequencing and analysis has determined that bacterial antibiotic resistance is often acquired and disseminated through the movement of mobile genetic elements, including insertion sequences (IS), transposons, integrons, and conjugative plasmids. In Acinetobacter specifically, resistance to carbapenems and cephalosporins is highly correlated with IS, as many ISAba elements encode strong outwardly facing promoters that are required for sufficient expression of β‐lactamases to confer clinical resistance. Here, we review the role of mobile genetic elements in antibiotic resistance in Acinetobacter species through the framework of the mechanism of resistance acquisition and with a focus on experimentally validated mechanisms.
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Date: 2022-10-27  ·  Issue: 2022  ·  Volume: 1518
The impact of obesity and adipokines on breast and gynecologic malignancies
Contributors: Surabhi Tewari| Roberto Vargas| Ofer Reizes|
Abstract: The link between obesity and multiple disease comorbidities is well established. In 2003, Calle and colleagues presented the relationship between obesity and several cancer types, including breast, ovarian, and endometrial malignancies. Nearly, 20% of cancer‐related deaths in females can be accounted for by obesity. Identifying obesity as a risk factor for cancer led to a focus on the role of fat‐secreted cytokines, known as adipokines, on carcinogenesis and tumor progression. Early studies indicated that the adipokine leptin increases cell proliferation, invasion, and inhibition of apoptosis in multiple cancer types. As a greater appreciation of the obesity–cancer link has amassed, we now know that additional adipokines can impact tumorigenesis. A deeper understanding of the adipokine‐activated signaling in cancer may identify new treatment strategies irrespective of obesity. Moreover, adipokines may serve as disease biomarkers, harnessing the potential of obesity‐associated factors to serve as indicators of treatment response and disease prognosis. As studies investigating obesity and women's cancers continue to expand, it has become evident that breast, ovarian, and uterine cancers are distinctly impacted by adipokines. While complex, these distinct interactions may provide insight into cancer progression in these organs and new opportunities for targeted therapies. This review aims to organize and present the literature from the last 5 years investigating the mechanisms and implications of adipokine signaling in breast, endometrial, and ovarian cancers with a special focus on leptin and adiponectin.
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Date: 2022-10-26  ·  Issue: 2022  ·  Volume: 1518
Evolution of neuroglia
Contributors: Alexei Verkhratsky| Amaia M. Arranz| Katarzyna Ciuba| Aleksandra Pękowska|
Abstract: The evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed of electrically excitable neuronal networks connected by chemical synapses and nonexcitable glial cells that provide for homeostasis and defense. The evolution of neuroglia began with the emergence of the centralized nervous system and proceeded through a continuous increase in their complexity. In the primate brain, especially in the brain of humans, the astrocyte lineage is exceedingly complex, with the emergence of new types of astroglial cells possibly involved in interlayer communication and integration.
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Date: 2022-10-26  ·  Issue: 2022  ·  Volume: 1518
How universal is preference for visual curvature? A systematic review and meta‐analysis
Contributors: Erick G. Chuquichambi| Oshin Vartanian| Martin Skov| Guido B. Corradi| Marcos Nadal| Paul J. Silvia| Enric Munar|
Abstract: Evidence dating back a century shows that humans are sensitive to and exhibit a preference for visual curvature. This effect has been observed in different age groups, human cultures, and primate species, suggesting that a preference for curvature could be universal. At the same time, several studies have found that preference for curvature is modulated by contextual and individual factors, casting doubt on this hypothesis. To resolve these conflicting findings, we conducted a systematic meta‐analysis of studies that have investigated the preference for visual curvature. Our meta‐analysis included 61 studies which provided 106 independent samples and 309 effect sizes. The results of a three‐level random effects model revealed a Hedges’ g of 0.39—consistent with a medium effect size. Further analyses revealed that preference for curvature is moderated by four factors: presentation time, stimulus type, expertise, and task. Together, our results suggest that preference for visual curvature is a reliable but not universal phenomenon and is influenced by factors other than perceptual information.
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Date: 2022-10-26  ·  Issue: 2023  · 
Evolution of neuroglia
Contributors: Alexei Verkhratsky| Amaia M. Arranz| Katarzyna Ciuba| Aleksandra Pękowska|
Abstract: The evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed of electrically excitable neuronal networks connected by chemical synapses and nonexcitable glial cells that provide for homeostasis and defense. The evolution of neuroglia began with the emergence of the centralized nervous system and proceeded through a continuous increase in their complexity. In the primate brain, especially in the brain of humans, the astrocyte lineage is exceedingly complex, with the emergence of new types of astroglial cells possibly involved in interlayer communication and integration.
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Date: 2022-10-18  ·  Issue: 2022  ·  Volume: 1518
Intense long‐term training impairs brain health compared with moderate exercise: Experimental evidence and mechanisms
Contributors: Gemma Sangüesa| Montserrat Batlle| Emma Muñoz‐Moreno| Guadalupe Soria| Anna Alcarraz| Cira Rubies| Laia Sitjà‐Roqueta| Elisabeth Solana| Eloy Martínez‐Heras| Aline Meza‐Ramos| Sergi Amaro| Sara Llufriu| Lluís Mont| Eduard Guasch|
Abstract: The consequences of extremely intense long‐term exercise for brain health remain unknown. We studied the effects of strenuous exercise on brain structure and function, its dose‒response relationship, and mechanisms in a rat model of endurance training. Five‐week‐old male Wistar rats were assigned to moderate (MOD) or intense (INT) exercise or a sedentary (SED) group for 16 weeks. MOD rats showed the highest motivation and learning capacity in operant conditioning experiments; SED and INT presented similar results. In vivo MRI demonstrated enhanced global and regional connectivity efficiency and clustering as well as a higher cerebral blood flow (CBF) in MOD but not INT rats compared with SED. In the cortex, downregulation of oxidative phosphorylation complex IV and AMPK activation denoted mitochondrial dysfunction in INT rats. An imbalance in cortical antioxidant capacity was found between MOD and INT rats. The MOD group showed the lowest hippocampal brain‐derived neurotrophic factor levels. The mRNA and protein levels of inflammatory markers were similar in all groups. In conclusion, strenuous long‐term exercise yields a lesser improvement in learning ability than moderate exercise. Blunting of MOD‐induced improvements in CBF and connectivity efficiency, accompanied by impaired mitochondrial energetics and, possibly, transient local oxidative stress, may underlie the findings in intensively trained rats.
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Date: 2022-10-17  ·  Issue: 2022  · 
Musical development during adolescence: Perceptual skills, cognitive resources, and musical training
Contributors: Daniel Müllensiefen| Paul Elvers| Klaus Frieler|
Abstract: Longitudinal studies on musical development can provide very valuable insights and potentially evidence for causal mechanisms driving the development of musical skills and cognitive resources, such as working memory and intelligence. Nonetheless, quantitative longitudinal studies on musical and cognitive development are very rare in the published literature. Hence, the aim of this paper is to document available longitudinal evidence on musical development from three different sources. In part I, data from a systematic literature review are presented in a graphical format, making developmental trends from five previous longitudinal studies comparable. Part II presents a model of musical development derived from music‐related variables that are part of the British Millennium Cohort Study. In part III, data from the ongoing LongGold project are analyzed answering five questions on the change of musical skills and cognitive resources across adolescence and on the role that musical training and activities might play in these developmental processes. Results provide evidence for substantial near transfer effects (from musical training to musical skills) and weaker evidence for far‐transfer to cognitive variables. But results also show evidence of cognitive profiles of high intelligence and working memory capacity that are conducive to strong subsequent growth rates of musical development.
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Date: 2022-10-17  ·  Issue: 2022  ·  Volume: 1518
Computational modeling to assist in the discovery of supramolecular materials
Contributors: Kim E. Jelfs|
Abstract: Computational modeling is increasingly used to assist in the discovery of supramolecular materials. Supramolecular materials are typically primarily built from organic components that are self‐assembled through noncovalent bonding and have potential applications, including in selective binding, sorption, molecular separations, catalysis, optoelectronics, sensing, and as molecular machines. In this review, the key areas where computational prediction can assist in the discovery of supramolecular materials, including in structure prediction, property prediction, and the prediction of how to synthesize a hypothetical material are discussed, before exploring the potential impact of artificial intelligence techniques on the field. Throughout, the importance of close integration with experimental materials discovery programs will be highlighted. A series of case studies from the author's work across some different supramolecular material classes will be discussed, before finishing with a discussion of the outlook for the field.
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Date: 2022-10-17  ·  Issue: 2022  ·  Volume: 1518
Musical development during adolescence: Perceptual skills, cognitive resources, and musical training
Contributors: Daniel Müllensiefen| Paul Elvers| Klaus Frieler|
Abstract: Longitudinal studies on musical development can provide very valuable insights and potentially evidence for causal mechanisms driving the development of musical skills and cognitive resources, such as working memory and intelligence. Nonetheless, quantitative longitudinal studies on musical and cognitive development are very rare in the published literature. Hence, the aim of this paper is to document available longitudinal evidence on musical development from three different sources. In part I, data from a systematic literature review are presented in a graphical format, making developmental trends from five previous longitudinal studies comparable. Part II presents a model of musical development derived from music‐related variables that are part of the British Millennium Cohort Study. In part III, data from the ongoing LongGold project are analyzed answering five questions on the change of musical skills and cognitive resources across adolescence and on the role that musical training and activities might play in these developmental processes. Results provide evidence for substantial near transfer effects (from musical training to musical skills) and weaker evidence for far‐transfer to cognitive variables. But results also show evidence of cognitive profiles of high intelligence and working memory capacity that are conducive to strong subsequent growth rates of musical development.
Read More  

Date: 2022-10-17  ·  Issue: 2022  · 
Computational modeling to assist in the discovery of supramolecular materials
Contributors: Kim E. Jelfs|
Abstract: Computational modeling is increasingly used to assist in the discovery of supramolecular materials. Supramolecular materials are typically primarily built from organic components that are self‐assembled through noncovalent bonding and have potential applications, including in selective binding, sorption, molecular separations, catalysis, optoelectronics, sensing, and as molecular machines. In this review, the key areas where computational prediction can assist in the discovery of supramolecular materials, including in structure prediction, property prediction, and the prediction of how to synthesize a hypothetical material are discussed, before exploring the potential impact of artificial intelligence techniques on the field. Throughout, the importance of close integration with experimental materials discovery programs will be highlighted. A series of case studies from the author's work across some different supramolecular material classes will be discussed, before finishing with a discussion of the outlook for the field.
Read More  

Date: 2022-10-14  ·  Issue: 2022  · 
Evaluation of global terrestrial near‐surface wind speed simulated by CMIP6 models and their future projections
Contributors: Cheng Shen| Jinlin Zha| Zhibo Li| Cesar Azorin‐Molina| Kaiqiang Deng| Lorenzo Minola| Deliang Chen|
Abstract: We evaluate the performance of Coupled Model Intercomparison Project Phase 6 (CMIP6) models in simulating the observed global terrestrial near‐surface wind speed (NSWS) and project its future changes under three different Shared Socioeconomic Pathways (SSPs). Results show that the CESM2 has the best ability in reproducing the observed NSWS trends, although all models examined are generally not doing well. Based on projections of CESM2, the global NSWS will decrease from 2021 to 2100 under all three SSPs. The projected NSWS declines significantly over the north of 20°N, especially across North America, Europe, and the mid‐to‐high latitudes of Asia; meanwhile, it increases over the south of 20°N. Under SSP585, there would be more light‐windy days and fewer strong‐windy days than those under SSP245, which leads to a significant global NSWS decline. Robust hemispheric‐asymmetric changes in the NSWS could be due to the temperature gradient in the two hemispheres under global warming, with −1.2%, −3.5%, and −4.1% in the Northern Hemisphere, and 0.8%, 1.0%, and 1.5% in the Southern Hemisphere, for the near‐term (2021–2040), mid‐term (2041–2060), and long‐term (2081–2100), respectively.
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Date: 2022-10-14  ·  Issue: 2022  ·  Volume: 1516
Issue Information
Contributors:
Abstract:
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Date: 2022-10-14  ·  Issue: 2022  ·  Volume: 1518
Evaluation of global terrestrial near‐surface wind speed simulated by CMIP6 models and their future projections
Contributors: Cheng Shen| Jinlin Zha| Zhibo Li| Cesar Azorin‐Molina| Kaiqiang Deng| Lorenzo Minola| Deliang Chen|
Abstract: We evaluate the performance of Coupled Model Intercomparison Project Phase 6 (CMIP6) models in simulating the observed global terrestrial near‐surface wind speed (NSWS) and project its future changes under three different Shared Socioeconomic Pathways (SSPs). Results show that the CESM2 has the best ability in reproducing the observed NSWS trends, although all models examined are generally not doing well. Based on projections of CESM2, the global NSWS will decrease from 2021 to 2100 under all three SSPs. The projected NSWS declines significantly over the north of 20°N, especially across North America, Europe, and the mid‐to‐high latitudes of Asia; meanwhile, it increases over the south of 20°N. Under SSP585, there would be more light‐windy days and fewer strong‐windy days than those under SSP245, which leads to a significant global NSWS decline. Robust hemispheric‐asymmetric changes in the NSWS could be due to the temperature gradient in the two hemispheres under global warming, with −1.2%, −3.5%, and −4.1% in the Northern Hemisphere, and 0.8%, 1.0%, and 1.5% in the Southern Hemisphere, for the near‐term (2021–2040), mid‐term (2041–2060), and long‐term (2081–2100), respectively.
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Date: 2022-10-06  ·  Issue: 2022  ·  Volume: 1518
Music‐based interventions in community settings: Navigating the tension between rigor and ecological validity
Contributors: Assal Habibi| Gunter Kreutz| Frank Russo| Mari Tervaniemi|
Abstract: Empirical research of community‐based music interventions has advanced to investigate the individual, social, and educational implications of arts‐for‐wellbeing practices. Here, we present the motivations, aims, hypotheses, and implications of this complex field of inquiry. We describe examples of recent large‐scale investigations to reflect on the major methodological challenges. Community‐based music interventions strike a balance between the empirical rigor of clinical trials and the demands of ecological validity. We argue that this balance should be viewed as an asset rather than a mere pragmatic compromise. We also offer some perspectives on best‐practice models for effectively engaging in this type of work.
Read More  

Date: 2022-10-06  ·  Issue: 2022  · 
Molecular mechanisms underlying paracellular calcium and magnesium reabsorption in the proximal tubule and thick ascending limb
Contributors: R. Todd Alexander| Henrik Dimke|
Abstract: Calcium and magnesium are the most abundant divalent cations in the body. The plasma level is controlled by coordinated interaction between intestinal absorption, reabsorption in the kidney, and, for calcium at least, bone storage and exchange. The kidney adjusts urinary excretion of these ions in response to alterations in their systemic concentration. Free ionized and anion‐complexed calcium and magnesium are filtered at the glomerulus. The majority (i.e., >85%) of filtered divalent cations are reabsorbed via paracellular pathways from the proximal tubule and thick ascending limb (TAL) of the loop of Henle. Interestingly, the largest fraction of filtered calcium is reabsorbed from the proximal tubule (65%), while the largest fraction of filtered magnesium is reclaimed from the TAL (60%). The paracellular pathways mediating these fluxes are composed of tight junctional pores formed by claudins. In the proximal tubule, claudin‐2 and claudin‐12 confer calcium permeability, while the exact identity of the magnesium pore remains to be determined. Claudin‐16 and claudin‐19 contribute to the calcium and magnesium permeable pathway in the TAL. In this review, we discuss the data supporting these conclusions and speculate as to why there is greater fractional calcium reabsorption from the proximal tubule and greater fractional magnesium reabsorption from the TAL.
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Date: 2022-10-06  ·  Issue: 2022  · 
Music‐based interventions in community settings: Navigating the tension between rigor and ecological validity
Contributors: Assal Habibi| Gunter Kreutz| Frank Russo| Mari Tervaniemi|
Abstract: Empirical research of community‐based music interventions has advanced to investigate the individual, social, and educational implications of arts‐for‐wellbeing practices. Here, we present the motivations, aims, hypotheses, and implications of this complex field of inquiry. We describe examples of recent large‐scale investigations to reflect on the major methodological challenges. Community‐based music interventions strike a balance between the empirical rigor of clinical trials and the demands of ecological validity. We argue that this balance should be viewed as an asset rather than a mere pragmatic compromise. We also offer some perspectives on best‐practice models for effectively engaging in this type of work.
Read More  

Date: 2022-10-06  ·  Issue: 2022  ·  Volume: 1518
Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell‐type lipidomics
Contributors: Isaac Asante| Stan Louie| Hussein N. Yassine|
Abstract: A chronic state of unresolved inflammation in Alzheimer's disease (AD) is intrinsically involved with the remodeling of brain lipids. This review highlights the effect of carrying the apolipoprotein E ε4 allele (APOE4) on various brain cell types in promoting an unresolved inflammatory state. Among its pleotropic effects on brain lipids, we focus on APOE4’s activation of Ca2+‐dependent phospholipase A2 (cPLA2) and its effects on arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid signaling cascades in the brain. During the process of neurodegeneration, various brain cell types, such as astrocytes, microglia, and neurons, together with the neurovascular unit, develop distinct inflammatory phenotypes that impact their functions and have characteristic lipidomic fingerprints. We propose that lipidomic phenotyping of single cell‐types harvested from brains differing by age, sex, disease severity stage, and dietary and genetic backgrounds can be employed to probe mechanisms of neurodegeneration. A better understanding of the brain cellular inflammatory/lipidomic response promises to guide the development of nutritional and drug interventions for AD dementia.
Read More  

Date: 2022-10-06  ·  Issue: 2022  ·  Volume: 1518
Molecular mechanisms underlying paracellular calcium and magnesium reabsorption in the proximal tubule and thick ascending limb
Contributors: R. Todd Alexander| Henrik Dimke|
Abstract: Calcium and magnesium are the most abundant divalent cations in the body. The plasma level is controlled by coordinated interaction between intestinal absorption, reabsorption in the kidney, and, for calcium at least, bone storage and exchange. The kidney adjusts urinary excretion of these ions in response to alterations in their systemic concentration. Free ionized and anion‐complexed calcium and magnesium are filtered at the glomerulus. The majority (i.e., >85%) of filtered divalent cations are reabsorbed via paracellular pathways from the proximal tubule and thick ascending limb (TAL) of the loop of Henle. Interestingly, the largest fraction of filtered calcium is reabsorbed from the proximal tubule (65%), while the largest fraction of filtered magnesium is reclaimed from the TAL (60%). The paracellular pathways mediating these fluxes are composed of tight junctional pores formed by claudins. In the proximal tubule, claudin‐2 and claudin‐12 confer calcium permeability, while the exact identity of the magnesium pore remains to be determined. Claudin‐16 and claudin‐19 contribute to the calcium and magnesium permeable pathway in the TAL. In this review, we discuss the data supporting these conclusions and speculate as to why there is greater fractional calcium reabsorption from the proximal tubule and greater fractional magnesium reabsorption from the TAL.
Read More  

Date: 2022-10-06  ·  Issue: 2023  · 
Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell‐type lipidomics
Contributors: Isaac Asante| Stan Louie| Hussein N. Yassine|
Abstract: A chronic state of unresolved inflammation in Alzheimer's disease (AD) is intrinsically involved with the remodeling of brain lipids. This review highlights the effect of carrying the apolipoprotein E ε4 allele (APOE4) on various brain cell types in promoting an unresolved inflammatory state. Among its pleotropic effects on brain lipids, we focus on APOE4’s activation of Ca2+‐dependent phospholipase A2 (cPLA2) and its effects on arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid signaling cascades in the brain. During the process of neurodegeneration, various brain cell types, such as astrocytes, microglia, and neurons, together with the neurovascular unit, develop distinct inflammatory phenotypes that impact their functions and have characteristic lipidomic fingerprints. We propose that lipidomic phenotyping of single cell‐types harvested from brains differing by age, sex, disease severity stage, and dietary and genetic backgrounds can be employed to probe mechanisms of neurodegeneration. A better understanding of the brain cellular inflammatory/lipidomic response promises to guide the development of nutritional and drug interventions for AD dementia.
Read More  

Date: 2022-10-02  ·  Issue: 2023  · 
Lessons from the pandemic: Responding to emerging zoonotic viral diseases—a Keystone Symposia report
Contributors: Jennifer Cable| Anthony Fauci| William E. Dowling| Stephan Günther| Dennis A. Bente| Pragya Dhruv Yadav| Lawrence C. Madoff| Lin‐Fa Wang| Rahul K. Arora| Maria Van Kerkhove| May C. Chu| Thomas Jaenisch| Jonathan H. Epstein| Simon David William Frost| Daniel G. Bausch| Lisa E. Hensley| Éric Bergeron| Ioannis Sitaras| Michael D. Gunn| Thomas W. Geisbert| César Muñoz‐Fontela| Florian Krammer| Emmie Wit| Pontus Nordenfelt| Erica Ollmann Saphire| Sarah C. Gilbert| Kizzmekia S. Corbett| Luis M. Branco| Sylvain Baize| Neeltje Doremalen| Marco A. Krieger| Sue Ann Costa Clemens| Renske Hesselink| Dan Hartman|
Abstract: The COVID‐19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10–13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium “Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases” to discuss the successes and challenges of the COVID‐19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID‐19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID‐19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements—notably, in low‐to‐middle income countries—must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.
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Date: 2022-10-02  ·  Issue: 2022  ·  Volume: 1518
Lessons from the pandemic: Responding to emerging zoonotic viral diseases—a Keystone Symposia report
Contributors: Jennifer Cable| Anthony Fauci| William E. Dowling| Stephan Günther| Dennis A. Bente| Pragya Dhruv Yadav| Lawrence C. Madoff| Lin‐Fa Wang| Rahul K. Arora| Maria Van Kerkhove| May C. Chu| Thomas Jaenisch| Jonathan H. Epstein| Simon David William Frost| Daniel G. Bausch| Lisa E. Hensley| Éric Bergeron| Ioannis Sitaras| Michael D. Gunn| Thomas W. Geisbert| César Muñoz‐Fontela| Florian Krammer| Emmie Wit| Pontus Nordenfelt| Erica Ollmann Saphire| Sarah C. Gilbert| Kizzmekia S. Corbett| Luis M. Branco| Sylvain Baize| Neeltje Doremalen| Marco A. Krieger| Sue Ann Costa Clemens| Renske Hesselink| Dan Hartman|
Abstract: The COVID‐19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10–13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium “Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases” to discuss the successes and challenges of the COVID‐19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID‐19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID‐19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements—notably, in low‐to‐middle income countries—must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.
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Date: 2022-10-02  ·  Issue: 2022  ·  Volume: 1518
Electrical conductivity through π–π stacking in a two‐dimensional porous gallium catecholate metal–organic framework
Contributors: Grigorii Skorupskii| Géraldine Chanteux| Khoa N. Le| Ivo Stassen| Christopher H. Hendon| Mircea Dincă|
Abstract: Metal–organic frameworks (MOFs) are hybrid materials known for their nanoscale pores, which give them high surface areas but generally lead to poor electrical conductivity. Recently, MOFs with high electrical conductivity were established as promising materials for a variety of applications in energy storage and catalysis. Many recent reports investigating the fundamentals of charge transport in these materials focus on the role of the organic ligands. Less consideration, however, is given to the metal ion forming the MOF, which is almost exclusively a late first‐row transition metal. Here, we report a moderately conductive porous MOF based on trivalent gallium and 2,3,6,7,10,11‐hexahydroxytriphenylene. Gallium, a metal that has not been featured in electrically conductive MOFs so far, has a closed‐shell electronic configuration and is present in its trivalent state—in contrast to most conductive MOFs, which are formed by open‐shell, divalent transition metals. Our material, made without using any harmful solvents, displays conductivities on the level of 3 mS/cm and a surface area of 196 m2/g, comparable to transition metal analogs.
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Date: 2022-09-30  ·  Issue: 2023  · 
Engineering multicellular living systems—a Keystone Symposia report
Contributors: Jennifer Cable| Paola Arlotta| Kevin Kit Parker| Alex J. Hughes| Katharine Goodwin| Christine L. Mummery| Roger D. Kamm| Sandra J. Engle| Danilo A. Tagle| Sylvia F. Boj| Alice E. Stanton| Yoshihiro Morishita| Melissa L. Kemp| Dennis A. Norfleet| Elebeoba E. May| Aric Lu| Rashid Bashir| Adam W. Feinberg| Sarah M. Hull| Anjelica L. Gonzalez| Michael R. Blatchley| Núria Montserrat Pulido| Ryuji Morizane| Todd C. McDevitt| Deepak Mishra| Adriana Mulero‐Russe|
Abstract: The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3–6, 2022, experts in the field met at the Keystone symposium “Engineering Multicellular Living Systems” to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ‐on‐a‐chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium “Organoids as Tools for Fundamental Discovery and Translation”.
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Date: 2022-09-30  ·  Issue: 2022  ·  Volume: 1518
The arts and sciences: The two cultures and the public face of science
Contributors: Nicholas B. Dirks|
Abstract: At a time when the culture of and discoveries by science are clearly in the ascendant, science needs the arts and humanities more than ever. Paradoxically, however, the two cultures—the arts and the sciences—have become increasingly distinct, seemingly ever more orthogonal to each other.
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Date: 2022-09-30  ·  Issue: 2022  ·  Volume: 1518
Putting music to trial: Consensus on key methodological challenges investigating music‐based rehabilitation
Contributors: Jennifer Grau‐Sánchez| Kevin Jamey| Evangelos Paraskevopoulos| Simone Dalla Bella| Christian Gold| Gottfried Schlaug| Sylvie Belleville| Antoni Rodríguez‐Fornells| Madeleine E. Hackney| Teppo Särkämö|
Abstract: Major advances in music neuroscience have fueled a growing interest in music‐based neurological rehabilitation among researchers and clinicians. Musical activities are excellently suited to be adapted for clinical practice because of their multisensory nature, their demands on cognitive, language, and motor functions, and music's ability to induce emotions and regulate mood. However, the overall quality of music‐based rehabilitation research remains low to moderate for most populations and outcomes. In this consensus article, expert panelists who participated in the Neuroscience and Music VII conference in June 2021 address methodological challenges relevant to music‐based rehabilitation research. The article aims to provide guidance on challenges related to treatment, outcomes, research designs, and implementation in music‐based rehabilitation research. The article addresses how to define music‐based rehabilitation, select appropriate control interventions and outcomes, incorporate technology, and consider individual differences, among other challenges. The article highlights the value of the framework for the development and evaluation of complex interventions for music‐based rehabilitation research and the need for stronger methodological rigor to allow the widespread implementation of music‐based rehabilitation into regular clinical practice.
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Date: 2022-09-30  ·  Issue: 2022  ·  Volume: 1518
Progranulin is essential for bone homeostasis and immunology
Contributors: Qian Chen| ZuPing Wu| Liang Xie|
Abstract: Intercellular communication or crosstalk between immune and skeletal cells is considered a crucial element in bone homeostasis modulation. Progranulin (PGRN) is an autocrine growth factor that is structured as beads‐on‐a‐string and participates in multiple pathophysiological processes, including atherosclerosis, arthritis, neurodegenerative pathologies, cancer, and wound repair. PGRN functions as a competitor that binds to tumor necrosis factor receptor 1 (TNFR1), thereby blocking the TNF‐α pathway. PGRN is regarded as an agonist of chondrogenesis and osteogenesis, delaying the progression of inflammation through the TNFR2 pathway. The exploitation of PGRN may bring benefits for inflammatory bone diseases and the stabilization of bone homeostasis. The PGRN‐modified analog Atsttrin possesses three TNFR‐binding fragments and thereby exerts superior therapeutic effects on multiple preclinical animal models compared to PGRN. In this review, we highlight the emerging roles of PGRN in bone formation, as well as in physiological and TNF‐α–mediated inflammatory conditions revealed in recent discoveries. We address potential therapies for the treatment of inflammatory bone conditions, such as periodontitis, by the use of PGRN and its derivative Atsttrin.
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Date: 2022-09-30  ·  Issue: 2022  ·  Volume: 1518
Organoids as tools for fundamental discovery and translation—a Keystone Symposia report
Contributors: Jennifer Cable| Matthias P. Lutolf| Jianping Fu| Sunghee Estelle Park| Athanasia Apostolou| Shuibing Chen| Cheng Jack Song| Jason R. Spence| Prisca Liberali| Madeline Lancaster| Anna B. Meier| Nicole Min Qian Pek| James M. Wells| Meghan M. Capeling| Ana Uzquiano| Samira Musah| Meritxell Huch| Mina Gouti| Pleun Hombrink| Giorgia Quadrato| Jean‐Paul Urenda|
Abstract: Complex three‐dimensional in vitro organ‐like models, or organoids, offer a unique biological tool with distinct advantages over two‐dimensional cell culture systems, which can be too simplistic, and animal models, which can be too complex and may fail to recapitulate human physiology and pathology. Significant progress has been made in driving stem cells to differentiate into different organoid types, though several challenges remain. For example, many organoid models suffer from high heterogeneity, and it can be difficult to fully incorporate the complexity of in vivo tissue and organ development to faithfully reproduce human biology. Successfully addressing such limitations would increase the viability of organoids as models for drug development and preclinical testing. On April 3–6, 2022, experts in organoid development and biology convened at the Keystone Symposium “Organoids as Tools for Fundamental Discovery and Translation” to discuss recent advances and insights from this relatively new model system into human development and disease.
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Date: 2022-09-30  ·  Issue: 2023  · 
The arts and sciences: The two cultures and the public face of science
Contributors: Nicholas B. Dirks|
Abstract: At a time when the culture of and discoveries by science are clearly in the ascendant, science needs the arts and humanities more than ever. Paradoxically, however, the two cultures—the arts and the sciences—have become increasingly distinct, seemingly ever more orthogonal to each other.
Read More  

Date: 2022-09-30  ·  Issue: 2022  ·  Volume: 1518
Engineering multicellular living systems—a Keystone Symposia report
Contributors: Jennifer Cable| Paola Arlotta| Kevin Kit Parker| Alex J. Hughes| Katharine Goodwin| Christine L. Mummery| Roger D. Kamm| Sandra J. Engle| Danilo A. Tagle| Sylvia F. Boj| Alice E. Stanton| Yoshihiro Morishita| Melissa L. Kemp| Dennis A. Norfleet| Elebeoba E. May| Aric Lu| Rashid Bashir| Adam W. Feinberg| Sarah M. Hull| Anjelica L. Gonzalez| Michael R. Blatchley| Núria Montserrat Pulido| Ryuji Morizane| Todd C. McDevitt| Deepak Mishra| Adriana Mulero‐Russe|
Abstract: The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3–6, 2022, experts in the field met at the Keystone symposium “Engineering Multicellular Living Systems” to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ‐on‐a‐chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium “Organoids as Tools for Fundamental Discovery and Translation”.
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Date: 2022-09-27  ·  Issue: 2022  ·  Volume: 1518
Racial/ethnic disparities in severe maternal morbidity: An intersectional lifecourse approach
Contributors: Elleni M. Hailu| Suzan L. Carmichael| Rachel L. Berkowitz| Jonathan M. Snowden| Audrey Lyndon| Elliott Main| Mahasin S. Mujahid|
Abstract: Despite long‐existing calls to address alarming racial/ethnic gaps in severe maternal morbidity (SMM), research that considers the impact of intersecting social inequities on SMM risk remains scarce. Invoking intersectionality theory, we sought to assess SMM risk at the nexus of racial/ethnic marginalization, weathering, and neighborhood/individual socioeconomic disadvantage. We used birth hospitalization records from California across 20 years (1997–2017, N = 9,806,406) on all live births ≥20 weeks gestation. We estimated adjusted average predicted probabilities of SMM at the combination of levels of race/ethnicity, age, and neighborhood deprivation or individual socioeconomic status (SES). The highest risk of SMM was observed among Black birthing people aged ≥35 years who either resided in the most deprived neighborhoods or had the lowest SES. Black birthing people conceptualized to be better off due to their social standing (aged 20–34 years and living in the least deprived neighborhoods or college graduates) had comparable and at times worse risk than White birthing people conceptualized to be worse off (aged ≥35 years and living in the most deprived neighborhoods or had a high‐school degree or less). Our findings highlight the need to explicitly address structural racism as the driver of racial/ethnic health inequities and the imperative to incorporate intersectional approaches.
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Date: 2022-09-22  ·  Issue: 2022  ·  Volume: 1517
The analgesic effect of nostalgia elicited by idiographic and nomothetic approaches on thermal stimulus
Contributors: Ming Zhang| Ziyan Yang| Jiahui Zhong| Yuqi Zhang| Xiaomin Lin| Jiyuan Wang| Huajian Cai| Yazhuo Kong|
Abstract: Nostalgia is shown to relieve an individual's perception of pain evoked by cold water, pressure, and thermal stimuli. However, there is no direct evidence to show the analgesic effects of different nostalgia‐inducing methods on various stimulus intensities. We conducted two studies to examine the analgesic effect, at different pain intensities, after inducing nostalgia either idiographically or nomothetically. Study 1 (N = 118) induced nostalgia through an idiographic approach (i.e., event reflection task) and found that nostalgia relieved both high and low thermal pain. Study 2 (N = 66) induced nostalgia through a nomothetic approach (i.e., viewing nostalgic pictures) and found that nostalgia relieved low but not high thermal pain. The findings verify the analgesic effect of nostalgia on thermal pain and suggest the potential moderating role of the nostalgia induction approach and pain intensity. Practically, these findings have implications for using nostalgia as a nonpharmacological treatment for pain.
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Date: 2022-09-19  ·  Issue: 2022  · 
Math anxiety as an independent psychological construct among social‐emotional attitudes: An exploratory factor analysis
Contributors: Dazhi Cheng| Bingqian Ren| Xiaodan Yu| Haitao Wang| Qian Chen| Xinlin Zhou|
Abstract: Math anxiety is a widespread problem for children and adolescents worldwide. However, the psychological trait of math anxiety is poorly understood. The present study aimed to examine the psychological construct of math anxiety among social‐emotional attitudes. A total of 28,726 students, including 17,378 fourth graders and 11,348 eighth graders, were selected from the Qingdao Basic Education Quality Assessment database using multi‐stage cluster random sampling. There were 10 questionnaires assessing social‐emotional attitudes in the database. Pearson's correlation analyses were performed to examine the intercorrelations between social‐emotional attitudes and mathematical performance. Exploratory factor analysis (EFA) was conducted to examine the psychological structure of these 10 social‐emotional attitudes. After controlling for other social‐emotional attitudes, math anxiety had a weak but significant correlation to mathematical performance in most subtests across grades. Among three‐factor, four‐factor, and five‐factor EFA models, math anxiety was an independent factor that was separate from other social‐emotional attitudes across six parallel subtests in grades four and eight. Math anxiety is a stable and independent psychological construct that is separate from other social‐emotional attitudes. It suggests that math anxiety should be considered as a distinct anxiety disorder specific to mathematical learning in subsequent versions of the Diagnostic and Statistical Manual of Mental Disorders.
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Date: 2022-09-19  ·  Issue: 2022  ·  Volume: 1517
Math anxiety as an independent psychological construct among social‐emotional attitudes: An exploratory factor analysis
Contributors: Dazhi Cheng| Bingqian Ren| Xiaodan Yu| Haitao Wang| Qian Chen| Xinlin Zhou|
Abstract: Math anxiety is a widespread problem for children and adolescents worldwide. However, the psychological trait of math anxiety is poorly understood. The present study aimed to examine the psychological construct of math anxiety among social‐emotional attitudes. A total of 28,726 students, including 17,378 fourth graders and 11,348 eighth graders, were selected from the Qingdao Basic Education Quality Assessment database using multi‐stage cluster random sampling. There were 10 questionnaires assessing social‐emotional attitudes in the database. Pearson's correlation analyses were performed to examine the intercorrelations between social‐emotional attitudes and mathematical performance. Exploratory factor analysis (EFA) was conducted to examine the psychological structure of these 10 social‐emotional attitudes. After controlling for other social‐emotional attitudes, math anxiety had a weak but significant correlation to mathematical performance in most subtests across grades. Among three‐factor, four‐factor, and five‐factor EFA models, math anxiety was an independent factor that was separate from other social‐emotional attitudes across six parallel subtests in grades four and eight. Math anxiety is a stable and independent psychological construct that is separate from other social‐emotional attitudes. It suggests that math anxiety should be considered as a distinct anxiety disorder specific to mathematical learning in subsequent versions of the Diagnostic and Statistical Manual of Mental Disorders.
