bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indirect traumatic optic neuropathy after head trauma in adolescent male mice is associated with behavioral visual impairment, neurodegeneration, and elevated endoplasmic reticulum stress markers at acute and subacute times
Authors: Cansler Shelby M. , Guilhaume-Correa Fernanda , Day Dylan , Bedolla Alicia , Evanson Nathan K. 
Published: June 2020

AbstractTraumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual symptoms after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we have previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice, and investigated visual impairment in the primary visual system, now including the retina, using behavioral and histologic methods at multiple time points. After injury, mice displayed evidence of decreased optomotor responses illustrated by decreased optokinetic nystagmus. There did not appear to be a significant change in circadian locomotor behavior patterns, although there was an overall decrease in locomotor behavior in mice with head injury. There was evidence of axonal degeneration of optic nerve fibers with associated retinal ganglion cell death. There was also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there was elevated expression of endoplasmic reticulum (ER) stress markers in retinas of injured mice. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persisted for at least 30 days after injury. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma, and suggest that axonal degeneration is associated with elevated ER stress in this model of TON.
Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness geneATOH1
Authors: Brownstein Zippora , Gulsuner Suleyman , Walsh Tom , Martins Fábio Tadeu Arrojo , Taiber Shahar , Isakov Ofer , Lee Ming K. , Bordeynik-Cohen Mor , Birkan Maria , Chang Weise , Casadei Silvia , Danial-Farran Nada , Abu-Rayyan Amal , Carlson Ryan , Kamal Lara , Arnþórsson Ásgeir Örn , Sokolov Meirav , Gilony Dror , Lipschitz Noga , Frydman Moshe , Davidov Bella , Macarov Michal , Sagi Michal , Vinkler Chana , Poran Hana , Sharony Reuven , Samara Nadra , Zvi Na’ama , Baris-Feldman Hagit , Singer Amihood , Handzel Ophir , Hertzano Ronna , Ali-Naffaa Doaa , Ruhrman-Shahar Noa , Madgar Ory , Sofrin Efrat , Peleg Amir , Khayat Morad , Shohat Mordechai , Basel-Salmon Lina , Pras Elon , Lev Dorit , Wolf Michael , Steingrimsson Eirikur , Shomron Noam , Kelley Matthew W. , Kanaan Moien , Allon-Shalev Stavit , King Mary-Claire , Avraham Karen B. 
Published: June 2020

AbstractMutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness-associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity. Genomic DNA samples from informative relatives of 88 multiplex families, all of self-identified Jewish ancestry, with either non-syndromic or syndromic hearing loss, were sequenced for known and candidate deafness genes using the HEar-Seq gene panel. The genetic causes of hearing loss were identified for 60% of the families. One gene was encountered for the first time in human hearing loss:ATOH1(Atonal), a basic helix-loop-helix transcription factor responsible for autosomal dominant progressive hearing loss in a five-generation family. Our results demonstrate that genomic sequencing with a gene panel dedicated to hearing loss is effective for genetic diagnoses in a diverse population. Comprehensive sequencing enables well-informed genetic counseling and clinical management by medical geneticists, otolaryngologists, audiologists, and speech therapists and can be integrated into newborn screening for deafness.
RPRH: a web-based tool for the inference of potential roles of plant microRNAs in human body
Authors: Gao Yuanxu , Cui Chunmei , Jia Kaiwen , Zhou Yuan , Cui Qinghua 
Published: June 2020

ABSTRACTRecently, increasing studies reported that plant microRNAs (miRNAs) from food could be absorbed through gastrointestinal tract to regulate the physiological processes of animals. These novel cross-kingdom regulatory roles of plant miRNAs open a new field in miRNA study and drug discovery, but the lack of corresponding bioinformatics tools limit the development of this field. In this study, we built a web-based tool, RPRH (Role of Plant microRNA in Human), to infer the potential roles of plant miRNAs in human and to profile the landscape of all documented plant miRNAs regulatory functions in human. Totally, RPRH included 10414 miRNAs from 82 plant species and 18062 annotation terms like diseases, pathway, gene ontology (GO), and drugs. RPRH represents a bioinformatics resource for further investigation of cross-kingdom regulations of plant miRNAs.Availabilityhttp://www.rnanut.net/rprh/
A two-locus system with strong epistasis underlies rapid parasite-mediated evolution of host resistance
Authors: Ameline Camille , Bourgeois Yann , Vögtli Felix , Savola Eevi , Andras Jason , Engelstädter Jan , Ebert Dieter 
Published: June 2020

