bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival Beyond the Perinatal Period Expands the Phenotypes Caused by Mutations inGLE1
Authors: Said Edith , Chong Jessica X. , Hempel Maja , Denecke Jonas , Soler Paul , Strom Tim , Nickerson Deborah A. , Kubisch Christian , Bamshad Michael ,   University of Washington Center for Mendelian Genomics, Lessel Davor 
Published: April 2017

AbstractMutations inGLE1underlie Lethal Congenital Contracture syndrome (LCCS1) and Lethal Arthrogryposis with Anterior Horn Cell Disease (LAAHD). Both LCCS1 and LAAHD are characterized by reduced fetal movements, congenital contractures, and a severe form of motor neuron disease that results in fetal death or death in the perinatal period, respectively. Via trio-exome sequencing, we identified bi-allelic mutations inGLE1in two unrelated individuals with motor delays, feeding difficulties and respiratory insufficiency who survived beyond the perinatal period. Each affected child had missense variants predicted to result in amino acid substitutions near the C-terminus of GLE1 that are predicted to disrupt protein-protein interaction or GLE1 protein targeting. We hypothesize that mutations that preserve function of the coiled-coil domain of GLE1 cause LAAHD whereas mutations that abolish the function of the coiled-coil domain cause LCCS1. The phenotype of LAAHD is now expanded to include multiple individuals surviving into childhood suggesting that LAAHD is a misnomer and should be re-named Arthrogryposis with Anterior Horn Cell Disease (AAHD). Too few cases have been reported to identify significant genotype-phenotype relationships, but given that perinatal lethality in AAHD typically resulted from respiratory failure, it is possible that early or aggressive airway management such as early tracheostomy and ventilation may enable survival beyond the perinatal period.
Dynamical Features of Human EEG Scale Systematically with Life Context
Authors: Parameshwaran Dhanya , Thiagarajan Tara C. 
Published: April 2017

ABSTRACTWe have previously shown that the complexity of human brain activity and the emergence and strength of alpha oscillation as measured by EEG scale dramatically with access to the features of modernization. Here we show that these features of the EEG, while correlated to one another are distinct in their origin and that while complexity is most strongly related to travel or geofootprint, energy of the alpha oscillation scales more systematically with fuel consumption. Finally, composite EEG scores representing the dominant principal component scale in remarkable lockstep with the dominant component of the features of modernization. This demonstrates that human brain dynamics, and therefore cognitive outcome, are profoundly and systematically tied to the context of life experience. Indeed the implication is that ‘normal’ brain function is not absolute and can only be considered in relation to or conditional on the context in which it is embedded.
Deep experimental profiling of microRNA diversity, deployment, and evolution across theDrosophilagenus
Authors: Mohammed Jaaved , Flynt Alex S. , Panzarino Alexandra M. , Mondal Md Mosharrof Hussein , Siepel Adam , Lai Eric C. 
Published: April 2017

