bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Data-Driven Model to Identify Fatigue Level Based on the Motion Data from a Smartphone
Authors: Karvekar Swapnali , Abdollahi Masoud , Rashedi Ehsan 
Published: October 2019

AbstractThe fatigue due to repetitive and physically challenging jobs may result in workers’ poor performance and Work-related Musculoskeletal Disorder (WMSD). Thus, it is imperative to frequently monitor fatigue and take necessary recovery actions. Our purpose was to develop a methodology to objectively classify subjects’ fatigue level in the workplace utilizing the motion sensors embedded in the smartphones. An experiment consisting of twenty-four participants (12 M, 12 F) with a smartphone attached to their right shank was conducted using a fatiguing exercise (squatting), targeted mainly the lower extremity musculature. After each set of an exercise (2-min squatting), participants were asked about their ratings of perceived exertion (RPE), then a reference gait data were collected during a straight walk of 20-32 steps. This process was continued until they reported strong fatigue (≥17). Using the RPE to label the gait data, we have developed machine learning algorithms (i.e., binary and multi-class SVM models) to classify the individuals’ gait into two (no-vs. strong-fatigue) and four levels (no-, low-, medium-, and strong-fatigue). The models reached the accuracies of 91% and 61% for two and four-level classification, respectively. The outcomes of this study may facilitate the implementation of a proactive approach in continuous monitoring of operators’ fatigue level, which may subsequently increase the workers’ performance and reduce the risk of WMSDs.
Isolation and maintenance of Batrachochytrium salamandrivorans cultures
Authors: Robinson Kristyn A. , Pereira Kenzie E. , Bletz Molly C. , Carter Edward Davis , Gray Matthew J. , Piovia-Scott Jonah , Romansic John M. , Woodhams Douglas C. , Fritz-Laylin Lillian 
Published: October 2019

AbstractDiscovered in 2013, Batrachochytrium salamandrivorans (Bsal) is an emerging amphibian pathogen that causes ulcerative skin lesions and multifocal erosion. A closely related pathogen, Batrachochytrium dendrobatidis (Bd), has devastated amphibian populations worldwide, suggesting that Bsal poses a significant threat to global salamander biodiversity. To expedite research into this emerging threat, we seek to standardize protocols across the field so that results of laboratory studies are reproducible and comparable. We have collated data and experience from multiple labs to standardize culturing practices of Bsal. Here we outline common culture practices including a media for optimal Bsal growth, standard culture protocols, and a method for isolating Bsal from infected tissue.
Sex-specific transgenerational plasticity II: Grandpaternal effects are lineage- and sex-specific in threespined sticklebacks
Authors: Hellmann Jennifer K , Carlson Erika R , Bell Alison M 
Published: October 2019

AbstractTransgenerational plasticity (TGP) occurs when the environment encountered by one generation (F0) alters the phenotypes of one or more future generations (e.g. F1 and F2). Sex selective TGP, via specific lineages or to only male or female descendants, has been underexplored in natural systems, and may be adaptive if it allows past generations to fine-tune the phenotypes of future generations in response to sex-specific life history strategies.We sought to understand if exposing males to predation risk can influence grandoffspring via sperm in threespined stickleback(Gasterosteus aculeatus).We specifically tested the hypothesis that grandparental effects are transmitted in a sex-specific way down the male lineage, from paternal grandfathers to F2 males.We reared F1 offspring of unexposed and predator-exposed F0 males under ‘control’ conditions and used them to generate F2s with control grandfathers, a predator-exposed maternal grandfather (i.e., predator-exposed F0 males to F1 daughters to F2 offspring), a predator-exposed paternal grandfather (i.e., predator-exposed F0 males to F1 sons to F2 offspring), or two predator-exposed grandfathers. We then assayed male and female F2s for a variety of traits related to antipredator defense.We found little evidence that transgenerational effects were mediated to only male descendants via the paternal lineage. Instead, grandpaternal effects depended on lineage and were mediated largely across sexes, from F1 males to F2 females and from F1 females to F2 males. When their paternal grandfather was exposed to predation risk, female F2s were heavier and showed a reduced change in behavior in response to a simulated predator attack relative to offspring of control, unexposed grandparents. In contrast, male F2s showed reduced antipredator behavior when their maternal grandfather was exposed to predation risk. However, these patterns were only evident when one grandfather, but not both grandfathers, was exposed to predation risk, suggesting the potential for non-additive interactions across lineages.If sex-specific and lineage effects are common, then grandparental effects are likely underestimated in the literature. These results draw attention to the importance of sex-selective inheritance of environmental effects and raise new questions about the proximate and ultimate causes of selective transmission across generations.
Sporulation environment drives phenotypic variation in the pathogenAspergillus fumigatus
Authors: Kang S. Earl , Momany Michelle 
Published: October 2019