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Date: 2022-09-16  ·  Issue: 2022  ·  Volume: 1517
Short‐term plasticity of neuro‐auditory processing induced by musical active listening training
Contributors: Peter Schneider| Christine Groß| Valdis Bernhofs| Markus Christiner| Jan Benner| Sabrina Turker| Bettina M. Zeidler| Annemarie Seither‐Preisler|
Abstract: Although there is strong evidence for the positive effects of musical training on auditory perception, processing, and training‐induced neuroplasticity, there is still little knowledge on the auditory and neurophysiological short‐term plasticity through listening training. In a sample of 37 adolescents (20 musicians and 17 nonmusicians) that was compared to a control group matched for age, gender, and musical experience, we conducted a 2‐week active listening training (AULOS: Active IndividUalized Listening OptimizationS). Using magnetoencephalography and psychoacoustic tests, the short‐term plasticity of auditory evoked fields and auditory skills were examined in a pre‐post design, adapted to the individual neuro‐auditory profiles. We found bilateral, but more pronounced plastic changes in the right auditory cortex. Moreover, we observed synchronization of the auditory evoked P1, N1, and P2 responses and threefold larger amplitudes of the late P2 response, similar to the reported effects of musical long‐term training. Auditory skills and thresholds benefited largely from the AULOS training. Remarkably, after training, the mean thresholds improved by 12 dB for bone conduction and by 3–4 dB for air conduction. Thus, our findings indicate a strong positive influence of active listening training on neural auditory processing and perception in adolescence, when the auditory system is still developing.
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Date: 2022-09-16  ·  Issue: 2022  · 
Unique structural features of claudin‐5 and claudin‐15 lead to functionally distinct tight junction strand architecture
Contributors: Nandhini Rajagopal| Shikha Nangia|
Abstract: Members of the claudin family impart unique paracellular selectivity to tight junctions. However, the structure–function relationship between claudin's strand architecture and the paracellular charge‐ and size‐selectivity is not well‐understood. This work examines the molecular assembly of claudin‐5, a barrier‐forming protein, and claudin‐15, a channel‐forming protein, to determine their structural and functional properties. We adopt a bottom‐up approach starting from claudin monomers to build the molecular architecture of the tight junction strands. First, we investigated the cis assembly of claudin‐5 and ‐15 dimers using the Protein Association Energy Landscape method. Out of the millions of dimer conformations, we narrowed down key cis claudin‐5 and ‐15 dimer conformations that were thermodynamically and kinetically stable. Second, we performed the trans assembly of dimers to identify the tetrameric building blocks that serve as the repeat units for strand formation. Finally, the strand assembly of the tetrameric repeat units showed fundamentally distinct strand architectures. In claudin‐5, the cis and trans interactions seal the paracellular space, while in claudin‐15, the gaps in the paracellular space lead to pore formation. This detailed study suggests that each member of the claudin family is unique and requires systematic molecular‐level analysis for determining the strand architecture.
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Date: 2022-09-16  ·  Issue: 2022  ·  Volume: 1517
Unique structural features of claudin‐5 and claudin‐15 lead to functionally distinct tight junction strand architecture
Contributors: Nandhini Rajagopal| Shikha Nangia|
Abstract: Members of the claudin family impart unique paracellular selectivity to tight junctions. However, the structure–function relationship between claudin's strand architecture and the paracellular charge‐ and size‐selectivity is not well‐understood. This work examines the molecular assembly of claudin‐5, a barrier‐forming protein, and claudin‐15, a channel‐forming protein, to determine their structural and functional properties. We adopt a bottom‐up approach starting from claudin monomers to build the molecular architecture of the tight junction strands. First, we investigated the cis assembly of claudin‐5 and ‐15 dimers using the Protein Association Energy Landscape method. Out of the millions of dimer conformations, we narrowed down key cis claudin‐5 and ‐15 dimer conformations that were thermodynamically and kinetically stable. Second, we performed the trans assembly of dimers to identify the tetrameric building blocks that serve as the repeat units for strand formation. Finally, the strand assembly of the tetrameric repeat units showed fundamentally distinct strand architectures. In claudin‐5, the cis and trans interactions seal the paracellular space, while in claudin‐15, the gaps in the paracellular space lead to pore formation. This detailed study suggests that each member of the claudin family is unique and requires systematic molecular‐level analysis for determining the strand architecture.
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Date: 2022-09-16  ·  Issue: 2022  · 
Short‐term plasticity of neuro‐auditory processing induced by musical active listening training
Contributors: Peter Schneider| Christine Groß| Valdis Bernhofs| Markus Christiner| Jan Benner| Sabrina Turker| Bettina M. Zeidler| Annemarie Seither‐Preisler|
Abstract: Although there is strong evidence for the positive effects of musical training on auditory perception, processing, and training‐induced neuroplasticity, there is still little knowledge on the auditory and neurophysiological short‐term plasticity through listening training. In a sample of 37 adolescents (20 musicians and 17 nonmusicians) that was compared to a control group matched for age, gender, and musical experience, we conducted a 2‐week active listening training (AULOS: Active IndividUalized Listening OptimizationS). Using magnetoencephalography and psychoacoustic tests, the short‐term plasticity of auditory evoked fields and auditory skills were examined in a pre‐post design, adapted to the individual neuro‐auditory profiles. We found bilateral, but more pronounced plastic changes in the right auditory cortex. Moreover, we observed synchronization of the auditory evoked P1, N1, and P2 responses and threefold larger amplitudes of the late P2 response, similar to the reported effects of musical long‐term training. Auditory skills and thresholds benefited largely from the AULOS training. Remarkably, after training, the mean thresholds improved by 12 dB for bone conduction and by 3–4 dB for air conduction. Thus, our findings indicate a strong positive influence of active listening training on neural auditory processing and perception in adolescence, when the auditory system is still developing.
Read More  

Date: 2022-09-08  ·  Issue: 2022  ·  Volume: 1517
Accurate tumor clonal structures require single‐cell analysis
Contributors: Xianbin Su| Shihao Bai| Gangcai Xie| Yi Shi| Linan Zhao| Guoliang Yang| Futong Tian| Kun‐Yan He| Lan Wang| Xiaolin Li| Qi Long| Ze‐Guang Han|
Abstract: Tumor clonal structure is closely related to future progression, which has been mainly investigated as mutation abundance clustering in bulk samples. With relatively limited studies at single‐cell resolution, a systematic comparison of the two approaches is still lacking. Here, using bulk and single‐cell mutational data from the liver and colorectal cancers, we checked whether co‐mutations determined by single‐cell analysis had corresponding bulk variant allele frequency (VAF) peaks. While bulk analysis suggested the absence of subclonal peaks and, possibly, neutral evolution in some cases, the single‐cell analysis identified coexisting subclones. The overlaps of bulk VAF ranges for co‐mutations from different subclones made it difficult to separate them. Complex subclonal structures and dynamic evolution could be hidden under the seemingly clonal neutral pattern at the bulk level, suggesting single‐cell analysis is necessary to avoid underestimation of tumor heterogeneity.
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Date: 2022-09-07  ·  Issue: 2022  · 
Effects of TAMP family on the tight junction strand network and barrier function in epithelial cells
Contributors: Akira C. Saito| Chisato Endo| Yugo Fukazawa| Tomohito Higashi| Hideki Chiba|
Abstract: Occludin, tricellulin, and marvelD3 belong to the tight junction (TJ)‐associated MARVEL protein family. Occludin and tricellulin jointly contribute to TJ strand branching point formation and epithelial barrier maintenance. However, whether marvelD3 has the same function remains unclear. Furthermore, the roles of the carboxy‐terminal cytoplasmic tail, which is conserved in occludin and tricellulin, on the regulation of TJ strand morphology have not yet been explored in epithelial cells. We established tricellulin/occludin/marveld3 triple‐gene knockout (tKO) MDCK II cells and evaluated the roles of marvelD3 in the TJ strand structure and barrier function using MDCK II cells and a mathematical model. The complexity of TJ strand networks and paracellular barrier did not change in tKO cells compared to that in tricellulin/occludin double‐gene knockout (dKO) cells. Exogenous marvelD3 expression in dKO cells did not increase the complexity of TJ strand networks and epithelial barrier tightness. The expression of the carboxy‐terminal truncation mutant of tricellulin restored the barrier function in the dKO cells, whereas occludin lacking the carboxy‐terminal cytoplasmic tail was not expressed on the plasma membrane. These data suggest that marvelD3 does not affect the morphology of TJ strands and barrier function in MDCK II cells and that the carboxy‐terminal cytoplasmic tail of tricellulin is dispensable for barrier improvement.
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Date: 2022-09-07  ·  Issue: 2022  ·  Volume: 1517
Effects of TAMP family on the tight junction strand network and barrier function in epithelial cells
Contributors: Akira C. Saito| Chisato Endo| Yugo Fukazawa| Tomohito Higashi| Hideki Chiba|
Abstract: Occludin, tricellulin, and marvelD3 belong to the tight junction (TJ)‐associated MARVEL protein family. Occludin and tricellulin jointly contribute to TJ strand branching point formation and epithelial barrier maintenance. However, whether marvelD3 has the same function remains unclear. Furthermore, the roles of the carboxy‐terminal cytoplasmic tail, which is conserved in occludin and tricellulin, on the regulation of TJ strand morphology have not yet been explored in epithelial cells. We established tricellulin/occludin/marveld3 triple‐gene knockout (tKO) MDCK II cells and evaluated the roles of marvelD3 in the TJ strand structure and barrier function using MDCK II cells and a mathematical model. The complexity of TJ strand networks and paracellular barrier did not change in tKO cells compared to that in tricellulin/occludin double‐gene knockout (dKO) cells. Exogenous marvelD3 expression in dKO cells did not increase the complexity of TJ strand networks and epithelial barrier tightness. The expression of the carboxy‐terminal truncation mutant of tricellulin restored the barrier function in the dKO cells, whereas occludin lacking the carboxy‐terminal cytoplasmic tail was not expressed on the plasma membrane. These data suggest that marvelD3 does not affect the morphology of TJ strands and barrier function in MDCK II cells and that the carboxy‐terminal cytoplasmic tail of tricellulin is dispensable for barrier improvement.
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Date: 2022-09-07  ·  Issue: 2022  ·  Volume: 1517
The pale spear‐nosed bat: A neuromolecular and transgenic model for vocal learning
Contributors: Sonja C. Vernes| Paolo Devanna| Stephen Gareth Hörpel| Ine Alvarez van Tussenbroek| Uwe Firzlaff| Peter Hagoort| Michael Hiller| Nienke Hoeksema| Graham M. Hughes| Ksenia Lavrichenko| Janine Mengede| Ariadna E. Morales| Maximilian Wiesmann|
Abstract: Vocal learning, the ability to produce modified vocalizations via learning from acoustic signals, is a key trait in the evolution of speech. While extensively studied in songbirds, mammalian models for vocal learning are rare. Bats present a promising study system given their gregarious natures, small size, and the ability of some species to be maintained in captive colonies. We utilize the pale spear‐nosed bat (Phyllostomus discolor) and report advances in establishing this species as a tractable model for understanding vocal learning. We have taken an interdisciplinary approach, aiming to provide an integrated understanding across genomics (Part I), neurobiology (Part II), and transgenics (Part III). In Part I, we generated new, high‐quality genome annotations of coding genes and noncoding microRNAs to facilitate functional and evolutionary studies. In Part II, we traced connections between auditory‐related brain regions and reported neuroimaging to explore the structure of the brain and gene expression patterns to highlight brain regions. In Part III, we created the first successful transgenic bats by manipulating the expression of FoxP2, a speech‐related gene. These interdisciplinary approaches are facilitating a mechanistic and evolutionary understanding of mammalian vocal learning and can also contribute to other areas of investigation that utilize P. discolor or bats as study species.
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Date: 2022-09-07  ·  Issue: 2022  · 
The pale spear‐nosed bat: A neuromolecular and transgenic model for vocal learning
Contributors: Sonja C. Vernes| Paolo Devanna| Stephen Gareth Hörpel| Ine Alvarez van Tussenbroek| Uwe Firzlaff| Peter Hagoort| Michael Hiller| Nienke Hoeksema| Graham M. Hughes| Ksenia Lavrichenko| Janine Mengede| Ariadna E. Morales| Maximilian Wiesmann|
Abstract: Vocal learning, the ability to produce modified vocalizations via learning from acoustic signals, is a key trait in the evolution of speech. While extensively studied in songbirds, mammalian models for vocal learning are rare. Bats present a promising study system given their gregarious natures, small size, and the ability of some species to be maintained in captive colonies. We utilize the pale spear‐nosed bat (Phyllostomus discolor) and report advances in establishing this species as a tractable model for understanding vocal learning. We have taken an interdisciplinary approach, aiming to provide an integrated understanding across genomics (Part I), neurobiology (Part II), and transgenics (Part III). In Part I, we generated new, high‐quality genome annotations of coding genes and noncoding microRNAs to facilitate functional and evolutionary studies. In Part II, we traced connections between auditory‐related brain regions and reported neuroimaging to explore the structure of the brain and gene expression patterns to highlight brain regions. In Part III, we created the first successful transgenic bats by manipulating the expression of FoxP2, a speech‐related gene. These interdisciplinary approaches are facilitating a mechanistic and evolutionary understanding of mammalian vocal learning and can also contribute to other areas of investigation that utilize P. discolor or bats as study species.
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Date: 2022-09-07  ·  Issue: 2022  ·  Volume: 1517
Myostatin inhibits insulin‐like growth factor 1–dependent citrate secretion and osteogenesis via nicotinamide adenine dinucleotide phosphate oxidase‐4 in a mouse mesenchymal stem cell line
Contributors: Xin‐Hua Liu| Jiang Ping Pan| William A. Bauman| Christopher Cardozo|
Abstract: Citrate is an indispensable component of bone. Reduced levels of citrate in bone and serum are reported in the elderly and in osteoporosis patients. Myostatin (Mstn) is implicated in skeletal homeostasis, but its effects on osteogenesis remain incompletely understood. Nox4 has critical roles in bone homeostasis. TGF‐β/Mstn‐associated Smad2/3 signaling has been linked to Nox4 expression. Insulin‐like growth factor (IGF‐1) has been shown to counteract many regulatory effects of Mstn. However, the crosstalk among Mstn, IGF‐1, and Nox4 is not well understood; the interactive effects of those factors on citrate secretion, osteogenic differentiation, and bone remodeling remain unclear. In this study, we demonstrated that osteogenic differentiation induced an IGF‐1–dependent upregulation of citrate secretion that was suppressed by Mstn. Inhibition of Nox4 prevented Mstn‐induced reduction of citrate secretion. In addition, Mstn reduced bone nodule formation; these changes were prevented by Nox4 inhibition. Moreover, Mstn increased the ratio of RANKL to OPG mRNAs to favor osteoclast activation. These results indicate that Mstn negatively regulates osteogenesis by increasing levels of Nox4, which reduced IGF‐1 expression, citrate secretion, and bone mineralization while also altering the RANKL to OPG ratio. These findings provide new and highly relevant insights into the osseous effects of myostatin.
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Date: 2022-09-05  ·  Issue: 2022  · 
A 90‐channel triaxial magnetoencephalography system using optically pumped magnetometers
Contributors: Molly Rea| Elena Boto| Niall Holmes| Ryan Hill| James Osborne| Natalie Rhodes| James Leggett| Lukas Rier| Richard Bowtell| Vishal Shah| Matthew J. Brookes|
Abstract: Magnetoencephalography (MEG) measures the small magnetic fields generated by current flow in neural networks, providing a noninvasive metric of brain function. MEG is well established as a powerful neuroscientific and clinical tool. However, current instrumentation is hampered by cumbersome cryogenic field‐sensing technologies. In contrast, MEG using optically pumped magnetometers (OPM‐MEG) employs small, lightweight, noncryogenic sensors that provide data with higher sensitivity and spatial resolution, a natural scanning environment (including participant movement), and adaptability to any age. However, OPM‐MEG is new and the optimum way to design a system is unknown. Here, we construct a novel, 90‐channel triaxial OPM‐MEG system and use it to map motor function during a naturalistic handwriting task. Results show that high‐precision magnetic field control reduced background fields to ∼200 pT, enabling free participant movement. Our triaxial array offered twice the total measured signal and better interference rejection compared to a conventional (single‐axis) design. We mapped neural oscillatory activity to the sensorimotor network, demonstrating significant differences in motor network activity and connectivity for left‐handed versus right‐handed handwriting. Repeatability across scans showed that we can map electrophysiological activity with an accuracy ∼4 mm. Overall, our study introduces a novel triaxial OPM‐MEG design and confirms its potential for high‐performance functional neuroimaging.
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Date: 2022-09-05  ·  Issue: 2022  ·  Volume: 1517
A 90‐channel triaxial magnetoencephalography system using optically pumped magnetometers
Contributors: Molly Rea| Elena Boto| Niall Holmes| Ryan Hill| James Osborne| Natalie Rhodes| James Leggett| Lukas Rier| Richard Bowtell| Vishal Shah| Matthew J. Brookes|
Abstract: Magnetoencephalography (MEG) measures the small magnetic fields generated by current flow in neural networks, providing a noninvasive metric of brain function. MEG is well established as a powerful neuroscientific and clinical tool. However, current instrumentation is hampered by cumbersome cryogenic field‐sensing technologies. In contrast, MEG using optically pumped magnetometers (OPM‐MEG) employs small, lightweight, noncryogenic sensors that provide data with higher sensitivity and spatial resolution, a natural scanning environment (including participant movement), and adaptability to any age. However, OPM‐MEG is new and the optimum way to design a system is unknown. Here, we construct a novel, 90‐channel triaxial OPM‐MEG system and use it to map motor function during a naturalistic handwriting task. Results show that high‐precision magnetic field control reduced background fields to ∼200 pT, enabling free participant movement. Our triaxial array offered twice the total measured signal and better interference rejection compared to a conventional (single‐axis) design. We mapped neural oscillatory activity to the sensorimotor network, demonstrating significant differences in motor network activity and connectivity for left‐handed versus right‐handed handwriting. Repeatability across scans showed that we can map electrophysiological activity with an accuracy ∼4 mm. Overall, our study introduces a novel triaxial OPM‐MEG design and confirms its potential for high‐performance functional neuroimaging.
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Date: 2022-09-02  ·  Issue: 2022  ·  Volume: 1517
Drought–heatwave nexus in Brazil and related impacts on health and fires: A comprehensive review
Contributors: Renata Libonati| João L. Geirinhas| Patrícia S. Silva| Djacinto Monteiro dos Santos| Julia A. Rodrigues| Ana Russo| Leonardo F. Peres| Luiza Narcizo| Monique E. R. Gomes| Andreza P. Rodrigues| Carlos C. DaCamara| José Miguel C. Pereira| Ricardo M. Trigo|
Abstract: Climate change is drastically altering the frequency, duration, and severity of compound drought‐heatwave (CDHW) episodes, which present a new challenge in environmental and socioeconomic sectors. These threats are of particular importance in low‐income regions with growing populations, fragile infrastructure, and threatened ecosystems. This review synthesizes emerging progress in the understanding of CDHW patterns in Brazil while providing insights about the impacts on fire occurrence and public health. Evidence is mounting that heatwaves are becoming increasingly linked with droughts in northeastern and southeastern Brazil, the Amazonia, and the Pantanal. In those regions, recent studies have begun to build a better understanding of the physical mechanisms behind CDHW events, such as the soil moisture–atmosphere coupling, promoted by exceptional atmospheric blocking conditions. Results hint at a synergy between CDHW events and high fire activity in the country over the last decades, with the most recent example being the catastrophic 2020 fires in the Pantanal. Moreover, we show that HWs were responsible for increasing mortality and preterm births during record‐breaking droughts in southeastern Brazil. This work paves the way for a more in‐depth understanding on CDHW events and their impacts, which is crucial to enhance the adaptive capacity of different Brazilian sectors.
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Date: 2022-09-02  ·  Issue: 2022  ·  Volume: 1517
Measurement of the neutral axis in avian eggshells reveals which species conform to the golden ratio
Contributors: Valeriy G. Narushin| Alexander W. Griffin| Michael N. Romanov| Darren K. Griffin|
Abstract: Avian eggs represent a striking evolutionary adaptation for which shell thickness is crucial. An understudied eggshell property includes the neutral axis, a line that is drawn through any bent structure and whose precise location is characterized by the k‐factor. Previous studies have established that, for chicken eggs, mean k corresponds to the golden ratio (Φ = 1.618, or 0.618 in its reciprocal form). We hypothesized whether such an arrangement of the neutral axis conforms to the eggshell of any bird or only to eggshells with a certain set of geometric parameters. Implementing a suite of innovative methodological approaches, we investigated variations in k of 435 avian species, exploring which correspond to Φ. We found that mean k is highly variable among birds and does not always conform to Φ, being much lower in spherical and ellipsoid eggs and higher in pyriform eggs. While 21 species had k values within 0.618 ± 0.02 (including four falcon species) and the Falconinae subfamily (six species) revealed a mean of 0.618, it is predominantly domesticated species (chicken, ducks, and geese) that lay eggs whose neutral axis corresponds to the golden ratio. Thus, the study of the mathematical secrets of the eggshell related to the golden ratio of its neutral axis suggests its species‐specific signatures in birds.
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Date: 2022-09-02  ·  Issue: 2022  · 
Drought–heatwave nexus in Brazil and related impacts on health and fires: A comprehensive review
Contributors: Renata Libonati| João L. Geirinhas| Patrícia S. Silva| Djacinto Monteiro dos Santos| Julia A. Rodrigues| Ana Russo| Leonardo F. Peres| Luiza Narcizo| Monique E. R. Gomes| Andreza P. Rodrigues| Carlos C. DaCamara| José Miguel C. Pereira| Ricardo M. Trigo|
Abstract: Climate change is drastically altering the frequency, duration, and severity of compound drought‐heatwave (CDHW) episodes, which present a new challenge in environmental and socioeconomic sectors. These threats are of particular importance in low‐income regions with growing populations, fragile infrastructure, and threatened ecosystems. This review synthesizes emerging progress in the understanding of CDHW patterns in Brazil while providing insights about the impacts on fire occurrence and public health. Evidence is mounting that heatwaves are becoming increasingly linked with droughts in northeastern and southeastern Brazil, the Amazonia, and the Pantanal. In those regions, recent studies have begun to build a better understanding of the physical mechanisms behind CDHW events, such as the soil moisture–atmosphere coupling, promoted by exceptional atmospheric blocking conditions. Results hint at a synergy between CDHW events and high fire activity in the country over the last decades, with the most recent example being the catastrophic 2020 fires in the Pantanal. Moreover, we show that HWs were responsible for increasing mortality and preterm births during record‐breaking droughts in southeastern Brazil. This work paves the way for a more in‐depth understanding on CDHW events and their impacts, which is crucial to enhance the adaptive capacity of different Brazilian sectors.
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Date: 2022-09-02  ·  Issue: 2022  ·  Volume: 1517
Tumor‐induced osteomalacia combined with acromegaly: A case report
Contributors: Xiang Li| Xiaolin Ni| Xiaofeng Chai| Linjie Wang| Yan Jiang| Hongli Jing| Li Huo| Huanwen Wu| Yong Yao| Jin Jin| Bin Feng| Yu Xia| Wei Yu| Yue Chi| Wei Liu| Qianqian Pang| Lijia Cui| Ruizhi Jiajue| Yiyi Gong| Ou Wang| Mei Li| Xiaoping Xing| Weibo Xia|
Abstract: Both acromegaly and tumor‐induced osteomalacia (TIO) are rare diseases caused by an excess hormone secreted by neuroendocrine neoplasms, which are growth hormone (GH) and fibroblast growth factor 23 (FGF23), respectively. GH elevates phosphate reabsorption via the effect of insulin‐like factor 1 (IGF‐1), while FGF23 inhibits phosphate reabsorption and reduces serum phosphate level markedly. A patient who developed a typical acromegaly appearance but was accompanied with height loss and hypophosphatemia for 2 years visited our hospital. Laboratory investigations showed GH and IGF‐1 hypersecretion, as well as hypophosphatemia caused by renal phosphate wasting. Magnetic resonance image revealed a pituitary somatotroph adenoma. Octreoscan scintigraphy also found a causative tumor on the right foot for hypophosphatemia. Then, he underwent resection of the tumor on the right foot. His serum phosphate returned to normal immediately but elevated gradually. Then, we removed the pituitary adenoma of the patient, and the GH and phosphate levels returned to the normal range. Here, we report the first case with acromegaly combined with TIO, the changing process of his phosphate concentration suggests an interesting concurrent effect of excess GH and FGF23 in this rare condition.
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Date: 2022-08-31  ·  Issue: 2022  ·  Volume: 1517
Calcium status assessment at the population level: Candidate approaches and challenges
Contributors: Ziaul H. Rana| Megan W. Bourassa| Filomena Gomes| Anuradha Khadilkar| Rubina Mandlik| Victor Owino| John M. Pettifor| Daniel E. Roth| Julie Shlisky| Prashanth Thankachan| Connie M. Weaver|
Abstract: Inadequate dietary calcium intake is a global public health problem that disproportionately affects low‐ and middle‐income countries. However, the calcium status of a population is challenging to measure, and there are no standard methods to identify high‐risk communities even in settings with an elevated prevalence of a disease caused or exacerbated by low calcium intake (e.g., rickets). The calcium status of a population depends on numerous factors, including intake of calcium‐rich foods; the bioavailability of the types of calcium consumed in foods and supplements; and population characteristics, including age, sex, vitamin D status, and genetic attributes that influence calcium retention and absorption. The aim of this narrative review was to assess candidate indicators of population‐level calcium status based on a range of biomarkers and measurement methods, including dietary assessment, calcium balance studies, hormonal factors related to calcium, and health outcomes associated with low calcium status. Several promising approaches were identified, but there was insufficient evidence of the suitability of any single indicator to assess population calcium status. Further research is required to develop and validate specific indicators of calcium status that could be derived from the analysis of data or samples that are feasibly collected in population‐based surveys.
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Date: 2022-08-29  ·  Issue: 2022  ·  Volume: 1517
The global regulatory framework for the commercialization of nutrient enriched biofortified foods
Contributors: Tora Mitra‐Ganguli| Wolfgang H. Pfeiffer| Jenny Walton|
Abstract: Nutrient enriched crops (NECs) were developed through biofortification as a tool to reach the world's most vulnerable. The delivery model developed by HarvestPlus for the scaling of NECs relies on commercial demand from food businesses and consumers, coupled with the ability to promote and market foods that comply with legislation. This review of standards, regulations, and laws across the value chain in 20 countries demonstrates that existing provisions for food labeling are sufficient to carry out sales and marketing of foods made from conventionally bred NECs. The term biofortification is not necessary to create demand and, potentially, is counterproductive. Promoting the natural source of vitamins and minerals and relevant nutrition claims is the most effective and simple way to signpost healthier products to consumers. Until 2021, it was not possible to distinguish NECs at the grain level from the market standard. The development of a globally relevant Publicly Available Specification allows traders to demand grains that offer a substantial increase in zinc, iron, or vitamin A. Addressing this gap at the grain level ensures that standards and regulations are available end‐to‐end in the food supply chain providing the enabling environment for the rapid scale of NECs.
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Date: 2022-08-29  ·  Issue: 2022  ·  Volume: 1514
Issue Information
Contributors:
Abstract:
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Date: 2022-08-26  ·  Issue: 2022  ·  Volume: 1517
Studying death and near‐death experiences requires neuroscientific expertise
Contributors: Charlotte Martial| Olivia Gosseries| Héléna Cassol| Daniel Kondziella|
Abstract: Parnia et al. recently published suggestions for the study of death and experiences recalled in a near‐death context. We have serious reservations about the authors’ statements. In this commentary, we discuss the omissions and knowledge gaps inherent to the authors’ paper, which among others include incorrect neurological claims about brain death and misunderstandings regarding the terminology of consciousness. Although we believe that (near‐)death research deserves a framework guideline, the paper by Parnia and colleagues is misleading and, contrary to the authors' intention, hinders the scientific understanding of near‐death experiences and the neural mechanisms occurring in the dying brain.
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Date: 2022-08-22  ·  Issue: 2022  · 
Unrecognized role of claudin‐10b in basolateral membrane infoldings of the thick ascending limb
Contributors: Catarina Quintanova| Nina Himmerkus| Samuel L. Svendsen| Otto Schwerdtner| Cosima Merkel| Lennart Pinckert| Kerim Mutig| Tilman Breiderhoff| Dominik Müller| Dorothee Günzel| Markus Bleich|
Abstract: Claudin‐10b is an important component of the tight junction in the thick ascending limb (TAL) of Henle's loop and allows paracellular sodium transport. In immunofluorescence stainings, claudin‐10b–positive cells exhibited extensive extra staining of basolateral, column‐like structures. The precise localization and function have so far remained elusive. In isolated cortical TAL segments from C57BL/6J mice, kidney‐specific claudin‐10 knockout mice (cKO), and respective litter mates (WT), we investigated the localization and protein expression and function by fluorescence microscopy and electrophysiological measurements. Ultrastructural analysis of TAL in kidney sections was performed by electron microscopy. Claudin‐10b colocalized with the basolateral Na+‐K+ ATPase and the Cl– channel subunit barttin, but the lack of claudin‐10b did not influence the localization or abundance of these proteins. However, the accessibility of the basolateral infolded extracellular space to ouabain or fluorescein was increased by basolateral Ca2+ removal and in the absence of claudin‐10b. Ultrastructural analysis by electron microscopy revealed a widening of basolateral membrane infoldings in cKO in comparison to WT. We hypothesize that claudin‐10b shapes neighboring membrane invaginations by trans interaction to stabilize and facilitate high‐flux salt transport in a water‐tight epithelium.
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Date: 2022-08-22  ·  Issue: 2022  ·  Volume: 1517
Claudin targeting as an effective tool for directed barrier modulation of the viable epidermis
Contributors: Laura‐Sophie Beier| Ayk Waldow| Saeed Khomeijani Farahani| Roman Mannweiler| Sabine Vidal‐Y‐Sy| Johanna M. Brandner| Jörg Piontek| Dorothee Günzel|
Abstract: Tight junction (TJ) formation is vital for epidermal barrier function. We aimed to specifically manipulate TJ barriers in the reconstructed human epidermis (RHE) by claudin‐1 and ‐4 knockdown (KD) and by claudin‐binding fusion proteins of glutathione S‐transferase and modified C‐terminal fragments of Clostridium perfringens enterotoxin (GST‐cCPE). Impedance spectroscopy and tracer permeability imaging were employed for functional barrier assessment and investigation of claudin contribution. KD of claudin‐1, but not claudin‐4, impaired the paracellular barrier in vitro. Similarly, claudin‐binding GST‐cCPE variants weakened the paracellular but not the stratum corneum barrier. Combining both TJ targeting methods, we found that claudin‐1 targeting by GST‐cCPE after claudin‐4 KD led to a marked decrease in paracellular barrier properties. Conversely, after claudin‐1 KD, GST‐cCPE did not further impair the barrier. Comparison of GST‐cCPE variants with different claudin‐1/claudin‐4 affinities, NHS‐fluorescein tracer detection, and immunostaining of RHE paraffin sections showed that GST‐cCPE variants bind to extrajunctional claudin‐1 and ‐4, which are differentially distributed along the stratum basale–stratum granulosum axis. GST‐cCPE binding blocks these claudins, thereby specifically opening the paracellular barrier of RHE. The data indicate a critical role for claudin‐1 in regulating paracellular permeability for ions and small molecules in the viable epidermis. Claudin targeting is presented as a proof‐of‐concept for precise barrier modulation.
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Date: 2022-08-22  ·  Issue: 2022  ·  Volume: 1517
Unrecognized role of claudin‐10b in basolateral membrane infoldings of the thick ascending limb
Contributors: Catarina Quintanova| Nina Himmerkus| Samuel L. Svendsen| Otto Schwerdtner| Cosima Merkel| Lennart Pinckert| Kerim Mutig| Tilman Breiderhoff| Dominik Müller| Dorothee Günzel| Markus Bleich|
Abstract: Claudin‐10b is an important component of the tight junction in the thick ascending limb (TAL) of Henle's loop and allows paracellular sodium transport. In immunofluorescence stainings, claudin‐10b–positive cells exhibited extensive extra staining of basolateral, column‐like structures. The precise localization and function have so far remained elusive. In isolated cortical TAL segments from C57BL/6J mice, kidney‐specific claudin‐10 knockout mice (cKO), and respective litter mates (WT), we investigated the localization and protein expression and function by fluorescence microscopy and electrophysiological measurements. Ultrastructural analysis of TAL in kidney sections was performed by electron microscopy. Claudin‐10b colocalized with the basolateral Na+‐K+ ATPase and the Cl– channel subunit barttin, but the lack of claudin‐10b did not influence the localization or abundance of these proteins. However, the accessibility of the basolateral infolded extracellular space to ouabain or fluorescein was increased by basolateral Ca2+ removal and in the absence of claudin‐10b. Ultrastructural analysis by electron microscopy revealed a widening of basolateral membrane infoldings in cKO in comparison to WT. We hypothesize that claudin‐10b shapes neighboring membrane invaginations by trans interaction to stabilize and facilitate high‐flux salt transport in a water‐tight epithelium.
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Date: 2022-08-22  ·  Issue: 2022  · 
Claudin targeting as an effective tool for directed barrier modulation of the viable epidermis
Contributors: Laura‐Sophie Beier| Ayk Waldow| Saeed Khomeijani Farahani| Roman Mannweiler| Sabine Vidal‐Y‐Sy| Johanna M. Brandner| Jörg Piontek| Dorothee Günzel|
Abstract: Tight junction (TJ) formation is vital for epidermal barrier function. We aimed to specifically manipulate TJ barriers in the reconstructed human epidermis (RHE) by claudin‐1 and ‐4 knockdown (KD) and by claudin‐binding fusion proteins of glutathione S‐transferase and modified C‐terminal fragments of Clostridium perfringens enterotoxin (GST‐cCPE). Impedance spectroscopy and tracer permeability imaging were employed for functional barrier assessment and investigation of claudin contribution. KD of claudin‐1, but not claudin‐4, impaired the paracellular barrier in vitro. Similarly, claudin‐binding GST‐cCPE variants weakened the paracellular but not the stratum corneum barrier. Combining both TJ targeting methods, we found that claudin‐1 targeting by GST‐cCPE after claudin‐4 KD led to a marked decrease in paracellular barrier properties. Conversely, after claudin‐1 KD, GST‐cCPE did not further impair the barrier. Comparison of GST‐cCPE variants with different claudin‐1/claudin‐4 affinities, NHS‐fluorescein tracer detection, and immunostaining of RHE paraffin sections showed that GST‐cCPE variants bind to extrajunctional claudin‐1 and ‐4, which are differentially distributed along the stratum basale–stratum granulosum axis. GST‐cCPE binding blocks these claudins, thereby specifically opening the paracellular barrier of RHE. The data indicate a critical role for claudin‐1 in regulating paracellular permeability for ions and small molecules in the viable epidermis. Claudin targeting is presented as a proof‐of‐concept for precise barrier modulation.
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Date: 2022-08-18  ·  Issue: 2022  ·  Volume: 1517
Integrated parent–child music classes for preschoolers with and without autism: Parent expectations and experiences
Contributors: Miriam Lense| Talia Liu| Lauren Booke| Zoe Crawley| Sara Beck|
Abstract: Integrated recreational programs designed to support neurodiverse children and their families are important vehicles for community participation. In this mixed‐methods study, we investigated the mechanisms by which parent–child music classes for autistic and neurotypical children can support community participation. Parents of autistic (n = 33) and typically developing (TD; n = 28) preschoolers were interviewed about their expectations for and experiences of participating in a 12‐week psychoeducational parent–child music program. Parents completed ratings of momentary affect and social connection, and researchers coded children's behavioral engagement during classes at multiple time points throughout the program. Primary motivations for enrolling in an integrated music class included children's interest in music and opportunities for child socialization. Parent‐focused reasons were less frequently endorsed as primary motivations for participation. Yet, momentary ratings indicated that music classes supported parents’ affect regulation and social connection with other parents at the level of individual classes and across the program. These in‐class experiences were echoed by interviews following program completion, which additionally highlighted the use of new parenting strategies through the musical activities. Since parental emotional experiences of activities, supportive community relationships, and parenting confidence are all linked with increased community participation, integrated music classes may support participation and satisfaction with community experiences.
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Date: 2022-08-18  ·  Issue: 2022  ·  Volume: 1517
Do variants in the coding regions of FOXP2, a gene implicated in speech disorder, confer a risk for congenital amusia?
Contributors: Isabelle Peretz| Jay Ross| Cynthia V. Bourassa| Louis‐Philippe Lemieux Perreault| Patrick A. Dion| Michael W. Weiss| Mihaela Felezeu| Guy A. Rouleau| Marie‐Pierre Dubé|
Abstract: Congenital amusia is a lifelong disorder that compromises the normal development of musical abilities in 1.5–4% of the general population. There is a substantial genetic contribution to congenital amusia, and it bears similarities to neurodevelopmental disorders of language. Here, we examine the extent to which variants in the forkhead box P2 gene (FOXP2)—the first gene to be identified as causal in developmental speech deficits—are associated with the amusic trait. Using a cohort of 49 individuals with amusia, of which 27 were unrelated, the role of FOXP2 variants in amusia was evaluated. Fourteen variants were examined in the cohort. None segregated with the amusic trait among participants for whom family information was available; nor were they predicted to be deleterious to protein function. Thus, variants in FOXP2 are not likely to cause amusia. Implications for ongoing debates about the distinction between musicality and language are discussed.