AbstractComparative genomic analyses of microRNAs (miRNAs) have yielded myriad insights into their biogenesis and regulatory activity. While miRNAs have been deeply annotated in a small cohort of model organisms, evolutionary assessments of miRNA flux are clouded by the functional uncertainty of orthologs in related species, and insufficient data regarding the extent of species-specific miRNAs. We address this by generating a comparative small RNA (sRNA) catalog of unprecedented breadth and depth across theDrosophilagenus, extending our extant deep analyses ofD. melanogasterwith sRNA data from multiple tissues of 11 other fly species. Aggregate analysis of several billion sRNA reads permits curation of accurate and holistic compendia of miRNAs across this genus, providing abundant opportunities to identify species- and clade-specific variation in miRNA identity, abundance, and processing. Amongst well-conserved miRNAs, we observe unexpected cases of clade-specific variation in 5′ end precision, occasional antisense loci, and some putatively non-canonical loci. We also employ strict criteria to identify a massive set (649) of novel, evolutionarily-restricted miRNAs. Amongst the bulk collection of species-restricted miRNAs, two notable subpopulations of rapidly-evolving miRNAs are splicing-derived mirtrons and testis-restricted, clustered (TRC) canonical miRNAs. We quantify rates of miRNA birth and death using our annotation and a phylogenetic model for estimating rates of miRNA turnover in the presence of annotation uncertainty. We show striking differences in birth and death rates across miRNA classes defined by biogenesis pathway, genomic clustering, and tissue restriction, and even identify variation heterogeneity amongstDrosophilaclades. In particular, distinct molecular rationales underlie the distinct evolutionary behavior of different miRNA classes. We broaden observations made fromD. melanogasteras Drosophilid-wide principles for opposing evolutionary viewpoints for miRNA maintenance. Mirtrons are associated with a high rate of 3′ untemplated addition, a mechanism that impedes their biogenesis, whereas TRC miRNAs appear to evolve under positive selection. Altogether, these data reveal miRNA diversity amongstDrosophilaspecies and permit future discoveries in understanding their emergence and evolution.
Compressed timeline of recent experience in monkey lPFC
Authors: Tiganj Zoran , Cromer Jason A. , Roy Jefferson E. , Miller Earl K. , Howard Marc W. 
Published: April 2017

AbstractCognitive theories suggest that working memory maintains not only the identity of recently-presented stimuli but also a sense of the elapsed time since the stimuli were presented. Previous studies of the neural underpinnings of working memory have focused on sustained firing, which can account for maintenance of the stimulus identity, but not for representation of the elapsed time. We analyzed single-unit recordings from the lateral prefrontal cortex (lPFC) of two macaque monkeys during performance of a delayed-match-to-category task. Each sample stimulus triggered a consistent sequence of neurons, with each neuron in the sequence firing during a circumscribed period of time. These sequences of neurons encoded both stimulus identity and the elapsed time. The encoding of the elapsed time became less precise as the sample stimulus receded into the past. These findings suggest that working memory includes a compressed timeline of what happened when, consistent with longstanding cognitive theories of human memory.Significance StatementPlace cells in the hippocampus and other brain regions provide basis functions to support the dimension of physical space. Time cells, which activate sequentially provide analogous support for the dimension of time. We observed time cells in the macaque lPFC during a working memory task. The time cells we observed were stimulus specific meaning that they provide not only information about timing, but also conjunctively code what and when information. This representation thus constitutes a manifold with both temporal dimension and a stimulus-coding dimension that could support working memory. These temporal basis functions maintain a logarithmically-compressed timeline of the recent past, providing strong empirical support to long-standing cognitive theories of human memory.
Anillin proteins stabilize the cytoplasmic bridge between the two primordial germ cells during C. elegans embryogenesis
Authors: Goupil Eugénie , Amini Rana , Labbé Jean-Claude 
Published: April 2017

ABSTRACTStable cytoplasmic bridges arise from failed cytokinesis, the last step of cell division, and are a key feature of syncytial architectures in the germ line of most metazoans. Whereas the C. elegans germ line is syncytial, its formation remains poorly understood. We studied the role of ANI-2, a noncanonical and shorter form of the actomyosin scaffold protein anillin that is expressed specifically during embryogenesis in the germ line precursor blastomere, P4. We found that the P4 blastomere does not complete abscission following cytokinesis, leaving a stable cytoplasmic bridge between the two daughter cells. Interestingly, depletion of ANI-2 results in a regression of the membrane partition between the two cells, indicating that ANI-2 is required to stabilize the cytoplasmic bridge. We identified several contractility regulators that, like ANI-2, localize to the cytoplasmic bridge and are required to stabilize it. Epistatic analysis of these regulators’ mutual dependencies revealed a pathway in which Rho regulators promote ANI-2 accumulation at the stable cytoplasmic bridge, which in turns promotes the accumulation of the non-muscle myosin II NMY-2 and the midbody component CYK-7 at the bridge, in part by limiting the accumulation of canonical anillin ANI-1. Our results uncover key steps in C. elegans germ line formation and define a set of conserved regulators that ensure the proper stability of the primordial germ cell cytoplasmic bridge during embryonic development.
Anterior cingulate cortex represents action-state predictions and causally mediates model-based reinforcement learning in a two-step decision task
Authors: Akam Thomas , Rodrigues-Vaz Ines , Marcelo Ivo , Zhang Xiangyu , Pereira Michael , Oliveira Rodrigo Freire , Dayan Peter , Costa Rui M. 
Published: April 2017