AbstractAspergillus fumigatuscauses more than 300,000 life-threatening infections annually and is widespread across varied environments with a single colony producing thousands of conidia, genetically-identical dormant spores. Conidia are easily wind-dispersed to new environments where they can germinate and, if inhaled by susceptible hosts, cause disease. Using high-throughput, single-cell analysis we show that germination phenotypes vary among genetically-identical individuals and that the environment of spore production determines the degree of germination heterogeneity.
Adaptive resetting of tuberoinfundibular dopamine (TIDA) network activity during lactation in mice
Authors: Pérez Carolina Thörn , Ferraris Jimena , van Lunteren Josina Anna , Hellysaz Arash , Iglesias María Jesús , Broberger Christian 
Published: October 2019

ABSTRACTGiving birth triggers a wide repertoire of physiological and behavioural changes in the mother to enable her to feed and care for her offspring. These changes require coordination and are often orchestrated from the central nervous system, through as of yet poorly understood mechanisms. A neuronal population with a central role in puerperal changes is the tuberoinfundibular dopamine (TIDA) neurons that control release of the pituitary hormone, prolactin, which triggers key maternal adaptations, including lactation and maternal care. Here, we used Ca2+ imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons in vitro to examine if they adapt their cellular and network activity according to reproductive state. In the high-prolactin state of lactation, TIDA neurons shift to faster membrane potential oscillations, a reconfiguration that reverses upon weaning. During the estrous cycle, however, which includes a brief, but pronounced, prolactin peak, oscillation frequency remains stable. An increase in the hyperpolarization-activated mixed cation current, Ih, possibly through unmasking as dopamine release drops during nursing, may explain the reconfiguration of TIDA rhythms. These findings identify a reversible plasticity in hypothalamic network activity that can serve to adapt the dam for motherhood.Significance StatementMotherhood requires profound behavioural and physiological adaptations to enable caring for offspring, but the underlying CNS changes are poorly understood. Here, we show that during lactation, neuroendocrine dopamine neurons, the “TIDA” cells that control prolactin secretion, reorganize their trademark oscillations to discharge in faster frequencies. Unlike previous studies, which typically have focused on structural and transcriptional changes during pregnancy and lactation, we demonstrate a functional switch in activity and one that, distinct from previously described puerperal modifications, reverses fully upon weaning. We further provide evidence that a specific conductance – Ih - may underlie the altered network rhythm. These findings identify a new facet of maternal brain plasticity at the level of membrane properties and consequent ensemble activity.
Astrovirus Replication Is Inhibited by NitazoxanideIn VitroandIn Vivo
Authors: Hargest Virginia , Sharp Bridgett , Livingston Brandi , Cortez Valerie , Schultz-Cherry Stacey 
Published: October 2019

AbstractAstroviruses (AstV) are a leading cause of diarrhea especially in the very young, the elderly, and immunocompromised populations. Despite their significant impact on public health, no drug therapies for astrovirus have been identified. In this study we fill this gap in knowledge and demonstrate that the FDA-approved broad-spectrum anti-infective drug nitazoxanide (NTZ) blocks astrovirus replicationin vitrowith a 50% effective concentration (EC50) of approximately 1.47μM. It can be administered up to 8 hours post-infection and is effective against multiple human astrovirus serotypes including clinical isolates. Most importantly, NTZ reduces viral shed and clinical disease (diarrhea)in vivo, exhibiting its potential as a future clinical therapeutic.ImportanceHuman astroviruses (HAstV) are thought to cause between 2 and 9% of acute, non-bacterial diarrhea cases in children worldwide. HAstV infection can be especially problematic in immunocompromised people and infants where the virus has been associated with necrotizing enterocolitis, severe and persistent diarrhea, as well as systemic and often fatal disease. Yet no antivirals have been identified to treat astrovirus infection. Our study provides the first evidence that nitazoxanide may be an effective therapeutic strategy against astrovirus disease.
TRMT2B is responsible for both tRNA and rRNA m5U-methylation in human mitochondria
Authors: Powell Christopher A. , Minczuk Michal 
Published: October 2019

