bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal discrimination in attractor networks with short-term synaptic plasticity
Authors: Shlaer Benjamin , Ballintyn Benjamin , Miller Paul 
Published: April 2018

AbstractWe demonstrate the ability of a randomly connected attractor network with dynamic synapses to discriminate between similar sequences containing multiple stimuli and suggest such networks provide a general basis for neural computations in the brain. The network is based on units representing assemblies of pools of neurons, with preferentially strong recurrent excitatory connections within each unit. Such excitatory feedback to a unit can generate bistability, though in many networks only under conditions of net excitatory input from other units. Weak interactions between units leads to a multiplicity of attractor states, within which information can persist beyond stimulus offset. When a new stimulus arrives, the prior state of the network impacts the encoding of the incoming information, with short-term synaptic depression ensuring an itinerancy between sets of active units. We assess the ability of such a network to encode the identity of sequences of stimuli, so as to provide a template for sequence recall, or decisions based on accumulation of evidence. Across a range of parameters, such networks produce the primacy (better final encoding of the earliest stimuli) and recency (better final encoding of the latest stimuli) observed in human recall data and can retain the information needed to make a binary choice based on total number of presentations of a specific stimulus. Similarities and differences in the final states of the network produced by different sequences lead to predictions of specific errors that could arise when an animal or human subject generalizes from training data, when the training data comprises a subset of the entire stimulus repertoire. We suggest that such networks can provide the robust general purpose computational engines needed for us to solve many cognitive tasks.
Historic collections as a tool for assessing the global pollinator crisis
Authors: Bartomeus I. , Stavert J.R. , Ward D. , Aguado O. 
Published: April 2018

AbstractThere is increasing concern about the decline of pollinators worldwide. However, despite reports that pollinator declines are widespread, data are scarce and often geographically and taxonomically biased. These biases limit robust inference about any potential pollinator crisis. Non-structured and opportunistic historical specimen collection data provide the only source of historical information which can serve as a baseline for identifying pollinator declines. Specimens historically collected and preserved in museums not only provide information on where and when species were collected, but also contain other ecological information such as species interactions and morphological traits. Here, we provide a synthesis of how researchers have used historical data to identify long-term changes in biodiversity, species abundances, morphology and pollination services. Despite recent advances, we show that information on the status and trends of most pollinators is absent, but we highlight opportunities and limitations to progress the assessment of pollinator declines globally. Finally, we demonstrate different approaches to analysing museum collection data using two contrasting case studies from distinct geographical regions (New Zealand and Spain) for which long-term pollinator declines have never been assessed. There is immense potential for museum specimens to play a central role in assessing the extent of the global pollination crisis.
Combining Digital Imaging and Genome Wide Association Mapping to Dissect Uncharacterized Traits in Plant/Pathogen Interactions
Authors: Fordyce Rachel F. , Soltis Nicole E. , Caseys Celine , Gwinner Raoni , Corwin Jason A. , Atwell Susana , Copeland Daniel , Feusier Julie , Subedy Anushriya , Eshbaugh Robert , Kliebenstein Daniel J. 
Published: April 2018

AbstractPlant resistance to generalist pathogens with broad host ranges, such as Botrytis cinerea, is typically quantitative and highly polygenic. Recent studies have begun to elucidate the molecular genetic basis underpinning plant-pathogen interactions using commonly measured traits including lesion size and/or pathogen biomass. Yet with the advent of digital imaging and phenomics, there are a large number of additional resistance traits available to study quantitative resistance. In this study, we used high-throughput digital imaging analysis to investigate previously uncharacterized visual traits of plant-pathogen interactions related disease resistance using the Arabidopsis thaliana/Botrytis cinerea pathosystem. Using a large collection of 75 visual traits collected from every lesion, we focused on lesion color, lesion shape, and lesion size, to test how these aspects of the interaction are genetically related. Using genome wide association (GWA) mapping in A. thaliana, we show that lesion color and shape are genetically separable traits associated with plant-disease resistance. Using defined mutants in 23 candidate genes from the GWA mapping, we could identify and show that novel loci associated with each different plant-pathogen interaction trait, which expands our understanding of the functional mechanisms driving plant disease resistance.SummaryDigital imaging allows the identification of genes controlling novel lesion traits.
Detecting Differential Variable microRNAs via Model-Based Clustering
Authors: Li Xuan , Fu Yuejiao , Wang Xiaogang , DeMeo Dawn L. , Tantisira Kelan , Weiss Scott , Qiu Weiliang 
Published: April 2018