SummaryThe anterior cingulate cortex (ACC) is implicated in learning the value of actions, but it remains poorly understood whether and how it contributes to model-based mechanisms that use action-state predictions and afford behavioural flexibility. To isolate these mechanisms, we developed a multi-step decision task for mice in which both action-state transition probabilities and reward probabilities changed over time. Calcium imaging revealed ramps of choice-selective neuronal activity, followed by an evolving representation of the state reached and trial outcome, with different neuronal populations representing reward in different states. ACC neurons represented the current action-state transition structure, whether state transitions were expected or surprising, and the predicted state given chosen action. Optogenetic inhibition of ACC blocked the influence of action-state transitions on subsequent choice, without affecting the influence of rewards. These data support a role for ACC in model-based reinforcement learning, specifically in using action-state transitions to guide subsequent choice.HighlightsA novel two-step task disambiguates model-based and model-free RL in mice.ACC represents all trial events, reward representation is contextualised by state.ACC represents action-state transition structure, predicted states, and surprise.Inhibiting ACC impedes action-state transitions from influencing subsequent choice.
Transcriptome sequencing and delimitation of cryptic Oscarella species (O. carmela and O. pearsei sp. nov) from California, USA
Authors: Ereskovsky Alexander , Richter Daniel J. , Lavrov Dennis V. , Schippers Klaske J. , Nichols Scott A. 
Published: April 2017

AbstractThe homoscleromorph sponge Oscarella carmela, first described from central California, USA is shown to represent two morphologically similar but phylogenetically distant species that are co-distributed. We here describe a new species as Oscarella pearsei, sp. nov. and redescribe Oscarella carmela; the original description was based upon material from both species. Further, we correct the identification of published genomic/transcriptomic resources that were originally attributed to O. carmela, and present new Illumina-sequenced transcriptome assemblies for each of these species, and the mitochondrial genome sequence for O. pearsei sp. nov. Using SSU and LSU ribosomal DNA and the mitochondrial genome, we report the phylogenetic relationships of these species relative to other Oscarella species, and find strong support for placement of O. pearsei sp. nov. in a clade defined by the presence of spherulous cells that contain paracrystalline inclusions; O. carmela lacks this cell type and is most closely related to the Western Pacific species, O. malakhovi. Oscarella pearsei sp. nov and O. carmela can be tentatively distinguished based upon gross morphological differences such as color, surface texture and extent of mucus production, but can be more reliably identified using mitochondrial and nuclear barcode sequencing, ultrastructural characteristics of cells in the mesohyl, and the morphology of the follicle epithelium which surrounds the developing embryo in reproductively active individuals. Usually, cryptic species are very closely related to each other, but in this case and in sponges generally, cryptic species may be very distantly related because sponges can be difficult to identify based upon gross morphological characteristics.
Household triclosan and triclocarban exposure impacts the adult intestinal microbiome but not the infant intestinal microbiome
Authors: Ribado Jessica V. , Ley Catherine , Haggerty Thomas D. , Tkachenko Ekaterina , Bhatt Ami S. , Parsonnet Julie 
Published: April 2017