AbstractParasites are a major evolutionary force, driving adaptive responses in host populations. Although the link between phenotypic response to parasite-mediated natural selection and the underlying genetic architecture often remains obscure, this link is crucial for understanding the evolution of resistance and predicting associated allele frequency changes in the population. To close this gap, we monitored the response to selection during epidemics of a virulent bacterial pathogen,Pasteuria ramosa, in a natural host population ofDaphnia magna. Across two epidemics, we observed a strong increase in the proportion of resistant phenotypes as the epidemics progressed. Field and laboratory experiments confirmed that this increase in resistance was caused by selection from the local parasite. Using a genome wide association study (GWAS), we obtained a genetic model in which two genomic regions with dominance and epistasis control resistance polymorphism in the host. We verified this model by selfing host genotypes with different resistance phenotypes and scoring their F1 for segregation of resistance and associated genetic markers. Applying the model to the dynamics of the field population revealed moderate changes in allele frequencies at the two resistance loci relative to the profound changes observed at the phenotypic level. This apparent discrepancy is explained by strong epistasis and dominance at the two resistance loci, which reduces the effect of selection on alleles at both loci. Such epistatic effects with strong fitness consequences in host-parasite coevolution are believed to be crucial in the Red Queen model for the evolution of genetic recombination.
Machine Learning Maps Research Needs in COVID-19 Literature
Authors: Doanvo Anhvinh , Qian Xiaolu , Ramjee Divya , Piontkivska Helen , Desai Angel , Majumder Maimuna 
Published: June 2020

AbstractSummaryManually assessing the scope of the thousands of publications on the COVID-19 (coronavirus disease 2019) pandemic is an overwhelming task. Shortcuts through metadata analysis (e.g., keywords) assume that studies are properly tagged. However, machine learning approaches can rapidly survey the actual text of coronavirus abstracts to identify research overlap between COVID-19 and other coronavirus diseases, research hotspots, and areas warranting exploration. We propose a fast, scalable, and reusable framework to parse novel disease literature. When applied to the COVID-19 Open Research Dataset (CORD-19), dimensionality reduction suggested that COVID-19 studies to date are primarily clinical-, modeling- or field-based, in contrast to the vast quantity of laboratory-driven research for other (non-COVID-19) coronavirus diseases. Topic modeling also indicated that COVID-19 publications have thus far focused primarily on public health, outbreak reporting, clinical care, and testing for coronaviruses, as opposed to the more limited number focused on basic microbiology, including pathogenesis and transmission.
Eco-evolutionary feedbacks and the maintenance of metacommunity diversity in a changing environment
Authors: Fielding Aidan P. , Pantel Jelena H. 
Published: June 2020

AbstractThe presence and strength of resource competition can influence how organisms adaptively respond to environmental change. Selection may thus reflect a balance between two forces, adaptation to an environmental optimum and evolution to avoid strong competition. While this phenomenon has previously been explored for single communities, its implications for eco-evolutionary dynamics at the metacommunity scale are unknown. We developed a simulation model for the evolution of a quantitative trait that influences both an organism’s carrying capacity and its intra- and interspecific competitive ability. In the model, multiple species inhabit a variable three-patch landscape, and we varied the connectivity level of the species among patches, the presence and pace of directional environmental change, and the strength of competition between the species. Our results reflect some patterns previously observed in evolving metacommunity models, such as species sorting and community monopolization. However species sorting was more likely to occur in evolving communities without dispersal, and monopolization was observed only when environmental change was very rapid. We also detected an eco-evolutionary feedback loop between local phenotypic evolution at one site and competition at another site, which maintains species diversity in some conditions. The existence of a feedback loop maintained by dispersal indicates that eco-evolutionary dynamics in communities operate at a landscape scale.
A new inference approach for training shallow and deep generalized linear models of noisy interacting neurons
Authors: Mahuas Gabriel , Isacchini Giulio , Marre Olivier , Ferrari Ulisse , Mora Thierry 
Published: June 2020

AbstractGeneralized linear models are one of the most efficient paradigms for predicting the correlated stochastic activity of neuronal networks in response to external stimuli, with applications in many brain areas. However, when dealing with complex stimuli, the inferred coupling parameters often do not generalize across different stimulus statistics, leading to degraded performance and blowup instabilities. Here, we develop a two-step inference strategy that allows us to train robust generalized linear models of interacting neurons, by explicitly separating the effects of correlations in the stimulus from network interactions in each training step. Applying this approach to the responses of retinal ganglion cells to complex visual stimuli, we show that, compared to classical methods, the models trained in this way exhibit improved performance, are more stable, yield robust interaction networks, and generalize well across complex visual statistics. The method can be extended to deep convolutional neural networks, leading to models with high predictive accuracy for both the neuron firing rates and their correlations.
Temporal dynamics of QTL effects on vegetative growth inArabidopsis thaliana
Authors: Meyer Rhonda C. , Weigelt-Fischer Kathleen , Knoch Dominic , Heuermann Marc , Zhao Yusheng , Altmann Thomas 
Published: June 2020