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Date: 2022-08-18  ·  Issue: 2022  · 
Integrated parent–child music classes for preschoolers with and without autism: Parent expectations and experiences
Contributors: Miriam Lense| Talia Liu| Lauren Booke| Zoe Crawley| Sara Beck|
Abstract: Integrated recreational programs designed to support neurodiverse children and their families are important vehicles for community participation. In this mixed‐methods study, we investigated the mechanisms by which parent–child music classes for autistic and neurotypical children can support community participation. Parents of autistic (n = 33) and typically developing (TD; n = 28) preschoolers were interviewed about their expectations for and experiences of participating in a 12‐week psychoeducational parent–child music program. Parents completed ratings of momentary affect and social connection, and researchers coded children's behavioral engagement during classes at multiple time points throughout the program. Primary motivations for enrolling in an integrated music class included children's interest in music and opportunities for child socialization. Parent‐focused reasons were less frequently endorsed as primary motivations for participation. Yet, momentary ratings indicated that music classes supported parents’ affect regulation and social connection with other parents at the level of individual classes and across the program. These in‐class experiences were echoed by interviews following program completion, which additionally highlighted the use of new parenting strategies through the musical activities. Since parental emotional experiences of activities, supportive community relationships, and parenting confidence are all linked with increased community participation, integrated music classes may support participation and satisfaction with community experiences.
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Date: 2022-08-17  ·  Issue: 2022  ·  Volume: 1517
Recent advancements for tropical cyclone data assimilation
Contributors: Hui Christophersen| Jason Sippel| Altug Aksoy| Nancy L. Baker|
Abstract: In this review, data assimilation (DA) techniques used for tropical cyclones (TCs) are briefly overviewed. The strength and weakness of variational methods, ensemble methods, hybrid methods, and particle filter methods are also discussed. Several global numerical weather prediction models and their corresponding DA systems frequently used for TC forecasting and verification are described first. The DA research and development efforts in the operational regional model from the National Centers for Environmental Prediction's Hurricane Weather Research and Forecasting are then discussed in greater detail. Focused remarks on TC observations from reconnaissance, ground‐based radar, enhanced satellite‐derived atmospheric motion vectors and all‐sky satellite radiances and their impacts on TC analyses and forecasts are addressed. Recent TC DA advancements and challenges on better use of observations and more advanced DA methods for TC application are also briefly reviewed.
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Date: 2022-08-17  ·  Issue: 2022  ·  Volume: 1517
Associations between red blood cell indices and iron status and neurocognitive function in young adults: Evidence from memory and executive function tests and event‐related potentials
Contributors: Sivan Raz| Ariel Koren| Carina Levin|
Abstract: Cognitive impairment has been associated with anemia and iron deficiency; however, brain electrophysiological studies correlating red blood cell (RBC) indices and iron status to cognition in adulthood are scarce. We aimed to assess neurocognitive function in young adults of the general population and its correlation with RBC indices and iron status. Neurocognitive function was investigated using scalp‐recorded event‐related potentials (ERPs) within the context of a task‐switching paradigm. ERPs and test performance were also compared across groups of “high”/“low” RBC and iron indices. Working memory was examined using the digit span test, in which mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), and ferritin were found to be significant predictors of test performance, with higher MCH/MCV/ferritin being associated with better test scores. In the switching task, MCH, MCV, and ferritin were found to be significant predictors of task performance, with higher MCH/MCV/ferritin levels associated with a lower percentage of errors. Electrophysiological results showed that MCH and MCV were significant predictors of ERPs amplitude, with lower MCH/MCV levels associated with greater amplitude, which may reflect compensatory processes. P1, N1, P2, and P3 were greater for the low MCH/MCV groups. This is the first evidence of association between levels of MCH/MCV and brain function while engaged in an executive function task; possibly reflecting brain iron availability.
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Date: 2022-08-17  ·  Issue: 2022  ·  Volume: 1517
Autistic traits heighten sensitivity to rejection‐induced social pain
Contributors: Xinxin Lin| Shiwei Zhuo| Zhouan Liu| Junsong Fan| Weiwei Peng|
Abstract: Autistic traits—subclinical forms of characteristics associated with autism spectrum disorders—are associated with poor social interactions and high risks for mental health disorders. We hypothesized that altered sensitivity to social rejection is an important contributor to psychological distress observed among individuals with high autistic traits. Experiment 1 adopted a social‐judgment task and compared behavioral and neural activity in response to social rejection between participants exhibiting either high or low autistic traits (HAT and LAT, respectively). Rejection‐induced hurt feelings, P3 amplitudes, and θ‐oscillation magnitudes were greater in the HAT group than in the LAT group. Mediation analysis indicated that autistic traits heighten rejection‐induced social pain through increasing frontal‐midline θ‐oscillations. Responses to nonsocial feedback in the age‐judgment task were comparable, confirming that the between‐group differences were specific to social negative feedback. Experiment 2 assessed the association between autistic traits, rejection sensitivity, and psychological distress among randomly recruited participants. Results showed that autistic traits affected depressive/anxious symptomatology partially through heightened rejection sensitivity. Therefore, autistic traits heighten sensitivity to rejection‐induced social pain that leads to psychological distress. This finding will help facilitate the development of strategies for coping with social pain and improving mental health for individuals with high autistic traits.
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Date: 2022-08-17  ·  Issue: 2022  · 
Rhythmic serious games as an inclusive tool for music‐based interventions
Contributors: Simone Dalla Bella|
Abstract: Technologies, such as mobile devices or sets of connected sensors, provide new and engaging opportunities to devise music‐based interventions. Among the different technological options, serious games offer a valuable alternative. Serious games can engage multisensory processes, creating a rich, rewarding, and motivating rehabilitation setting. Moreover, they can be targeted to specific musical features, such as pitch production or synchronization to a beat. Because serious games are typically low cost and enjoy wide access, they are inclusive tools perfectly suited for remote at‐home interventions using music in various patient populations and environments. The focus of this article is in particular on the use of rhythmic serious games for training auditory–motor synchronization. After reviewing the existing rhythmic games, initial evidence from a recent proof‐of‐concept study in Parkinson's disease is provided. It is shown that rhythmic video games using finger tapping can be used with success as an at‐home protocol, and bring about beneficial effects on motor performance in patients. The use and benefits of rhythmic serious games can extend beyond the rehabilitation of patients with movement disorders, such as to neurodevelopmental disorders, including dyslexia and autism spectrum disorder.
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Date: 2022-08-17  ·  Issue: 2022  ·  Volume: 1517
Rhythmic serious games as an inclusive tool for music‐based interventions
Contributors: Simone Dalla Bella|
Abstract: Technologies, such as mobile devices or sets of connected sensors, provide new and engaging opportunities to devise music‐based interventions. Among the different technological options, serious games offer a valuable alternative. Serious games can engage multisensory processes, creating a rich, rewarding, and motivating rehabilitation setting. Moreover, they can be targeted to specific musical features, such as pitch production or synchronization to a beat. Because serious games are typically low cost and enjoy wide access, they are inclusive tools perfectly suited for remote at‐home interventions using music in various patient populations and environments. The focus of this article is in particular on the use of rhythmic serious games for training auditory–motor synchronization. After reviewing the existing rhythmic games, initial evidence from a recent proof‐of‐concept study in Parkinson's disease is provided. It is shown that rhythmic video games using finger tapping can be used with success as an at‐home protocol, and bring about beneficial effects on motor performance in patients. The use and benefits of rhythmic serious games can extend beyond the rehabilitation of patients with movement disorders, such as to neurodevelopmental disorders, including dyslexia and autism spectrum disorder.
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Date: 2022-08-09  ·  Issue: 2022  ·  Volume: 1516
Tight junction formation by a claudin mutant lacking the COOH‐terminal PDZ domain‐binding motif
Contributors: Sachiko Fujiwara| Thanh Phuong Nguyen| Kyoko Furuse| Yugo Fukazawa| Tetsuhisa Otani| Mikio Furuse|
Abstract: Claudin‐based tight junctions (TJs) are formed at the most apical part of cell–cell contacts in epithelial cells. Previous studies suggest that scaffolding proteins ZO‐1 and ZO‐2 (ZO proteins) determine the location of TJs by interacting with claudins, but this idea is not conclusive. To address the role of the ZO proteins binding to claudins at TJs, a COOH‐terminal PDZ domain binding motif‐deleted claudin‐3 mutant, which lacks the ZO protein binding, was stably expressed in claudin‐deficient MDCK cells. The COOH‐terminus‐deleted claudin‐3 was localized at the apicolateral region similar to full‐length claudin‐3. Consistently, freeze‐fracture electron microscopy revealed that the COOH‐terminus‐deleted claudin‐3‐expressing cells reconstituted belts of TJs at the most apical region of the lateral membrane and restored functional epithelial barriers. These results suggest that the interaction of claudins with ZO proteins is not a prerequisite for TJ formation at the most apical part of cell–cell contacts.
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Date: 2022-08-02  ·  Issue: 2022  ·  Volume: 1516
PGC‐1 alpha regulates mitochondrial biogenesis to ameliorate hypoxia‐inhibited cementoblast mineralization
Contributors: Huiyi Wang| Xiaoxuan Wang| Li Ma| Xin Huang| Yan Peng| Hantao Huang| Xudong Gao| Yuan Chen| Zhengguo Cao|
Abstract: Hypoxia often occurs in inflammatory tissues, such as tissues affected by periodontitis and apical periodontitis lesions. Mitochondrial biogenesis can be disrupted in hypoxia. Peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (PGC‐1α) is a core factor required for mitochondrial biogenesis. Cementoblasts are root surface lining cells that play an integral role in cementum formation. There is a dearth of research on the effect of hypoxia on cementoblasts and underlying mechanisms, particularly in relation to mitochondrial biogenesis during the hypoxic process. In this study, we found that the expression of hypoxia inducible factor‐1α was elevated in apical periodontitis tissues in vivo. In contrast, periapical lesions exhibited a reduction of PGC‐1α expression. For in vitro experiments, cobalt chloride (CoCl2) was used to induce hypoxia. We observed that CoCl2‐induced hypoxia suppressed the mineralization ability and mitochondrial biogenesis of cementoblasts, accompanied by abnormal mitochondria morphology. Furthermore, we found that CoCl2 blocked the p38 pathway, while it activated the Erk1/2 pathway, with the former upregulating the expression of PGC‐1α, while the latter reversed the effects. Overall, our findings demonstrate that mitochondrial biogenesis, especially via PGC‐1α, is impaired during cementogenesis in the context of CoCl2‐induced hypoxia, dependent on the mitogen‐activated protein kinase signaling pathway.
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Date: 2022-08-02  ·  Issue: 2022  · 
Melodic Intonation Therapy for aphasia: A multi‐level meta‐analysis of randomized controlled trials and individual participant data
Contributors: Tudor Popescu| Benjamin Stahl| Brenton M. Wiernik| Felix Haiduk| Michaela Zemanek| Hannah Helm| Theresa Matzinger| Roland Beisteiner| W. Tecumseh Fitch|
Abstract: Melodic Intonation Therapy (MIT) is a prominent rehabilitation program for individuals with post‐stroke aphasia. Our meta‐analysis investigated the efficacy of MIT while considering quality of outcomes, experimental design, influence of spontaneous recovery, MIT protocol variant, and level of generalization. Extensive literature search identified 606 studies in major databases and trial registers; of those, 22 studies—overall 129 participants—met all eligibility criteria. Multi‐level mixed‐ and random‐effects models served to separately meta‐analyze randomized controlled trial (RCT) and non‐RCT data. RCT evidence on validated outcomes revealed a small‐to‐moderate standardized effect in noncommunicative language expression for MIT—with substantial uncertainty. Unvalidated outcomes attenuated MIT's effect size compared to validated tests. MIT's effect size was 5.7 times larger for non‐RCT data compared to RCT data (g̅case report = 2.01 vs. g̅RCT = 0.35 for validated Non‐Communicative Language Expression measures). Effect size for non‐RCT data decreased with number of months post‐stroke, suggesting confound through spontaneous recovery. Deviation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression, such as everyday communication ability. Our results confirm the promising role of MIT in improving trained and untrained performance on unvalidated outcomes, alongside validated repetition tasks, and highlight possible limitations in promoting everyday communication ability.
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Date: 2022-08-02  ·  Issue: 2022  ·  Volume: 1516
Melodic Intonation Therapy for aphasia: A multi‐level meta‐analysis of randomized controlled trials and individual participant data
Contributors: Tudor Popescu| Benjamin Stahl| Brenton M. Wiernik| Felix Haiduk| Michaela Zemanek| Hannah Helm| Theresa Matzinger| Roland Beisteiner| W. Tecumseh Fitch|
Abstract: Melodic Intonation Therapy (MIT) is a prominent rehabilitation program for individuals with post‐stroke aphasia. Our meta‐analysis investigated the efficacy of MIT while considering quality of outcomes, experimental design, influence of spontaneous recovery, MIT protocol variant, and level of generalization. Extensive literature search identified 606 studies in major databases and trial registers; of those, 22 studies—overall 129 participants—met all eligibility criteria. Multi‐level mixed‐ and random‐effects models served to separately meta‐analyze randomized controlled trial (RCT) and non‐RCT data. RCT evidence on validated outcomes revealed a small‐to‐moderate standardized effect in noncommunicative language expression for MIT—with substantial uncertainty. Unvalidated outcomes attenuated MIT's effect size compared to validated tests. MIT's effect size was 5.7 times larger for non‐RCT data compared to RCT data (g̅case report = 2.01 vs. g̅RCT = 0.35 for validated Non‐Communicative Language Expression measures). Effect size for non‐RCT data decreased with number of months post‐stroke, suggesting confound through spontaneous recovery. Deviation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression, such as everyday communication ability. Our results confirm the promising role of MIT in improving trained and untrained performance on unvalidated outcomes, alongside validated repetition tasks, and highlight possible limitations in promoting everyday communication ability.
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Date: 2022-07-27  ·  Issue: 2022  ·  Volume: 1516
Multimodal music training enhances executive functions in children: Results of a randomized controlled trial
Contributors: Jennifer A. Bugos| Darlene DeMarie| Christina Stokes| Lindsay P. Power|
Abstract: Music training programs have shown mixed results on children's executive functions. The purpose of the present study was to evaluate the impact of a 10‐week multimodal music program with vocal development, bimanual coordination, and musical improvisation, on children's executive functions. We hypothesized that a 10‐week music program would enhance executive functions in working memory in 4‐ to 6‐year‐old children. Eighty‐four children were randomly assigned to a multimodal music program, an active control Lego program, or no treatment control condition (i.e., randomized controlled design). All children completed measures of music aptitude, music achievement, and executive functions (i.e., EF Touch) pre‐ and post‐training. Results revealed enhanced pitch accuracy and working memory for children in the music training group as compared to the other conditions. Children in the Lego condition demonstrated significant enhancements of spatial working memory. Tonal music aptitude significantly predicted performance on measures of working memory. Contributions to the literature include the randomized controlled design, group multimodal music program appropriate for 4‐ to 6‐year‐old children, and the use of executive function measures sensitive to individual differences.
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Date: 2022-07-27  ·  Issue: 2022  · 
Multimodal music training enhances executive functions in children: Results of a randomized controlled trial
Contributors: Jennifer A. Bugos| Darlene DeMarie| Christina Stokes| Lindsay P. Power|
Abstract: Music training programs have shown mixed results on children's executive functions. The purpose of the present study was to evaluate the impact of a 10‐week multimodal music program with vocal development, bimanual coordination, and musical improvisation, on children's executive functions. We hypothesized that a 10‐week music program would enhance executive functions in working memory in 4‐ to 6‐year‐old children. Eighty‐four children were randomly assigned to a multimodal music program, an active control Lego program, or no treatment control condition (i.e., randomized controlled design). All children completed measures of music aptitude, music achievement, and executive functions (i.e., EF Touch) pre‐ and post‐training. Results revealed enhanced pitch accuracy and working memory for children in the music training group as compared to the other conditions. Children in the Lego condition demonstrated significant enhancements of spatial working memory. Tonal music aptitude significantly predicted performance on measures of working memory. Contributions to the literature include the randomized controlled design, group multimodal music program appropriate for 4‐ to 6‐year‐old children, and the use of executive function measures sensitive to individual differences.
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Date: 2022-07-27  ·  Issue: 2022  ·  Volume: 1516
Personality traits modulate the neural responses to handwriting processing
Contributors: Yang Yang| Junjun Li| Jun Zhang| Ke Zhou| Henry S. R. Kao| Hong‐Yan Bi| Min Xu|
Abstract: Handwriting is a vital skill for everyday human activities. It has a wealth of information about writers’ characteristics and can hint toward underlying neurological conditions, such as Parkinson's disease, autism, dyslexia, and attention‐deficit/hyperactivity disorder (ADHD). Many previous studies have reported a link between personality and individual differences in handwriting, but the evidence for the relationship tends to be anecdotal in nature. Using functional magnetic resonance imaging (fMRI), we examined whether the association between personality traits and handwriting was instantiated at the neural level. Results showed that the personality trait of conscientiousness modulated brain activation in the left premotor cortex and right inferior/middle frontal gyrus, which may reflect the impact of personality on orthography‐to‐grapheme transformation and executive control involved in handwriting. Such correlations were not observed in symbol‐drawing or word‐reading tasks, suggesting the specificity of the link between conscientiousness and handwriting in these regions. Moreover, using a connectome‐based predictive modeling approach, we found that individuals’ conscientiousness scores could be predicted based on handwriting‐related functional brain networks, suggesting that the influence of personality on handwriting may occur within a broader network. Our findings provide neural evidence for the link between personality and handwriting processing, extending our understanding of the nature of individual differences in handwriting.
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Date: 2022-07-26  ·  Issue: 2022  · 
Unraveling the intestinal epithelial barrier in cyanotoxin microcystin‐treated Caco‐2 cell monolayers
Contributors: Jan‐Leo Kaak| Fábia D. Lobo de Sá| Jerrold R. Turner| Jörg‐Dieter Schulzke| Roland Bücker|
Abstract: Microcystin is a widespread cyanobacterial toxin that affects the intestine to produce diarrheal symptoms after ingestion of freshwater blue‐green algae. Our study aimed to characterize the mechanism by which the toxin leads to diarrhea via epithelial barrier dysfunction in a small intestine Caco‐2 cell model. Microcystin‐treated human Caco‐2 epithelial monolayers were functionally and molecularly analyzed for barrier dysfunction. Tight junctions (TJs) and cell damage were analyzed in relation to transepithelial electrical resistance (TER) changes. TER of microcystin‐treated Caco‐2 cells was reduced by 65% of the initial value after 24 h; concomitantly, permeability for fluorescein increased 2.6‐fold. Western blot analysis showed reduced claudin‐1 expression, while expression of claudin‐3 and ‐4 remained unchanged. Super‐resolution stimulated emission depletion microscopy revealed that TJ integrity was compromised by fraying and splitting of the TJ domain of the epithelial cells. Epithelial apoptosis did not significantly contribute to epithelial barrier dysfunction, while cytoskeletal actomyosin constriction was associated with TJ disintegration and the barrier defect. Our results indicate that microcystin causes intestinal barrier leakiness, which helps to explain the leak flux type of diarrhea as the main pathomechanism after ingestion of cyanobacterial toxin.
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Date: 2022-07-26  ·  Issue: 2022  ·  Volume: 1516
Herbivores in Arctic ecosystems: Effects of climate change and implications for carbon and nutrient cycling
Contributors: Amanda M. Koltz| Laura Gough| Jennie R. McLaren|
Abstract: Arctic terrestrial herbivores influence tundra carbon and nutrient dynamics through their consumption of resources, waste production, and habitat‐modifying behaviors. The strength of these effects is likely to change spatially and temporally as climate change drives shifts in herbivore abundance, distribution, and activity timing. Here, we review how herbivores influence tundra carbon and nutrient dynamics through their consumptive and nonconsumptive effects. We also present evidence for herbivore responses to climate change and discuss how these responses may alter the spatial and temporal distribution of herbivore impacts. Several current knowledge gaps limit our understanding of the changing functional roles of herbivores; these include limited characterization of the spatial and temporal variability in herbivore impacts and of how herbivore activities influence the cycling of elements beyond carbon. We conclude by highlighting approaches that will promote better understanding of herbivore effects on tundra ecosystems, including their integration into existing biogeochemical models, new applications of remote sensing techniques, and the continued use of distributed experiments.
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Date: 2022-07-26  ·  Issue: 2022  · 
Herbivores in Arctic ecosystems: Effects of climate change and implications for carbon and nutrient cycling
Contributors: Amanda M. Koltz| Laura Gough| Jennie R. McLaren|
Abstract: Arctic terrestrial herbivores influence tundra carbon and nutrient dynamics through their consumption of resources, waste production, and habitat‐modifying behaviors. The strength of these effects is likely to change spatially and temporally as climate change drives shifts in herbivore abundance, distribution, and activity timing. Here, we review how herbivores influence tundra carbon and nutrient dynamics through their consumptive and nonconsumptive effects. We also present evidence for herbivore responses to climate change and discuss how these responses may alter the spatial and temporal distribution of herbivore impacts. Several current knowledge gaps limit our understanding of the changing functional roles of herbivores; these include limited characterization of the spatial and temporal variability in herbivore impacts and of how herbivore activities influence the cycling of elements beyond carbon. We conclude by highlighting approaches that will promote better understanding of herbivore effects on tundra ecosystems, including their integration into existing biogeochemical models, new applications of remote sensing techniques, and the continued use of distributed experiments.
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Date: 2022-07-26  ·  Issue: 2022  ·  Volume: 1516
Unraveling the intestinal epithelial barrier in cyanotoxin microcystin‐treated Caco‐2 cell monolayers
Contributors: Jan‐Leo Kaak| Fábia D. Lobo de Sá| Jerrold R. Turner| Jörg‐Dieter Schulzke| Roland Bücker|
Abstract: Microcystin is a widespread cyanobacterial toxin that affects the intestine to produce diarrheal symptoms after ingestion of freshwater blue‐green algae. Our study aimed to characterize the mechanism by which the toxin leads to diarrhea via epithelial barrier dysfunction in a small intestine Caco‐2 cell model. Microcystin‐treated human Caco‐2 epithelial monolayers were functionally and molecularly analyzed for barrier dysfunction. Tight junctions (TJs) and cell damage were analyzed in relation to transepithelial electrical resistance (TER) changes. TER of microcystin‐treated Caco‐2 cells was reduced by 65% of the initial value after 24 h; concomitantly, permeability for fluorescein increased 2.6‐fold. Western blot analysis showed reduced claudin‐1 expression, while expression of claudin‐3 and ‐4 remained unchanged. Super‐resolution stimulated emission depletion microscopy revealed that TJ integrity was compromised by fraying and splitting of the TJ domain of the epithelial cells. Epithelial apoptosis did not significantly contribute to epithelial barrier dysfunction, while cytoskeletal actomyosin constriction was associated with TJ disintegration and the barrier defect. Our results indicate that microcystin causes intestinal barrier leakiness, which helps to explain the leak flux type of diarrhea as the main pathomechanism after ingestion of cyanobacterial toxin.
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Date: 2022-07-25  ·  Issue: 2022  ·  Volume: 1516
Memory modulations through musical pleasure
Contributors: Laura Ferreri| Antoni Rodriguez‐Fornells|
Abstract: Music, thanks to its strong evocative power, is considered a powerful mnemonic tool for both normal and clinical populations. However, the mechanisms underpinning the music‐driven benefits on memory remain unclear. In memory research, reward dopaminergic signals have been highlighted as a major modulator of memory traces consolidation. Over the last years, via behavioral and pharmacological approaches, we have investigated the hypothesis that dopaminergic‐dependent musical pleasure is a crucial mechanism underpinning music‐driven memory benefits. Our results show that the pleasure felt during music listening, modulated by both the dopaminergic transmission and participants’ sensitivity to music reward, can increase episodic memory performance for the music itself as well as for nonmusical‐associated information. In this commentary paper, we aim to review the main findings obtained from three different studies, in order to discuss current advances and future directions in this research area.
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Date: 2022-07-25  ·  Issue: 2022  · 
Memory modulations through musical pleasure
Contributors: Laura Ferreri| Antoni Rodriguez‐Fornells|
Abstract: Music, thanks to its strong evocative power, is considered a powerful mnemonic tool for both normal and clinical populations. However, the mechanisms underpinning the music‐driven benefits on memory remain unclear. In memory research, reward dopaminergic signals have been highlighted as a major modulator of memory traces consolidation. Over the last years, via behavioral and pharmacological approaches, we have investigated the hypothesis that dopaminergic‐dependent musical pleasure is a crucial mechanism underpinning music‐driven memory benefits. Our results show that the pleasure felt during music listening, modulated by both the dopaminergic transmission and participants’ sensitivity to music reward, can increase episodic memory performance for the music itself as well as for nonmusical‐associated information. In this commentary paper, we aim to review the main findings obtained from three different studies, in order to discuss current advances and future directions in this research area.
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Date: 2022-07-25  ·  Issue: 2022  ·  Volume: 1516
‘biogeom’: An R package for simulating and fitting natural shapes
Contributors: Peijian Shi| Johan Gielis| Brady K. Quinn| Karl J. Niklas| David A. Ratkowsky| Julian Schrader| Honghua Ruan| Lin Wang| Ülo Niinemets|
Abstract: Many natural objects exhibit radial or axial symmetry in a single plane. However, a universal tool for simulating and fitting the shapes of such objects is lacking. Herein, we present an R package called ‘biogeom’ that simulates and fits many shapes found in nature. The package incorporates novel universal parametric equations that generate the profiles of bird eggs, flowers, linear and lanceolate leaves, seeds, starfish, and tree‐rings, and three growth‐rate equations that generate the profiles of ovate leaves and the ontogenetic growth curves of animals and plants. ‘biogeom’ includes several empirical datasets comprising the boundary coordinates of bird eggs, fruits, lanceolate and ovate leaves, tree rings, seeds, and sea stars. The package can also be applied to other kinds of natural shapes similar to those in the datasets. In addition, the package includes sigmoid curves derived from the three growth‐rate equations, which can be used to model animal and plant growth trajectories and predict the times associated with maximum growth rate. ‘biogeom’ can quantify the intra‐ or interspecific similarity of natural outlines, and it provides quantitative information of shape and ontogenetic modification of shape with important ecological and evolutionary implications for the growth and form of the living world.
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Date: 2022-07-19  ·  Issue: 2022  ·  Volume: 1516
Music training modulates theta brain oscillations associated with response suppression
Contributors: Jing Lu| Aline Moussard| Sijia Guo| Yunjo Lee| Gavin M. Bidelman| Sylvain Moreno| Cassandra Skrotzki| Jennifer Bugos| Dawei Shen| Dezhong Yao| Claude Alain|
Abstract: There is growing interest in developing training programs to mitigate cognitive decline associated with normal aging. Here, we assessed the effect of 3‐month music and visual art training programs on the oscillatory brain activity of older adults using a partially randomized intervention design. High‐density electroencephalography (EEG) was measured during the pre‐ and post‐training sessions while participants completed a visual GoNoGo task. Time‐frequency representations were calculated in regions of interest encompassing the visual, parietal, and prefrontal cortices. Before training, NoGo trials generated greater theta power than Go trials from 300 to 500 ms post‐stimulus in mid‐central and frontal brain areas. Theta power indexing response suppression was significantly reduced after music training. There was no significant difference between pre‐ and post‐test for the visual art or the control group. The effect of music training on theta power indexing response suppression was associated with reduced functional connectivity between prefrontal, visual, and auditory regions. These results suggest that theta power indexes executive control mechanisms in older adults. Music training affects theta power and functional connectivity associated with response suppression. These findings contribute to a better understanding of inhibitory control ability in older adults and the neuroplastic effects of music interventions.
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Date: 2022-07-19  ·  Issue: 2022  ·  Volume: 1516
Identification by RNA‐Seq of let‐7 clusters as prenatal biomarkers for nonsyndromic cleft lip with palate
Contributors: Shanshan Jia| Qiang Zhang| Yu Wang| Xiaowei Wei| Hui Gu| Dan Liu| Wei Ma| Yiwen He| Wenting Luo| Zhengwei Yuan|
Abstract: Nonsyndromic cleft lip with palate (nsCLP) is a common congenital malformation; however, early prenatal diagnosis is challenging and pathogenesis remains unclear. The purpose of this study was to determine the diagnostic potential of miRNAs in plasma‐derived exosomes and whole plasma of pregnant women to identify nsCLP and an underlying mechanism. Combined RNA sequencing analysis was performed on samples from plasma exosomes and whole plasma of pregnant women carrying normal fetuses or fetuses with nsCLP in an ongoing birth cohort, in addition to lip samples from nsCLP fetuses and healthy controls. Eight let‐7 cluster miRNAs (hsa‐let‐7a‐3p, hsa‐let‐7a‐5p, hsa‐let‐7c‐5p, hsa‐let‐7d‐3p, hsa‐let‐7d‐5p, hsa‐let‐7e‐5p, hsa‐let‐7f‐5p, and hsa‐miR‐98‐5p) in plasma exosomes from pregnant women provided higher sensitivity/specificity for diagnosing fetal nsCLP than those in plasma. Area under the receiver operating characteristic curve value of the eight miRNAs from plasma exosomes was 0.992. Among them, hsa‐let‐7a‐3p showed better diagnostic capability and was downregulated in nsCLP fetal lip tissues. Upstream and downstream target genes of hsa‐let‐7a‐3p were screened and confirmed. Our work highlights the potential clinical application value of let‐7 clusters in predicting nsCLP and associates as a new regulatory axis (EN2–LIN28A–hsa‐let‐7a‐3p–HHIP–GLI2) with human nsCLP pathogenesis.
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Date: 2022-07-19  ·  Issue: 2022  · 
Music training modulates theta brain oscillations associated with response suppression
Contributors: Jing Lu| Aline Moussard| Sijia Guo| Yunjo Lee| Gavin M. Bidelman| Sylvain Moreno| Cassandra Skrotzki| Jennifer Bugos| Dawei Shen| Dezhong Yao| Claude Alain|
Abstract: There is growing interest in developing training programs to mitigate cognitive decline associated with normal aging. Here, we assessed the effect of 3‐month music and visual art training programs on the oscillatory brain activity of older adults using a partially randomized intervention design. High‐density electroencephalography (EEG) was measured during the pre‐ and post‐training sessions while participants completed a visual GoNoGo task. Time‐frequency representations were calculated in regions of interest encompassing the visual, parietal, and prefrontal cortices. Before training, NoGo trials generated greater theta power than Go trials from 300 to 500 ms post‐stimulus in mid‐central and frontal brain areas. Theta power indexing response suppression was significantly reduced after music training. There was no significant difference between pre‐ and post‐test for the visual art or the control group. The effect of music training on theta power indexing response suppression was associated with reduced functional connectivity between prefrontal, visual, and auditory regions. These results suggest that theta power indexes executive control mechanisms in older adults. Music training affects theta power and functional connectivity associated with response suppression. These findings contribute to a better understanding of inhibitory control ability in older adults and the neuroplastic effects of music interventions.
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Date: 2022-07-18  ·  Issue: 2022  ·  Volume: 1516
The promise of music therapy for Alzheimer's disease: A review
Contributors: Anna Maria Matziorinis| Stefan Koelsch|
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with cognitive decline. Memory problems are typically among the first signs of cognitive impairment in AD, and they worsen considerably as the disease progresses. However, musical memory is partially spared in patients with AD, despite severe deficits in episodic (and partly semantic) memory. AD patients can learn new songs, encode novel verbal information, and react emotionally to music. These effects of music have encouraged the use and development of music therapy (MT) for AD management. MT is easy to implement and well‐tolerated by most patients and their caregivers. Effects of MT in patients with AD include improved mood, reduced depressive scores and trait anxiety, enhanced autobiographical recall, verbal fluency, and cognition. Here, we review musical memory in AD, therapeutic effects of studies using MT on AD, and potential mechanisms underlying those therapeutic effects. We argue that, because AD begins decades before the presentation of clinical symptoms, music interventions might be a promising means to delay and decelerate the neurodegeneration in individuals at risk for AD, such as individuals with genetic risk or subjective cognitive decline.
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Date: 2022-07-12  ·  Issue: 2022  ·  Volume: 1516
Nanoarchitecture and molecular interactions of epithelial cell junction proteins revealed by super‐resolution microscopy
Contributors: Amna N. Naser| William Guiler| Qun Lu| Yan‐Hua Chen|
Abstract: Epithelial cells are polarized with defined apical tight junctions (TJs), lateral adherens junctions (AJs), and basal integrin–matrix interactions. However, it is increasingly recognized that resident cell junction proteins can be found in varying locations and with previously unrecognized functions. Our study here presents the nanoarchitecture and nanocolocalization of cell junction proteins in culture and tissue by stochastic optical reconstruction microscopy (STORM). The Z‐axial view of noncancerous MDCK‐II and PZ‐HPV‐7 cell–cell junctions resolved β‐catenin and p120ctn localizations to TJs and AJs, with p120ctn apical to β‐catenin and colocalizing with TJ protein claudin‐7. More basally, p120ctn and β‐catenin become colocalized. This topography was lost in isogenic Ras‐transformed MDCK cells and cancerous PC3 cells, where p120ctn becomes basally localized in relation to β‐catenin. Claudin‐7 gene conditional knockout (cKO) in mice also have altered polarity of p120ctn relative to β‐catenin, like that seen in normal‐to‐cancer cell phenotypic transformation. Additionally, claudin‐7 cKO resulted in redistribution and relocalization of other cell junction proteins, including claudin‐1, zonula occludens‐1, integrin α2, epithelial cell adhesion molecule, and focal adhesion kinase (FAK); specifically, integrin α2 and FAK were observed at the apical–lateral compartment. Our data show that STORM reveals regional cellular junction nanoarchitecture previously uncharacterized, providing new insight into potential trans‐compartmental modulation of protein functions.
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Date: 2022-07-12  ·  Issue: 2022  · 
Creating a shared musical interpretation: Changes in coordination dynamics while learning unfamiliar music together
Contributors: Emily A. Wood| Andrew Chang| Dan Bosnyak| Lucas Klein| Elger Baraku| Dobromir Dotov| Laurel J. Trainor|
Abstract: The ability to coordinate with others is fundamental for humans to achieve shared goals. Often, harmonious interpersonal coordination requires learning, such as ensemble musicians rehearing together to synchronize their low‐level timing and high‐level aesthetic musical expressions. We investigated how the coordination dynamics of a professional string quartet changed as they learned unfamiliar pieces together across eight trials. During all trials, we recorded each musician's body sway motion data, and quantified the group's body sway similarity (cross‐correlation) and information flow (Granger causality) on each trial. In line with our hypothesis, group similarity increased, while group information flow decreased significantly across trials. In addition, there was a trend such that group similarity, but not information flow, was related to the quality of the performances. As the ensemble converged on a joint interpretation through rehearsing, their body sways reflected the change from interpersonal information flow for coordinative mutual adaptations and corrections, to synchronous musical coordination made possible by the musicians learning a common internally based expressive interpretation.
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Date: 2022-07-12  ·  Issue: 2022  ·  Volume: 1516
Fumarate hydratase gene germline variants and mosaicism associated with pheochromocytoma and paraganglioma
Contributors: Xiaosen Ma| Yunying Cui| Yinjie Gao| Xuebin Zhang| Min Nie| Anli Tong|
Abstract: Fumarate hydratase (FH) catalyzes the conversion of fumaric acid to L‐malic acid. Heterozygous variants of the human fumarate hydratase gene (FH) predispose to hereditary leiomyomatosis and renal cell cancer and, rarely, pheochromocytoma/paraganglioma (PPGL). No mosaic variant in FH has been reported yet. Using next‐generation sequencing, five individuals with FH variants were found in 319 PPGL patients. Immunohistochemistry staining and loss of heterozygosity analysis in tumor tissues were performed to determine the pathogenicity of the variants. Deep targeted sequencing was performed on the peripheral blood DNA of a pheochromocytoma (PCC) patient with uterine leiomyomas. Finally, two of the five variants were found to be pathogenic. A germline variant (c.817G>A, p.Ala273Thr) was found in a patient with a PPGL family history. A mosaic variant (c.206G>A, p.Gly69Asp) with an allelic ratio of 5% in blood DNA was confirmed in the PCC patient with uterine leiomyomas. No metastatic PPGL was observed in the two PPGL patients with FH pathogenic variants. In summary, we report mosaicism in FH and the first PPGL pedigree with an FH pathogenic germline variant. Both germline variants and mosaicism should be taken into account during genetic testing.
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Date: 2022-07-11  ·  Issue: 2022  ·  Volume: 1516
Sexually antagonistic selection on educational attainment and body size in Estonian children
Contributors: Markus Valge| Richard Meitern| Peeter Hõrak|
Abstract: Natural selection is a key mechanism of evolution, which results from the differential reproduction of phenotypes. We describe fecundity selection at different parity transitions on 15 anthropometric traits and educational attainment in Estonian children sampled in the middle of 20th century. The direction of selection on educational attainment and bodily traits was sexually antagonistic, and it occurred via different parity transitions in boys and girls. Compared to boys with primary education, obtaining tertiary education was associated with 3.5 times and secondary education two times higher odds of becoming a father. Transition to motherhood was not related to educational attainment, while education above primary was associated with lower odds (OR = 0.5–0.7) to progression to parities above one and two. Selection on anthropometric traits occurred almost exclusively via childlessness in boys, while among the girls, most of the traits that were associated with becoming a mother were additionally associated with a transition from one child to higher parities. Male (but not female) fitness was thus primarily determined by traits related to mating success. Selection favored stronger and larger boys and smaller girls. Selection on girls favored some traits that associate with perceived femininity, while other feminine traits were selected against.