AbstractRNA species play host to a plethora of post-transcriptional modifications which together make up the epitranscriptome. 5-methyluridine (m5U) is one of the most common modifications made to cellular RNA, where it is found almost ubiquitously in bacterial and eukaryotic cytosolic tRNAs at position 54. Here, we demonstrate that m5U54 in human mitochondrial tRNAs is catalysed by the nuclear-encoded enzyme TRMT2B, and that its repertoire of substrates is expanded to ribosomal RNAs, catalysing m5U429 in 12S rRNA. We show that TRMT2B is not essential for viability in human cells and that knocking-out the gene shows no obvious phenotype with regards to RNA stability, mitochondrial translation, or cellular growth.
Ecology, phylogeny, and the evolution of developmental duration in birds
Authors: Cooney Christopher R. , Sheard Catherine , Clark Andrew D. , Healy Susan D. , Liker András , Street Sally E. , Troisi Camille A. , Thomas Gavin H. , Székely Tamás , Hemmings Nicola , Wright Alison E. 
Published: October 2019

ABSTRACTThe duration of the developmental period represents a fundamental axis of life history variation in animals, yet broad insights regarding the drivers of this diversity are currently lacking. Here using embryological data combined with information on incubation and fledging periods for 3096 species, we test key mechanistic and adaptive explanations for the evolutionary diversification of developmental durations in birds. First, using data on embryonic development for 20 model species, we show that developmental phases associated primarily with growth are longer and more variable than earlier phases, consistent with a role for allometric constraint in determining the duration of development. Second, using phylogenetic comparative methods, we find that avian developmental durations retain a strong imprint of deep evolutionary history, and that after accounting for these effects, body size differences among species explain less variation (5-22%) in developmental period lengths than previously thought. Finally, by collecting data for a suite of potential explanatory variables, our analyses reveal broad-scale ecological correlates of developmental durations, including variables associated with the relative safety of the developmental environment (e.g. nest height, insularity) and pressures of breeding phenology (e.g. migration). Overall, our results reveal that the combined effects of species’ body size, ecology, and phylogenetic history can account for 62-93% of the variation in developmental durations across birds, providing broad-scale quantitative insight into the relative importance of mechanistic constraints, adaptive evolution and evolutionary constraints in shaping the diversification of this key life-history trait.
Computational insights into mechanism of AIM4-mediated inhibition of aggregation of TDP-43 protein implicated in ALS and evidence for in vitro inhibition of liquid-liquid phase separation (LLPS) of TDP-432C-A315T by AIM4
Authors: Girdhar Amandeep , Bharathi Vidhya , Tiwari Vikas Ramyagya , Abhishek Suman , Mahawar Usha Saraswat , Raju Gembali , Singh Sandeep Kumar , Prabusankar Ganesan , Rajakumara Eerappa , Patel Basant K 
Published: October 2019