AbstractIn 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products. This decision was due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the intestinal microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction of either infant or maternal intestinal microbiotas following 10 months of exposure after birth. However, broadly antibiotic-resistant species from the phylum Proteobacteria were enriched in stool samples from mothers in TC households only after the introduction of triclosan-containing toothpaste. Despite the minimal effects of TC exposure from wash products on the gut microbial community of infants and adults, these results suggest detected taxonomic differences are associated with potential harmful effects on host physiology, highlighting the need for consumer safety testing of self-care products not subject to the ban on the human microbiome and health outcomes.
Stags, Hawks, and Doves: Social Evolution Theory and Individual Variation in Cooperation
Authors: Van Cleve Jeremy 
Published: April 2017

AbstractOne of the triumphs of evolutionary biology is the discovery of robust mechanisms that promote the evolution of cooperative behaviors even when those behaviors reduce the fertility or survival of cooperators. Though these mechanisms, kin selection, reciprocity, and nonlinear payoffs to cooperation, have been extensively studied separately, investigating their joint effect on the evolution of cooperation has been more difficult. Moreover, how these mechanisms shape variation in cooperation is not well known. Such variation is crucial for understanding the evolution of behavioral syndromes and animal personality. Here, I use the tools of kin selection theory and evolutionary game theory to build a framework that integrates these mechanisms for pairwise social interactions. Using relatedness as a measure of the strength of kin selection, responsiveness as a measure of reciprocity, and synergy as a measure of payoff nonlinearity, I show how different combinations of these three parameters produce directional selection for or against cooperation or variation in levels of cooperation via balancing or diversifying selection. Moreover, each of these outcomes maps uniquely to one of four classic games from evolutionary game theory, which means that modulating relatedness, responsiveness, and synergy effectively transforms the payoff matrix from one the evolutionary game to another. Assuming that cooperation exacts a fertility cost on cooperators and provides a fertility benefit to social partners, a prisoner’s dilemma game and directional selection against cooperation occur when relatedness and responsiveness are low and synergy is not too positive. Enough positive synergy in these conditions generates a stag-hunt game and diversifying selection. High levels of relatedness or responsiveness turn cooperation from a fitness cost into a fitness benefit, which produces a mutualism game and directional selection for cooperation when synergy is not too negative. Sufficiently negative synergy in this case creates a hawk-dove game and balancing selection for cooperation. I extend the results with relatedness and synergy to larger social groups and show that how group size changes the effect of relatedness and synergy on selection for cooperation depends on how the per capita benefit of cooperation changes with group size. Together, these results provide a general framework with which to generate comparative predictions that can be tested using quantitative genetic techniques and experimental techniques that manipulate investment in cooperation. These predictions will help us understand both interspecific variation in cooperation as well as within-population and within-group variation in cooperation related to behavioral syndromes.
Estimating the Biological Validity of the DSM for Attention Deficit/Hyperactivity Disorder Using Multivariate Analysis for Small Samples
Authors: Abramov Dimitri M. , Vigneau Evelyne , Gomes-Junior Saint-Clair , Mourão-Júnior Carlos Alberto , Castro-Pontes Monique , Cunha Carla Quero , deAzevedo Leonardo C. , Lazarev Vladimir V. 
Published: April 2017