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Date: 2022-07-10  ·  Issue: 2022  ·  Volume: 1516
Advances in the observation and understanding of changes in sea level and tides
Contributors: Philip L. Woodworth|
Abstract: Climate change, of which sea level change is one component, is seldom out of the news. This paper reviews developments in the measurement and understanding of changes in sea level and tides, focusing on the changes during the past century. The main aim has been to demonstrate how sea level and tidal science are now connected intimately with the fields of climate change and geodesy.
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Date: 2022-07-10  ·  Issue: 2022  ·  Volume: 1516
Computational study of ion permeation through claudin‐4 paracellular channels
Contributors: Alessandro Berselli| Giulio Alberini| Fabio Benfenati| Luca Maragliano|
Abstract: Claudins (Cldns) form a large family of protein homologs that are essential for the assembly of paracellular tight junctions (TJs), where they form channels or barriers with tissue‐specific selectivity for permeants. In contrast to several family members whose physiological role has been identified, the function of claudin 4 (Cldn4) remains elusive, despite experimental evidence suggesting that it can form anion‐selective TJ channels in the renal epithelium. Computational approaches have recently been employed to elucidate the molecular basis of Cldns’ function, and hence could help in clarifying the role of Cldn4. In this work, we use structural modeling and all‐atom molecular dynamics simulations to transfer two previously introduced structural models of Cldn‐based paracellular complexes to Cldn4 to reproduce a paracellular anion channel. Free energy calculations for ionic transport through the pores allow us to establish the thermodynamic properties driving the ion‐selectivity of the structures. While one model shows a cavity permeable to chloride and repulsive to cations, the other forms barrier to the passage of all the major physiological ions. Furthermore, our results confirm the charge selectivity role of the residue Lys65 in the first extracellular loop of the protein, rationalizing Cldn4 control of paracellular permeability.
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Date: 2022-07-10  ·  Issue: 2022  · 
Computational study of ion permeation through claudin‐4 paracellular channels
Contributors: Alessandro Berselli| Giulio Alberini| Fabio Benfenati| Luca Maragliano|
Abstract: Claudins (Cldns) form a large family of protein homologs that are essential for the assembly of paracellular tight junctions (TJs), where they form channels or barriers with tissue‐specific selectivity for permeants. In contrast to several family members whose physiological role has been identified, the function of claudin 4 (Cldn4) remains elusive, despite experimental evidence suggesting that it can form anion‐selective TJ channels in the renal epithelium. Computational approaches have recently been employed to elucidate the molecular basis of Cldns’ function, and hence could help in clarifying the role of Cldn4. In this work, we use structural modeling and all‐atom molecular dynamics simulations to transfer two previously introduced structural models of Cldn‐based paracellular complexes to Cldn4 to reproduce a paracellular anion channel. Free energy calculations for ionic transport through the pores allow us to establish the thermodynamic properties driving the ion‐selectivity of the structures. While one model shows a cavity permeable to chloride and repulsive to cations, the other forms barrier to the passage of all the major physiological ions. Furthermore, our results confirm the charge selectivity role of the residue Lys65 in the first extracellular loop of the protein, rationalizing Cldn4 control of paracellular permeability.
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Date: 2022-07-01  ·  Issue: 2022  ·  Volume: 1516
Histone demethylase KDM3C regulates the lncRNA GAS5–miR‐495‐3p–PHF8 axis in cardiac hypertrophy
Contributors: Linlin Zhao| Feng Qi| Dongdong Du| Naishi Wu|
Abstract: Cardiac hypertrophy (CH) is a pathological phenotype of cardiomyopathy. Epigenetic modification is a mechanism associated with CH. Our study here investigated the histone demethylase KDM3C in relation to epigenetic regulation in CH. We found that KDM3C mRNA silencing alleviated CH, as evidenced by reduced ANP, BNP, and β‐MHC mRNAs, increased α‐MHC mRNA, decreased cell surface area, and reduced cellular protein/DNA ratios. Specifically, KDM3C upregulated miR‐200c‐3p expression through demethylation of H3K9me2, leading to enhanced binding of miR‐200c‐3p to GAS5 and suppression of GAS5 expression; these effects then led to reduced binding of GAS5 to miR‐495‐3p, increased miR‐495‐3p expression, and repression of PHF8 transcription. Through these mechanisms, our data indicate that KDM3C‐dependent epigenetic modification promotes CH.
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Date: 2022-06-29  ·  Issue: 2022  ·  Volume: 1516
Probing the leak pathway: Live‐cell imaging of macromolecule passage through epithelia
Contributors: Jan F. Richter| Markus Hildner| Ralf Mrowka| Ralf Schmauder|
Abstract: Epithelia compartmentalize multicellular organisms and provide interfacing between the inside and outside. Apart from regulating the exchange of solutes, uptake of nutrients, and excretion of waste products, their major function is to prevent uncontrolled access of foreign material to immune‐competent compartments. Progress in understanding this barrier function toward larger solutes and its possible defects, as can be seen in a variety of diseases, is largely hampered by a lack of methods to spatiotemporally resolve transepithelial passage of macromolecules. Using different cell culture epithelia, we applied biotinylated dextran tracers carrying an acceptor fluorophore. These bind to cell‐adherent avidin carrying donor fluorophore at the basolateral membranes of single‐layered epithelial sheets. Confocal fluorescence microscopy was applied to living epithelia in order to image apical‐to‐basolateral tracer passage as a Förster resonance energy transfer signal of the fluorescent dextran–avidin pair over time. Stimulated macromolecule passage using barrier‐perturbing agents proved its effectiveness for the leak imaging method presented herein. Over hours of imaging, spontaneous leaks were rare, occurring transiently on the scale of minutes and for the most part associated with rearranging cell junctions. The discussed approach to leak imaging is expected to promote the understanding of epithelial barriers, particularly, the nature and dynamics of the epithelial cell leak pathway.
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Date: 2022-06-29  ·  Issue: 2022  · 
Probing the leak pathway: Live‐cell imaging of macromolecule passage through epithelia
Contributors: Jan F. Richter| Markus Hildner| Ralf Mrowka| Ralf Schmauder|
Abstract: Epithelia compartmentalize multicellular organisms and provide interfacing between the inside and outside. Apart from regulating the exchange of solutes, uptake of nutrients, and excretion of waste products, their major function is to prevent uncontrolled access of foreign material to immune‐competent compartments. Progress in understanding this barrier function toward larger solutes and its possible defects, as can be seen in a variety of diseases, is largely hampered by a lack of methods to spatiotemporally resolve transepithelial passage of macromolecules. Using different cell culture epithelia, we applied biotinylated dextran tracers carrying an acceptor fluorophore. These bind to cell‐adherent avidin carrying donor fluorophore at the basolateral membranes of single‐layered epithelial sheets. Confocal fluorescence microscopy was applied to living epithelia in order to image apical‐to‐basolateral tracer passage as a Förster resonance energy transfer signal of the fluorescent dextran–avidin pair over time. Stimulated macromolecule passage using barrier‐perturbing agents proved its effectiveness for the leak imaging method presented herein. Over hours of imaging, spontaneous leaks were rare, occurring transiently on the scale of minutes and for the most part associated with rearranging cell junctions. The discussed approach to leak imaging is expected to promote the understanding of epithelial barriers, particularly, the nature and dynamics of the epithelial cell leak pathway.
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Date: 2022-06-28  ·  Issue: 2022  ·  Volume: 1515
Evening blue‐light exposure, maternal glucose, and infant birthweight
Contributors: Bilgay Izci Balserak| Renata Hermann| Teri L. Hernandez| Catalin Buhimschi| Chung Park|
Abstract: Maternal–fetal consequences of exposure to blue‐wavelength light are poorly understood. This study tested the hypothesis that evening blue‐light exposure is associated with maternal fasting glucose and infant birthweight. Forty‐one pregnant women (body mass index = 32.90 ± 6.35 kg/m2; 24–39 years old; 16 with gestational diabetes mellitus [GDM]) wore actigraphs for 7 days, underwent polysomnography, and completed study questionnaires during gestational week 30 ± 3.76. Infant birthweight (n = 41) and maternal fasting glucose (n = 30; range = 16–36 weeks) were recorded from the mothers’ medical charts. Blue‐light exposure was obtained from Actiwatch‐Spectrum recordings. Adjusted and unadjusted linear regression analyses were performed to determine sleep characteristics associated with maternal fasting glucose and infant‐birthweight. The mean fasting mid‐ to late‐gestation glucose was 95.73 ± 24.68 mg/dl and infant birthweight was 3271 ± 436 g. In unadjusted analysis, maternal fasting glucose was associated with blue‐light exposure (β = 3.82, p = 0.03). In the final model of multiple linear regression for fasting glucose, evening blue‐light exposure (β = 4.00, p = 0.01) remained significant after controlling for gestational weight gain, parity, sleep duration, and GDM. Similarly, blue‐light exposure was associated with infant birthweight (69.79, p = 0.006) in the unadjusted model, and remained significant (β = 70.38, p = 0.01) after adjusting for weight gain, wakefulness after sleep onset, gestational age at delivery, and GDM. Higher blue‐light exposure in pregnancy is associated with higher fasting glucose and infant birthweight. Reduced use of electronic devices before bedtime is a modifiable behavior.
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Date: 2022-06-28  ·  Issue: 2022  · 
MAOA‐LPR polymorphism and math anxiety: A marker of genetic susceptibility to social influences in girls?
Contributors: Maria Raquel Santos Carvalho| André Henrique Barbosa de Carvalho| Giulia Moreira Paiva| Carolina de Castro Andrade Jorge| Fernanda Caroline dos Santos| Gabriella Koltermann| Jerusa Fumagalli Salles| Korbinian Moeller| Guilherme Maia de Oliveira Wood| Vitor Geraldi Haase|
Abstract: Math anxiety (MA) seems to result from an interaction of genetic vulnerability with negative experiences learning mathematics. Although mathematics achievement does not substantially differ between the sexes, MA levels are usually higher in girls. Molecular genetic markers of MA vulnerability have been seldom explored. This article examines the contribution of the monoamine oxidase A gene (MAOA) to MA and to sex differences in MA. Five hundred and sixty‐eight third to fifth graders were genotyped for the MAOA‐LPR polymorphism (a repetitive element in MAOA promoter that has been associated with MAOA enzymatic activity), and assessed on general cognitive ability, mathematics achievement, and the cognitive and affective dimensions of MA. MAOA‐LPR genotypes were classified as high (MAOA‐H) or low (MAOA‐L) according to their predicted enzymatic activity. Mixed models controlling for effects of school, sex, general cognitive ability, and mathematics achievement were evaluated. The best fitting model included school, math achievement, sex, MAOA‐LPR, and the MAOA‐LPR by sex interaction. This indicated that under the MAOA‐H dominant model, anxiety toward mathematics interacted with the MAOA genotype: girls with an MAOA‐L genotype exhibited higher levels of MA, with a small but significant effect. The association between MAOA‐L genotype and MA in girls may represent an example of developmental plasticity.
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Date: 2022-06-28  ·  Issue: 2022  ·  Volume: 1516
MAOA‐LPR polymorphism and math anxiety: A marker of genetic susceptibility to social influences in girls?
Contributors: Maria Raquel Santos Carvalho| André Henrique Barbosa de Carvalho| Giulia Moreira Paiva| Carolina de Castro Andrade Jorge| Fernanda Caroline dos Santos| Gabriella Koltermann| Jerusa Fumagalli Salles| Korbinian Moeller| Guilherme Maia de Oliveira Wood| Vitor Geraldi Haase|
Abstract: Math anxiety (MA) seems to result from an interaction of genetic vulnerability with negative experiences learning mathematics. Although mathematics achievement does not substantially differ between the sexes, MA levels are usually higher in girls. Molecular genetic markers of MA vulnerability have been seldom explored. This article examines the contribution of the monoamine oxidase A gene (MAOA) to MA and to sex differences in MA. Five hundred and sixty‐eight third to fifth graders were genotyped for the MAOA‐LPR polymorphism (a repetitive element in MAOA promoter that has been associated with MAOA enzymatic activity), and assessed on general cognitive ability, mathematics achievement, and the cognitive and affective dimensions of MA. MAOA‐LPR genotypes were classified as high (MAOA‐H) or low (MAOA‐L) according to their predicted enzymatic activity. Mixed models controlling for effects of school, sex, general cognitive ability, and mathematics achievement were evaluated. The best fitting model included school, math achievement, sex, MAOA‐LPR, and the MAOA‐LPR by sex interaction. This indicated that under the MAOA‐H dominant model, anxiety toward mathematics interacted with the MAOA genotype: girls with an MAOA‐L genotype exhibited higher levels of MA, with a small but significant effect. The association between MAOA‐L genotype and MA in girls may represent an example of developmental plasticity.
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Date: 2022-06-28  ·  Issue: 2022  · 
The supercontinent cycle and Earth's long‐term climate
Contributors: R. Damian Nance|
Abstract: Earth's long‐term climate has been profoundly influenced by the episodic assembly and breakup of supercontinents at intervals of ca. 500 m.y. This reflects the cycle's impact on global sea level and atmospheric CO2 (and other greenhouse gases), the levels of which have fluctuated in response to variations in input from volcanism and removal (as carbonate) by the chemical weathering of silicate minerals. Supercontinent amalgamation tends to coincide with climatic cooling due to drawdown of atmospheric CO2 through enhanced weathering of the orogens of supercontinent assembly and a thermally uplifted supercontinent. Conversely, breakup tends to coincide with increased atmospheric CO2 and global warming as the dispersing continental fragments cool and subside, and weathering decreases as sea level rises. Supercontinents may also influence global climate through their causal connection to mantle plumes and large igneous provinces (LIPs) linked to their breakup. LIPs may amplify the warming trend of breakup by releasing greenhouse gases or may cause cooling and glaciation through sulfate aerosol release and drawdown of CO2 through the chemical weathering of LIP basalts. Hence, Earth's long‐term climatic trends likely reflect the cycle's influence on sea level, as evidenced by Pangea, whereas its influence on LIP volcanism may have orchestrated between Earth's various climatic states.
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Date: 2022-06-28  ·  Issue: 2022  · 
Musical experience partially counteracts temporal speech processing deficits in putative mild cognitive impairment
Contributors: Caitlin N. Price| Gavin M. Bidelman|
Abstract: Mild cognitive impairment (MCI) commonly results in more rapid cognitive and behavioral declines than typical aging. Individuals with MCI can exhibit impaired receptive speech abilities that may reflect neurophysiological changes in auditory‐sensory processing prior to usual cognitive deficits. Benefits from current interventions targeting communication difficulties in MCI are limited. Yet, neuroplasticity associated with musical experience has been implicated in improving neural representations of speech and offsetting age‐related declines in perception. Here, we asked whether these experience‐dependent effects of musical experience might extend to aberrant aging and offer some degree of cognitive protection against MCI. During a vowel categorization task, we recorded single‐channel electroencephalograms (EEGs) in older adults with putative MCI to evaluate speech encoding across subcortical and cortical levels of the auditory system. Critically, listeners varied in their duration of formal musical experience (0–21 years). Musical experience sharpened temporal precision in auditory cortical responses, suggesting that musical experience produces more efficient processing of acoustic features by counteracting age‐related neural delays. Additionally, robustness of brainstem responses predicted the severity of cognitive decline, suggesting that early speech representations are sensitive to preclinical stages of cognitive impairment. Our results extend prior studies by demonstrating positive benefits of musical experience in older adults with emergent cognitive impairments.
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Date: 2022-06-28  ·  Issue: 2022  ·  Volume: 1515
The supercontinent cycle and Earth's long‐term climate
Contributors: R. Damian Nance|
Abstract: Earth's long‐term climate has been profoundly influenced by the episodic assembly and breakup of supercontinents at intervals of ca. 500 m.y. This reflects the cycle's impact on global sea level and atmospheric CO2 (and other greenhouse gases), the levels of which have fluctuated in response to variations in input from volcanism and removal (as carbonate) by the chemical weathering of silicate minerals. Supercontinent amalgamation tends to coincide with climatic cooling due to drawdown of atmospheric CO2 through enhanced weathering of the orogens of supercontinent assembly and a thermally uplifted supercontinent. Conversely, breakup tends to coincide with increased atmospheric CO2 and global warming as the dispersing continental fragments cool and subside, and weathering decreases as sea level rises. Supercontinents may also influence global climate through their causal connection to mantle plumes and large igneous provinces (LIPs) linked to their breakup. LIPs may amplify the warming trend of breakup by releasing greenhouse gases or may cause cooling and glaciation through sulfate aerosol release and drawdown of CO2 through the chemical weathering of LIP basalts. Hence, Earth's long‐term climatic trends likely reflect the cycle's influence on sea level, as evidenced by Pangea, whereas its influence on LIP volcanism may have orchestrated between Earth's various climatic states.
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Date: 2022-06-25  ·  Issue: 2022  ·  Volume: 1515
Transcorneal electrical stimulation enhances cognitive functions in aged and 5XFAD mouse models
Contributors: Wing Shan Yu| Luca Aquili| Kah Hui Wong| Amy Cheuk Yin Lo| Leanne Lai Hang Chan| Ying‐Shing Chan| Lee Wei Lim|
Abstract: Dementia is a major burden on global health for which there are no effective treatments. The use of noninvasive visual stimulation to ameliorate cognitive deficits is a novel concept that may be applicable for treating dementia. In this study, we investigated the effects of transcorneal electrical stimulation (TES) on memory enhancement using two mouse models, in aged mice and in the 5XFAD model of Alzheimer's disease. After 3 weeks of TES treatment, mice were subjected to Y‐maze and Morris water maze tests to assess hippocampal‐dependent learning and memory. Immunostaining of the hippocampus of 5XFAD mice was also performed to examine the effects of TES on amyloid plaque pathology. The results showed that TES improved the performance of both aged and 5XFAD mice in memory tests. TES also reduced hippocampal plaque deposition in male, but not female, 5XFAD mice. Moreover, TES significantly reversed the downregulated level of postsynaptic protein 95 in the hippocampus of male 5XFAD mice, suggesting the effects of TES involve a postsynaptic mechanism. Overall, these findings support further investigation of TES as a potential treatment for cognitive dysfunction and mechanistic studies of TES effects in other dementia models.
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Date: 2022-06-21  ·  Issue: 2022  ·  Volume: 1515
Gesture–vocal coupling in Karnatak music performance: A neuro–bodily distributed aesthetic entanglement
Contributors: Lara Pearson| Wim Pouw|
Abstract: In many musical styles, vocalists manually gesture while they sing. Coupling between gesture kinematics and vocalization has been examined in speech contexts, but it is an open question how these couple in music making. We examine this in a corpus of South Indian, Karnatak vocal music that includes motion‐capture data. Through peak magnitude analysis (linear mixed regression) and continuous time‐series analyses (generalized additive modeling), we assessed whether vocal trajectories around peaks in vertical velocity, speed, or acceleration were coupling with changes in vocal acoustics (namely, F0 and amplitude). Kinematic coupling was stronger for F0 change versus amplitude, pointing to F0's musical significance. Acceleration was the most predictive for F0 change and had the most reliable magnitude coupling, showing a one‐third power relation. That acceleration, rather than other kinematics, is maximally predictive for vocalization is interesting because acceleration entails force transfers onto the body. As a theoretical contribution, we argue that gesturing in musical contexts should be understood in relation to the physical connections between gesturing and vocal production that are brought into harmony with the vocalists’ (enculturated) performance goals. Gesture–vocal coupling should, therefore, be viewed as a neuro–bodily distributed aesthetic entanglement.
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Date: 2022-06-20  ·  Issue: 2022  · 
PI3Kγ is a novel regulator of TNFα signaling in the human colon cell line HT29/B6
Contributors: Franz‐Leonard Klaus| Cornelia Kirsch| Jörg P. Müller| Otmar Huber| Juliane Reiche|
Abstract: Phosphoinositide 3‐kinases (PI3Ks) are a family of enzymes phosphorylating phospholipids in the membrane, thereby, promoting the PI3K/AKT signaling cascade. PI3Ks are involved in a variety of fundamental cellular functions, including tumor necrosis factor α (TNFα)‐induced tight junction (TJ) impairment—a hallmark of inflammatory bowel diseases. Most of the studies analyzing the role of class I PI3K signaling in epithelial barrier maintenance did not decipher which of the isoforms are responsible for the observed effects. By using wild‐type and PI3Kγ‐deficient HT‐29/B6 cells, we characterized the functional role of PI3Kγ in these cells under inflammatory conditions. Measurement of the transepithelial electrical resistance and the paracellular flux of macromolecules revealed that monolayers of PI3Kγ‐deficient cells, compared with wild‐type cells, were protected against TNFα‐induced barrier dysfunction. This effect was independent of any PI3K activity because treatment with a pan‐PI3K inhibitor did not alter this observation. By immunostaining, we found correlative changes in the distribution of the TJ marker ZO‐1. Furthermore, the absence of PI3Kγ reduced the basal level of the pore‐forming TJ protein claudin‐2. Our study suggests a novel noncanonical, kinase‐independent scaffolding function of PI3Kγ in TNFα‐induced barrier dysfunction.
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Date: 2022-06-20  ·  Issue: 2022  ·  Volume: 1515
PI3Kγ is a novel regulator of TNFα signaling in the human colon cell line HT29/B6
Contributors: Franz‐Leonard Klaus| Cornelia Kirsch| Jörg P. Müller| Otmar Huber| Juliane Reiche|
Abstract: Phosphoinositide 3‐kinases (PI3Ks) are a family of enzymes phosphorylating phospholipids in the membrane, thereby, promoting the PI3K/AKT signaling cascade. PI3Ks are involved in a variety of fundamental cellular functions, including tumor necrosis factor α (TNFα)‐induced tight junction (TJ) impairment—a hallmark of inflammatory bowel diseases. Most of the studies analyzing the role of class I PI3K signaling in epithelial barrier maintenance did not decipher which of the isoforms are responsible for the observed effects. By using wild‐type and PI3Kγ‐deficient HT‐29/B6 cells, we characterized the functional role of PI3Kγ in these cells under inflammatory conditions. Measurement of the transepithelial electrical resistance and the paracellular flux of macromolecules revealed that monolayers of PI3Kγ‐deficient cells, compared with wild‐type cells, were protected against TNFα‐induced barrier dysfunction. This effect was independent of any PI3K activity because treatment with a pan‐PI3K inhibitor did not alter this observation. By immunostaining, we found correlative changes in the distribution of the TJ marker ZO‐1. Furthermore, the absence of PI3Kγ reduced the basal level of the pore‐forming TJ protein claudin‐2. Our study suggests a novel noncanonical, kinase‐independent scaffolding function of PI3Kγ in TNFα‐induced barrier dysfunction.
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Date: 2022-06-18  ·  Issue: 2022  ·  Volume: 1515
MicroRNA‐21‐5p functions via RECK/MMP9 as a proalgesic regulator of the blood nerve barrier in nerve injury
Contributors: Ann Kristin Reinhold| Susanne M. Krug| Ellaine Salvador| Reine S. Sauer| Franziska Karl‐Schöller| Marzia Malcangio| Claudia Sommer| Heike L. Rittner|
Abstract: Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired—partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA‐21‐5p (miR‐21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR‐21 in neuropathic pain and its impact on the BNB in a human‐murine back translational approach. MiR‐21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin‐1 in both injured and spared nerves. Moreover, the putative miR‐21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR‐21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR‐21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR‐21 after nerve injury reversed it. In summary, the data support a novel role for miR‐21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9.
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Date: 2022-06-18  ·  Issue: 2022  ·  Volume: 1512
Issue Information
Contributors:
Abstract:
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Date: 2022-06-18  ·  Issue: 2022  · 
MicroRNA‐21‐5p functions via RECK/MMP9 as a proalgesic regulator of the blood nerve barrier in nerve injury
Contributors: Ann Kristin Reinhold| Susanne M. Krug| Ellaine Salvador| Reine S. Sauer| Franziska Karl‐Schöller| Marzia Malcangio| Claudia Sommer| Heike L. Rittner|
Abstract: Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired—partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA‐21‐5p (miR‐21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR‐21 in neuropathic pain and its impact on the BNB in a human‐murine back translational approach. MiR‐21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin‐1 in both injured and spared nerves. Moreover, the putative miR‐21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR‐21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR‐21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR‐21 after nerve injury reversed it. In summary, the data support a novel role for miR‐21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9.
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Date: 2022-06-16  ·  Issue: 2022  · 
Singing accuracy across the lifespan
Contributors: Peter Q. Pfordresher|
Abstract: Although singing is a nearly universal human behavior, many adults consider themselves poor singers and avoid singing based on self‐assessment of pitch matching accuracy during singing (here referred to as singing accuracy), in contrast to the uninhibited singing exhibited by children. In this article, I report results that shed light on how singing accuracy changes across the lifespan, using data from a large online sample, including participants ranging from 6 to 99 years old. Results suggest that singing accuracy improves dramatically from childhood to young adulthood, unperturbed by voice changes during adolescence, and remain at a similarly high level for the remainder of life, exhibiting no strong tendency toward age‐related decline. Vocal or instrumental musical training has significant positive effects on singing accuracy, particularly in childhood, though there was no evidence for gender differences. Finally, pitch discrimination varied with age similarly to singing accuracy, in support of views that singing accuracy reflects sensorimotor learning. Taken together, these results are consistent with the view that singing accuracy is a learned motor skill that benefits from engagement and can remain a fruitful endeavor into old age.
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Date: 2022-06-16  ·  Issue: 2022  ·  Volume: 1515
Spef1/CLAMP binds microtubules and actin‐based structures and regulates cell migration and epithelia cell polarity
Contributors: Rocio Tapia| Gail A. Hecht|
Abstract: During migration, cells invade, repair, and create barriers leading to the formation of new cellular contacts in target tissues. Cell migration requires many proteins that collectively form the cytoskeleton. The main cytoskeletal elements are actin filaments, microtubules (MTs), and intermediate filaments. These structures work in concert with a large number of accessory proteins that contribute in a variety of ways to regulate filament assembly and turnover, to alter the configuration or arrangement of filaments by bundling or crosslinking, to link the cytoskeleton to other structures in the cell, such as membranes and junctions, and to transport cargo along the filaments. Sperm flagella protein‐1 (Spef1), also designated calponin homology and microtubules‐associated protein (CLAMP), is a multifunctional protein that interacts with cytoskeletal structures, including MTs, actin filaments, and focal adhesions in epithelia. In this review, we outline Spef1/CLAMP structure and expression in several cellular models. The function of Spef1/CLAMP in flagellar and ciliary motility, MT‐binding and stability, regulation of planar cell polarity, and potential contribution to the maintenance of actin‐based structures, such as lamellipodia and filopodia during cell migration, are also discussed.
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Date: 2022-06-15  ·  Issue: 2023  · 
Staphylococcus aureus adhesion to the host
Contributors: Kirsten A. Berry| Mackenzie T. A. Verhoef| Allison C. Leonard| Georgina Cox|
Abstract: Staphylococcus aureus is a pathobiont capable of colonizing and infecting most tissues within the human body, resulting in a multitude of different clinical outcomes. Adhesion of S. aureus to the host is crucial for both host colonization and the establishment of infections. Underlying the pathogen's success is a complex and diverse arsenal of adhesins. In this review, we discuss the different classes of adhesins, including a consideration of the various adhesion sites throughout the body and the clinical outcomes of each infection type. The development of therapeutics targeting the S. aureus host–pathogen interaction is a relatively understudied area. Due to the increasing global threat of antimicrobial resistance, it is crucial that innovative and alternative approaches are considered. Neutralizing virulence factors, through the development of antivirulence agents, could reduce bacterial pathogenicity and the ever‐increasing burden of S. aureus infections. This review provides insight into potentially efficacious adhesion‐associated targets for the development of novel decolonizing and antivirulence strategies.
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Date: 2022-06-09  ·  Issue: 2022  ·  Volume: 1515
Role of hair follicles in the pathogenesis of arsenical‐induced cutaneous damage
Contributors: Ritesh K. Srivastava| Yong Wang| Jasim Khan| Suhail Muzaffar| Madison B. Lee| Zhiping Weng| Claire Croutch| Anupam Agarwal| Jessy Deshane| Mohammad Athar|
Abstract: Arsenical vesicants cause skin inflammation, blistering, and pain. The lack of appropriate animal models causes difficulty in defining their molecular pathogenesis. Here, Ptch1+/–/C57BL/6 mice were employed to investigate the pathobiology of the arsenicals lewisite and phenylarsine oxide (PAO). Following lewisite or PAO challenge (24 h), the skin of animals becomes grayish‐white, thick, leathery, and wrinkled with increased bi‐fold thickness, Draize score, and necrotic patches. In histopathology, infiltrating leukocytes (macrophages and neutrophils), epidermal–dermal separation, edema, apoptotic cells, and disruption of tight and adherens junction proteins can be visualized. PCR arrays and nanoString analyses showed significant increases in cytokines/chemokines and other proinflammatory mediators. As hair follicles (HFs), which provide an immune‐privileged environment, may affect immune cell trafficking and consequent inflammatory responses, we compared the pathogenesis of these chemicals in this model to that in Ptch1+/–/SKH‐1 hairless mice. Ptch1+/–/SKH‐1 mice have rudimentary, whereas Ptch1+/–/C57BL/6 mice have well‐developed HFs. Although no significant differences were observed in qualitative inflammatory responses between the two strains, levels of cytokines/chemokines differed. Importantly, the mechanism of inflammation was identical; both reactive oxygen species induction and consequent activation of unfolded protein response signaling were similar. These data reveal that the acute molecular pathogenesis of arsenicals in these two murine models is similar.
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Date: 2022-06-08  ·  Issue: 2022  ·  Volume: 1515
Cognitive efficacy and neural mechanisms of music‐based neurological rehabilitation for traumatic brain injury
Contributors: Noelia Martínez‐Molina| Sini‐Tuuli Siponkoski| Teppo Särkämö|
Abstract: Traumatic brain injury (TBI) causes lifelong cognitive deficits, most often in executive function (EF). Both musical training and music‐based rehabilitation have been shown to enhance EF and neuroplasticity. Thus far, however, there is little evidence for the potential rehabilitative effects of music for TBI. Here, we review the core findings from our recent cross‐over randomized controlled trial in which a 10‐week music‐based neurological rehabilitation (MBNR) protocol was administered to 40 patients with moderate‐to‐severe TBI. Neuropsychological testing and structural/functional magnetic resonance imaging were collected at three time points (baseline, 3 months, and 6 months); one group received the MBNR between time points 1 and 2, while a second group received it between time points 2 and 3. We found that both general EF and set shifting improved after the intervention, and this effect was maintained long term. Morphometric analyses revealed therapy‐induced gray matter volume changes most consistently in the right inferior frontal gyrus, changes that correlated with better outcomes in set shifting. Finally, we found changes in the between‐ and within‐network functional connectivity of large‐scale resting‐state networks after MBNR, which also correlated with measures of EF. Taken together, the data provide evidence for concluding that MBNR improves EF in TBI; also, the data show that morphometric and resting‐state functional connectivity are sensitive markers with which to monitor the neuroplasticity induced by the MBNR intervention.
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Date: 2022-06-08  ·  Issue: 2022  · 
Cognitive efficacy and neural mechanisms of music‐based neurological rehabilitation for traumatic brain injury
Contributors: Noelia Martínez‐Molina| Sini‐Tuuli Siponkoski| Teppo Särkämö|
Abstract: Traumatic brain injury (TBI) causes lifelong cognitive deficits, most often in executive function (EF). Both musical training and music‐based rehabilitation have been shown to enhance EF and neuroplasticity. Thus far, however, there is little evidence for the potential rehabilitative effects of music for TBI. Here, we review the core findings from our recent cross‐over randomized controlled trial in which a 10‐week music‐based neurological rehabilitation (MBNR) protocol was administered to 40 patients with moderate‐to‐severe TBI. Neuropsychological testing and structural/functional magnetic resonance imaging were collected at three time points (baseline, 3 months, and 6 months); one group received the MBNR between time points 1 and 2, while a second group received it between time points 2 and 3. We found that both general EF and set shifting improved after the intervention, and this effect was maintained long term. Morphometric analyses revealed therapy‐induced gray matter volume changes most consistently in the right inferior frontal gyrus, changes that correlated with better outcomes in set shifting. Finally, we found changes in the between‐ and within‐network functional connectivity of large‐scale resting‐state networks after MBNR, which also correlated with measures of EF. Taken together, the data provide evidence for concluding that MBNR improves EF in TBI; also, the data show that morphometric and resting‐state functional connectivity are sensitive markers with which to monitor the neuroplasticity induced by the MBNR intervention.
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Date: 2022-06-07  ·  Issue: 2022  · 
Unique and redundant functions of cytoplasmic actins and nonmuscle myosin II isoforms at epithelial junctions
Contributors: Andrei I. Ivanov| Susana Lechuga| Armando Marino‐Melendez| Nayden G. Naydenov|
Abstract: The integrity and functions of epithelial barriers depend on the formation of adherens junctions (AJs) and tight junctions (TJs). A characteristic feature of AJs and TJs is their association with the cortical cytoskeleton composed of actin filaments and nonmuscle myosin II (NM‐II) motors. Mechanical forces generated by the actomyosin cytoskeleton are essential for junctional assembly, stability, and remodeling. Epithelial cells express two different actin proteins and three NM‐II isoforms, all known to be associated with AJs and TJs. Despite their structural similarity, different actin and NM‐II isoforms have distinct biochemical properties, cellular distribution, and functions. The diversity of epithelial actins and myosin motors could be essential for the regulation of different steps of junctional formation, maturation, and disassembly. This review focuses on the roles of actin and NM‐II isoforms in controlling the integrity and barrier properties of various epithelia. We discuss the effects of the depletion of individual actin isoforms and NM‐II motors on the assembly and barrier function of AJs and TJs in model epithelial monolayers in vitro. We also describe the functional consequences of either total or tissue‐specific gene knockout of different actins and NM‐II motors, with a focus on the development and integrity of different epithelia in vivo.
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Date: 2022-06-07  ·  Issue: 2022  ·  Volume: 1515
Unique and redundant functions of cytoplasmic actins and nonmuscle myosin II isoforms at epithelial junctions
Contributors: Andrei I. Ivanov| Susana Lechuga| Armando Marino‐Melendez| Nayden G. Naydenov|
Abstract: The integrity and functions of epithelial barriers depend on the formation of adherens junctions (AJs) and tight junctions (TJs). A characteristic feature of AJs and TJs is their association with the cortical cytoskeleton composed of actin filaments and nonmuscle myosin II (NM‐II) motors. Mechanical forces generated by the actomyosin cytoskeleton are essential for junctional assembly, stability, and remodeling. Epithelial cells express two different actin proteins and three NM‐II isoforms, all known to be associated with AJs and TJs. Despite their structural similarity, different actin and NM‐II isoforms have distinct biochemical properties, cellular distribution, and functions. The diversity of epithelial actins and myosin motors could be essential for the regulation of different steps of junctional formation, maturation, and disassembly. This review focuses on the roles of actin and NM‐II isoforms in controlling the integrity and barrier properties of various epithelia. We discuss the effects of the depletion of individual actin isoforms and NM‐II motors on the assembly and barrier function of AJs and TJs in model epithelial monolayers in vitro. We also describe the functional consequences of either total or tissue‐specific gene knockout of different actins and NM‐II motors, with a focus on the development and integrity of different epithelia in vivo.
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Date: 2022-06-06  ·  Issue: 2022  ·  Volume: 1515
Appraisals of previous math experiences play an important role in math anxiety
Contributors: Thomas E. Hunt| Erin A. Maloney|
Abstract: Math anxiety affects many people, from young children through to older adults. While there has been debate concerning the developmental trajectory of math anxiety and negative math attitudes, little attention has been given to the role of appraisals of previous math experiences. We surveyed 308 adults (mean age = 27.56 years, SD = 11.25) and assessed self‐reported measures of math anxiety, mathematical resilience, math attitudes, and appraisal of previous math experiences. As hypothesized, all variables were found to be interrelated. Math anxiety was significantly negatively related to appraisal of previous math experiences, mathematical resilience, and math attitudes. Moreover, appraisal of previous math experiences was shown to mediate the relations between (1) math anxiety and math attitudes, and (2) mathematical resilience and math attitudes. The findings demonstrate the importance of considering current appraisals of previous math experiences and are consistent with an interpretation account of math anxiety. This may help inform cognitive‐based interventions that focus on one's interpretation of past events to support current and future math learning and engagement.