ABSTRACTIdentifying genomic probes (e.g., DNA methylation marks) is becoming a new approach to detect novel genomic risk factors for complex human diseases. The F test is the standard equal-variance test in Statistics. For high-throughput genomic data, the probe-wise F test has been successfully used to detect biologically relevant DNA methylation marks that have different variances between two groups of subjects (e.g., cases vs. controls). In addition to DNA methylation, microRNA is another mechanism of epigenetics. However, to the best of our knowledge, no studies have identified differentially variable (DV) microRNAs. In this article, we proposed a novel model-based clustering to improve the power of the probe-wise F test to detect DV microRNAs. We imposed special structures on covariance matrices for each cluster of microRNAs based on the prior information about the relationship between variance in cases and variance in controls and about the independence among cases and controls. To the best of our knowledge, the proposed method is the first clustering algorithm that aims to detect DV genomic probes. Simulation studies showed that the proposed method outperformed the probe-wise F test and had certain robustness to the violation of the normality assumption. Based on two real datasets about human hepatocellular carcinoma (HCC), we identified 7 DV-only microRNAs (hsa-miR-1826, hsa-miR-191, hsa-miR-194-star, hsa-miR-222, hsa-miR-502-3p, hsa-miR-93, and hsa-miR-99b) using the proposed method, one (hsa-miR-1826) of which has not yet been reported to relate to HCC in the literature.
Isolation of Genomic Deoxyxylulose Phosphate Reductoisomerase (DXR) Mutations Conferring Resistance to Fosmidomycin
Authors: Pines Gur , Bassalo Marcelo C. , Oh Eun Joong , Choudhury Alaksh , Garst Andrew D. , Gill Ryan T. 
Published: April 2018

AbstractSequence to activity mapping technologies are rapidly developing, enabling the isolation of mutations that confer novel phenotypes. Here we used the CRISPR EnAbled Trackable genome Engineering (CREATE) technology to investigate the inhibition of the essential IspC gene in Escherichia coli. IspC gene product, Deoxyxylulose Phosphate Reductoisomerase (DXR), converts 1-deoxy-D-xylulose 5-phosphate to 2-C-methyl-D-erythritol 4-phosphate in the DXP pathway. Since this pathway is shared with many pathogenic bacteria and protozoa and is missing in humans, it is an appealing target for inhibition. We created a full saturation library of 33 sites proximal to ligand binding and other sites and challenged it with the DXR-specific inhibitor, fosmidomycin. We identified several mutations that confer fosmidomycin resistance. All sites are highly conserved and also exist in pathogens including the malaria-inducing Plasmodium falciparum. These findings may have general implications on the isolation of resistance-conferring mutations and specifically, may affect the design of future generations of fosmidomycin-based drugs.SignificanceThe emergence of acquired drug resistance is a natural process that is likely to occur under most circumstances. Recently-developed technologies allow to map relative fitness contribution of multiple mutations in parallel. Such approaches may be used to predict which mutations are most likely to confer resistance, instead of waiting for them to evolve spontaneously. In this study, a rationally-designed IspC mutant library was generated genomically in E. coli. Mutants resistant to fosmidomycin, an antimalarial drug were identified, and most were in the highly conserved proline at position 274. These results may have implications on next-generation fosmidomycin drug design, and more broadly, this approach may be used for predicting mutational acquired resistance.
Mechanisms of selection for the control of action inDrosophila melanogaster
Authors: Frighetto Giovanni , Zordan Mauro A. , Castiello Umberto , Megighian Aram 
Published: April 2018

ABSTRACTIn the last few years several studies have investigated the neural mechanisms underlying spatial orientation inDrosophila melanogaster. Convergent results suggest that this mechanism is associated with specific neural circuits located within the Central Complex (CC). Furthermore such circuits appear to be associated with visual attention, specifically with selective attention processes implicated in the control of action. Our aim was to understand how wild-type flies react to the abrupt appearance of a visual distractor during an ongoing locomotor action. Thus, we adapted the well-known ‘Buridan paradigm’, used to study walking behaviour in flies, so we could specifically address the mechanisms involved in action selection. We found that flies tended to react in one of two ways when confronted with a visual distractor during ongoing locomotion. Flies either: (i) committed to a new path situated midway between the original target and the distractor, consistent with a novelty effect; or (ii) remained on the original trajectory with a slight deviation in direction of the distractor. We believe that these results provide the first indication of how flies react, from the motor point of view, in a bi-stable context requiring the presence of selection-for-action mechanisms. Some considerations on the neural circuits underlying such behavioural responses are advanced.
Sensory learning and inference is impaired in the non-clinical continuum of psychosis: a replication study
Authors: Dzafic Ilvana , Randeniya Roshini , Harris Clare D. , Bammel Moritz , Garrido Marta I. 
Published: April 2018