AbstractBackground.Psychiatric nosology lacks objective biological foundation, as well as typical biomarkers for diagnoses, which raises questions about its validity. The problem is particularly evident concerning Attention Deficit/Hyperactivity Disorder (ADHD). The objective of this study is to estimate whether the “Diagnostic and Statistical Manual of Mental Disorders” (DSM) is biologically valid for ADHD diagnosis using a multivariate analysis for small samples from a large dataset concerning neurophysiological, behavioral, and psychological variables.Methods:Twenty typically developing boys and 19 boys diagnosed with ADHD, aged 10-13 years, were examined using the Attentional Network Test (ANT) with records of event-related potentials (ERPs). From 815 variables, a reduced number of latent variables (LVs) were extracted with a clustering method, for further reclassification of subjects using the k-means method. This approach allowed multivariate analysis to be applied to a significantly larger number of variables than the number of cases (E. Wigneau et al., 2003, 2015)Results:From datasets including ERPs from the mid-frontal, mid-parietal, right frontal, and central channels, only seven subjects were miss-reclassified by the LVs. An estimated specificity of 75.00% and sensitivity of 89.47% for DSM were found in the reclassification. The kappa index between DSM and behavioral/psychological/neurophysiological data was 0.75, which is regarded as a “substantial level of agreement”.Discussion:Results showed that CLV is a useful method for diagnostic classification using a large dataset of small samples, suggesting the biological validity of DSM for ADHD diagnosis, in accordance to alterations in fronto-striatal networks previously related to ADHD.
ETV4 and AP1 transcription factors form multivalent interactions with three sites on the MED25 activator-interacting domain
Authors: Currie Simon L. , Doane Jedediah J. , Evans Kathryn S. , Bhachech Niraja , Madison Bethany J. , Lau Desmond K. W. , McIntosh Lawrence P. , Skalicky Jack J. , Clark Kathleen A. , Graves Barbara J. 
Published: April 2017

AbstractThe recruitment of transcriptional cofactors by sequence-specific transcription factors challenges the basis of high affinity and selective interactions. Extending previous studies that the N-terminal activation domain (AD) of ETV5 interacts with Mediator subunit 25 (MED25), we establish that similar, aromatic-rich motifs located both in the AD and in the DNA-binding domain (DBD) of the related ETS factor ETV4 interact with MED25. These ETV4 regions bind MED25 independently, display distinct kinetics, and combine to contribute to a high-affinity interaction of full-length ETV4 with MED25. Within the ETS family, high-affinity interactions with MED25 are specific for the ETV1/4/5 subfamily as other ETS factors display weaker or no detectable binding. The AD binds to a single site on MED25 and the DBD interacts with three MED25 sites, allowing for simultaneous binding of both domains in full-length ETV4. MED25 also stimulates thein vitroDNA binding activity of ETV4 by relieving autoinhibition. ETV1/4/5 factors are often overexpressed in prostate cancer and genome-wide studies in a prostate cancer cell line indicate that ETV4 and MED25 occupy enhancers that are enriched for ETS-binding sequences and are both functionally important for the transcription of genes regulated by these enhancers. AP1-binding sequences were observed in MED25-occupied regions and JUN/FOS also contact MED25; FOS strongly binds to the same MED25 site as ETV4 AD and JUN interacts with the other two MED25 sites. In summary, we describe features of the multivalent ETV4- and AP1-MED25 interactions, thereby implicating these factors in the recruitment of MED25 to transcriptional control elements.
Cell type boundaries organize plant development
Authors: Caggiano Monica Pia , Yu Xiulian , Bhatia Neha , Larsson André , Ram Hasthi , Ohno Carolyn , Sappl Pia , Meyerowitz Elliot M. , Jönsson Henrik , Heisler Marcus G. 
Published: April 2017

AbstractIn plants the dorsoventral boundary of leaves defines an axis of symmetry through the centre of the organ separating the top (dorsal) and bottom (ventral) tissues. Although the positioning of this boundary is critical for leaf morphogenesis, how the boundary is established and how it influences development remains unclear. Using live-imaging and perturbation experiments we show that leaf orientation, morphology and position are pre-patterned by HD-ZIPIII and KAN gene expression in the shoot, leading to a model in which dorsoventral genes coordinate to regulate plant development by localizing auxin response between their expression domains. However we also find that auxin levels feedback on dorsoventral patterning by spatially organizing HD-ZIPIII and KAN expression in the shoot periphery. By demonstrating that the regulation of these genes by auxin also governs their response to wounds, our results also provide a parsimonious explanation for the influence of wounds on leaf dorsoventrality.