ABSTRACTWe assessed early vegetative growth in a population of 382 accessions ofArabidopsis thalianausing automated non-invasive high-throughput phenotyping. All accessions were imaged daily from seven to 18 days after sowing in three independent experiments and genotyped using the Affymetrix 250k SNP array. Projected leaf area (PLA) was derived from image analysis and used to calculate relative growth rates (RGR). In addition, initial seed size was determined. The generated data sets were used jointly for a genome-wide association study that identified 238 marker-trait associations (MTAs) individually explaining up to 8 % of the total phenotypic variation. Co-localisation of MTAs occurred at 33 genomic positions. At 21 of these positions, sequential co-localisation of MTAs for two to nine consecutive days was observed. The detected MTAs for PLA and RGR could be grouped according to their temporal expression patterns, emphasising that temporal variation of MTA action can be observed even during the vegetative growth phase, a period of continuous formation and enlargement of seemingly similar rosette leaves. This indicates that causal genes may be differentially expressed in successive periods. Analyses of the temporal dynamics of biological processes are needed to gain important insight into the molecular mechanisms of growth-controlling processes in plants.HighlightA genome-wide association study including the factor time highlighted that early plant growth in Arabidopsis is governed by several medium and many small effect loci, most of which act only during short phases of two to nine days.
Dissociable control of unconditioned responses and associative fear learning by parabrachial CGRP neurons
Authors: Bowen Anna J. , Chen Jane Y. , Huang Y. Waterlily , Baertsch Nathan A. , Park Sekun , Palmiter Richard D. 
Published: June 2020

AbstractParabrachial CGRP neurons receive diverse threat-related signals and contribute to multiple phases of adaptive threat responses, with their inactivation attenuating both unconditioned behavioral responses to somatic pain and fear-memory formation. Because CGRPPBNneurons respond broadly to multi-modal threats, it remains unknown how these distinct adaptive processes are individually engaged. We show that while three partially separable subsets of CGRPPBNneurons broadly collateralize to their respective downstream partners, individual projections accomplish distinct functions: hypothalamic and extended amygdalar projections elicit assorted unconditioned threat responses including autonomic arousal, anxiety, and freezing behavior, while thalamic and basal forebrain projections generate freezing behavior and, unexpectedly, contribute to associative fear learning. Moreover, the unconditioned responses generated by individual projections are complementary, with simultaneous activation of multiple sites driving profound freezing behavior and bradycardia that are not elicited by any individual projection. This semi-parallel, scalable connectivity schema likely contributes to flexible control of threat responses in unpredictable environments.
Tabula-rasa exploration decreases during youth and is linked to ADHD symptoms
Authors: Dubois M , Bowler A , Moses-Payne ME , Habicht J , Steinbeis N , Hauser TU 
Published: June 2020

AbstractDuring childhood and adolescence, exploring the unknown is important to build a better model of the world. This means that youths have to regularly solve the exploration-exploitation trade-off, a dilemma in which adults are known to deploy a mixture of computationally light and heavy exploration strategies. In this developmental study, we investigated how youths (aged 8 to 17) performed an exploration task that allows us to dissociate these different exploration strategies. Using computational modelling, we demonstrate that tabula-rasa exploration, a computationally light exploration heuristic, is used to a higher degree in children and younger adolescents compared to older adolescents. Additionally, we show that this tabula-rasa exploration is more extensively used by youths with high attention-deficit/hyperactivity disorder (ADHD) traits. In the light of ongoing brain development, our findings show that children and younger adolescents use computationally less burdensome strategies, but that an excessive use thereof might be a risk for mental health conditions.
Selection on phenotypic plasticity favors thermal canalization
Authors: Svensson Erik I. , Gomez-Llano Miguel , Waller John T. 
Published: June 2020