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Date: 2022-06-06  ·  Issue: 2022  · 
Human duodenal organoid‐derived monolayers serve as a suitable barrier model for duodenal tissue
Contributors: Franziska Weiß| David Holthaus| Martin Kraft| Christian Klotz| Martina Schneemann| Jörg D. Schulzke| Susanne M. Krug|
Abstract: Usually, duodenal barriers are investigated using intestinal cell lines like Caco‐2, which in contrast to native tissue are limited in cell‐type representation. Organoids can consist of all intestinal cell types and are supposed to better reflect the in vivo situation. Growing three‐dimensionally, with the apical side facing the lumen, application of typical physiological techniques to analyze the barrier is difficult. Organoid‐derived monolayers (ODMs) were developed to overcome this. After optimizing culturing conditions, ODMs were characterized and compared to Caco‐2 and duodenal tissue. Tight junction composition and appearance were analyzed, and electrophysiological barrier properties, like paracellular and transcellular barrier function and macromolecule permeability, were evaluated. Furthermore, transcriptomic data were analyzed. ODMs had tight junction protein expression and paracellular barrier properties much more resembling the originating tissue than Caco‐2. Transcellular barrier was similar between ODMs and native tissue but was increased in Caco‐2. Transcriptomic data showed that Caco‐2 expressed fewer solute carriers than ODMs and native tissue. In conclusion, while Caco‐2 cells differ mostly in transcellular properties, ODMs reflect trans‐ and paracellular properties of the originating tissue. If cultured under optimized conditions, ODMs possess reproducible functionality, and the variety of different cell types makes them a suitable model for human tissue‐specific investigations.
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Date: 2022-06-06  ·  Issue: 2022  ·  Volume: 1515
Exploring epigenomic mechanisms of neural tube defects using multi‐omics methods and data
Contributors: Wanqi Huang| Zhengwei Yuan| Hui Gu|
Abstract: Neural tube defects (NTDs) are a heterogeneous set of malformations attributed to disruption in normal neural tube closure during early embryogenesis. An in‐depth understanding of NTD etiology and mechanisms remains elusive, however. Among the proposed mechanisms, epigenetic changes are thought to play an important role in the formation of NTDs. Epigenomics covers a wide spectrum of genomic DNA sequence modifications that can be investigated via high‐throughput techniques. Recent advances in epigenomic technologies have enabled epigenetic studies of congenital malformations and facilitated the integration of big data into the understanding of NTDs. Herein, we review clinical epigenomic data that focuses on DNA methylation, histone modification, and miRNA alterations in human neural tissues, placental tissues, and leukocytes to explore potential mechanisms by which candidate genes affect human NTD pathogenesis. We discuss the links between epigenomics and gene regulatory mechanisms, and the effects of epigenetic alterations in human tissues on neural tube closure.
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Date: 2022-06-06  ·  Issue: 2022  · 
Appraisals of previous math experiences play an important role in math anxiety
Contributors: Thomas E. Hunt| Erin A. Maloney|
Abstract: Math anxiety affects many people, from young children through to older adults. While there has been debate concerning the developmental trajectory of math anxiety and negative math attitudes, little attention has been given to the role of appraisals of previous math experiences. We surveyed 308 adults (mean age = 27.56 years, SD = 11.25) and assessed self‐reported measures of math anxiety, mathematical resilience, math attitudes, and appraisal of previous math experiences. As hypothesized, all variables were found to be interrelated. Math anxiety was significantly negatively related to appraisal of previous math experiences, mathematical resilience, and math attitudes. Moreover, appraisal of previous math experiences was shown to mediate the relations between (1) math anxiety and math attitudes, and (2) mathematical resilience and math attitudes. The findings demonstrate the importance of considering current appraisals of previous math experiences and are consistent with an interpretation account of math anxiety. This may help inform cognitive‐based interventions that focus on one's interpretation of past events to support current and future math learning and engagement.
Read More  

Date: 2022-06-06  ·  Issue: 2022  ·  Volume: 1515
Human duodenal organoid‐derived monolayers serve as a suitable barrier model for duodenal tissue
Contributors: Franziska Weiß| David Holthaus| Martin Kraft| Christian Klotz| Martina Schneemann| Jörg D. Schulzke| Susanne M. Krug|
Abstract: Usually, duodenal barriers are investigated using intestinal cell lines like Caco‐2, which in contrast to native tissue are limited in cell‐type representation. Organoids can consist of all intestinal cell types and are supposed to better reflect the in vivo situation. Growing three‐dimensionally, with the apical side facing the lumen, application of typical physiological techniques to analyze the barrier is difficult. Organoid‐derived monolayers (ODMs) were developed to overcome this. After optimizing culturing conditions, ODMs were characterized and compared to Caco‐2 and duodenal tissue. Tight junction composition and appearance were analyzed, and electrophysiological barrier properties, like paracellular and transcellular barrier function and macromolecule permeability, were evaluated. Furthermore, transcriptomic data were analyzed. ODMs had tight junction protein expression and paracellular barrier properties much more resembling the originating tissue than Caco‐2. Transcellular barrier was similar between ODMs and native tissue but was increased in Caco‐2. Transcriptomic data showed that Caco‐2 expressed fewer solute carriers than ODMs and native tissue. In conclusion, while Caco‐2 cells differ mostly in transcellular properties, ODMs reflect trans‐ and paracellular properties of the originating tissue. If cultured under optimized conditions, ODMs possess reproducible functionality, and the variety of different cell types makes them a suitable model for human tissue‐specific investigations.
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Date: 2022-06-01  ·  Issue: 2022  · 
The importance of the motor system in the development of music‐based forms of auditory rehabilitation
Contributors: Benjamin Rich Zendel|
Abstract: Hearing abilities decline with age, and one of the most commonly reported hearing issues in older adults is a difficulty understanding speech when there is loud background noise. Understanding speech in noise relies on numerous cognitive processes, including working memory, and is supported by numerous brain regions, including the motor and motor planning systems. Indeed, many working memory processes are supported by motor and premotor cortical regions. Interestingly, lifelong musicians and nonmusicians given music training over the course of weeks or months show an improved ability to understand speech when there is loud background noise. These benefits are associated with enhanced working memory abilities, and enhanced activity in motor and premotor cortical regions. Accordingly, it is likely that music training improves the coupling between the auditory and motor systems and promotes plasticity in these regions and regions that feed into auditory/motor areas. This leads to an enhanced ability to dynamically process incoming acoustic information, and is likely the reason that musicians and those who receive laboratory‐based music training are better able to understand speech when there is background noise. Critically, these findings suggest that music‐based forms of auditory rehabilitation are possible and should focus on tasks that promote auditory–motor interactions.
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Date: 2022-06-01  ·  Issue: 2022  ·  Volume: 1515
Tight junction channels claudin‐10b and claudin‐15: Functional mapping of pore‐lining residues
Contributors: Caroline Hempel| Rita Rosenthal| Anja Fromm| Susanne M. Krug| Michael Fromm| Dorothee Günzel| Jörg Piontek|
Abstract: Although functional and structural models for paracellular channels formed by claudins have been reported, mechanisms regulating charge and size selectivity of these channels are unknown in detail. Here, claudin‐15 and claudin‐10b cation channels showing high‐sequence similarity but differing channel properties were analyzed. Mutants of pore‐lining residues were expressed in MDCK‐C7 cells. In claudin‐15, proposed ion interaction sites (D55 and E64) conserved between both claudins were neutralized. D55N and E64Q substitutions decreased ion permeabilities, and D55N/E64Q had partly additive effects. D55N increased cation dehydration capability and decreased pore diameter. Additionally, residues differing between claudin‐15 and ‐10b close to pore center were analyzed. Claudin‐10b–mimicking W63K affected neither assembly nor function of claudin‐15 channels. In contrast, in claudin‐10b, corresponding (claudin‐15b‐mimicking) K64W and K64M substitutions disturbed integration into tight junction and slightly altered relative permeabilities for differently sized monovalent cations. Removal of claudin‐10b–specific negative charge (D36A substitution) was without effect. The data suggest that a common tetra‐aspartate ring (D55/D56) in pore center of claudin‐15/‐10b channels directly attracts cations, while E64/D65 may be at least partly shielded by W63/K64. Charge at position W63/K64 affects assembly and properties for claudin‐10b but not for claudin‐15 channels. Our findings add to the mechanistic understanding of the determinants of paracellular cation permeability.
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Date: 2022-06-01  ·  Issue: 2022  · 
Tight junction channels claudin‐10b and claudin‐15: Functional mapping of pore‐lining residues
Contributors: Caroline Hempel| Rita Rosenthal| Anja Fromm| Susanne M. Krug| Michael Fromm| Dorothee Günzel| Jörg Piontek|
Abstract: Although functional and structural models for paracellular channels formed by claudins have been reported, mechanisms regulating charge and size selectivity of these channels are unknown in detail. Here, claudin‐15 and claudin‐10b cation channels showing high‐sequence similarity but differing channel properties were analyzed. Mutants of pore‐lining residues were expressed in MDCK‐C7 cells. In claudin‐15, proposed ion interaction sites (D55 and E64) conserved between both claudins were neutralized. D55N and E64Q substitutions decreased ion permeabilities, and D55N/E64Q had partly additive effects. D55N increased cation dehydration capability and decreased pore diameter. Additionally, residues differing between claudin‐15 and ‐10b close to pore center were analyzed. Claudin‐10b–mimicking W63K affected neither assembly nor function of claudin‐15 channels. In contrast, in claudin‐10b, corresponding (claudin‐15b‐mimicking) K64W and K64M substitutions disturbed integration into tight junction and slightly altered relative permeabilities for differently sized monovalent cations. Removal of claudin‐10b–specific negative charge (D36A substitution) was without effect. The data suggest that a common tetra‐aspartate ring (D55/D56) in pore center of claudin‐15/‐10b channels directly attracts cations, while E64/D65 may be at least partly shielded by W63/K64. Charge at position W63/K64 affects assembly and properties for claudin‐10b but not for claudin‐15 channels. Our findings add to the mechanistic understanding of the determinants of paracellular cation permeability.
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Date: 2022-05-31  ·  Issue: 2022  ·  Volume: 1514
Comparison of a universal (but complex) model for avian egg shape with a simpler model
Contributors: Peijian Shi| Johan Gielis| Karl J. Niklas|
Abstract: Recently, a universal equation by Narushin, Romanov, and Griffin (hereafter, the NRGE) was proposed to describe the shape of avian eggs. While NRGE can simulate the shape of spherical, ellipsoidal, ovoidal, and pyriform eggs, its predictions were not tested against actual data. Here, we tested the validity of the NRGE by fitting actual data of egg shapes and compared this with the predictions of our simpler model for egg shape (hereafter, the SGE). The eggs of nine bird species were sampled for this purpose. NRGE was found to fit the empirical data of egg shape well, but it did not define the egg length axis (i.e., the rotational symmetric axis), which significantly affected the prediction accuracy. The egg length axis under the NRGE is defined as the maximum distance between two points on the scanned perimeter of the egg's shape. In contrast, the SGE fitted the empirical data better, and had a smaller root‐mean‐square error than the NRGE for each of the nine eggs. Based on its mathematical simplicity and goodness‐of‐fit, the SGE appears to be a reliable and useful model for describing egg shape.
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Date: 2022-05-27  ·  Issue: 2022  ·  Volume: 1514
World enough and time—Brazil, slavery, and Charles Darwin's untaken road to the United States
Contributors: Tom Chaffin|
Abstract:
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Date: 2022-05-27  ·  Issue: 2023  · 
Chaffin's “World enough and time—Brazil, slavery, and Charles Darwin's untaken road to the United States”
Contributors: Douglas Braaten|
Abstract:
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Date: 2022-05-27  ·  Issue: 2023  · 
World enough and time—Brazil, slavery, and Charles Darwin's untaken road to the United States
Contributors: Tom Chaffin|
Abstract:
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Date: 2022-05-26  ·  Issue: 2022  ·  Volume: 1514
Self‐efficacy matters: Influence of students’ perceived self‐efficacy on statistics anxiety
Contributors: Liane Kaufmann| Manuel Ninaus| Elisabeth M. Weiss| Walter Gruber| Guilherme Wood|
Abstract: Statistical knowledge is a key competency for psychologists in order to correctly interpret assessment outcomes. Importantly, when learning statistics (and its mathematical foundations), self‐efficacy (defined as an individual's belief to successfully accomplish specific performance attainments) is a central predictor of students’ motivation to learn, learning engagement, and actual achievement. Therefore, it is crucial to gain a better understanding of students’ self‐efficacy for statistics and its interrelations with statistics anxiety and students’ belief in the relevance of statistics. Here, we present results showing development and validation of a self‐assessment questionnaire for examining self‐efficacy for statistics in psychology students (Self‐Efficacy for Learning Statistics for Psychologists, SES‐Psy). Upon using different methodological approaches, we demonstrate that the SES‐Psy questionnaire has (1) sound psychometric properties, and within our sample of university students, (2) a robust latent structure disclosing three clearly distinctive profiles that are characterized by a complex and nonlinear interplay between perceived self‐efficacy (for basic and advanced statistics), statistics anxiety, and students’ belief in the relevance of statistics. Implications for educational settings and future research are discussed.
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Date: 2022-05-26  ·  Issue: 2022  · 
Self‐efficacy matters: Influence of students’ perceived self‐efficacy on statistics anxiety
Contributors: Liane Kaufmann| Manuel Ninaus| Elisabeth M. Weiss| Walter Gruber| Guilherme Wood|
Abstract: Statistical knowledge is a key competency for psychologists in order to correctly interpret assessment outcomes. Importantly, when learning statistics (and its mathematical foundations), self‐efficacy (defined as an individual's belief to successfully accomplish specific performance attainments) is a central predictor of students’ motivation to learn, learning engagement, and actual achievement. Therefore, it is crucial to gain a better understanding of students’ self‐efficacy for statistics and its interrelations with statistics anxiety and students’ belief in the relevance of statistics. Here, we present results showing development and validation of a self‐assessment questionnaire for examining self‐efficacy for statistics in psychology students (Self‐Efficacy for Learning Statistics for Psychologists, SES‐Psy). Upon using different methodological approaches, we demonstrate that the SES‐Psy questionnaire has (1) sound psychometric properties, and within our sample of university students, (2) a robust latent structure disclosing three clearly distinctive profiles that are characterized by a complex and nonlinear interplay between perceived self‐efficacy (for basic and advanced statistics), statistics anxiety, and students’ belief in the relevance of statistics. Implications for educational settings and future research are discussed.
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Date: 2022-05-25  ·  Issue: 2022  ·  Volume: 1514
Excessive iodine in iodized household salt in Nepal
Contributors: Basant Giri| Shishir Pandey| Sadiksha Shakya| Bhanu Bhakta Neupane| Krishna Prasad Kandel| Chandradip Kumar Yadav| Ram Prabodh Yadav| Bishnu Prasad Neupane| Rajendra Bahadur GC| Prem Singh Saud| Meghraj Yonjan|
Abstract: Iodine is an essential trace element required for the regulation of physiological processes involving the thyroid gland. However, inadequate and excessive intake of iodine are responsible for health problems, such as iodine deficiency disorders, hypothyroidism, hyperthyroidism, thyroiditis, thyroid papillary cancer, and thyrotoxicosis. The Universal Salt Iodization (USI) program has become successful in providing supplemental iodine at the population level globally. Packaging quality, fortification level, and transportation and storage conditions of iodized salt determine the availability of iodine. Previous studies have reported severe health issues caused by excessive iodine intake after the implementation of the USI program. To understand the levels of iodine, we collected 2117 household salt samples from seven districts of Nepal and tested them for iodine content; among them, 98.1% were iodized. Overall median concentration of iodine was 53.9 ppm (range: 43.5–61.4 ppm). The majority (67.2%) of samples had iodine in the range of 45–75 ppm. Approximately 0.9% of samples had inadequate, 13.3% contained adequate, and 83.9% had excessive iodine than the World Health Organization‐recommended value. Iodine content varied among the sampling districts and seasons, to some extent. Our study confirmed that iodized salt is widely used in Nepal and is excessively iodized. Excessive intake of iodine through iodized salt requires further attention by policy makers. The iodine level may need adjustment to address the health impact.
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Date: 2022-05-24  ·  Issue: 2022  ·  Volume: 1514
Gaze patterns reveal aesthetic distance while viewing art
Contributors: Manuela M. Marin| Helmut Leder|
Abstract: For centuries, Western philosophers have argued that aesthetic experiences differ from common, everyday pleasing sensations, and further, that mental states, such as disinterested contemplation and aesthetic distance, underlie these complex experiences. We empirically tested whether basic perceptual processes of information intake reveal evidence for aesthetic distance, specifically toward visual art. We conducted two eye tracking experiments using appropriately matched visual stimuli (environmental scenes and representational paintings) with 59 participants using two different presentation durations (25 and 6 s). Linear mixed‐effects models considering individual differences showed that affective content (pleasantness and arousal), but not stimulus composition (complexity), leads to differential effects when viewing representational paintings in comparison to environmental scenes. We demonstrate that an increase in aesthetic pleasantness induced by representational paintings during a free‐viewing task leads to a slower and deeper processing mode than when viewing environmental scenes of motivational relevance, for which we observed the opposite effect. In addition, long presentation durations led to an increase in scanning behavior during visual art perception. These empirical findings inform the debate about how aesthetic experiences differ from everyday perceptual processes by showing that the notion of aesthetic distance may be better understood by examining different modes of viewing.
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Date: 2022-05-23  ·  Issue: 2022  ·  Volume: 1514
Corrigendum for Ann. N. Y. Acad. Sci. (2018), 1423, 166–175.
Contributors:
Abstract:
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Date: 2022-05-21  ·  Issue: 2022  · 
Benefits of choir singing on complex auditory encoding in the aging brain: An ERP study
Contributors: Emmi Pentikäinen| Lilli Kimppa| Tommi Makkonen| Mikko Putkonen| Anni Pitkäniemi| Ilja Salakka| Petri Paavilainen| Mari Tervaniemi| Teppo Särkämö|
Abstract: Aging is accompanied by difficulties in auditory information processing, especially in more complex sound environments. Choir singing requires efficient processing of multiple sound features and could, therefore, mitigate the detrimental effects of aging on complex auditory encoding. We recorded auditory event‐related potentials during passive listening of sounds in healthy older adult (≥ 60 years) choir singers and nonsinger controls. We conducted a complex oddball condition involving encoding of abstract regularities in combinations of pitch and location features, as well as in two simple oddball conditions, in which only either the pitch or spatial location of the sounds was varied. We analyzed change‐related mismatch negativity (MMN) and obligatory P1 and N1 responses in each condition. In the complex condition, the choir singers showed a larger MMN than the controls, which also correlated with better performance in a verbal fluency test. In the simple pitch and location conditions, the choir singers had smaller N1 responses compared to the control subjects, whereas the MMN responses did not differ between groups. These results suggest that regular choir singing is associated both with more enhanced encoding of complex auditory regularities and more effective adaptation to simple sound features.
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Date: 2022-05-21  ·  Issue: 2022  ·  Volume: 1514
Benefits of choir singing on complex auditory encoding in the aging brain: An ERP study
Contributors: Emmi Pentikäinen| Lilli Kimppa| Tommi Makkonen| Mikko Putkonen| Anni Pitkäniemi| Ilja Salakka| Petri Paavilainen| Mari Tervaniemi| Teppo Särkämö|
Abstract: Aging is accompanied by difficulties in auditory information processing, especially in more complex sound environments. Choir singing requires efficient processing of multiple sound features and could, therefore, mitigate the detrimental effects of aging on complex auditory encoding. We recorded auditory event‐related potentials during passive listening of sounds in healthy older adult (≥ 60 years) choir singers and nonsinger controls. We conducted a complex oddball condition involving encoding of abstract regularities in combinations of pitch and location features, as well as in two simple oddball conditions, in which only either the pitch or spatial location of the sounds was varied. We analyzed change‐related mismatch negativity (MMN) and obligatory P1 and N1 responses in each condition. In the complex condition, the choir singers showed a larger MMN than the controls, which also correlated with better performance in a verbal fluency test. In the simple pitch and location conditions, the choir singers had smaller N1 responses compared to the control subjects, whereas the MMN responses did not differ between groups. These results suggest that regular choir singing is associated both with more enhanced encoding of complex auditory regularities and more effective adaptation to simple sound features.
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Date: 2022-05-19  ·  Issue: 2022  ·  Volume: 1514
The forgotten role of absorption in music reward
Contributors: Gemma Cardona| Laura Ferreri| Urbano Lorenzo‐Seva| Frank A. Russo| Antoni Rodriguez‐Fornells|
Abstract: Interindividual differences in music‐related reward have been characterized as involving five main facets: musical seeking, emotion evocation, mood regulation, social reward, and sensory‐motor. An interesting concept related to how humans decode music as a rewarding experience is music transcendence or absorption (i.e., music‐driven states of complete immersion, including momentary loss of self‐consciousness or even time‐space disorientation). Here, we investigated the relation between previously characterized facets of music reward and individual differences in music absorption. A first sample of participants (N = 370) completed both the Barcelona Music Reward Questionnaire (BMRQ) and the Absorption in Music Scale (AIMS). Results showed that both constructs were highly interrelated (r = 0.78, p < 0.001), indicating that higher music reward sensitivity is associated with a greater tendency to music‐related absorption states. In addition, four items from the AIMS were identified as suitable to be added to an extended version of the BMRQ (eBMRQ). A second sample (N = 550) completed the eBMRQ for a validation study. Exploratory and confirmatory factor analyses on the whole sample (N = 920) showed the reliable psychometric properties of the eBMRQ and suggested that taking into account an absorption facet could contribute to a better characterization of individual differences in the sensitivity to experience music‐related reward and pleasure.
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Date: 2022-05-17  ·  Issue: 2022  · 
Tight junction proteins occludin and ZO‐1 as regulators of epithelial proliferation and survival
Contributors: Wei‐Ting Kuo| Matthew A. Odenwald| Jerrold R. Turner| Li Zuo|
Abstract: Epithelial cells are the first line of mucosal defense. In the intestine, a single layer of epithelial cells must establish a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing the leakage of potentially harmful luminal materials. Key to this is the tight junction, which seals the paracellular space and prevents unrestricted leakage. The tight junction is a protein complex established by interactions between members of the claudin, zonula occludens, and tight junction‐associated MARVEL protein (TAMP) families. Claudins form the characteristic tight junction strands seen by freeze‐fracture microscopy and create paracellular channels, but the functions of ZO‐1 and occludin, founding members of the zonula occludens and TAMP families, respectively, are less well defined. Recent studies have revealed that these proteins have essential noncanonical (nonbarrier) functions that allow them to regulate epithelial apoptosis and proliferation, facilitate viral entry, and organize specialized epithelial structures. Surprisingly, neither is required for intestinal barrier function or overall health in the absence of exogenous stressors. Here, we provide a brief overview of ZO‐1 and occludin canonical (barrier‐related) functions, and a more detailed examination of their noncanonical functions.
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Date: 2022-05-17  ·  Issue: 2022  ·  Volume: 1514
Longitudinal and situational associations between math anxiety and performance among early adolescents
Contributors: Riikka Sorvo| Noona Kiuru| Tuire Koponen| Tuija Aro| Helena Viholainen| Timo Ahonen| Mikko Aro|
Abstract: Studies have found math anxiety and achievement to be related from the beginning of formal schooling, but the knowledge regarding the direction of the relationship is vague. The purpose of the present study was to study this relationship. We investigated math anxiety from two points of view: trait and state anxiety. In the first substudy, we investigated the longitudinal relationship between math anxiety and performance from sixth to seventh grade (n = 848) with cross‐lagged modeling. In the second substudy, we investigated the situational relationship of anxiety and performance by giving the participants (n = 149) challenging and nonchallenging math tasks adapted to their skill level, and then examining the association between anxiety and the performance. The results suggest that math anxiety has a small longitudinal effect on performance: High anxiety in sixth grade predicted low performance in seventh grade. Anxiety also had a situational association with performance: when anxiety was aroused, the participants performed more poorly compared to their skill level. The results adduce the two‐fold effect of anxiety on achievement: math anxiety seems to have both a real‐time association with performance and a long‐term effect on the development of basic arithmetic skills.
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Date: 2022-05-17  ·  Issue: 2022  ·  Volume: 1514
Predictive models for human–AI nexus in group decision making
Contributors: Omid Askarisichani| Francesco Bullo| Noah E. Friedkin| Ambuj K. Singh|
Abstract: Machine learning (ML) and artificial intelligence (AI) have had a profound impact on our lives. Domains like health and learning are naturally helped by human–AI interactions and decision making. In these areas, as ML algorithms prove their value in making important decisions, humans add their distinctive expertise and judgment on social and interpersonal issues that need to be considered in tandem with algorithmic inputs of information. Some questions naturally arise. What rules and regulations should be invoked on the employment of AI, and what protocols should be in place to evaluate available AI resources? What are the forms of effective communication and coordination with AI that best promote effective human–AI teamwork? In this review, we highlight factors that we believe are especially important in assembling and managing human–AI decision making in a group setting.
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Date: 2022-05-17  ·  Issue: 2022  ·  Volume: 1514
Tight junction proteins occludin and ZO‐1 as regulators of epithelial proliferation and survival
Contributors: Wei‐Ting Kuo| Matthew A. Odenwald| Jerrold R. Turner| Li Zuo|
Abstract: Epithelial cells are the first line of mucosal defense. In the intestine, a single layer of epithelial cells must establish a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing the leakage of potentially harmful luminal materials. Key to this is the tight junction, which seals the paracellular space and prevents unrestricted leakage. The tight junction is a protein complex established by interactions between members of the claudin, zonula occludens, and tight junction‐associated MARVEL protein (TAMP) families. Claudins form the characteristic tight junction strands seen by freeze‐fracture microscopy and create paracellular channels, but the functions of ZO‐1 and occludin, founding members of the zonula occludens and TAMP families, respectively, are less well defined. Recent studies have revealed that these proteins have essential noncanonical (nonbarrier) functions that allow them to regulate epithelial apoptosis and proliferation, facilitate viral entry, and organize specialized epithelial structures. Surprisingly, neither is required for intestinal barrier function or overall health in the absence of exogenous stressors. Here, we provide a brief overview of ZO‐1 and occludin canonical (barrier‐related) functions, and a more detailed examination of their noncanonical functions.
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Date: 2022-05-17  ·  Issue: 2022  ·  Volume: 1514
The dual GLP‐1 and GLP‐2 receptor agonist dapiglutide promotes barrier function in murine short bowel
Contributors: Johannes Reiner| Johanna Thiery| Jascha Held| Peggy Berlin| Jolanta Skarbaliene| Brigitte Vollmar| Robert Jaster| Per‐Olof Eriksson| Georg Lamprecht| Maria Witte|
Abstract: Short bowel syndrome can occur after extensive intestinal resection, causing intestinal insufficiency or intestinal failure, which requires long‐term parenteral nutrition. Glucagon‐like peptide‐2 (GLP‐2) pharmacotherapy is now clinically used to reduce the disease burden of intestinal failure. However, many patients still cannot be weaned off from parenteral nutrition completely. The novel dual GLP‐1 and GLP‐2 receptor agonist dapiglutide has previously been shown to be highly effective in a preclinical murine short bowel model. Here, we studied the effects of dapiglutide on intestinal epithelial barrier function. In the jejunum, dapiglutide increased claudin‐7 expression and tightened the paracellular tight junction leak pathway. At the same time, dapiglutide promoted paracellular tight junction cation size selectivity in the jejunum. This was paralleled by extension of the cation selective tight junction proteins claudin‐2 and claudin‐10b and preserved claudin‐15 expression and localization along the crypt–villus axis in the jejunum. In the colon, no barrier effects from dapiglutide were observed. In the colon, dapiglutide attenuated the short bowel–associated, compensatorily increased epithelial sodium channel activity, likely secondary, by improved volume status. Future studies are needed to address the intestinal adaptation of the colon.
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Date: 2022-05-17  ·  Issue: 2022  · 
The dual GLP‐1 and GLP‐2 receptor agonist dapiglutide promotes barrier function in murine short bowel
Contributors: Johannes Reiner| Johanna Thiery| Jascha Held| Peggy Berlin| Jolanta Skarbaliene| Brigitte Vollmar| Robert Jaster| Per‐Olof Eriksson| Georg Lamprecht| Maria Witte|
Abstract: Short bowel syndrome can occur after extensive intestinal resection, causing intestinal insufficiency or intestinal failure, which requires long‐term parenteral nutrition. Glucagon‐like peptide‐2 (GLP‐2) pharmacotherapy is now clinically used to reduce the disease burden of intestinal failure. However, many patients still cannot be weaned off from parenteral nutrition completely. The novel dual GLP‐1 and GLP‐2 receptor agonist dapiglutide has previously been shown to be highly effective in a preclinical murine short bowel model. Here, we studied the effects of dapiglutide on intestinal epithelial barrier function. In the jejunum, dapiglutide increased claudin‐7 expression and tightened the paracellular tight junction leak pathway. At the same time, dapiglutide promoted paracellular tight junction cation size selectivity in the jejunum. This was paralleled by extension of the cation selective tight junction proteins claudin‐2 and claudin‐10b and preserved claudin‐15 expression and localization along the crypt–villus axis in the jejunum. In the colon, no barrier effects from dapiglutide were observed. In the colon, dapiglutide attenuated the short bowel–associated, compensatorily increased epithelial sodium channel activity, likely secondary, by improved volume status. Future studies are needed to address the intestinal adaptation of the colon.
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Date: 2022-05-17  ·  Issue: 2022  · 
Longitudinal and situational associations between math anxiety and performance among early adolescents
Contributors: Riikka Sorvo| Noona Kiuru| Tuire Koponen| Tuija Aro| Helena Viholainen| Timo Ahonen| Mikko Aro|
Abstract: Studies have found math anxiety and achievement to be related from the beginning of formal schooling, but the knowledge regarding the direction of the relationship is vague. The purpose of the present study was to study this relationship. We investigated math anxiety from two points of view: trait and state anxiety. In the first substudy, we investigated the longitudinal relationship between math anxiety and performance from sixth to seventh grade (n = 848) with cross‐lagged modeling. In the second substudy, we investigated the situational relationship of anxiety and performance by giving the participants (n = 149) challenging and nonchallenging math tasks adapted to their skill level, and then examining the association between anxiety and the performance. The results suggest that math anxiety has a small longitudinal effect on performance: High anxiety in sixth grade predicted low performance in seventh grade. Anxiety also had a situational association with performance: when anxiety was aroused, the participants performed more poorly compared to their skill level. The results adduce the two‐fold effect of anxiety on achievement: math anxiety seems to have both a real‐time association with performance and a long‐term effect on the development of basic arithmetic skills.
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Date: 2022-05-16  ·  Issue: 2022  ·  Volume: 1511
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Date: 2022-05-08  ·  Issue: 2022  ·  Volume: 1514
Brain somatic mutations as RNA therapeutic targets in neurological disorders
Contributors: Sungyul Lee| Jeong Ho Lee|
Abstract: Research into the genetic etiology of a neurological disorder can provide directions for genetic diagnosis and targeted therapy. In the past, germline mutations, which are transmitted from parents or newly arise from parental germ cells, were considered as major genetic causes of neurological disorders. However, recent evidence has shown that somatic mutations in the brain, which can arise from neural stem cells during development or over aging, account for a significant number of brain disorders, ranging from neurodevelopmental, neurodegenerative, and neuropsychiatric to neoplastic disease. Moreover, the identification of disease‐causing somatic mutations or mutated genes has provided new insights into molecular pathogenesis and unveiled potential therapeutic targets for treating neurological disorders that have few, or no, therapeutic options. RNA therapeutics, including antisense oligonucleotide (ASO) and small interfering RNA (siRNA), are emerging as promising therapeutic tools for treating genetic neurological disorders. As the number of approved and investigational ASO and siRNA drugs for neurological disorders associated with germline mutations increases, they may also prove to be attractive modalities for treating neurologic disorders resulting from somatic mutations. In this perspective, we highlight several neurological diseases caused by brain somatic mutations and discuss the potential role of RNA therapeutics in these conditions.
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Date: 2022-05-08  ·  Issue: 2022  · 
Brain somatic mutations as RNA therapeutic targets in neurological disorders
Contributors: Sungyul Lee| Jeong Ho Lee|
Abstract: Research into the genetic etiology of a neurological disorder can provide directions for genetic diagnosis and targeted therapy. In the past, germline mutations, which are transmitted from parents or newly arise from parental germ cells, were considered as major genetic causes of neurological disorders. However, recent evidence has shown that somatic mutations in the brain, which can arise from neural stem cells during development or over aging, account for a significant number of brain disorders, ranging from neurodevelopmental, neurodegenerative, and neuropsychiatric to neoplastic disease. Moreover, the identification of disease‐causing somatic mutations or mutated genes has provided new insights into molecular pathogenesis and unveiled potential therapeutic targets for treating neurological disorders that have few, or no, therapeutic options. RNA therapeutics, including antisense oligonucleotide (ASO) and small interfering RNA (siRNA), are emerging as promising therapeutic tools for treating genetic neurological disorders. As the number of approved and investigational ASO and siRNA drugs for neurological disorders associated with germline mutations increases, they may also prove to be attractive modalities for treating neurologic disorders resulting from somatic mutations. In this perspective, we highlight several neurological diseases caused by brain somatic mutations and discuss the potential role of RNA therapeutics in these conditions.
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Date: 2022-05-04  ·  Issue: 2022  · 
From island biogeography to landscape and metacommunity ecology: A macroecological perspective of bat communities
Contributors: Steven J. Presley| Michael R. Willig|
Abstract: The equilibrium theory of island biogeography and its quantitative consideration of origination and extinction dynamics as they relate to island area and distance from source populations have evolved over time and enriched theory related to many disciplines in spatial ecology. Indeed, the island focus was catalytic to the emergence of landscape ecology and macroecology in the late 20th century. We integrate concepts and perspectives of island biogeography, landscape ecology, macroecology, and metacommunity ecology, and show how these disciplines have advanced the understanding of variation in abundance, biodiversity, and composition of bat communities. We leverage the well‐studied bat fauna of the islands in the Caribbean to illustrate the complex interplay of ecological, biogeographical, and evolutionary processes in molding local biodiversity and system‐wide structure. Thereafter, we highlight the role of habitat loss and fragmentation, which is increasing at an accelerating rate during the Anthropocene, on the structure of local bat communities and regional metacommunities across landscapes. Bat species richness increases with the amount of available habitat, often forming nested subsets along gradients of patch or island area. Similarly, the distance to and identity of sources of colonization influence the richness, composition, and metacommunity structure of islands and landscape networks.
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Date: 2022-05-04  ·  Issue: 2022  ·  Volume: 1514
Modifying the blood–brain barrier by targeting claudin‐5: Safety and risks
Contributors: Erika Wakayama| Taiki Kuzu| Keisuke Tachibana| Ryuichi Hirayama| Yoshiaki Okada| Masuo Kondoh|
Abstract: The blood–brain barrier is a major obstacle to the delivery of drugs to the central nervous system. In the blood–brain barrier, the spaces between adjacent brain microvascular endothelial cells are sealed by multiprotein complexes known as tight junctions. Among the many components of the tight junction, claudin‐5 has received the most attention as a target for loosening the tight‐junction seal and allowing drugs to be delivered to the brain. In mice, transient knockdown of claudin‐5 and the use of claudin‐5 binders have been shown to enhance the permeation of small molecules from the blood into the brain without apparent adverse effects. However, sustained knockdown of claudin‐5 in mice is lethal within 40 days, and administration of an anti‐claudin‐5 antibody induced convulsions in a nonhuman primate. Here, we review the safety concerns of claudin‐5–targeted technologies with respect to their clinical application.
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Date: 2022-05-04  ·  Issue: 2022  ·  Volume: 1514
Social communication therapy for children at risk for neurodevelopmental difficulties: Protocol for a clinical trial
Contributors: Priscilla B. G. Godoy| Elizabeth Shephard| Adriana Argeu| Leticia R. Silveira| Erica Salomone| Catherine Aldred| Jonathan Green| Guilherme V. Polanczyk| Alicia Matijasevich|
Abstract: Exposure to adverse environments are risk factors for neurodevelopmental problems in childhood. Children exposed to such environments may benefit from interventions that target social communication abilities, since these are protective factors for healthy neurodevelopment. This randomized controlled trial will test the efficacy of Paediatric Autism Communication Therapy (PACT) in improving social communication development in young children at risk for neurodevelopmental difficulties living in poverty in Brazil. Participants will be 160 children aged 2–4 years with lower‐than‐average social communication abilities and their primary caregivers. Child–caregiver dyads will be recruited from public childhood education centers in impoverished urban regions of the city of São Paulo, Brazil. Lower‐than‐average social communication abilities will be defined by standard scores (≤84) on the socialization and/or communication domains of the Vineland Adaptive Behavior Scales. Child–caregiver dyads will be randomized to receive 12 sessions of the PACT intervention (n = 80) or 5 months of community support as usual plus psychoeducation (n = 80). The primary outcome (parent–child interaction) and secondary outcomes (parent‐reported social communication abilities and neurophysiological activity during a live social interaction) will be measured pre‐ and postintervention. This study may lead to new interventions for vulnerable young children in Brazil and better understanding of the neural mechanisms of PACT.
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Date: 2022-05-04  ·  Issue: 2022  · 
Modifying the blood–brain barrier by targeting claudin‐5: Safety and risks
Contributors: Erika Wakayama| Taiki Kuzu| Keisuke Tachibana| Ryuichi Hirayama| Yoshiaki Okada| Masuo Kondoh|
Abstract: The blood–brain barrier is a major obstacle to the delivery of drugs to the central nervous system. In the blood–brain barrier, the spaces between adjacent brain microvascular endothelial cells are sealed by multiprotein complexes known as tight junctions. Among the many components of the tight junction, claudin‐5 has received the most attention as a target for loosening the tight‐junction seal and allowing drugs to be delivered to the brain. In mice, transient knockdown of claudin‐5 and the use of claudin‐5 binders have been shown to enhance the permeation of small molecules from the blood into the brain without apparent adverse effects. However, sustained knockdown of claudin‐5 in mice is lethal within 40 days, and administration of an anti‐claudin‐5 antibody induced convulsions in a nonhuman primate. Here, we review the safety concerns of claudin‐5–targeted technologies with respect to their clinical application.