AbstractTDP-43 is an RNA/DNA-binding protein of versatile physiological functions and it is also implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) disease in addition to several other implicated proteins such as mutant SOD1 and FUS etc. Cytoplasmic mis-localization, liquid-liquid phase separation (LLPS) due to RNA depletion and aggregation of TDP-43 are suggested to be important TDP-43-toxicity causing mechanisms for the ALS manifestation. So far, therapeutic options for ALS are extremely minimal and ineffective therefore, multi-faceted approaches such as treating the oxidative stress and inhibiting the TDP-43’s aggregation are being actively pursued. In our recent study, an acridine imidazolium derivative compound, AIM4, has been identified to have anti-TDP-43 aggregation propensity however, its mechanism of inhibition is not deciphered. In this study, we have utilized computational methods to examine binding site(s) of AIM4 in the TDP-43 structure and have also compared its binding efficiency with several other relevant compounds. We find that AIM4 has a binding site in the C-terminal amyloidogenic core region of amino acids aa: 288-319, which coincides with one of the key residue motifs that could potentially mediate liquid-liquid phase separation (LLPS) of TDP-43. Importantly, alike to the previously reported effects exerted by RNA molecules, we found that AIM4 could also inhibit the in vitro LLPS of a recombinantly purified C-terminal fragment TDP-432C bearing an A315T familial mutation. Antagonistic effects of AIM4 towards LLPS which is believed as the precursor process to the TDP-43’s aggregation and the in silico prediction of a binding site of AIM4 on TDP-43 occurring in the same region, assert that AIM4 could be an important molecule for further investigations on TDP-43’s anti-aggregation effects with relevance to the ALS pathogenesis.
Biophysical properties of intermediate states of EMT outperform both epithelial and mesenchymal states
Authors: Margaron Yoran , Nagai Tomoaki , Guyon Laurent , Kurzawa Laetitia , Morel Anne-Pierre , Pinheiro Alice , Blanchoin Laurent , Reyal Fabien , Puisieux Alain , Théry Manuel 
Published: October 2019

AbstractPotential metastatic cells can dissociate from a primary breast tumor by undergoing an epithelial-to-mesenchymal transmission (EMT). Recent work has revealed that cells in intermediate states of EMT acquire an augmented capacity for tumor-cell dissemination. These states have been characterized by molecular markers, but the structural features and the cellular mechanisms that underlie the acquisition of their invasive properties are still unknown. Using human mammary epithelial cells, we generated cells in intermediate states of EMT through the induction of a single EMT-inducing transcription factor, ZEB1, and cells in a mesenchymal state by stimulation with TGFβ. In stereotypic and spatially-defined culture conditions, the architecture, internal organization and mechanical properties of cells in the epithelial, intermediate and mesenchymal state were measured and compared. We found that the lack of intercellular cohesiveness in epithelial and mesenchymal cells can be detected early by microtubule destabilization and the repositioning of the centrosome from the cell-cell junction to the cell center. Consistent with their high migration velocities, cells in intermediate states produced low contractile forces compared with epithelial and mesenchymal cells. The high contractile forces in mesenchymal cells powered a retrograde flow pushing the nucleus away from cell adhesion to the extracellular matrix. Therefore, cells in intermediate state had structural and mechanical properties that were distinct but not necessarily intermediate between epithelial and mesenchymal cells. Based on these observations, we found that a panel of triple-negative breast cancer lines had intermediate rather than mesenchymal characteristics suggesting that the structural and mechanical properties of the intermediate state are important for understanding tumor-cell dissemination.
Factors associated with normal linear growth among pre-school children living in better-off households: a multi-country analysis of nationally representative data
Authors: Amugsi Dickson A. , Dimbuene Zacharie T. , Kimani-Murage Elizabeth W. 
Published: October 2019