AbstractOur perceptions result from the brain’s ability to make inferences, or predictive models, of sensory information. Recently, it has been proposed that psychotic traits may be linked to impaired predictive processes. Here, we examine the brain dynamics underlying sensory learning and inference in stable and volatile environments, in a population of healthy individuals (N=75) with a range of psychotic-like experiences. We measured prediction error responses to sound sequences with electroencephalography, gauged sensory inference explicitly by behaviourally recording sensory ‘regularity’ learning errors, and used dynamic causal modelling to tap into the underlying neural circuitry. We discuss the findings that were robust to replication across the two experiments (N=31 and N=44 for the discovery and the validation datasets, respectively). First, we found that during stable conditions, participants demonstrated a stronger predictive model, reflected in a larger prediction error response to unexpected sounds, and decreased regularity learning errors. Moreover, individuals with attenuated prediction errors in stable conditions were found to make greater incorrect predictions about sensory information. Critically, we show that greater errors in sensory learning and inference are related to increased psychotic-like experiences. These findings link neurophysiology to behaviour during sensory learning and prediction formation, as well as providing further evidence for the idea of a continuum of psychosis in the healthy, non-clinical population.Significance StatementWhilst perceiving the world, we make inferences by learning the regularities present in the sensory environment. It has been argued that psychosis may emerge due to a failure to learn sensory regularities, resulting in an impaired representation of the world. Recently it has been proposed that psychosis exists on a continuum; however, there is conflicting evidence on whether sensory learning deficits align on the non-clinical end of the psychosis continuum. We found that sensory learning is associated with brain prediction errors, and critically, it is impaired in healthy people who report more psychotic-like experiences. We replicated these findings in an independent sample, demonstrating strengthened credibility to support that the continuum of psychosis extends into the non-clinical population.
The transcriptional and translational landscape of equine torovirus
Authors: Stewart Hazel , Brown Katherine , Dinan Adam M. , Irigoyen Nerea , Snijder Eric J. , Firth Andrew E. 
Published: April 2018

AbstractThe genusTorovirus(subfamilyTorovirinae, familyCoronaviridae, orderNidovirales) encompasses a range of species that infect domestic ungulates including cattle, sheep, goats, pigs and horses, causing an acute self-limiting gastroenteritis. Using the prototype species equine torovirus (EToV) we performed parallel RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) to analyse the relative expression levels of the known torovirus proteins and transcripts, chimaeric sequences produced via discontinuous RNA synthesis (a characteristic of the nidovirus replication cycle) and changes in host transcription and translation as a result of EToV infection. RNA sequencing confirmed that EToV utilises a unique combination of discontinuous and non-discontinuous RNA synthesis to produce its subgenomic RNAs; indeed, we identified transcripts arising from both mechanisms that would result in sgRNAs encoding the nucleocapsid. Our ribosome profiling analysis revealed that ribosomes efficiently translate two novel CUG-initiated ORFs, located within the so-called 5’ UTR. We have termed the resulting proteins U1 and U2. Comparative genomic analysis confirmed that these ORFs are conserved across all available torovirus sequences and the inferred amino acid sequences are subject to purifying selection, indicating that U1 and U2 are functionally relevant. This study provides the first high-resolution analysis of transcription and translation in this neglected group of livestock pathogens.ImportanceToroviruses infect cattle, goats, pigs and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens including severe acute respiratory syndrome (SARS) coronavirus and they share some common features, however the mechanism that they use to produce subgenomic RNA molecules differs. Here we performed deep sequencing to determine how equine torovirus produces subgenomic RNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.
Oxidative stress resistance and fitness-compensatory response in vancomycin-intermediate Staphylococcus aureus (VISA)
Authors: Tan Xin-Ee , Neoh Hui-min , Cui Longzhu , Hiramatsu Keiichi , Jamal Rahman 
Published: April 2018

AbstractIn this study, VISA cells carrying vraS and/or graR mutations were shown to be more resistant to oxidative stress. Caenorhabditis elegans infected with these strains in turn demonstrated lower survival. Altered regulation in oxidative stress response and virulence appears to be physiological adaptations associated with VISA phenotype in the Mu50 lineage.
Combination of tenofovir and emtricitabine with efavirenz does not moderate inhibitory effect of efavirenz on mitochondrial function and cholesterol biosynthesis in human T lymphoblastoid cell line
Authors: Li Min , Sopeyin Anuoluwapo , Paintsil Elijah 
Published: April 2018