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Date: 2022-05-04  ·  Issue: 2022  ·  Volume: 1514
From island biogeography to landscape and metacommunity ecology: A macroecological perspective of bat communities
Contributors: Steven J. Presley| Michael R. Willig|
Abstract: The equilibrium theory of island biogeography and its quantitative consideration of origination and extinction dynamics as they relate to island area and distance from source populations have evolved over time and enriched theory related to many disciplines in spatial ecology. Indeed, the island focus was catalytic to the emergence of landscape ecology and macroecology in the late 20th century. We integrate concepts and perspectives of island biogeography, landscape ecology, macroecology, and metacommunity ecology, and show how these disciplines have advanced the understanding of variation in abundance, biodiversity, and composition of bat communities. We leverage the well‐studied bat fauna of the islands in the Caribbean to illustrate the complex interplay of ecological, biogeographical, and evolutionary processes in molding local biodiversity and system‐wide structure. Thereafter, we highlight the role of habitat loss and fragmentation, which is increasing at an accelerating rate during the Anthropocene, on the structure of local bat communities and regional metacommunities across landscapes. Bat species richness increases with the amount of available habitat, often forming nested subsets along gradients of patch or island area. Similarly, the distance to and identity of sources of colonization influence the richness, composition, and metacommunity structure of islands and landscape networks.
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Date: 2022-05-04  ·  Issue: 2022  ·  Volume: 1514
Cross‐talk of four types of RNA modification writers defines the immune microenvironment in severe asthma
Contributors: Qibin Lin| Haiyang Ni| Zhishui Zheng| Jieying Zhong| Hanxiang Nie|
Abstract: Adenine modifications, including m6A, m1A, APA, and A‐to‐I modifications, are the most impactful RNA modifications. These modifications are primarily produced by enzymes called writers. The main purpose of this study was to explore the cross‐talk and potential roles of these writers in severe asthma. We found 13 RNA writers potentially related to severe asthma and three RNA modification patterns. Cluster 3 showed predominant neutrophil infiltration and C‐type lectin receptor signaling; cluster 1 showed predominant innate immune cell infiltration and ubiquitin–proteasome system activation; and cluster 2 did not show obvious immune infiltration characteristics. We found that RNA modification writers modified immune cell–related genes and led to both accumulation of different immune cells in the airways and activation of a series of biological processes, which ultimately leads to severe asthma. TRMT6, WTAP, and TRMT6A were included in a random forest model as predictors. Cromoglicic acid, thioperamide, and fluvastatin were potential drugs for clusters 1, 2, and 3, respectively. We found that cross‐talk of RNA modifications is significant in severe asthma, which provides insight into severe asthma pathogenesis and possible treatment avenues.
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Date: 2022-04-20  ·  Issue: 2022  ·  Volume: 1513
Nutrition modeling tools: a qualitative study of influence on policy decision making and determining factors
Contributors: Frances Knight| Megan W. Bourassa| Elaine Ferguson| Helen Walls| Saskia Pee| Stephen Vosti| Homero Martinez| Carol Levin| Monica Woldt| Kavita Sethurman| Gilles Bergeron|
Abstract: Nutrition modeling tools (NMTs) generate evidence to inform policy and program decision making; however, the literature is generally limited to modeling methods and results, rather than use cases and their impacts. We aimed to document the policy influences of 12 NMTs and identify factors influencing them. We conducted semistructured interviews with 109 informants from 30 low‐ and middle‐income country case studies and used thematic analysis to understand the data. NMTs were mostly applied by international organizations to inform national government decision making. NMT applications contributed to enabling environments for nutrition and influenced program design and policy in most cases; however, this influence could be strengthened. Influence was shaped by processes for applying the NMTs; ownership of the analysis and data inputs, and capacity building in NMT methods, encouraged uptake. Targeting evidence generation at specific policy cycle stages promoted uptake; however, where advocacy capacity allowed, modeling was embedded ad hoc into emerging policy discussions and had broader influence. Meanwhile, external factors, such as political change and resource constraints of local partner organizations, challenged NMT implementation. Importantly, policy uptake was never the result of NMTs exclusively, indicating they should be nested persistently and strategically within the wider evidence and advocacy continuum, rather than being stand‐alone activities.
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Date: 2022-04-18  ·  Issue: 2022  ·  Volume: 1513
Embodied learning in multiple sclerosis using melodic, sound, and visual feedback: a potential rehabilitation approach
Contributors: Lousin Moumdjian| Joren Six| Renee Veldkamp| Jenke Geys| Channa Van Der Linden| Mieke Goetschalckx| Johan Van Nieuwenhoven| Ilse Bosmans| Marc Leman| Peter Feys|
Abstract: Given the prevalence of motor and cognitive functions in persons with multiple sclerosis (PwMS), we proposed that the theoretical framework of embodiment could provide a rehabilitation avenue to train these functions as one functional unit. PwMS (n = 31) and age‐ and gender‐matched healthy controls (n = 30) underwent an embodied learning protocol. This involved learning a cognitive sequence while performing it through bodily stepping movement under three feedback conditions (melody, sound, and visual). Cognitive and movement performance was assessed by a delayed recall 15 min after undergoing the embodied learning protocol. Half of participants correctly recalled the sequence in all three conditions, while 70% of healthy controls achieved correct recall within the melody condition. Balance impairment predicted the speed of executing the sequence irrespective of learning, most apparent in the melody condition. Information processing speed predicted the speed of executing the sequence in the melody and sound conditions between participants as well as over time. Those who learned performed the sequence faster in the melody condition only and overall were faster over time. We propose how embodied learning could expand the current context of rehabilitation of cognitive and motor control in PwMS.
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Date: 2022-04-18  ·  Issue: 2022  · 
Embodied learning in multiple sclerosis using melodic, sound, and visual feedback: a potential rehabilitation approach
Contributors: Lousin Moumdjian| Joren Six| Renee Veldkamp| Jenke Geys| Channa Van Der Linden| Mieke Goetschalckx| Johan Van Nieuwenhoven| Ilse Bosmans| Marc Leman| Peter Feys|
Abstract: Given the prevalence of motor and cognitive functions in persons with multiple sclerosis (PwMS), we proposed that the theoretical framework of embodiment could provide a rehabilitation avenue to train these functions as one functional unit. PwMS (n = 31) and age‐ and gender‐matched healthy controls (n = 30) underwent an embodied learning protocol. This involved learning a cognitive sequence while performing it through bodily stepping movement under three feedback conditions (melody, sound, and visual). Cognitive and movement performance was assessed by a delayed recall 15 min after undergoing the embodied learning protocol. Half of participants correctly recalled the sequence in all three conditions, while 70% of healthy controls achieved correct recall within the melody condition. Balance impairment predicted the speed of executing the sequence irrespective of learning, most apparent in the melody condition. Information processing speed predicted the speed of executing the sequence in the melody and sound conditions between participants as well as over time. Those who learned performed the sequence faster in the melody condition only and overall were faster over time. We propose how embodied learning could expand the current context of rehabilitation of cognitive and motor control in PwMS.
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Date: 2022-04-16  ·  Issue: 2022  · 
Mathematics–gender stereotype endorsement influences mathematics anxiety, self‐concept, and performance differently in men and women
Contributors: Serena Rossi| Iro Xenidou‐Dervou| Emine Simsek| Christina Artemenko| Gabriella Daroczy| Hans‐Christoph Nuerk| Krzysztof Cipora|
Abstract: Mathematics anxiety (MA) is negatively associated with mathematics performance. Although some aspects, such as mathematics self‐concept (M self‐concept), seem to modulate this association, the underlying mechanism is still unclear. In addition, the false gender stereotype that women are worse than men in mathematics can have a detrimental effect on women. The role that the endorsement of this stereotype (mathematics–gender stereotype (MGS) endorsement) can play may differ between men and women. In this study, we investigated how MA and mathematics self‐concept relate to arithmetic performance when considering one's MGS endorsement and gender in a large sample (n = 923) of university students. Using a structural equation modeling approach, we found that MA and mathematics self‐concept mediated the effect of MGS endorsement in both men and women. For women, MGS endorsement increased their MA level, while in men, it had the opposite effect (albeit weak). Specifically, in men, MGS endorsement influenced the level of the numerical components of MA, but, unlike women, it also positively influenced their mathematics self‐concept. Moreover, men and women perceived the questions included in the considered instruments differently, implying that the scores obtained in these questionnaires may not be directly comparable between genders, which has even broader theoretical and methodological implications for MA research.
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Date: 2022-04-16  ·  Issue: 2022  ·  Volume: 1513
Mathematics–gender stereotype endorsement influences mathematics anxiety, self‐concept, and performance differently in men and women
Contributors: Serena Rossi| Iro Xenidou‐Dervou| Emine Simsek| Christina Artemenko| Gabriella Daroczy| Hans‐Christoph Nuerk| Krzysztof Cipora|
Abstract: Mathematics anxiety (MA) is negatively associated with mathematics performance. Although some aspects, such as mathematics self‐concept (M self‐concept), seem to modulate this association, the underlying mechanism is still unclear. In addition, the false gender stereotype that women are worse than men in mathematics can have a detrimental effect on women. The role that the endorsement of this stereotype (mathematics–gender stereotype (MGS) endorsement) can play may differ between men and women. In this study, we investigated how MA and mathematics self‐concept relate to arithmetic performance when considering one's MGS endorsement and gender in a large sample (n = 923) of university students. Using a structural equation modeling approach, we found that MA and mathematics self‐concept mediated the effect of MGS endorsement in both men and women. For women, MGS endorsement increased their MA level, while in men, it had the opposite effect (albeit weak). Specifically, in men, MGS endorsement influenced the level of the numerical components of MA, but, unlike women, it also positively influenced their mathematics self‐concept. Moreover, men and women perceived the questions included in the considered instruments differently, implying that the scores obtained in these questionnaires may not be directly comparable between genders, which has even broader theoretical and methodological implications for MA research.
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Date: 2022-04-13  ·  Issue: 2022  ·  Volume: 1513
Cortistatin attenuates titanium particle–induced osteolysis through regulation of TNFR1–ROS–caspase‐3 signaling in osteoblasts
Contributors: Jiankang Cao| Xiaojie Ma| Long Liu| Gaorui Zhang| Yawei Wu| Yu Fu| Ao Gong| Zhongbo Yang| Yunpeng Zhao| Lei Zhang| Yuhua Li|
Abstract: Aseptic loosening is a major complication of prosthetic joint surgery and is associated with impaired osteoblast homeostasis. Cortistatin (CST) is a neuropeptide that protects against inflammatory conditions. In this study, we found that expression of CST was diminished in patients with prosthetic joint loosening and in titanium (Ti) particle–induced animal models. A Ti particle–induced calvarial osteolysis model was established in wild‐type and CST gene knockout mice; CST deficiency enhanced, while exogenously added CST attenuated, the severity of Ti particle–mediated osteolysis. CST protected against inflammation as well as apoptosis and maintained the osteogenic function of MC3T3‐E1 osteoblasts upon stimulation with Ti particles. Furthermore, CST antagonized reactive oxygen species production and suppressed caspase‐3–associated apoptosis mediated by Ti particles in osteoblasts. Additionally, CST protects against Ti particle–induced osteolysis through tumor necrosis factor receptor 1. Taken together, CST might provide a therapeutic strategy for wear debris–induced inflammatory osteolysis.
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Date: 2022-04-13  ·  Issue: 2022  ·  Volume: 1510
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Date: 2022-04-07  ·  Issue: 2022  · 
Math anxiety and deficient executive control: does reappraisal modulate this link?
Contributors: Lital Daches Cohen| Orly Rubinsten|
Abstract: The literature suggests an interplay between executive control functions and emotion regulation processes, with each playing a key role in math anxiety. We examined the relation between the use of two different emotion regulation strategies (reappraisal and suppression) and the ability to reduce emotional interference in high‐conflict situations (i.e., executive control of attention) in cases of math anxiety. A sample of 107 adults completed emotion regulation tendencies and math anxiety questionnaires and performed a flanker task following the priming of a math‐related or negative word. The findings revealed: (1) highly math‐anxious individuals had difficulty controlling emotional distractions induced by math information, even as simple as math‐related words, in high‐conflict conditions; and (2) the tendency to use reappraisal in everyday situations was associated with math‐anxious individuals’ ability to avoid heightened emotional reactions when encountering math‐related (i.e., threatening) information. These findings point to the efficacy of reappraisal‐focused intervention and suggest an innovative mechanism through which reappraisal reduces emotional reactions and improves performance among math‐anxious individuals, indicating a new way to approach interventions for math anxiety.
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Date: 2022-04-01  ·  Issue: 2022  · 
Mathematics anxiety in deaf, hard of hearing, and hearing college students
Contributors: Akriti Mishra| Kristin Walker| Briana Oshiro| Clifton Langdon| Marie Coppola|
Abstract: While mathematics anxiety (MA) has been widely researched in recent decades, this study addresses significant gaps: namely, research that explores the relationship between MA and self‐reported mathematics experiences; samples adults with a range of MA levels; and controls for general anxiety. Additionally, the study sampled deaf and hard of hearing (DHH) students, whose diverse life and educational experiences often differ from hearing students’. We investigated whether DHH students’ experiences with mathematics (i.e., parental behaviors, school environment, and mathematics feelings) and demographic variables (i.e., hearing status, age, and gender) predict their MA, and whether these relationships differ from those in hearing students. Self‐report questionnaires were completed by 296 DHH and hearing college students. Linear regression analyses controlling for general anxiety led to the following inference: DHH students who reported more positive attitudes toward mathematics and school environments demonstrated higher MA. Also, the relationships between mathematics feelings, parental behaviors, and MA differed between DHH and hearing students. Logistic regression analyses showed no contribution of MA to students’ likelihood of pursuing STEM degrees in either DHH or between DHH and hearing groups. Overall, this work breaks new ground in the study of MA in DHH students and challenges standard views of the relationships between MA and individual experiences.
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Date: 2022-04-01  ·  Issue: 2022  ·  Volume: 1513
Mathematics anxiety in deaf, hard of hearing, and hearing college students
Contributors: Akriti Mishra| Kristin Walker| Briana Oshiro| Clifton Langdon| Marie Coppola|
Abstract: While mathematics anxiety (MA) has been widely researched in recent decades, this study addresses significant gaps: namely, research that explores the relationship between MA and self‐reported mathematics experiences; samples adults with a range of MA levels; and controls for general anxiety. Additionally, the study sampled deaf and hard of hearing (DHH) students, whose diverse life and educational experiences often differ from hearing students’. We investigated whether DHH students’ experiences with mathematics (i.e., parental behaviors, school environment, and mathematics feelings) and demographic variables (i.e., hearing status, age, and gender) predict their MA, and whether these relationships differ from those in hearing students. Self‐report questionnaires were completed by 296 DHH and hearing college students. Linear regression analyses controlling for general anxiety led to the following inference: DHH students who reported more positive attitudes toward mathematics and school environments demonstrated higher MA. Also, the relationships between mathematics feelings, parental behaviors, and MA differed between DHH and hearing students. Logistic regression analyses showed no contribution of MA to students’ likelihood of pursuing STEM degrees in either DHH or between DHH and hearing groups. Overall, this work breaks new ground in the study of MA in DHH students and challenges standard views of the relationships between MA and individual experiences.
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Date: 2022-03-31  ·  Issue: 2022  ·  Volume: 1513
Fortification of staple foods with calcium: a novel costing tool to inform decision making
Contributors: Alfredo Palacios| Carlos Rojas‐Roque| Dario Balan| Isabela Sosa Estani| José M. Belizán| Gabriela Cormick| Federico Augustovski|
Abstract: Low calcium intake and its impact on maternal and child health are a major concern in low‐ and middle‐income countries. Given the low calcium in diet, as well as the low adherence and acceptability of calcium pills in those settings, the discussion about policies to increase calcium intake has moved toward staple food fortification strategies. Nevertheless, there is scarce information on the economic feasibility of implementing these strategies. We aimed to design and propose a novel costing tool to estimate the cost of the flour fortification with calcium by carrying out a literature review about costing studies for staple food fortification programs and costing tools previously developed. A deliberative meeting with stakeholders was held to discuss and face‐validate the conceptual framework proposed. We showed the costing tool application for the case of Costa Rica (a country with a population with low calcium intake), including the absolute cost of the staple food fortification production process, the incremental cost of fortification according to the public/private sector, and the incremental cost by target population. This open‐source and publicly available costing tool can be useful to inform policymaking in countries considering the implementation of staple food fortification programs.
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Date: 2022-03-27  ·  Issue: 2022  ·  Volume: 1510
Corrigendum for Ann. N. Y. Acad. Sci. 2020. 1478: 18–42
Contributors:
Abstract:
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Date: 2022-03-25  ·  Issue: 2022  ·  Volume: 1513
Mathematical progression of avian egg shape with associated area and volume determinations
Contributors: Valeriy G. Narushin| Michael N. Romanov| Birendra Mishra| Darren K. Griffin|
Abstract: Development of nondestructive techniques for estimating egg parameters requires a comprehensive approach based on mathematical theory. Basic properties used to solve theoretical and applied problems in this respect are volume (V) and surface area (S). There are respective formulae for calculating V and S of spherical, ellipsoidal, and ovoid eggs in classical egg geometry; however, the mathematical description and calculation of these parameters for pyriform eggs have remained elusive. In the present study, we derived the appropriate formulae and established that this would be not only applicable and valid for the category of pyriform eggs, but also universal and explicit for all other naturally occurring avian egg shapes. Thus, we have demonstrated “mathematical progression” of this natural object, considering the egg as a sequence of geometric figures that transform from one to another in the following sequence of shapes: sphere → ellipsoid → ovoid (whose profile corresponds to Hügelschäffer's model) → pyriform ovoid.
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Date: 2022-03-23  ·  Issue: 2022  ·  Volume: 1513
Mathematics anxiety—where are we and where shall we go?
Contributors: Krzysztof Cipora| Flavia H. Santos| Karin Kucian| Ann Dowker|
Abstract: In this paper, we discuss several largely undisputed claims about mathematics anxiety (MA) and propose where MA research should focus, including theoretical clarifications on what MA is and what constitutes its opposite pole; discussion of construct validity, specifically relations between self‐descriptive, neurophysiological, and cognitive measures; exploration of the discrepancy between state and trait MA and theoretical and practical consequences; discussion of the prevalence of MA and the need for establishing external criteria for estimating prevalence and a proposal for such criteria; exploration of the effects of MA in different groups, such as highly anxious and high math–performing individuals; classroom and policy applications of MA knowledge; the effects of MA outside educational settings; and the consequences of MA on mental health and well‐being.
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Date: 2022-03-23  ·  Issue: 2022  · 
Mathematics anxiety—where are we and where shall we go?
Contributors: Krzysztof Cipora| Flavia H. Santos| Karin Kucian| Ann Dowker|
Abstract: In this paper, we discuss several largely undisputed claims about mathematics anxiety (MA) and propose where MA research should focus, including theoretical clarifications on what MA is and what constitutes its opposite pole; discussion of construct validity, specifically relations between self‐descriptive, neurophysiological, and cognitive measures; exploration of the discrepancy between state and trait MA and theoretical and practical consequences; discussion of the prevalence of MA and the need for establishing external criteria for estimating prevalence and a proposal for such criteria; exploration of the effects of MA in different groups, such as highly anxious and high math–performing individuals; classroom and policy applications of MA knowledge; the effects of MA outside educational settings; and the consequences of MA on mental health and well‐being.
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Date: 2022-03-21  ·  Issue: 2022  ·  Volume: 1513
How have COVID‐19 stringency measures changed scholarly activity?
Contributors: Kim M. Caudwell| Alessandro Soranzo| Lee Wei Lim| Luca Aquili|
Abstract: Government restrictions to the movement of people due to the COVID‐19 pandemic have had a wide range of effects on scientific activity. Here, we show that during the pandemic there has been a reduction in the number of registered non‐COVID‐19 clinical trials. Furthermore, using the Oxford COVID‐19 Government Response Tracker Stringency Index (SI) as an indicator of COVID‐19–related workplace adjustment (e.g., restrictions on gatherings, workplace closures, and stay‐at‐home orders), we demonstrate that this drop in clinical trial registration has been greater in countries with a higher SI. This could have significant consequences for the discovery of treatments that are required to reduce the global burden of disease.
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Date: 2022-03-15  ·  Issue: 2022  · 
Evidence of cortical thickness increases in bilateral auditory brain structures following piano learning in older adults
Contributors: Florian Worschech| Eckart Altenmüller| Kristin Jünemann| Christopher Sinke| Tillmann H. C. Krüger| Daniel S. Scholz| Cécile A. H. Müller| Matthias Kliegel| Clara E. James| Damien Marie|
Abstract: Morphological differences in the auditory brain of musicians compared to nonmusicians are often associated with life‐long musical activity. Cross‐sectional studies, however, do not allow for any causal inferences, and most experimental studies testing music‐driven adaptations investigated children. Although the importance of the age at which musical training begins is widely recognized to impact neuroplasticity, there have been few longitudinal studies examining music‐related changes in the brains of older adults. Using magnetic resonance imaging, we measured cortical thickness (CT) of 12 auditory‐related regions of interest before and after 6 months of musical instruction in 134 healthy, right‐handed, normal‐hearing, musically‐naive older adults (64–76 years old). Prior to the study, all participants were randomly assigned to either piano training or to a musical culture/music listening group. In five regions—left Heschl's gyrus, left planum polare, bilateral superior temporal sulcus, and right Heschl's sulcus—we found an increase in CT in the piano training group compared with the musical culture group. Furthermore, CT of the right Heschl's gyrus could be identified as a morphological substrate supporting speech in noise perception. The results support the conclusion that playing an instrument is an effective stimulator for cortical plasticity, even in older adults.
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Date: 2022-03-15  ·  Issue: 2022  ·  Volume: 1513
Evidence of cortical thickness increases in bilateral auditory brain structures following piano learning in older adults
Contributors: Florian Worschech| Eckart Altenmüller| Kristin Jünemann| Christopher Sinke| Tillmann H. C. Krüger| Daniel S. Scholz| Cécile A. H. Müller| Matthias Kliegel| Clara E. James| Damien Marie|
Abstract: Morphological differences in the auditory brain of musicians compared to nonmusicians are often associated with life‐long musical activity. Cross‐sectional studies, however, do not allow for any causal inferences, and most experimental studies testing music‐driven adaptations investigated children. Although the importance of the age at which musical training begins is widely recognized to impact neuroplasticity, there have been few longitudinal studies examining music‐related changes in the brains of older adults. Using magnetic resonance imaging, we measured cortical thickness (CT) of 12 auditory‐related regions of interest before and after 6 months of musical instruction in 134 healthy, right‐handed, normal‐hearing, musically‐naive older adults (64–76 years old). Prior to the study, all participants were randomly assigned to either piano training or to a musical culture/music listening group. In five regions—left Heschl's gyrus, left planum polare, bilateral superior temporal sulcus, and right Heschl's sulcus—we found an increase in CT in the piano training group compared with the musical culture group. Furthermore, CT of the right Heschl's gyrus could be identified as a morphological substrate supporting speech in noise perception. The results support the conclusion that playing an instrument is an effective stimulator for cortical plasticity, even in older adults.
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Date: 2022-03-14  ·  Issue: 2022  ·  Volume: 1513
Biomimetic approach to articular cartilage tissue engineering using carbon nanotube–coated and textured polydimethylsiloxane scaffolds
Contributors: Katrín Lind Elídóttir| Louie Scott| Rebecca Lewis| Izabela Jurewicz|
Abstract: There is a significant need to understand the complexity and heterogeneity of articular cartilage to develop more effective therapeutic strategies for diseases such as osteoarthritis. Here, we show that carbon nanotubes (CNTs) are excellent candidates as a material for synthetic scaffolds to support the growth of chondrocytes—the cells that produce and maintain cartilage. Chondrocyte morphology, proliferation, and alignment were investigated as nanoscale CNT networks were applied to macroscopically textured polydimethylsiloxane (PDMS) scaffolds. The application of CNTs to the surface of PDMS‐based scaffolds resulted in an up to 10‐fold increase in cell adherence and 240% increase in proliferation, which is attributable to increased nanoscale roughness and hydrophilicity. The introduction of macroscale features to PDMS induced alignment of chondrocytes, successfully mimicking the cell behavior observed in the superficial layer of cartilage. Raman spectroscopy was used as a noninvasive, label‐free method to monitor extracellular matrix production and chondrocyte phenotype. Chondrocytes on these scaffolds successfully produced collagen, glycosaminoglycan, and aggrecan. This study demonstrates that introducing physical features at different length scales allows for a high level of control over tissue scaffold design and, thus, cell behavior. Ultimately, these textured scaffolds can serve as platforms to improve the understanding of osteoarthritis and for early‐stage therapeutic testing.
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Date: 2022-03-11  ·  Issue: 2022  ·  Volume: 1509
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Date: 2022-03-11  ·  Issue: 2022  ·  Volume: 1509
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Date: 2022-03-10  ·  Issue: 2022  ·  Volume: 1512
A new method for training creativity: narrative as an alternative to divergent thinking
Contributors: Angus Fletcher| Mike Benveniste|
Abstract: Creativity is a major source of innovation, growth, adaptability, and psychological resilience, making it a top priority of governments, global corporations, educational institutions, and other organizations that collectively invest hundreds of millions of dollars annually into training. The current foundation of creativity training is the technique known as divergent thinking; yet for decades, concerns have been raised about the adequacy of divergent thinking: it is incongruent with the creative processes of children and most adult creatives, and it has failed to yield expected downstream results in creative production. In this article, we present an alternative approach to creativity training, based in neural processes different from those involved in divergent thinking and drawing upon a previously unused resource for creativity research: narrative theory. We outline a narrative theory of creativity training; illustrate with examples of training and assessment from our ongoing work with the U.S. Department of Defense, Fortune 50 companies, and graduate and professional schools; and explain how the theory can help fill prominent lacunae and gaps in existing creativity research, including the creativity of children, the psychological mechanisms of scientific and technological innovation, and the failure of computer artificial intelligence to replicate human creativity.
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Date: 2022-03-10  ·  Issue: 2022  ·  Volume: 1512
Spatialization in working memory and its relation to math anxiety
Contributors: Jean‐Philippe Dijck| Wim Fias| Krzysztof Cipora|
Abstract: Working memory (WM) is one of the most important cognitive functions that may play a role in the relation between math anxiety (MA) and math performance. The processing efficiency theory proposes that rumination and worrisome thoughts (induced by MA) result in less available WM resources (which are needed to solve math problems). At the same time, high MA individuals have lower verbal and spatial WM capacity in general. Extending these findings, we found that MA is also linked to the spatial coding of serial order in verbal WM: subjects who organize sequences from left‐to‐right in verbal WM show lower levels of MA compared with those who do not spatialize. Furthermore, these spatial coders have higher verbal WM capacity, better numerical order judgment abilities, and higher math scores. These findings suggest that spatially structuring the verbal mind is a promising cognitive correlate of MA and opens new avenues for exploring causal links between elementary cognitive processes and MA.
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Date: 2022-03-10  ·  Issue: 2022  · 
Spatialization in working memory and its relation to math anxiety
Contributors: Jean‐Philippe Dijck| Wim Fias| Krzysztof Cipora|
Abstract: Working memory (WM) is one of the most important cognitive functions that may play a role in the relation between math anxiety (MA) and math performance. The processing efficiency theory proposes that rumination and worrisome thoughts (induced by MA) result in less available WM resources (which are needed to solve math problems). At the same time, high MA individuals have lower verbal and spatial WM capacity in general. Extending these findings, we found that MA is also linked to the spatial coding of serial order in verbal WM: subjects who organize sequences from left‐to‐right in verbal WM show lower levels of MA compared with those who do not spatialize. Furthermore, these spatial coders have higher verbal WM capacity, better numerical order judgment abilities, and higher math scores. These findings suggest that spatially structuring the verbal mind is a promising cognitive correlate of MA and opens new avenues for exploring causal links between elementary cognitive processes and MA.
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Date: 2022-03-05  ·  Issue: 2022  ·  Volume: 1512
Calcium deficiency worldwide: prevalence of inadequate intakes and associated health outcomes
Contributors: Julie Shlisky| Rubina Mandlik| Sufia Askari| Steven Abrams| Jose M. Belizan| Megan W. Bourassa| Gabriela Cormick| Amalia Driller‐Colangelo| Filomena Gomes| Anuradha Khadilkar| Victor Owino| John M. Pettifor| Ziaul H. Rana| Daniel E. Roth| Connie Weaver|
Abstract: Dietary calcium deficiency is considered to be widespread globally, with published estimates suggesting that approximately half of the world's population has inadequate access to dietary calcium. Calcium is essential for bone health, but inadequate intakes have also been linked to other health outcomes, including pregnancy complications, cancers, and cardiovascular disease. Populations in low‐ and middle‐income countries (LMICs) are at greatest risk of low calcium intakes, although many individuals in high‐income countries (HICs) also do not meet recommendations. Paradoxically, many LMICs with lower calcium intakes show lower rates of osteoporotic fracture as compared with HICs, though data are sparse. Calcium intake recommendations vary across agencies and may need to be customized based on other dietary factors, health‐related behaviors, or the risk of calcium‐related health outcomes. The lack of standard methods to assess the calcium status of an individual or population has challenged efforts to estimate the prevalence of calcium deficiency and the global burden of related adverse health consequences. This paper aims to consolidate available evidence related to the global prevalence of inadequate calcium intakes and associated health outcomes, with the goal of providing a foundation for developing policies and population‐level interventions to safely improve calcium intake and status where necessary.
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Date: 2022-03-05  ·  Issue: 2022  ·  Volume: 1512
Ovarian cancer‐specific dysregulated genes with prognostic significance: scRNA‐Seq with bulk RNA‐Seq data and experimental validation
Contributors: Chang Liu| Ying Zhang| Xiaohan Li| Dandan Wang|
Abstract: A major cause of gynecological cancer ‐related deaths worldwide, ovarian cancer is characterized by heterogeneity in both tumor cells and the tumor microenvironment (TME). Our study aimed to characterize tumor cell heterogeneity and the infiltration of M2 tumor‐associated macrophages (TAMs) in the ovarian cancer TME by single‐cell RNA‐Seq (scRNA‐Seq) analysis combined with bulk RNA sequencing (bulk RNA‐Seq). Several highly variable genes were identified in ovarian cancer tissues, and tumor cell heterogeneity and infiltrating immune tumor cell heterogeneity were characterized in ovarian cancer cells. M2 TAMs in the TME were the predominant phenotype of TAM. Further, M2 TAM infiltration in the TME was negatively correlated with poor prognosis of ovarian cancer patients. Four M2 TAM‐associated genes (SLAMF7, GNAS, TBX2‐AS1, and LYPD6) correlated with the prognostic survival of ovarian cancer patients. Knockdown of SLAMF7 or GNAS mRNA repressed malignancy and cisplatin resistance of ovarian cancer cells. ScRNA‐Seq combined with bulk RNA‐Seq identified the same four genes associated with M2 TAMs. The prognostic risk score model based on these four genes may hold favorable predictive value for the prognosis of ovarian cancer patients.
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Date: 2022-02-28  ·  Issue: 2022  ·  Volume: 1512
Vocal melody and musical background are simultaneously processed by the brain for musical predictions
Contributors: Thibault Chabin| Lionel Pazart| Damien Gabriel|
Abstract: Musical pleasure is related to the capacity to predict and anticipate the music. By recording early cerebral responses of 16 participants with electroencephalography during periods of silence inserted in known and unknown songs, we aimed to measure the contribution of different musical attributes to musical predictions. We investigated the mismatch between past encoded musical features and the current sensory inputs when listening to lyrics associated with vocal melody, only background instrumental material, or both attributes grouped together. When participants were listening to chords and lyrics for known songs, the brain responses related to musical violation produced event‐related potential responses around 150–200 ms that were of a larger amplitude than for chords or lyrics only. Microstate analysis also revealed that for chords and lyrics, the global field power had an increased stability and a longer duration. The source localization identified that the right superior temporal and frontal gyri and the inferior and medial frontal gyri were activated for a longer time for chords and lyrics, likely caused by the increased complexity of the stimuli. We conclude that grouped together, a broader integration and retrieval of several musical attributes at the same time recruit larger neuronal networks that lead to more accurate predictions.
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Date: 2022-02-27  ·  Issue: 2022  · 
Testing the specificity of links between anxiety and performance within mathematics and spatial reasoning
Contributors: Richard J. Daker| Véronic Delage| Erin A. Maloney| Ian M. Lyons|
Abstract: Anxiety within the domains of math and spatial reasoning have consistently been shown to predict performance within those domains. However, little work has focused on how specific these associations are. Across two studies, we systematically tested the degree of specificity in relations between anxiety and performance within math and spatial reasoning. Results consistently showed that anxiety within a cognitive domain predicted performance in that domain even when controlling for other forms of anxiety, providing evidence that cognition‐specific anxieties are valuable for understanding cognition‐specific performance. We also found that general trait anxiety did not explain a significant portion the anxiety–performance link in either math or spatial reasoning, suggesting that these anxiety–performance associations are not due to the propensity to feel anxious generally. Interestingly, while spatial anxiety did not explain any of the anxiety–performance association in math, math anxiety did explain a significant portion of the anxiety–performance link in spatial reasoning. These results suggest that, while links between anxiety and performance cannot be reduced to a single underlying general anxiety construct, there may nevertheless be overlap between domain anxieties. We end by calling for a more detailed examination of the unique and shared mechanisms linking anxiety and performance across disparate cognitive domains.
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Date: 2022-02-25  ·  Issue: 2022  ·  Volume: 1512
A bias toward the unknown: individual and environmental factors influencing exploratory behavior
Contributors: Tara M. Petzke| Judith Schomaker|
Abstract: With limited resources, exploring new opportunities is crucial for survival. Exploring novel options, however, comes at the cost of uncertainty. Therefore, there is a trade‐off between exploiting options with a known beneficial outcome and exploring novel options with a potentially higher gain. Computational models have suggested that novelty may promote exploratory behavior by inducing a so‐called novelty bonus through reward‐related processes. So far, few studies have provided behavioral evidence for such a novelty bonus. In this study, we aimed to investigate whether spatial novelty can stimulate exploratory behavior (Experiment 1), and whether age, novelty‐seeking, and reduced action radius or social interactions due to COVID‐19 restrictions influenced the exploration–exploitation trade‐off (Experiment 2). In both experiments, we employed a novel paradigm in which participants made binary decisions between food items, while on rare trials, a surprise option was presented. Results from Experiment 1 are in line with a novelty bonus, with spatial novelty promoting exploratory behavior. In Experiment 2, we found that exploratory behavior declined with age, high novelty seekers made more exploratory choices than low novelty seekers, and participants with a smaller action radius made fewer exploratory choices. These findings are consistent with previous findings in animals and predictions from computational models.
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Date: 2022-02-25  ·  Issue: 2022  · 
Multiple micronutrient supplements versus iron‐folic acid supplements and maternal anemia outcomes: an iron dose analysis
Contributors: Filomena Gomes| Rina Agustina| Robert E. Black| Parul Christian| Kathryn G. Dewey| Klaus Kraemer| Anuraj H. Shankar| Emily R. Smith| Andrew Thorne‐Lyman| Alison Tumilowicz| Megan W. Bourassa|
Abstract: Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of −0.26 g/L (95% CI: −1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92–1.07) for anemia, and 1.31 (95% CI: 0.66–2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.
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Date: 2022-02-25  ·  Issue: 2022  ·  Volume: 1512
Multiple micronutrient supplements versus iron‐folic acid supplements and maternal anemia outcomes: an iron dose analysis
Contributors: Filomena Gomes| Rina Agustina| Robert E. Black| Parul Christian| Kathryn G. Dewey| Klaus Kraemer| Anuraj H. Shankar| Emily R. Smith| Andrew Thorne‐Lyman| Alison Tumilowicz| Megan W. Bourassa|
Abstract: Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of −0.26 g/L (95% CI: −1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92–1.07) for anemia, and 1.31 (95% CI: 0.66–2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.
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Date: 2022-02-24  ·  Issue: 2022  ·  Volume: 1512
Mediating factors of statistics anxiety in university students: a systematic review and meta‐analysis
Contributors: Angélica P. Trassi| Sophie J. Leonard| Larissa D. Rodrigues| Jose A. Rodas| Flávia H. Santos|
Abstract: Statistics plays a key role in many areas of modern society, including technology, social and behavior studies, economics, and the sciences. Statistics anxiety (SA) has a detrimental impact on academic experiences in university populations, although the mediating factors remain underexplored. We conducted the first systematic review and meta‐analysis focused on SA in university students in the context of statistical performance, individual differences in statistical learning, self‐perceptions regarding the statistics course and instructor, and sociodemographic factors. Searches were carried out in the PsycINFO, PubMed, Scielo, and Web of Science databases according to our preregistration. Forty studies were selected for systematic review. Seventeen were included in a series of six meta‐analyses concerning academic achievement, attitudes, self‐perception, procrastination, and gender. The findings reveal learning strategies, procrastination, self‐efficacy, and self‐awareness as predictors of SA. However, the impact of sociodemographic data in these moderators is still uncharted. We conclude with a critical appraisal of the selected studies and present future directions for research in SA.