AbstractThis study examined the factors associated with normal linear growth among pre-school children living in better-off households, using survey data from Ghana, Kenya, Nigeria, Mozambique and Democratic Republic of Congo (DRC). The primary outcome variable was child height-for-age z-scores (HAZ), categorised into HAZ≥-2SD (normal growth/not stunted) and HAZ<–2 (stunted). Using logistic regression, we estimated adjusted odds ratios (aORs) of the factors associated with normal growth. Higher maternal weight (measured by body mass index) was associated with increased odds of normal growth in Mozambique, DRC, Kenya and Nigeria. A unit increase in maternal years of education was associated with increased odds in normal growth in DRC (aOR=1.06, 95% CI=1.03, 1.09), Ghana (aOR=1.08, 95% CI=1.04, 1.12), Mozambique (aOR=1.08, 95% CI=1.05, 1.11) and Nigeria (aOR=1.07, 95% CI=1.06, 1.08). A year increase in maternal age was positively associated with normal growth in all the five countries. Breastfeeding was associated with increased odds of normal growth in Nigeria (aOR= 1.30, 95% CI=1.16, 1.46) and Kenya (aOR=1.37, 95% CI=1.05, 1.79). Children of working mothers had 25% (aOR=0.75, 95% CI=0.60, 0.93) reduced odds of normal growth in DRC. A unit change in maternal parity was associated with 10% (aOR=0.90, 95% CI=0.84, 0.97), 23% (aOR=0.77, 95% CI=0.63, 0.93), 25% (aOR=0.75, 95% CI=0.69, 0.82), 6% (aOR=0.94, 95% CI=0.89, 0.99) and 5% (aOR=0.95, 95% CI=0.92, 0.99) reduced odds of normal growth in DRC, Ghana, Kenya, Mozambique and Nigeria respectively. A child being a male was associated with 16% (aOR=0.82, 95% CI=0.68, 0.98), 40% (aOR=0.60, 95% CI=0.40, 0.89), 37% (aOR=0.63, 95% CI=0.51, 0.77) and 21% (aOR=0.79, 95% CI=0.71, 0.87) reduced odds of normal child growth in DRC, Ghana, Kenya and Nigeria respectively. In conclusion, maternal education, weight, age, breastfeeding and antenatal care are positively associated with normal child growth, while maternal parity, employment, and child sex and age are associated negatively with normal growth. Interventions to improve child growth should take into account these differential effects.
Chromatin-mediated alternative splicing regulates cocaine reward behavior
Authors: Xu Song-Jun , Lombroso Sonia I. , Carpenter Marco , Marchione Dylan M. , Hamilton Peter J. , Lim Carissa J. , Neve Rachel L , Heller Elizabeth A. 
Published: October 2019

ABSTRACTAlternative splicing is a key mechanism for neuronal gene regulation, and is grossly altered in mouse brain reward regions following investigator-administered cocaine. It is well established that cocaine epigenetically regulates transcription, yet mechanism(s) by which cocaine-induced epigenetic modifications regulate alternative splicing is largely unexplored. Our group and others have previously identified the histone modification, H3K36me3, as a putative splicing regulator. However, it has not yet been possible to establish the direct causal relevance of this modification to alternative splicing in brain or any other context. We found that mouse cocaine self-administration caused widespread alternative splicing, concomitant with enrichment of H3K36me3 at splice junctions. Differentially spliced genes were enriched in the motif for splice factor, Srsf11, which was both differentially spliced and enriched in H3K36me3. Epigenetic editing led us to conclude that H3K36me3 functions directly in alternative splicing of Srsf11, and that Set2 mediated H3K36me3 bidirectionally regulates cocaine intake.
Reduced Hippocampal and Amygdala Volumes as Mechanisms of Stress Sensitization to Depression following Childhood Violence Exposure
Authors: Weissman David G. , Lambert Hilary K. , Rodman Alexandra M. , Peverill Matthew , Sheridan Margaret A. , McLaughlin Katie A. 
Published: October 2019

AbstractOBJECTIVEStressful life events are more likely to trigger depression among individuals exposed to childhood adversity. However, the mechanisms underlying this stress sensitization remain largely unknown. Any such mechanism must be altered by childhood adversity and interact with recent stressful life events, magnifying their association with depression. This study investigated whether reduced hippocampal and amygdala volumes are mechanisms of stress sensitization following childhood violence exposure.METHODSA sample of 149 youth (aged 8-17 years), with (N=76) and without (N=73) exposure to physical abuse, sexual abuse, or domestic violence participated. Participants completed a structural MRI scan and were assessed for symptoms of depression. Approximately two years later, stressful life events were assessed along with depression symptoms in 120 participants (57 violence-exposed).RESULTSChildhood violence exposure was associated with smaller hippocampal and amygdala volumes. Stressful life events occurring during the follow-up period predicted worsening depression over time, and this association was magnified among those with smaller hippocampal and amygdala volumes. Significant moderated mediation models revealed indirect effects of violence exposure on increasing depression over time through hippocampal and amygdala volumes, particularly among youths who experienced more stressful life events.CONCLUSIONSThese results provide novel evidence for reduced hippocampal and amygdala volumes as mechanisms of stress sensitization to depression following exposure to violence. These findings suggest that hippocampal and amygdala-mediated emotional and cognitive processes may contribute to vulnerability to stressful life events following childhood violence exposure.