ABSTRACTEfavirenz (EFV), the most popular non-nucleoside reverse transcriptase inhibitor, has been associated with mitochondrial dysfunction in most in vitro studies. However, in real life the prevalence of EFV-induced mitochondrial toxicity is relatively low. We hypothesized that the agents given in combination with EFV might moderate the effect of EFV on mitochondrial function. To test this hypothesis, we cultured human T lymphoblastoid cell line (CEM cells) with EFV alone and in combination with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) to investigate the effects on mitochondrial respiration and function and cholesterol biosynthesis.There was a statistically significant concentration- and time-dependent apoptosis, reduction in mitochondrial membrane potential (ΔΨ), and increase production of reactive oxygen species (ROS) in cells treated with either EVF alone or in combination with TDF/FTC. EFV treated cells compared to DMSO treated cells had significant reduction in oxygen consumption rate (OCR) contributed by mitochondrial respiration, ATP production-linked respiration, and spare respiratory capacity (SRC). Treatment with EFV resulted in a decrease in mitochondrial DNA content, and perturbation of more coding genes (n=13); among these were 11 genes associated with lipid or cholesterol biosynthesis. Our findings support the growing body of knowledge on the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis.Interestingly, combining TDF/FTC with EFV did not alter the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis. The gap between the prevalence of EFV-induced mitochondrial toxicityin vitroandin vivostudies may be explained by individual differences in the pharmacokinetic of EFV.
Born to run? Quantifying the balance of prior bias and new information in prey escape decisions
Authors: Sutton Nicholas M. , O’Dwyer James P. 
Published: April 2018

AbstractAnimal behaviors can often be challenging to model and predict, though optimality theory has improved our ability to do so. While many qualitative predictions of behavior exist, accurate quantitative models, tested by empirical data, are often lacking. This is likely due to variation in biases across individuals and variation in the way new information is gathered and used. We propose a modeling framework based on a novel interpretation of Bayes’ theorem to integrate optimization of energetic constraints with both prior biases and specific sources of new information gathered by individuals. We present methods for inferring distributions of prior biases within populations rather than assuming known priors, as is common in Bayesian approaches to modelling behavior, and for evaluating the goodness of fit of overall model descriptions. We apply this framework to predict optimal escape during predator-prey encounters, based on prior biases and variation in what information prey use. Using this approach we collected and analyzed data characterizing white-tailed deer (Odocoileus virginianus) escape behavior in response to human approaches. We found that distance to predator alone was not sufficient for predicting deer flight response, and have shown that the inclusion of additional information is necessary. Additionally, we compared differences in the inferred distributions of prior biases across different populations and discuss the possible role of human activity in influencing these distributions.
Flat-field illumination for quantitative fluorescence imaging
Authors: Khaw Ian , Croop Benjamin , Tang Jialei , Möhl Anna , Fuchs Ulrike , Han Kyu Young 
Published: April 2018

AbstractThe uneven illumination of a Gaussian profile makes quantitative analysis highly challenging in laser-based wide-field fluorescence microscopy. Here we present flat-field illumination (FFI) where the Gaussian beam is reshaped into a uniform flat-top profile using a high-precision refractive optical component. The long working distance and high spatial coherence of FFI allows us to accomplish uniform epi and TIRF illumination for multi-color single-molecule imaging. In addition, high-throughput borderless imaging is demonstrated with minimal image overlap.
Identifying progressive gene network perturbation from single-cell RNA-seq data
Authors: Mukherjee Sumit , Carignano Alberto , Seelig Georg , Lee Su-In 
Published: April 2018

AbstractIdentifying the gene regulatory networks that control development or disease is one of the most important problems in biology. Here, we introduce a computational approach, called PIPER (ProgressIve networkPERturbation), to identify theperturbed genesthat drive differences in the gene regulatory network across different points in a biological progression. PIPER employs algorithms tailor-made for single cell RNA sequencing (scRNA-seq) data to jointly identify gene networks for multiple progressive conditions. It then performs differential network analysis along the identified gene networks to identify master regulators. We demonstrate that PIPER outperforms state-of-the-art alternative methods on simulated data and is able to predict known key regulators of differentiation on real scRNA-Seq datasets.