AbstractClimate change affects organisms worldwide with profound ecological and evolutionary consequences, often increasing population extinction risk. Climatic factors can increase the strength, variability or direction of natural selection on phenotypic traits, potentially driving adaptive evolution. Phenotypic plasticity in relation to temperature can allow organisms to maintain fitness in response to increasing temperatures, thereby “buying time” for subsequent genetic adaptation and promoting evolutionary rescue. Although many studies have shown that organisms respond plastically to increasing temperatures, it is unclear if such thermal plasticity is adaptive. Moreover, we know little about how natural and sexual selection operate on thermal reaction norms reflecting such plasticity. Here, we investigate how natural and sexual selection shape phenotypic plasticity in two congeneric and phenotypically similar sympatric insect species. We show that the thermal optima for longevity and mating success differ, suggesting temperature-dependent trade-offs between survival and reproduction. Males in these species have similar thermal reaction norm slopes but have diverged in baseline body temperature (intercepts), being higher for the more northern species. Natural selection favoured reduced thermal reaction norm slopes at high ambient temperatures, suggesting that the current level of thermal plasticity is maladaptive in the context of anthropogenic climate change and that selection now promotes thermal canalization and robustness. Our results show that ectothermic animals also at high latitudes can suffer from overheating and challenge the common view of phenotypic plasticity as being beneficial in harsh and novel environments.Significance StatementOrganisms are increasingly challenged by increasing temperatures due to climate change. In insects, body temperatures are strongly affected by ambient temperatures, and insects are therefore expected to suffer increasingly from heat stress, potentially reducing survival and reproductive success leading to elevated extinction risks. We investigated how ambient temperature affected fitness in two insect species in the temperate zone. Male and female survivorship benefitted more from low temperatures than did reproductive success, which increased with higher temperatures, revealing a thermal conflict between fitness components. Male body temperature plasticity reduced survival, and natural and sexual selection operated on such thermal plasticity. Our results reveal the negative consequences of thermal plasticity and show that these insects have limited ability to buffer heat stress.
Identification of pathogenic missense mutations using protein stability predictors
Authors: Gerasimavicius Lukas , Liu Xin , Marsh Joseph A 
Published: June 2020

AbstractAttempts at using protein structures to identify disease-causing mutations have been dominated by the idea that most pathogenic mutations are disruptive at a structural level. Therefore, computational stability predictors, which assess whether a mutation is likely to be stabilising or destabilising to protein structure, have been commonly used when evaluating new candidate disease variants, despite not having been developed specifically for this purpose. We therefore tested 12 different stability predictors for their ability to discriminate between pathogenic and putatively benign missense variants. We find that one method, FoldX, considerably outperforms all others in the identification of disease variants. Moreover, we demonstrate that employing absolute energy change scores improves performance of nearly all predictors. Importantly, however, we observe that the utility of computational stability predictors is highly heterogeneous across different proteins, and that they are all are inferior to the best performing variant effect predictors for identifying pathogenic mutations. We suggest that this is largely due to alternate molecular mechanisms other than protein destabilisation underlying many pathogenic mutations. Thus, better ways of incorporating protein structural information and molecular mechanisms into computational variant effect predictors will be required for improved disease variant prioritisation.
Gene expression variability in human and chimpanzee populations share common determinants
Authors: Fair Benjamin J. , Blake Lauren E. , Sarkar Abhishek , Pavlovic Bryan J. , Cuevas Claudia , Gilad Yoav 
Published: June 2020

AbstractInter-individual variation in gene expression has been shown to be heritable and it is often associated with differences in disease susceptibility between individuals. Many studies focused on mapping associations between genetic and gene regulatory variation, yet much less attention has been paid to the evolutionary processes that shape the observed differences in gene regulation between individuals in humans or any other primate. To begin addressing this gap, we performed a comparative analysis of gene expression variability and expression quantitative trait loci (eQTLs) in humans and chimpanzees, using gene expression data from primary heart samples. We found that expression variability in both species is often determined by non-genetic sources, such as cell-type heterogeneity. However, we also provide evidence that inter-individual variation in gene regulation can be genetically controlled, and that the degree of such variability is generally conserved in humans and chimpanzees. In particular, we found a significant overlap of orthologous genes associated with eQTLs in both species. We conclude that gene expression variability in humans and chimpanzees often evolves under similar evolutionary pressures.
The transposable elements of theDrosophila serratareference panel
Authors: Tiedeman Zachary , Signor Sarah 
Published: June 2020

AbstractTransposable elements are an important element of the complex genomic ecosystem, proving to be both adaptive and deleterious - repressed by the piRNA system and fixed by selection. Transposable element insertion also appears to be bursty – either due to invasion of new transposable elements that are not yet repressed, de-repression due to instability of organismal defense systems, stress, or genetic variation in hosts. Here, we characterize the transposable element landscape in an important modelDrosophila, D. serrata, and investigate variation in transposable element copy number between genotypes and in the population at large. We find that a subset of transposable elements are clearly related to elements annotated inD. melanogasterandD. simulans, suggesting they spread between species more recently than other transposable elements. We also find that transposable elements do proliferate in particular genotypes, and that often if an individual is host to a proliferating transposable element, it is host to more than one proliferating transposable element. In addition, if a transposable element is active in a genotype, it is often active in more than one genotype. This suggests that there is an interaction between the host and the transposable element, such as a permissive genetic background and the presence of potentially active transposable element copies. In natural populations an active transposable element and a permissive background would not be held in association as in inbred lines, suggesting the magnitude of the burst would be much lower. Yet many of the inbred lines have actively proliferating transposable elements suggesting this is an important mechanism by which transposable elements maintain themselves in populations.