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Date: 2022-02-24  ·  Issue: 2022  · 
Mediating factors of statistics anxiety in university students: a systematic review and meta‐analysis
Contributors: Angélica P. Trassi| Sophie J. Leonard| Larissa D. Rodrigues| Jose A. Rodas| Flávia H. Santos|
Abstract: Statistics plays a key role in many areas of modern society, including technology, social and behavior studies, economics, and the sciences. Statistics anxiety (SA) has a detrimental impact on academic experiences in university populations, although the mediating factors remain underexplored. We conducted the first systematic review and meta‐analysis focused on SA in university students in the context of statistical performance, individual differences in statistical learning, self‐perceptions regarding the statistics course and instructor, and sociodemographic factors. Searches were carried out in the PsycINFO, PubMed, Scielo, and Web of Science databases according to our preregistration. Forty studies were selected for systematic review. Seventeen were included in a series of six meta‐analyses concerning academic achievement, attitudes, self‐perception, procrastination, and gender. The findings reveal learning strategies, procrastination, self‐efficacy, and self‐awareness as predictors of SA. However, the impact of sociodemographic data in these moderators is still uncharted. We conclude with a critical appraisal of the selected studies and present future directions for research in SA.
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Date: 2022-02-22  ·  Issue: 2022  ·  Volume: 1511
Symmetric and asymmetric bimanual coordination and freezing of gait in Parkinsonian patients in drug phases
Contributors: Zeinab Fathipour‐Azar| Akram Azad| Malahat Akbarfahimi| Saeed Behzadipour| Ghorban Taghizadeh|
Abstract: Freezing of gait (FOG) is a debilitating symptom in patients with Parkinson's disease (PD), which may be associated with motor control impairments in tasks other than gait. This study aimed to examine whether symmetric and asymmetric bimanual coordination is impaired in PD with FOG (PD +FOG) patients and whether dual‐task and drug phases may affect bimanual coordination in these patients. Twenty PD +FOG patients, 20 PD patients without FOG (PD –FOG) performed symmetric and asymmetric functional bimanual tasks (reach to and pick up a box and open a drawer to press a pushbutton inside it, respectively) under single‐task and dual‐task conditions. PD patients were evaluated during on‐ and off‐drug phases. Kinematic and coordination measures were calculated for each task. PD +FOG patients demonstrated exacerbated impairments of bimanual coordination while performing goal‐directed bimanual tasks, which was more evident in the asymmetric bimanual task and under dual‐task conditions, highlighting the need for rehabilitation interventions for bimanual tasks that include different cognitive loads in these patients. Interestingly, 25% and 5% of participants in the PD +FOG and –FOG groups developed upper limb freezing 2 years later, respectively. This study aimed to examine whether symmetric and asymmetric bimanual coordination is impaired in Parkinson's disease with freezing of gait (PD +FOG) patients and whether dual‐task and drug phases may affect bimanual coordination in these patients. PD +FOG patients demonstrated exacerbated impairment of bimanual coordination while performing goal‐directed bimanual tasks, highlighting the need for rehabilitation interventions for bimanual tasks that include different cognitive loads in these patients.
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Date: 2022-02-21  ·  Issue: 2022  ·  Volume: 1511
Experimental functional shift–induced osteoarthritis‐like changes at the TMJ and altered integrin expression in a rat model
Contributors: Yuchun Zou| Senxin Cai| Hanyu Lin| Jingwen Cai| Da‐Li Zheng| You‐Guang Lu| Linyu Xu|
Abstract: Mandibular deviation affects the biomechanical environment of the temporomandibular joint (TMJ) and causes thinning of cartilage on the deviated side. We aimed to evaluate, using a rat model, the effect of mandibular functional deviation on the TMJ in relation to the functional roles of integrin β family members. The effects of experimental functional deviation on the TMJ of 6‐week‐old Sprague–Dawley female rats, randomly assigned to control (n = 42) and experimental groups (n = 42), were evaluated at 3 days and 1, 2, 4, and 8 weeks by histological staining, immunofluorescence, real‐time quantitative polymerase chain reaction, and micro‐computed tomography. The results showed that the experimental functional shift changed the shape of condyles, thinned the cartilage, and increased the proportion of the hypertrophic layer on the deviated sides of condyles. In addition, the extracellular matrix of the condyle cartilage exhibited degradation at 1 week and subchondral trabecular bone was lost at 4 and 8 weeks. Osteoarthritis (OA)‐like changes occurred in the left and right condyles of rats in the experimental group and were aggravated over time. Integrin β family expression, especially integrin β2, was altered from week 1, possibly related to the OA‐like changes. These data may provide insight into the onset of TMJ OA.
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Date: 2022-02-21  ·  Issue: 2022  ·  Volume: 1511
Novelty processing associated with neural beta oscillations improves recognition memory in young and older adults
Contributors: Tineke K. Steiger| Alexandra Sobczak| Ramona Reineke| Nico Bunzeck|
Abstract: Novelty anticipation activates the mesolimbic system and promotes subsequent long‐term memory in younger adults. Importantly, mesolimbic structures typically degenerate with age, which might reduce positive effects of novelty anticipation. Here, we used electroencephalography in combination with an established paradigm in healthy young (19–33 years old, n = 28) and older (53–84, n = 27) humans. Colored cues predicted the subsequent presentation of either a novel or previously familiarized image (75% cue validity). On the subsequent day, recognition memory for the novel images was tested. Behaviorally, novelty anticipation improved recollection‐based but not familiarity‐based recognition memory in both groups, and this effect was more pronounced in older subjects. Furthermore, novelty and familiarity cues increased theta (4–8 Hz) and decreased alpha/beta power (9–20 Hz); at outcome, expected novel and familiar images both increased beta power (13–25 Hz). Finally, a subsequent memory effect for expected novel images was associated with increases in beta power independent of age. Together, novelty anticipation drives hippocampus‐dependent long‐term recognition memory across the life span, and this effect appears to be related to neural beta oscillations.
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Date: 2022-02-18  ·  Issue: 2022  ·  Volume: 1511
Guidelines and standards for the study of death and recalled experiences of death––a multidisciplinary consensus statement and proposed future directions
Contributors: Sam Parnia| Stephen G. Post| Matthew T. Lee| Sonja Lyubomirsky| Tom P. Aufderheide| Charles D. Deakin| Bruce Greyson| Jeffrey Long| Anelly M. Gonzales| Elise L. Huppert| Analise Dickinson| Stephan Mayer| Briana Locicero| Jeff Levin| Anthony Bossis| Everett Worthington| Peter Fenwick| Tara Keshavarz Shirazi|
Abstract: An inadvertent consequence of advances in stem cell research, neuroscience, and resuscitation science has been to enable scientific insights regarding what happens to the human brain in relation to death. The scientific exploration of death is in large part possible due to the recognition that brain cells are more resilient to the effects of anoxia than assumed. Hence, brain cells become irreversibly damaged and “die” over hours to days postmortem. Resuscitation science has enabled life to be restored to millions of people after their hearts had stopped. These survivors have described a unique set of recollections in relation to death that appear universal. We review the literature, with a focus on death, the recalled experiences in relation to cardiac arrest, post–intensive care syndrome, and related phenomena that provide insights into potential mechanisms, ethical implications, and methodologic considerations for systematic investigation. We also identify issues and controversies related to the study of consciousness and the recalled experience of cardiac arrest and death in subjects who have been in a coma, with a view to standardize and facilitate future research.
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Date: 2022-02-15  ·  Issue: 2022  ·  Volume: 1508
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Date: 2022-02-05  ·  Issue: 2022  ·  Volume: 1511
Intermodality differences in statistical learning: phylogenetic and ontogenetic influences
Contributors: Leona Polyanskaya| Héctor M. Manrique| Arthur G. Samuel| Antonio Marín| Azucena García‐Palacios| Mikhail Ordin|
Abstract: In Basque–Spanish bilinguals, statistical learning (SL) in the visual modality was more efficient on nonlinguistic than linguistic input; in the auditory modality, we found the reverse pattern of results. We hypothesize that SL was shaped for processing nonlinguistic environmental stimuli and only later, as the language faculty emerged, recycled for speech processing. This led to further adaptive changes in the neurocognitive mechanisms underlying speech processing, including SL. By contrast, as a recent cultural innovation, written language has not yet led to adaptations. The current study investigated whether such phylogenetic influences on SL can be modulated by ontogenetic influences on a shorter timescale, over the course of individual development. We explored how SL is modulated by the ambient linguistic environment. We found that SL in the auditory modality can be further modulated by exposure to a bilingual environment, in which speakers need to process a wider range of diverse speech cues. This effect was observed only on linguistic, not nonlinguistic, material. We conclude that ontogenetic factors modulate the efficiency of already existing SL ability, honing it for specific types of input, by providing new targets for selection via exposure to different cues in the sensory input.
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Date: 2022-02-04  ·  Issue: 2022  ·  Volume: 1511
Group decision making under uncertain preferences: powered by AI, empowered by AI
Contributors: Lirong Xia|
Abstract: Group decision making is an important, long‐standing, and ubiquitous problem in all societies, where collective decisions must be made by a group of agents despite individual conflicting preferences. This has been a classical and active topic for research in many disciplines, including economics, political science, cognitive and behavioral sciences, statistics, mathematics, and computer science. In this article, I survey some recent progress in theoretical, algorithmic, and engineering work toward building AI‐powered intelligent systems to help agents make group decisions based on uncertain preferences; these systems leverage principles, ideas, and methodologies from multiple disciplines. Empowered by AI, group decision making can handle a broader range of situations at relatively large scales.
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Date: 2022-02-04  ·  Issue: 2022  · 
Group decision making under uncertain preferences: powered by AI, empowered by AI
Contributors: Lirong Xia|
Abstract: Group decision making is an important, long‐standing, and ubiquitous problem in all societies, where collective decisions must be made by a group of agents despite individual conflicting preferences. This has been a classical and active topic for research in many disciplines, including economics, political science, cognitive and behavioral sciences, statistics, mathematics, and computer science. In this article, I survey some recent progress in theoretical, algorithmic, and engineering work toward building AI‐powered intelligent systems to help agents make group decisions based on uncertain preferences; these systems leverage principles, ideas, and methodologies from multiple disciplines. Empowered by AI, group decision making can handle a broader range of situations at relatively large scales.
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Date: 2022-01-31  ·  Issue: 2022  · 
Interventions to improve calcium intake through foods in populations with low intake
Contributors: Megan W. Bourassa| Steven A. Abrams| José M. Belizán| Erick Boy| Gabriela Cormick| Carolina Diaz Quijano| Sarah Gibson| Filomena Gomes| G. Justus Hofmeyr| Jean Humphrey| Klaus Kraemer| Keith Lividini| Lynnette M. Neufeld| Cristina Palacios| Julie Shlisky| Prashanth Thankachan| Salvador Villalpando| Connie M. Weaver|
Abstract: Calcium intake remains inadequate in many low‐ and middle‐income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food‐based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium‐deficiency rickets). Specifically, some animal‐source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple‐food fortification with calcium can also be a cost‐effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high‐calcium varieties or through the application of calcium‐rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.
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Date: 2022-01-31  ·  Issue: 2022  ·  Volume: 1511
Interventions to improve calcium intake through foods in populations with low intake
Contributors: Megan W. Bourassa| Steven A. Abrams| José M. Belizán| Erick Boy| Gabriela Cormick| Carolina Diaz Quijano| Sarah Gibson| Filomena Gomes| G. Justus Hofmeyr| Jean Humphrey| Klaus Kraemer| Keith Lividini| Lynnette M. Neufeld| Cristina Palacios| Julie Shlisky| Prashanth Thankachan| Salvador Villalpando| Connie M. Weaver|
Abstract: Calcium intake remains inadequate in many low‐ and middle‐income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food‐based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium‐deficiency rickets). Specifically, some animal‐source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple‐food fortification with calcium can also be a cost‐effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high‐calcium varieties or through the application of calcium‐rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.
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Date: 2022-01-28  ·  Issue: 2022  ·  Volume: 1511
Teasing apart the unique contributions of cognitive and affective predictors of math performance
Contributors: Alex M. Silver| Leanne Elliott| Bert Reynvoet| Delphine Sasanguie| Melissa E. Libertus|
Abstract: Math permeates everyday life, and math skills are linked to general educational attainment, income, career choice, likelihood of full‐time employment, and health and financial decision making. Thus, researchers have attempted to understand factors predicting math performance in order to identify ways of supporting math development. Work examining individual differences in math performance typically focuses on either cognitive predictors, including inhibitory control and the approximate number system (ANS; a nonsymbolic numerical comparison system), or affective predictors, like math anxiety. Studies with children suggest that these factors are interrelated, warranting examination of whether and how each uniquely and independently contributes to math performance in adulthood. Here, we examined how inhibitory control, the ANS, and math anxiety predicted college students’ math performance (n = 122, mean age = 19.70 years). Using structural equation modeling, we find that although inhibitory control and the ANS were closely related to each other, they did not predict math performance above and beyond the effects of the other while also controlling for math anxiety. Instead, math anxiety was the only unique predictor of math performance. These findings contradict previous results in children and reinforce the need to consider affective factors in our discussions and interventions for supporting math performance in college students.
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Date: 2022-01-21  ·  Issue: 2022  ·  Volume: 1507
Erratum for Ann. N.Y. Acad. Sci. 2021. Vol. 1506: 118–141
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Date: 2022-01-21  ·  Issue: 2022  ·  Volume: 1507
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Date: 2022-01-21  ·  Issue: 2022  · 
Mathematical modeling to inform the development of national guidelines on infant feeding in Thailand
Contributors: Uraiporn Chittchang| Nipa Rojroongwasiukul| Pattanee Winnichagoon| Louise Watson| Elaine Ferguson|
Abstract: The development of national dietary guidelines promoting healthy food choices is a public health priority in Thailand. In developing the recent national complementary feeding guidelines (CFGs) for 6‐ to 12‐month‐old children, mathematical modeling was used to inform decisions. Model parameters were derived from nationally representative dietary data and analyzed for 11 micronutrients by age group, using linear programming analysis in Optifood. Models were run to identify micronutrients whose nutrient reference values could not be met using local foods as consumed (problem nutrients), evaluate the original 2012 Thai CFGs, and predict the nutritional benefits of a specific fortified complementary food. The results identified three problem nutrients (iron, calcium, and zinc), which, for 9‐ to 11‐month‐olds, were reduced to one when the fortified food was modeled. The number of servings/week of vegetables and meat, fish or eggs were higher, and of oil and fruit were lower, in the modeled nutritionally best rather than observed diets (medians). When modeled, the original Thai CFGs were not feasible because the energy constraint was exceeded; hence, in revising them, the recommended number of servings/week of oil and fruit were reduced. This study demonstrates the advantages of using mathematical modeling, when revising national CFGs, to evaluate and improve them.
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Date: 2022-01-21  ·  Issue: 2022  ·  Volume: 1511
Molecular docking of brazilin and its analogs to barrier‐to‐autointegration factor 1 (BAF1)
Contributors: Maria de Nazaré Correia Soeiro| Gérard Vergoten| Christian Bailly|
Abstract: The tetracyclic phenolic compound brazilin, derived from the wood of Caesalpinia sappan, has been shown to bind to the chromatin protein BAF1 (barrier‐to‐autointegration factor 1), a protein essential to maintain integrity of the nuclear envelope in cells. BAF1 plays a role in cancer development. Using molecular docking, we have located the binding site for brazilin on the surface of the BAF1 monomer and compared its binding to that of four analogs. The oxidized product brazilein (ΔE = −57.7 kcal/mol) exhibits a higher affinity for BAF1 compared to the reduced form brazilin (ΔE = −38.2 kcal/mol). Incorporation of a 4‐hydroxyl substituent on the indenochromene unit affords hematoxylin and hematein. In silico analysis predicts that the oxidized form hematein (ΔE = −66.2 kcal/mol) displays a higher affinity for BAF1 than the reduced form hematoxylin (ΔE = −42.2 kcal/mol). In contrast, the atypical bis‐lactone product brazilide A cannot form good complexes with BAF1. The analysis points to the formation of more stable BAF1 complexes with the oxidized molecules compared to the reduced ones, but the position of the binding site on the protein cavity is different for brazilin/hematoxylin compared to brazilein/hematein. Our study may be useful to guide the design of BAF1 ligands.
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Date: 2022-01-14  ·  Issue: 2022  ·  Volume: 1511
Combining vascular and nerve fiber layer thickness measurements to model glaucomatous focal visual field loss
Contributors: Martin Kallab| Nikolaus Hommer| Andreas Schlatter| Jacqueline Chua| Bingyao Tan| Doreen Schmidl| Cornelia Hirn| Oliver Findl| Leopold Schmetterer| Gerhard Garhöfer| Damon Wong|
Abstract: We compare the focal structure–function correlation of structural measurements of peripapillary retinal nerve fiber layer thickness (RNFL‐T) using optical coherence tomography (OCT), capillary density (CD) measurements using OCT‐angiography (OCT‐A), or a combination of both, with visual field deviation (VFD) in early to advanced glaucoma. Primary open angle glaucoma patients (n = 46, mean ± SD age: 67 ± 10 years; VF mean deviation: −10.41 ± 6.76 dB) were included in this cross‐sectional study. We performed 30–2 standard automated perimetry OCT (3.5‐mm diameter ring scan) and 15°×15° OCT‐A (superficial vascular complex slab). Based on a nerve fiber trajectory model, each VF test spot was assigned to an OCT‐A wedge and an OCT ring‐sector. Two univariate linear models (Mv and Mt) using either CD‐based vascular (Mv) or RNFL‐T–based thickness information (Mt) and one multivariate model using both (Mv:t) were compared in their associations with measured focal VFD, which were higher for the multivariate model Mv:t (mean ± SD correlation coefficient: 0.710 ± 0.086) than for either nested model (0.627 ± 0.078 for Mv and 0.578 ± 0.095 for Mt). Using a focal visual field approach, the combination of RNFL‐T and CD showed better structure–function correlations than thickness or vascular information only.
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Date: 2022-01-14  ·  Issue: 2023  · 
Innovative vaccine approaches—a Keystone Symposia report
Contributors: Jennifer Cable| Rino Rappuoli| Elizabeth J. Klemm| Gagandeep Kang| Ankur Mutreja| Gavin J. Wright| Mariagrazia Pizza| Sowmya Ajay Castro| Joseph P. Hoffmann| Galit Alter| Andrea Carfi| Andrew J. Pollard| Florian Krammer| Ravindra K. Gupta| Caroline E. Wagner| Viviane Machado| Kayvon Modjarrad| Lawrence Corey| Peter B. Gilbert| Gordon Dougan| Nicole Lurie| Pamela J. Bjorkman| Christopher Chiu| Elisa Nemes| Stephen B. Gordon| Andrew C. Steer| Thomas Rudel| Catherine A. Blish| John Tyler Sandberg| Kiva Brennan| Keith P. Klugman| Lynda M. Stuart| Shabir A. Madhi| Christopher L. Karp|
Abstract: The rapid development of COVID‐19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically improve global health, low‐and‐middle‐income countries around the world often experience reduced access to vaccines and reduced vaccine efficacy. Addressing these issues will require novel vaccine approaches and platforms, deeper insight how vaccines mediate protection, and innovative trial designs and models. On June 28–30, 2021, experts in vaccine research, development, manufacturing, and deployment met virtually for the Keystone eSymposium “Innovative Vaccine Approaches” to discuss advances in vaccine research and development.
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Date: 2022-01-14  ·  Issue: 2022  · 
Conceptualizing the factor structure of parents’ math anxiety and associations with children's mathematics skills
Contributors: Jimena Cosso| Alexa Ellis| Connor D. O'Rear| Erica L. Zippert| Sara A. Schmitt| David J. Purpura|
Abstract: There is a growing literature examining the association between parents’ math anxiety and children's mathematics skills. Previous research has considered parents’ math anxiety as a unidimensional construct that primarily focused on parents’ experiences doing mathematics themselves. However, this research did not account for parents’ experiences when doing mathematics with their children. Thus, there were two goals of the present study: (1) to identify the structure of parents’ math anxiety when considering context‐dependent situations, and (2) to determine whether parental math anxiety was related to children's early numeracy skills. We conducted a series of confirmatory factor analyses using a sample of 155 preschool children (Mage = 4.20 years, SD = 0.71; 51% female). The best fitting model of parents’ math anxiety was a bifactor model, suggesting that parents’ math anxiety was best conceptualized as a multidimensional construct. However, structural equation models showed parent math anxiety was not a significant predictor of children's numeracy performance. These findings provide a foundation for understanding parents’ math anxiety as multidimensional and raise questions about potential mechanisms that may explain prior work finding mixed relations between math anxiety and children's numeracy performance.
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Date: 2022-01-14  ·  Issue: 2022  ·  Volume: 1511
Conceptualizing the factor structure of parents’ math anxiety and associations with children's mathematics skills
Contributors: Jimena Cosso| Alexa Ellis| Connor D. O'Rear| Erica L. Zippert| Sara A. Schmitt| David J. Purpura|
Abstract: There is a growing literature examining the association between parents’ math anxiety and children's mathematics skills. Previous research has considered parents’ math anxiety as a unidimensional construct that primarily focused on parents’ experiences doing mathematics themselves. However, this research did not account for parents’ experiences when doing mathematics with their children. Thus, there were two goals of the present study: (1) to identify the structure of parents’ math anxiety when considering context‐dependent situations, and (2) to determine whether parental math anxiety was related to children's early numeracy skills. We conducted a series of confirmatory factor analyses using a sample of 155 preschool children (Mage = 4.20 years, SD = 0.71; 51% female). The best fitting model of parents’ math anxiety was a bifactor model, suggesting that parents’ math anxiety was best conceptualized as a multidimensional construct. However, structural equation models showed parent math anxiety was not a significant predictor of children's numeracy performance. These findings provide a foundation for understanding parents’ math anxiety as multidimensional and raise questions about potential mechanisms that may explain prior work finding mixed relations between math anxiety and children's numeracy performance.
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Date: 2022-01-14  ·  Issue: 2022  ·  Volume: 1511
Innovative vaccine approaches—a Keystone Symposia report
Contributors: Jennifer Cable| Rino Rappuoli| Elizabeth J. Klemm| Gagandeep Kang| Ankur Mutreja| Gavin J. Wright| Mariagrazia Pizza| Sowmya Ajay Castro| Joseph P. Hoffmann| Galit Alter| Andrea Carfi| Andrew J. Pollard| Florian Krammer| Ravindra K. Gupta| Caroline E. Wagner| Viviane Machado| Kayvon Modjarrad| Lawrence Corey| Peter B. Gilbert| Gordon Dougan| Nicole Lurie| Pamela J. Bjorkman| Christopher Chiu| Elisa Nemes| Stephen B. Gordon| Andrew C. Steer| Thomas Rudel| Catherine A. Blish| John Tyler Sandberg| Kiva Brennan| Keith P. Klugman| Lynda M. Stuart| Shabir A. Madhi| Christopher L. Karp|
Abstract: The rapid development of COVID‐19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically improve global health, low‐and‐middle‐income countries around the world often experience reduced access to vaccines and reduced vaccine efficacy. Addressing these issues will require novel vaccine approaches and platforms, deeper insight how vaccines mediate protection, and innovative trial designs and models. On June 28–30, 2021, experts in vaccine research, development, manufacturing, and deployment met virtually for the Keystone eSymposium “Innovative Vaccine Approaches” to discuss advances in vaccine research and development.
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Date: 2022-01-08  ·  Issue: 2022  · 
Calcium supplementation for the prevention of hypertensive disorders of pregnancy: current evidence and programmatic considerations
Contributors: Filomena Gomes| Per Ashorn| Sufia Askari| Jose M. Belizan| Erick Boy| Gabriela Cormick| Katherine L. Dickin| Amalia R. Driller‐Colangelo| Wafaie Fawzi| G. Justus Hofmeyr| Jean Humphrey| Anuradha Khadilkar| Rubina Mandlik| Lynnette M. Neufeld| Cristina Palacios| Daniel E. Roth| Julie Shlisky| Christopher R. Sudfeld| Connie Weaver| Megan W. Bourassa|
Abstract: Most low‐ and middle‐income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500‐mg doses/day). WHO recommends 1.5–2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low‐dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost‐effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron‐containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food‐based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation.
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Date: 2022-01-08  ·  Issue: 2023  · 
Targeted protein degradation: from small molecules to complex organelles—a Keystone Symposia report
Contributors: Jennifer Cable| Eilika Weber‐Ban| Tim Clausen| Kylie J. Walters| Michal Sharon| Daniel J. Finley| Yangnan Gu| John Hanna| Yue Feng| Sascha Martens| Anne Simonsen| Malene Hansen| Hong Zhang| Jonathan M. Goodwin| Alessio Reggio| Chunmei Chang| Liang Ge| Brenda A. Schulman| Raymond J. Deshaies| Ivan Dikic| J. Wade Harper| Ingrid E. Wertz| Nicolas H. Thomä| Mikołaj Słabicki| Judith Frydman| Ursula Jakob| Della C. David| Eric J. Bennett| Carolyn R. Bertozzi| Richa Sardana| Vinay V. Eapen| Serena Carra|
Abstract: Targeted protein degradation is critical for proper cellular function and development. Protein degradation pathways, such as the ubiquitin proteasomes system, autophagy, and endosome–lysosome pathway, must be tightly regulated to ensure proper elimination of misfolded and aggregated proteins and regulate changing protein levels during cellular differentiation, while ensuring that normal proteins remain unscathed. Protein degradation pathways have also garnered interest as a means to selectively eliminate target proteins that may be difficult to inhibit via other mechanisms. On June 7 and 8, 2021, several experts in protein degradation pathways met virtually for the Keystone eSymposium “Targeting protein degradation: from small molecules to complex organelles.” The event brought together researchers working in different protein degradation pathways in an effort to begin to develop a holistic, integrated vision of protein degradation that incorporates all the major pathways to understand how changes in them can lead to disease pathology and, alternatively, how they can be leveraged for novel therapeutics.
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Date: 2022-01-08  ·  Issue: 2022  ·  Volume: 1510
Calcium supplementation for the prevention of hypertensive disorders of pregnancy: current evidence and programmatic considerations
Contributors: Filomena Gomes| Per Ashorn| Sufia Askari| Jose M. Belizan| Erick Boy| Gabriela Cormick| Katherine L. Dickin| Amalia R. Driller‐Colangelo| Wafaie Fawzi| G. Justus Hofmeyr| Jean Humphrey| Anuradha Khadilkar| Rubina Mandlik| Lynnette M. Neufeld| Cristina Palacios| Daniel E. Roth| Julie Shlisky| Christopher R. Sudfeld| Connie Weaver| Megan W. Bourassa|
Abstract: Most low‐ and middle‐income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500‐mg doses/day). WHO recommends 1.5–2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low‐dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost‐effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron‐containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food‐based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation.
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Date: 2022-01-03  ·  Issue: 2022  · 
Calcium supplementation during pregnancy and long‐term offspring outcome: a systematic literature review and meta‐analysis
Contributors: Päivi Korhonen| Kati Tihtonen| Jaana Isojärvi| Riitta Ojala| Ulla Ashorn| Per Ashorn| Outi Tammela|
Abstract: The World Health Organization currently recommends calcium supplementation for pregnant women, especially those with low calcium intakes, to reduce the risk of hypertension and preeclampsia. We aimed to evaluate the effect of this intervention on selected offspring outcomes. A systematic search was conducted in 11 databases for published randomized controlled trials (RCTs) on the effect of maternal calcium supplementation with or without vitamin D during pregnancy on selected offspring cardiovascular, growth, and metabolic and neurodevelopmental outcomes. Screening of titles and abstracts of 3555 records and full texts of 31 records yielded six RCTs (nine reports, n = 1616). Forest plot analyses were performed if at least two studies presented comparable data on the same outcome. In one study (n = 591), high‐dose calcium supplementation during pregnancy was associated with a decreased risk of offspring high systolic blood pressure at 5–7 years of age (risk ratio = 0.59; 95% confidence interval: 0.39–0.90). The effects of the intervention on offspring growth, metabolic, and neurodevelopmental outcomes remain unknown because of conflicting or insufficient data. High risk of attrition bias decreased the quality of the evidence. Limited available data from RCTs do not provide sufficient evidence to conclude that prenatal calcium supplementation influences offspring health outcomes beyond the newborn period.
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Date: 2021-12-24  ·  Issue: 2022  ·  Volume: 1510
Identification of maternal serum biomarkers for prenatal diagnosis of nonsyndromic orofacial clefts
Contributors: Xinhuan Wang| Xiaohong Yang| Pei Huang| Xiujiao Meng| Zhuan Bian| Liuyan Meng|
Abstract: Nonsyndromic orofacial clefts (NSOFCs) are the most common congenital defects in the oral and maxillofacial regions. It is mainly diagnosed prenatally through fetal ultrasonography. However, the accuracy of ultrasonography for NSOFC is unreliable. Maternal serological screening is a noninvasive method for the diagnosis of fetal malformations. In our study, we sought to identify specific biomarkers in maternal serum for predicting NSOFC prenatally. We quantified the alterations in maternal serum protein profiles between 20 pregnant women with NSOFC fetuses and 20 pregnant women with healthy fetuses by using isobaric tags for relative and absolute quantitation‐based mass spectrometry (MS). The serum levels of 75 elevated and 50 decreased proteins in the NSOFC group were detected. Twenty‐eight candidate biomarkers were selected for further confirmation by multiple reaction monitoring‐MS; of these, 16 proteins were found to be significantly different. More importantly, the levels of three proteins (APOA, HPT, and CRP) were verified by ELISAs to be obviously altered in serum from pregnancies carrying fetuses with NSOFC. Our results indicate that analysis of the maternal serum proteome is a feasible strategy for biomarker discovery of NSOFC, and APOA, HPT, and CRP proteins are potential serum biomarkers for prenatal diagnosis of NSOFC.
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Date: 2021-12-24  ·  Issue: 2022  · 
The interplay between math anxiety and working memory on math performance: a longitudinal study
Contributors: Sandra Pellizzoni| Elisa Cargnelutti| Alessandro Cuder| Maria Chiara Passolunghi|
Abstract: Mathematical skills are essential to mastering everyday activities, making professional choices, and exercising citizenship in a numerate society. There is extensive evidence of the relationship between math anxiety (MA) and working memory (WM) influencing math attainment. Studies have mainly considered adult samples, however, leaving primary school children almost unexplored. This study is a first attempt to examine how the complex interplay between MA and WM affects math achievement from a developmental perspective. A total of 148 third graders were assessed with WM, general anxiety (GA), MA, and math tasks. Anxiety and WM were assessed at the beginning of the school year when children started attending grade 3, while math achievement was tested twice at the start of grades 3 and 4. The findings seem to confirm that GA has both a direct and an indirect effect (mediated by WM) on math performance in third and fourth graders. MA has a direct effect on math performance in grade 4, but only an indirect effect in grade 3, suggesting MA has a developmental trajectory, becoming stronger over time. The implications in the educational setting are discussed, pointing to the importance of a combined intervention on MA and WM.
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Date: 2021-12-24  ·  Issue: 2022  ·  Volume: 1510
The interplay between math anxiety and working memory on math performance: a longitudinal study
Contributors: Sandra Pellizzoni| Elisa Cargnelutti| Alessandro Cuder| Maria Chiara Passolunghi|
Abstract: Mathematical skills are essential to mastering everyday activities, making professional choices, and exercising citizenship in a numerate society. There is extensive evidence of the relationship between math anxiety (MA) and working memory (WM) influencing math attainment. Studies have mainly considered adult samples, however, leaving primary school children almost unexplored. This study is a first attempt to examine how the complex interplay between MA and WM affects math achievement from a developmental perspective. A total of 148 third graders were assessed with WM, general anxiety (GA), MA, and math tasks. Anxiety and WM were assessed at the beginning of the school year when children started attending grade 3, while math achievement was tested twice at the start of grades 3 and 4. The findings seem to confirm that GA has both a direct and an indirect effect (mediated by WM) on math performance in third and fourth graders. MA has a direct effect on math performance in grade 4, but only an indirect effect in grade 3, suggesting MA has a developmental trajectory, becoming stronger over time. The implications in the educational setting are discussed, pointing to the importance of a combined intervention on MA and WM.
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Date: 2021-12-23  ·  Issue: 2022  ·  Volume: 1510
Novelty exposure induces stronger sensorimotor representations during a manual adaptation task
Contributors: Marit F. L. Ruitenberg| Vincent Koppelmans| Rachael D. Seidler| Judith Schomaker|
Abstract: Active exploration of novel spatial environments enhances memory for subsequently presented explicit, declarative information in humans. These effects have been attributed to novelty promoting dopamine release via mesolimbic dopaminergic pathways in the brain. As procedural motor learning has been linked to dopamine as well, we predict that novelty effects extend to this domain. To test this hypothesis, the present study examined whether spatial novelty exploration benefits subsequent sensorimotor adaptation. Participants explored either two different virtual environments (i.e., novelty condition; n = 210) or two identical environments (i.e., familiar condition; n = 253). They then performed a manual adaptation task in which they had to adapt joystick movements to a visual perturbation. We assessed the rate of adaptation following the introduction of this perturbation, and the rate of deadaptation following its removal. While results showed reliable adaptation patterns and similar adaptation rates across both conditions, individuals in the novelty condition showed slower deadaptation. This suggests that exposure to spatial novelty induced stronger sensorimotor representations during adaptation, potentially through novelty‐induced dopaminergic effects in mesocortical and/or nigrostriatal pathways. Novelty exposure may be employed to promote motor learning on tasks that require precision movements in altered sensory contexts, for example, in astronauts moving in microgravity or patients with impaired motor processing.
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Date: 2021-12-20  ·  Issue: 2022  ·  Volume: 1510
A heuristic underlies the search for relief in Drosophila melanogaster
Contributors: Nicola Meda| Giulio Maria Menti| Aram Megighian| Mauro Agostino Zordan|
Abstract: Humans rely on multiple types of sensory information to make decisions, and strategies that shorten decision‐making time by taking into account fewer but essential elements of information are preferred to strategies that require complex analyses. Such shortcuts to decision making are known as heuristics. The identification of heuristic principles in species phylogenetically distant to humans would shed light on the evolutionary origin of speed–accuracy trade‐offs and offer the possibility for investigating the brain representations of such trade‐offs, urgency and uncertainty. By performing experiments on spatial learning in the invertebrate Drosophila melanogaster, we show that the fly's search strategies conform to a spatial heuristic—the nearest neighbor rule—to avoid bitter taste (a negative stimulation). That is, Drosophila visits a salient location closest to its current position to stop the negative stimulation; only if this strategy proves unsuccessful does the fly use other learned associations to avoid bitter taste. Characterizing a heuristic in D. melanogaster supports the view that invertebrates can, when making choices, operate on economic principles, as well as the conclusion that heuristic decision making dates to at least 600 million years ago.
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Date: 2021-12-20  ·  Issue: 2021  ·  Volume: 1506
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Date: 2021-12-17  ·  Issue: 2021  ·  Volume: 1505
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Date: 2021-12-17  ·  Issue: 2022  ·  Volume: 1510
An update on current treatment strategies for laryngopharyngeal reflux symptoms
Contributors: Amanda J. Krause| Erin H. Walsh| Philip A. Weissbrod| Tiffany H. Taft| Rena Yadlapati|
Abstract: Laryngopharyngeal reflux (LPR) is a syndrome caused by reflux of gastric contents into the pharynx or larynx, which leads to symptoms of throat clearing, hoarseness, pain, globus sensation, cough, excess mucus production in the throat, and dysphonia. LPR is a challenging condition, as there is currently no gold standard for diagnosis or treatment, and thus this presents a burden to the healthcare system. Strategies for treatment of LPR are numerous. Medical therapies include proton pump inhibitors, which are first line, H2 receptor antagonists, alginates, and baclofen. Other noninvasive treatment options include lifestyle therapy and the external upper esophageal sphincter compression device. Endoscopic and surgical options include antireflux surgery, magnetic sphincter augmentation, and transoral incisionless fundoplication. Functional laryngeal disorders and laryngeal hypersensitivity can present as LPR symptoms with or without gastroesophageal reflux disease. Though there are minimal studies in this area, neuromodulators and behavioral interventions are potential treatment options. Given the complexity of these patients and numerous available treatment options, we propose a treatment algorithm to help clinicians diagnose and triage patients into an appropriate therapy.
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Date: 2021-12-10  ·  Issue: 2022  ·  Volume: 1510
Quantification of intrinsic optical signals in the outer human retina using optical coherence tomography
Contributors: Alina Messner| Valentin Aranha dos Santos| Hannes Stegmann| Stefan Puchner| Doreen Schmidl| Rainer Leitgeb| Leopold Schmetterer| René M. Werkmeister|
Abstract: Intrinsic optical signals constitute a noninvasive biomarker promising the objective assessment of retinal photoreceptor function. We employed a commercial optical coherence tomography (OCT) system and an OCT signal model for evaluation of optical path length (OPL) changes in the temporal outer retina of five healthy subjects during light adaptation. Data were acquired at 30 time points, in ambient light and during long duration stimulation with white light, and analyzed, employing a signal model based on the sum of seven Gaussian curves corresponding to all relevant anatomical structures of the outer retina. During light stimulation, mean OPL between rod outer segment tips (ROST) and the retinal pigment epithelium (RPE) decreased by 21.4 ± 3.5%. Further, OPL between the external‐limiting membrane (ELM) and the RPE decreased by 5.2 ± 0.9% versus baseline, while OPL between ELM and ROST showed an initial decrease by 2.1 ± 1.6% versus baseline and, thereafter, increased by 2.8 ± 2.1% versus baseline. Thus, the presented approach allowed for assess to dynamic changes in the outer retina in response to light. The change in the subretinal space occurring in the context of light adaptation could be measured using a standard OCT platform and a dedicated signal model.
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Date: 2021-12-09  ·  Issue: 2022  · 
Comparing estimated cost‐effectiveness of micronutrient intervention programs using primary and secondary data: evidence from Cameroon
Contributors: Katherine P. Adams| Hanqi Luo| Stephen A. Vosti| Justin Kagin| Ismael Ngnie‐Teta| Alex Ndjebayi| Jules Guintang Assiene| Reina Engle‐Stone|
Abstract: Designing a cost‐effective portfolio of micronutrient intervention programs is complex and generally undertaken with limited data. We developed the MINIMOD‐Secondary Data (MINIMOD‐SD) tool, which uses household consumption and expenditure survey data and other secondary data to estimate apparent nutrient intakes and model the effectiveness and cost‐effectiveness of micronutrient intervention programs. We present the SD tool methodology and results in the context of Cameroon, with a particular focus on vitamin A (VA) for children and folate for women of reproductive age (WRA). We compared the MINIMOD‐SD tool estimates with those of the full MINIMOD tool, which uses 24‐h dietary recall data. The SD tool consistently underestimated folate intake among women (median (IQR): 230 (143,352) versus 303 (244,367) μg dietary folate equivalents (DFEs)/day) and especially VA among children (141 (64,279) versus 227 (102,369)). Qualitatively, however, the two tools were generally consistent in predicted subnational patterns of micronutrient adequacy and identification of effective and cost‐effective (cost per child/WRA moving from inadequate to adequate intake) interventions. Secondary data and the MINIMOD‐SD tool can provide policymakers with information to qualitatively assess deficiency risks and identify cost‐effective interventions. However, accurately quantifying individual‐level deficiency or dietary inadequacy and intervention effectiveness and cost‐effectiveness will likely require individual‐level dietary data and biomarker measurements.
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Date: 2021-12-09  ·  Issue: 2022  ·  Volume: 1510
Comparing estimated cost‐effectiveness of micronutrient intervention programs using primary and secondary data: evidence from Cameroon
Contributors: Katherine P. Adams| Hanqi Luo| Stephen A. Vosti| Justin Kagin| Ismael Ngnie‐Teta| Alex Ndjebayi| Jules Guintang Assiene| Reina Engle‐Stone|
Abstract: Designing a cost‐effective portfolio of micronutrient intervention programs is complex and generally undertaken with limited data. We developed the MINIMOD‐Secondary Data (MINIMOD‐SD) tool, which uses household consumption and expenditure survey data and other secondary data to estimate apparent nutrient intakes and model the effectiveness and cost‐effectiveness of micronutrient intervention programs. We present the SD tool methodology and results in the context of Cameroon, with a particular focus on vitamin A (VA) for children and folate for women of reproductive age (WRA). We compared the MINIMOD‐SD tool estimates with those of the full MINIMOD tool, which uses 24‐h dietary recall data. The SD tool consistently underestimated folate intake among women (median (IQR): 230 (143,352) versus 303 (244,367) μg dietary folate equivalents (DFEs)/day) and especially VA among children (141 (64,279) versus 227 (102,369)). Qualitatively, however, the two tools were generally consistent in predicted subnational patterns of micronutrient adequacy and identification of effective and cost‐effective (cost per child/WRA moving from inadequate to adequate intake) interventions. Secondary data and the MINIMOD‐SD tool can provide policymakers with information to qualitatively assess deficiency risks and identify cost‐effective interventions. However, accurately quantifying individual‐level deficiency or dietary inadequacy and intervention effectiveness and cost‐effectiveness will likely require individual‐level dietary data and biomarker measurements.
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Date: 2021-12-08  ·  Issue: 2022  ·  Volume: 1510
A case of hominin scavenging 1.84 million years ago from Olduvai Gorge (Tanzania)
Contributors: Manuel Domínguez‐Rodrigo| Lloyd A. Courtenay| Lucía Cobo‐Sánchez| Enrique Baquedano| Audax Mabulla|
Abstract: Meat eating is one of the hallmarks of human evolution. It has been linked to the beginning of stone tool use, to physiological changes leading to crucial anatomical transformations defining our genus, and to new socioreproductive and cognitive behaviors. Uncontroversial evidence of meat eating goes back to 2.6 million years ago; however, little is known about the frequency and timing with which early hominins acquired animal resources. Here, we show that the combination of hunting and scavenging documented in some modern human foragers may have a long evolutionary trajectory. Using a new set of artificial intelligence methods for objective identification, we present direct evidence of an episode of hominins scavenging from large felids—probably lions—discovered at Olduvai Gorge (DS site, Bed I). This casts a new perspective on the diversity of hominin carcass acquisition behaviors and survival strategies, and places some early Pleistocene hominins in ecological proximity to African large carnivore guilds.
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Date: 2021-12-07  ·  Issue: 2022  ·  Volume: 1509
Different priming effects of empathy on neural processing associated with firsthand pain and nonpain perception
Contributors: Qiaoyue Ren| Ye Yang| Ye Wo| Xuejing Lu| Li Hu|
Abstract: The shared‐representation model of empathy is still debated. One of the major questions is whether empathy‐eliciting stimuli depicting others’ pain selectively activate the representations of self‐pain. To address this issue, we assessed the priming effects of empathy‐eliciting pictures on firsthand pain and nonpain perception, as well as its associated neural processing. In Experiment 1, when compared with nonpainful pictures depicting individuals’ body parts with no injury, participants primed by painful pictures showing individuals’ body parts with injury reported higher ratings for perceived intensity, unpleasantness, and salience of nociceptive and auditory stimuli, but they only exhibited increased N2 amplitude in response to nociceptive stimuli. In Experiment 2, the results from another group of participants replicated the observations of Experiment 1 and validated the findings in the non‐nociceptive somatosensory modality. Importantly, participants’ concern ratings for priming pictures predicted their unpleasantness ratings for subsequent nociceptive stimuli, while participants’ attention ratings predicted their unpleasantness ratings for subsequent auditory and tactile stimuli. This finding implies that empathy for pain might influence pain and nonpain perception via different psychological mechanisms. In summary, our findings highlight the existence of pain‐selective representations in empathy for pain and contribute to a better understanding of the shared‐representation model of empathy.
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Date: 2021-12-02  ·  Issue: 2022  ·  Volume: 1509
Emergency preservation and resuscitation for cardiac arrest from trauma
Contributors: Samuel A. Tisherman|
Abstract: Patients who suffer a cardiac arrest from trauma rarely survive. Surgical control of hemorrhage cannot be obtained in time to prevent irreversible organ damage. Emergency preservation and resuscitation (EPR) was developed to utilize hypothermia to buy time to achieve hemostasis and allow delayed resuscitation. Large animal studies have demonstrated that cooling to tympanic membrane temperature 10 °C during exsanguination cardiac arrest can allow up to 2 h of circulatory arrest and repair of simulated injuries with normal neurologic recovery. The Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR‐CAT) trial is testing the feasibility and safety of initiating EPR. Study subjects include patients with penetrating trauma who lose a pulse within 5 minutes of hospital arrival and remain pulseless despite standard care. EPR is initiated via an intra‐aortic flush of ice‐cold saline solution. Following hemostasis, delayed resuscitation and rewarming are accomplished with cardiopulmonary bypass. The primary outcome is survival to hospital discharge without significant neurologic deficits. If trained team members are available, subjects can undergo EPR. If not, subjects can be enrolled as concurrent controls. Ten EPR and 10 control subjects will be enrolled. If successful, EPR could save the lives of trauma patients who are currently dying from exsanguinating hemorrhage.
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Date: 2021-11-30  ·  Issue: 2022  ·  Volume: 1509
Household‐level consumption data can be redistributed for individual‐level Optifood diet modeling: analysis from four countries
Contributors: Frances Knight| Monica Woldt| Kavita Sethuraman| Gilles Bergeron| Elaine Ferguson|
Abstract: A barrier to using Optifood linear programming (LP), which identifies nutrient gaps and supports population‐specific food‐based recommendation (FBR) development, is the requirement for dietary intake data. We investigated whether Household Consumption and Expenditure Surveys (HCESs) could be used instead of individual‐level 24‐h recalls (24HRs). The 24HR data from 12‐ to 23‐month‐old breastfeeding children in rural Kenya, Uganda, Guatemala, and Bangladesh were paired with HCES food consumption data from similar areas (n = 8) and time periods. HCES food intakes (g/week) were estimated using adult male equivalents, adjusted for breastfeeding. Paired HCES‐ and 24HR‐defined LP inputs and outputs were compared using percentage agreement. Mean overall percentage agreements were 42%, 63%, and 80%, for food, food subgroup, and food‐group model parameters, respectively. HCES food lists were on average 1.3 times longer than 24HR. Similar nutrient gaps (77–100% agreement), food sources of nutrients (71–100% agreement), and FBRs (80–100% agreement) were identified. The results suggest that HCES data can be used in Optifood analyses for 12‐ to 23‐month‐old children, despite recognized challenges of using it to estimate dietary intakes of young children compared with older age groups. Further analyses, however, are required for different age groups and locations to confirm expectations that it would perform equally well.
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Date: 2021-11-30  ·  Issue: 2022  · 
Household‐level consumption data can be redistributed for individual‐level Optifood diet modeling: analysis from four countries
Contributors: Frances Knight| Monica Woldt| Kavita Sethuraman| Gilles Bergeron| Elaine Ferguson|
Abstract: A barrier to using Optifood linear programming (LP), which identifies nutrient gaps and supports population‐specific food‐based recommendation (FBR) development, is the requirement for dietary intake data. We investigated whether Household Consumption and Expenditure Surveys (HCESs) could be used instead of individual‐level 24‐h recalls (24HRs). The 24HR data from 12‐ to 23‐month‐old breastfeeding children in rural Kenya, Uganda, Guatemala, and Bangladesh were paired with HCES food consumption data from similar areas (n = 8) and time periods. HCES food intakes (g/week) were estimated using adult male equivalents, adjusted for breastfeeding. Paired HCES‐ and 24HR‐defined LP inputs and outputs were compared using percentage agreement. Mean overall percentage agreements were 42%, 63%, and 80%, for food, food subgroup, and food‐group model parameters, respectively. HCES food lists were on average 1.3 times longer than 24HR. Similar nutrient gaps (77–100% agreement), food sources of nutrients (71–100% agreement), and FBRs (80–100% agreement) were identified. The results suggest that HCES data can be used in Optifood analyses for 12‐ to 23‐month‐old children, despite recognized challenges of using it to estimate dietary intakes of young children compared with older age groups. Further analyses, however, are required for different age groups and locations to confirm expectations that it would perform equally well.
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Date: 2021-11-30  ·  Issue: 2021  ·  Volume: 1506
Cancer stem cells: advances in biology and clinical translation—a Keystone Symposia report
Contributors: Jennifer Cable| Duanqing Pei| Lola M. Reid| Xin Wei Wang| Sonam Bhatia| Panagiotis Karras| Jan Joseph Melenhorst| Markus Grompe| Justin D. Lathia| Erwei Song| Calvin J. Kuo| Ning Zhang| Richard M. White| Stephanie Ky Ma| Lichun Ma| Y. Rebecca Chin| Michael M. Shen| Irene Oi Lin Ng| Klaus H. Kaestner| Lei Zhou| Shaheen Sikandar| Clemens A. Schmitt| Wei Guo| Carmen Chak‐Lui Wong| Junfang Ji| Dean G. Tang| Anna Dubrovska| Chunzhang Yang| Wolf R. Wiedemeyer| Irving L. Weissman|
Abstract: The test for the cancer stem cell (CSC) hypothesis is to find a target expressed on all, and only CSCs in a patient tumor, then eliminate all cells with that target that eliminates the cancer. That test has not yet been achieved, but CSC diagnostics and targets found on CSCs and some other cells have resulted in a few clinically relevant therapies. However, it has become apparent that eliminating the subset of tumor cells characterized by self‐renewal properties is essential for long‐term tumor control. CSCs are able to regenerate and initiate tumor growth, recapitulating the heterogeneity present in the tumor before treatment. As great progress has been made in identifying and elucidating the biology of CSCs as well as their interactions with the tumor microenvironment, the time seems ripe for novel therapeutic strategies that target CSCs to find clinical applicability. On May 19–21, 2021, researchers in cancer stem cells met virtually for the Keystone eSymposium “Cancer Stem Cells: Advances in Biology and Clinical Translation” to discuss recent advances in the understanding of CSCs as well as clinical efforts to target these populations.
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Date: 2021-11-23  ·  Issue: 2021  ·  Volume: 1504
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Contributors:
Abstract:
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Date: 2021-11-20  ·  Issue: 2021  ·  Volume: 1503
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Date: 2021-11-17  ·  Issue: 2022  ·  Volume: 1509
Whole‐brain morphometry in Canadian soldiers with posttraumatic stress disorder
Contributors: Olivier Roy| Jean Levasseur‐Moreau| Emmanuelle Renauld| Luc J. Hébert| Jean Leblond| Mathieu Bilodeau| Shirley Fecteau|
Abstract: Patients with posttraumatic stress disorder (PTSD) display several structural brain differences when compared with healthy individuals. However, findings are particularly inconsistent for soldiers with PTSD. Here, we characterized the brain morphometry of 37 soldiers from the Canadian Armed Forces with adulthood war‐related PTSD using structural magnetic resonance imaging. We assessed time since trauma, as well as PTSD, depressive, and anxiety symptoms with the Modified PTSD Symptoms Scale, Beck Depression Inventory, and Beck Anxiety Inventory, respectively. Whole‐brain morphometry was extracted with FreeSurfer and compared with a validated normative database of more than 2700 healthy individuals. Volume and thickness from several regions differed from the norms. Frontal regions were smaller and thinner, particularly the superior and rostral middle frontal gyri. Furthermore, smaller left rostral middle frontal gyrus, left pericalcarine cortex, and right fusiform gyrus were associated with more recent trauma. All subcortical structures were bigger, except the hippocampus. These findings suggest a particular brain morphometric signature of PTSD in soldiers. Smaller and thinner frontal and larger subcortical regions support impaired top‐down and/or downregulation of emotional response in PTSD. Finally, the correlation of smaller frontal, temporal, and occipital regions with more recent trauma might inform future therapeutic approaches.
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Date: 2021-11-17  ·  Issue: 2022  ·  Volume: 1509
A latent profile analysis of math anxiety and core beliefs toward mathematics among children
Contributors: Lars Orbach| Annemarie Fritz|
Abstract: Recent findings on the negative impacts of math anxiety (MA) have raised questions for educational and clinical research regarding effective intervention programs. One basic approach for developing intervention programs in the field of cognitive behavioral therapy is to gain an in‐depth understanding of the cognitive beliefs of children with a specific mental problem. By applying latent profile analysis (LPA), the present study aimed at identifying different patterns of MA and providing further insights into its cognitive phenomenology. For this purpose, trait‐MA, state‐MA, attitudes toward math, academic self‐concepts, fixed/growth mindsets, executive functions, and math performance of 475 fourth and fifth graders (48.2% girls) were assessed. LPA indicated seven distinct profiles characterized by different dimensions and patterns of state‐MA, trait‐MA, and core beliefs toward math. Furthermore, the profiles showed clearly different math performances. The weakest performances were found for a profile with highest state‐MA, high trait‐MA, and negative cognitive beliefs toward math and a profile with average state‐MA, high trait‐MA, and negative cognitive beliefs toward math, whereas the highest achieving profile had no state‐MA, high trait‐MA, and very positive cognitive beliefs toward math. The findings underline the complexity of MA and emphasize the necessity to develop interventions with careful consideration of the heterogeneous patterns.
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Date: 2021-11-17  ·  Issue: 2021  ·  Volume: 1506
Noncoding RNAs: biology and applications—a Keystone Symposia report
Contributors: Jennifer Cable| Edith Heard| Tetsuro Hirose| Kannanganattu V. Prasanth| Ling‐Ling Chen| Jonathan E. Henninger| Sofia A. Quinodoz| David L. Spector| Sarah D. Diermeier| Allison M. Porman| Dhiraj Kumar| Mark W. Feinberg| Xiaohua Shen| Juan Pablo Unfried| Rory Johnson| Chun‐Kan Chen| Jeremy E. Wilusz| Adelheid Lempradl| Sean E. McGeary| Lamia Wahba| Anna Marie Pyle| Amanda E. Hargrove| Matthew D. Simon| Marco Marcia| Róża K. Przanowska| Howard Y. Chang| Samie R. Jaffrey| Lydia M. Contreras| Qi Chen| Junchao Shi| Joshua T. Mendell| Lin He| Erwei Song| John L. Rinn| Mukesh Kumar Lalwani| Murat Can Kalem| Edward B. Chuong| Lynne E. Maquat| Xuhang Liu|
Abstract: The human transcriptome contains many types of noncoding RNAs, which rival the number of protein‐coding species. From long noncoding RNAs (lncRNAs) that are over 200 nucleotides long to piwi‐interacting RNAs (piRNAs) of only 20 nucleotides, noncoding RNAs play important roles in regulating transcription, epigenetic modifications, translation, and cell signaling. Roles for noncoding RNAs in disease mechanisms are also being uncovered, and several species have been identified as potential drug targets. On May 11–14, 2021, the Keystone eSymposium “Noncoding RNAs: Biology and Applications” brought together researchers working in RNA biology, structure, and technologies to accelerate both the understanding of RNA basic biology and the translation of those findings into clinical applications.
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Date: 2021-11-17  ·  Issue: 2023  · 
Noncoding RNAs: biology and applications—a Keystone Symposia report
Contributors: Jennifer Cable| Edith Heard| Tetsuro Hirose| Kannanganattu V. Prasanth| Ling‐Ling Chen| Jonathan E. Henninger| Sofia A. Quinodoz| David L. Spector| Sarah D. Diermeier| Allison M. Porman| Dhiraj Kumar| Mark W. Feinberg| Xiaohua Shen| Juan Pablo Unfried| Rory Johnson| Chun‐Kan Chen| Jeremy E. Wilusz| Adelheid Lempradl| Sean E. McGeary| Lamia Wahba| Anna Marie Pyle| Amanda E. Hargrove| Matthew D. Simon| Marco Marcia| Róża K. Przanowska| Howard Y. Chang| Samie R. Jaffrey| Lydia M. Contreras| Qi Chen| Junchao Shi| Joshua T. Mendell| Lin He| Erwei Song| John L. Rinn| Mukesh Kumar Lalwani| Murat Can Kalem| Edward B. Chuong| Lynne E. Maquat| Xuhang Liu|
Abstract: The human transcriptome contains many types of noncoding RNAs, which rival the number of protein‐coding species. From long noncoding RNAs (lncRNAs) that are over 200 nucleotides long to piwi‐interacting RNAs (piRNAs) of only 20 nucleotides, noncoding RNAs play important roles in regulating transcription, epigenetic modifications, translation, and cell signaling. Roles for noncoding RNAs in disease mechanisms are also being uncovered, and several species have been identified as potential drug targets. On May 11–14, 2021, the Keystone eSymposium “Noncoding RNAs: Biology and Applications” brought together researchers working in RNA biology, structure, and technologies to accelerate both the understanding of RNA basic biology and the translation of those findings into clinical applications.
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Date: 2021-11-16  ·  Issue: 2021  ·  Volume: 1506
Synthetic biology: at the crossroads of genetic engineering and human therapeutics—a Keystone Symposia report
Contributors: Jennifer Cable| Joshua N. Leonard| Timothy K. Lu| Zhen Xie| Matthew Wook Chang| Luis Ángel Fernández| José M. Lora| Howard L. Kaufman| Francisco J. Quintana| Roger Geiger| Cammie F. Lesser| Jason P. Lynch| David L. Hava| Virginia W. Cornish| Gary K. Lee| Breanna DiAndreth| Michael Fero| Rajkamal Srivastava| Tim De Coster| Kole T. Roybal| Owen J. L. Rackham| Samira Kiani| Iowis Zhu| Rogelio A. Hernandez‐Lopez| Tingxi Guo| William C. W. Chen|
Abstract: Synthetic biology has the potential to transform cell‐ and gene‐based therapies for a variety of diseases. Sophisticated tools are now available for both eukaryotic and prokaryotic cells to engineer cells to selectively achieve therapeutic effects in response to one or more disease‐related signals, thus sparing healthy tissue from potentially cytotoxic effects. This report summarizes the Keystone eSymposium “Synthetic Biology: At the Crossroads of Genetic Engineering and Human Therapeutics,” which took place on May 3 and 4, 2021. Given that several therapies engineered using synthetic biology have entered clinical trials, there was a clear need for a synthetic biology symposium that emphasizes the therapeutic applications of synthetic biology as opposed to the technical aspects. Presenters discussed the use of synthetic biology to improve T cell, gene, and viral therapies, to engineer probiotics, and to expand upon existing modalities and functions of cell‐based therapies.
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Date: 2021-11-16  ·  Issue: 2023  · 
Synthetic biology: at the crossroads of genetic engineering and human therapeutics—a Keystone Symposia report
Contributors: Jennifer Cable| Joshua N. Leonard| Timothy K. Lu| Zhen Xie| Matthew Wook Chang| Luis Ángel Fernández| José M. Lora| Howard L. Kaufman| Francisco J. Quintana| Roger Geiger| Cammie F. Lesser| Jason P. Lynch| David L. Hava| Virginia W. Cornish| Gary K. Lee| Breanna DiAndreth| Michael Fero| Rajkamal Srivastava| Tim De Coster| Kole T. Roybal| Owen J. L. Rackham| Samira Kiani| Iowis Zhu| Rogelio A. Hernandez‐Lopez| Tingxi Guo| William C. W. Chen|
Abstract: Synthetic biology has the potential to transform cell‐ and gene‐based therapies for a variety of diseases. Sophisticated tools are now available for both eukaryotic and prokaryotic cells to engineer cells to selectively achieve therapeutic effects in response to one or more disease‐related signals, thus sparing healthy tissue from potentially cytotoxic effects. This report summarizes the Keystone eSymposium “Synthetic Biology: At the Crossroads of Genetic Engineering and Human Therapeutics,” which took place on May 3 and 4, 2021. Given that several therapies engineered using synthetic biology have entered clinical trials, there was a clear need for a synthetic biology symposium that emphasizes the therapeutic applications of synthetic biology as opposed to the technical aspects. Presenters discussed the use of synthetic biology to improve T cell, gene, and viral therapies, to engineer probiotics, and to expand upon existing modalities and functions of cell‐based therapies.
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Date: 2021-11-15  ·  Issue: 2022  ·  Volume: 1509
Cerebral oximetry: a developing tool for monitoring cerebral oxygenation during cardiopulmonary resuscitation
Contributors: Elise L. Huppert| Sam Parnia|
Abstract: Despite improvements in cardiopulmonary resuscitation (CPR), survival and neurologic recovery after cardiac arrest remain very poor because of the impact of severe ischemia and subsequent reperfusion injury. As the likelihood of survival and favorable neurologic outcome decreases with increasing severity of ischemia during CPR, developing methods to measure the magnitude of ischemia during resuscitation, particularly cerebral ischemia, is critical for improving overall outcomes. Cerebral oximetry, which measures regional cerebral oxygen saturation (rSO2) by near‐infrared spectroscopy, has emerged as a potentially beneficial marker of cerebral ischemia during CPR. In numerous preclinical and clinical studies, higher rSO2 during CPR has been associated with improved cardiac arrest survival and neurologic outcome. In this narrative review, we summarize the scientific rationale and validation of cerebral oximetry across populations and pathophysiologic states, discuss the evidence surrounding its use to predict return of spontaneous circulation, rearrest, and neurologic outcome, and provide suggestions for incorporation of cerebral oximetry into CPR practice.
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Date: 2021-11-15  ·  Issue: 2022  · 
Calcium supplementation during pregnancy and maternal and offspring bone health: a systematic review and meta‐analysis
Contributors: Kati Tihtonen| Päivi Korhonen| Jaana Isojärvi| Riitta Ojala| Ulla Ashorn| Per Ashorn| Outi Tammela|
Abstract: Insufficient calcium intake during pregnancy may lead to maternal bone resorption and lower bone density of offspring. We evaluated the impact of supplementary calcium with or without vitamin D during pregnancy on maternal and offspring bone mineral density (BMD) and teeth firmness of the offspring. Randomized controlled trials (RCTs) were searched systematically in 11 databases. Two researchers independently screened the titles and abstracts of 3555 records and the full texts of 31 records to examine eligibility. The search yielded seven RCTs (11 reports, n = 1566).  No advantage of calcium supplementation was found on maternal BMD after delivery or during breastfeeding, or on offspring BMD, even when dietary calcium intake was low. The results were neither modified by the dose of calcium nor concomitant vitamin D administration. A suspicion of some long‐term harm of the intervention on maternal BMD and growth of female offspring was raised based on the data. One study suggested some benefit of high‐dose calcium supplementation on offspring teeth firmness at 12 years old. A low number of the studies and abundant missing data reduced the quality of the findings. The impact of calcium supplementation on maternal and offspring bone health was deemed unknown because of inconclusive research results.
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Date: 2021-11-15  ·  Issue: 2022  ·  Volume: 1509
Calcium supplementation during pregnancy and maternal and offspring bone health: a systematic review and meta‐analysis
Contributors: Kati Tihtonen| Päivi Korhonen| Jaana Isojärvi| Riitta Ojala| Ulla Ashorn| Per Ashorn| Outi Tammela|
Abstract: Insufficient calcium intake during pregnancy may lead to maternal bone resorption and lower bone density of offspring. We evaluated the impact of supplementary calcium with or without vitamin D during pregnancy on maternal and offspring bone mineral density (BMD) and teeth firmness of the offspring. Randomized controlled trials (RCTs) were searched systematically in 11 databases. Two researchers independently screened the titles and abstracts of 3555 records and the full texts of 31 records to examine eligibility. The search yielded seven RCTs (11 reports, n = 1566).  No advantage of calcium supplementation was found on maternal BMD after delivery or during breastfeeding, or on offspring BMD, even when dietary calcium intake was low. The results were neither modified by the dose of calcium nor concomitant vitamin D administration. A suspicion of some long‐term harm of the intervention on maternal BMD and growth of female offspring was raised based on the data. One study suggested some benefit of high‐dose calcium supplementation on offspring teeth firmness at 12 years old. A low number of the studies and abundant missing data reduced the quality of the findings. The impact of calcium supplementation on maternal and offspring bone health was deemed unknown because of inconclusive research results.
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Date: 2021-11-15  ·  Issue: 2022  · 
Math anxiety differentially impairs symbolic, but not nonsymbolic, fraction skills across development
Contributors: Isabella Starling‐Alves| Matthew R. Wronski| Edward M. Hubbard|
Abstract: Although important for the acquisition of later math skills, fractions are notoriously difficult. Previous studies have shown that higher math anxiety (MA) is associated with lower performance in symbolic fraction tasks in adults and have suggested that MA may negatively impact the acquisition of fractions in children. However, the effects of MA on fraction skills in school‐aged children remain underexplored. We, therefore, investigated the impact of MA on the performance of younger (second and third graders) and older (fifth and sixth graders) children in math fluency (MF), written calculation, fraction knowledge (FK), and symbolic fraction and nonsymbolic ratio processing. On the basis of our prior work suggesting a perceptual foundation for fraction processing, we predicted that symbolic, but not nonsymbolic, math skills (especially fractions) would be impaired by MA. As predicted, higher MA was associated with lower performance in general mathematics achievement and symbolic fraction tasks, but nonsymbolic ratio processing was not affected by MA in either age group. Furthermore, working memory capacity partially mediated the effects of MA on general mathematics achievement, FK, and symbolic fraction processing. These results suggest that understanding the bidirectional interactions between MA and fractions may be important for helping children acquire these critical skills.
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Date: 2021-11-11  ·  Issue: 2022  ·  Volume: 1509
6‐Benzyladenine increasing subsequent waterlogging‐induced waterlogging tolerance of summer maize by increasing hormone signal transduction
Contributors: Juan Hu| Baizhao Ren| Shuting Dong| Peng Liu| Bin Zhao| Jiwang Zhang|
Abstract: Summer maize is frequently subjected to waterlogging damage because of increased and variable rainfall during the growing season. The application of 6‐benzyladenine (6‐BA) can effectively mitigate the waterlogging effects on plant growth and increase the grain yield of waterlogged summer maize. However, the mechanisms underlying this process and the involvement of 6‐BA in relevant signal transduction pathways remain unclear. In this study, we explored the effects of 6‐BA on waterlogged summer maize using a phosphoproteomic technique to better understand the mechanism by which summer maize growth improves following waterlogging. Application of 6‐BA inhibited the waterlogging‐induced increase in abscisic acid (ABA) content and increased the phosphorylation levels of proteins involved in ABA signaling; accordingly, stomatal responsiveness to exogenous ABA increased. In addition, the application of 6‐BA had a long‐term effect on signal transduction pathways and contributed to rapid responses to subsequent stresses. Plants primed with 6‐BA accumulated more ethylene and jasmonic acid in response to subsequent waterlogging; accordingly, leaf SPAD, antioxidase activity, and root traits improved by 6‐BA priming. These results suggest that the effects of 6‐BA on hormone signal transduction pathways are anamnestic, which enables plants to show faster or stronger defense responses to stress.
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Date: 2021-11-10  ·  Issue: 2022  ·  Volume: 1509
Individuality and function of chemical signals during conflict resolution of a mammal
Contributors: Chunmian Zhang| Congnan Sun| Jeffrey R. Lucas| Hao Gu| Jiang Feng| Tinglei Jiang|
Abstract: Individual recognition via communication signals is a critical component of social behavior, and provides the basis of conflict resolution, territorial behavior, and mate choice. However, the function of chemical signals in mammalian individual recognition and conflict resolution has largely been unexplored despite olfaction being a dominant sensory modality in many mammalian species. Here, we describe behavioral tests designed to evaluate the potential role of forehead gland secretions during conflict related to territorial defense in male Great Himalayan leaf‐nosed bats. We used gas chromatography–mass spectrometry to quantify the chemical composition. Our results showed that forehead gland secretions contain 16 categories of compounds, including 84 volatile compounds. The concentrations of compounds and their categories differed significantly among individuals. Moreover, behavioral studies indicated that males can use chemical signals for individual recognition. Contests were staged between males with or without functioning forehead glands. Paired males without functioning forehead glands displayed more physical contact and longer contest duration compared with pairs with functioning glands. Moreover, males with a functioning gland were more likely to win in contests when paired with males without a functioning gland. These findings support a growing amount of evidence that chemical signals play a vital role in conflict resolution in mammals.
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Date: 2021-11-09  ·  Issue: 2022  ·  Volume: 1509
Genetic support of carbapenemases: a One Health systematic review and meta‐analysis of current trends in Africa
Contributors: Suzan Mohammed Ragheb| Usha Govinden| John Osei Sekyere|
Abstract: Antimicrobial resistance (AMR) is a public health threat globally. Carbapenems are β‐lactam antibiotics used as last‐resort agents for treating antibiotic‐resistant infections. Mobile genetic elements (MGEs) play an important role in the dissemination and expression of antimicrobial resistance genes (ARGs), including the mobilization of ARGs within and between species. The presence of MGEs around carbapenem‐hydrolyzing enzymes, called carbapenemases, in bacterial isolates in Africa is concerning. The association between MGEs and carbapenemases is described herein. Specific plasmid replicons, integrons, transposons, and insertion sequences were found flanking specific and different carbapenemases across the same and different clones and species isolated from humans, animals, and the environment. Notably, similar genetic contexts have been reported in non‐African countries, supporting the importance of MGEs in driving the intra‐ and interclonal and species transmission of carbapenemases in Africa and globally. Technical and budgetary limitations remain challenges for epidemiological analysis of carbapenemases in Africa, as studies undertaken with whole‐genome sequencing remained relatively few. Characterization of MGEs in antibiotic‐resistant infections can deepen our understanding of carbapenemase epidemiology and facilitate the control of AMR in Africa. Investment in genomic epidemiology will facilitate faster clinical interventions and containment of outbreaks.
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Date: 2021-11-09  ·  Issue: 2022  ·  Volume: 1508
Interbrain emotional connection during music performances is driven by physical proximity and individual traits
Contributors: Thibault Chabin| Damien Gabriel| Alexandre Comte| Emmanuel Haffen| Thierry Moulin| Lionel Pazart|
Abstract: How musical emotions and the pleasure derived from music, regardless of the musical valence, can be shared between individuals is a fascinating question, and investigating it can shed light on the function of musical reward. We carried out our investigations in a natural setting during an international competition for orchestra conductors. Participants (n = 15) used a dedicated smartphone app to report their subjective emotional experiences in real time while we recorded their cerebral activity using electroencephalography and their electrodermal activity. The overall behavioral real‐time behavioral ratings suggest a possible social influence on the reported and felt pleasure. The physically closer the participants, the more similar their reported pleasure. By calculating the interindividual cerebral coherence (n = 21 pairs), we showed that when people simultaneously reported either high or low pleasure, their cerebral activities were closer than for simultaneous neutral pleasure reports. Participants’ skin conductance levels were also more coupled when reporting higher emotional degrees simultaneously. More importantly, the participants who were physically closer had higher cerebral coherence, but only when they simultaneously reported a high level of pleasure. We propose that emotional contagion and/or emotional resonance mechanisms could explain why a form of “emotional connecting force” arises between people during shared appraisal situations.
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Date: 2021-11-06  ·  Issue: 2022  ·  Volume: 1508
The roles of mitochondrial dynamics and NLRP3 inflammasomes in the pathogenesis of retinal light damage
Contributors: Rong Rong| Rongliang Yang| Haibo Li| Mengling You| Zhuotao Liang| Zhou Zeng| Rongrong Zhou| Xiaobo Xia| Dan Ji|
Abstract: With the widespread popularity of electronic products and the diversification of lighting equipment, ocular photochemical damage caused by light has attracted research attention. Although such equipment mainly cause damage to the retina, the specific pathogenesis has not been systematically elucidated. Thus, the goal of this study was to explore the relationship between mitochondrial dysfunction and the activation of the NOD‐like receptor protein 3 (NLRP3) inflammasome in retinal cell death caused by light damage. We used a white light–emitting diode source to establish a mouse model of retinal light damage and observed significant changes of retinal structure and an impairment of visual function. Further experiments revealed that dynamin‐related protein 1 (Drp1)–mediated excessive mitochondrial fission induced overproduction of reactive oxygen species in the retinal cells, leading to apoptosis, activation of microglia, and formation of the NLRP3 inflammasome. This, in turn, triggered a series of inflammatory cascade reactions, leading to pyroptosis. We also carried out red light and Drp1 inhibitor treatment and found that retinal damage and the decline in visual function caused by white light could be partially ameliorated. In conclusion, this study clarified the association between mitochondrial dynamics and the NLRP3 inflammasome in retinal light damage and provides opportunities for therapeutic intervention.
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Date: 2021-11-06  ·  Issue: 2022  ·  Volume: 1508
Transtheoretical model for lifestyle changes in older persons: a systematic review protocol
Contributors: Melissa Côrtes da Rosa| Carolina Böettge Rosa| Raquel de Melo Boff| Margareth Silva Oliveira| Carla Helena Augustin Schwanke|
Abstract: Adherence to lifestyle changes is a major challenge for healthcare professionals. The transtheoretical model (TTM) was proposed to promote behavioral changes, used in different health conditions (smoking, alcoholism, drug addiction, and obesity) and age groups. However, the effectiveness of the model in older persons is not yet known. This systematic review protocol follows the PRISMA‐P guidance. The question the review will address is, Are interventions based on the TTM, compared with conventional interventions, associated with lifestyle changes in older adults? Databases MEDLINE/PubMed, EMBASE, LILACS, CENTRAL, WoS, and PsycINFO will be searched. Randomized clinical controlled trials and quasi‐experimental studies describing the effectiveness of TTM‐based interventions in changing the lifestyle of individuals aged 65 and over, compared with conventional interventions for lifestyle changes, will be included. Studies that do not address the stages of change characteristic of TTM or that use pharmacological interventions as a comparator will be excluded. Reviewers independently will screen papers for eligibility criteria, and, extracting data, assess the risk of bias for included studies and will evaluate the overall quality of evidence (GRADE system). If possible, a meta‐analysis will be conducted. Otherwise, a narrative synthesis will be prepared according