bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extrastriate Connectivity of the Mouse Dorsal Lateral Geniculate Thalamus
Authors: Bienkowski Michael S. , Benavidez Nora L. , Wu Kevin , Gou Lin , Becerra Marlene , Dong Hong-Wei 
Published: June 2018

AbstractThe mammalian visual system is one of the most well-studied brain systems. Visual information from the retina is relayed to the dorsal lateral geniculate nucleus of the thalamus (LGd). The LGd then projects topographically to primary visual cortex (VISp) to mediate visual perception. In this view, the VISp is a critical network hub where visual information must traverse LGd-VISp circuits to reach higher-order ‘extrastriate’ visual cortices. However, decades of conflicting reports in a variety of mammals support or refute the existence of extrastriate LGd connections that can bypass the VISp. Here, we provide evidence of bidirectional extrastriate connectivity with the mouse LGd. Using small, discrete coinjections of anterograde and retrograde tracers within the thalamus and cortex, our cross-validated approach identified bidirectional thalamocortical connectivity between LGd and extrastriate visual cortices. Our findings support the existence of extrastriate LGd circuits and provide novel understanding of LGd organization in rodent visual system.
Reparametrizing the Sigmoid Model of Gene Regulation for Bayesian Inference
Authors: Modrák Martin 
Published: June 2018

AbstractThis poster describes a novel reparametrization of a fre-quently used non-linear ordinary differential equation (ODE) model of gene regulation. We show that in its commonly used form, the model cannot reliably distinguish between both quantitatively and qualitatively different parameter combinations. The proposed reparametrization makes inference over the model stable and amenable to fully Bayesian treatment with state of the art Hamiltonian Monte Carlo methods.Complete source code and a more detailed explanation of the model is available at https://github.com/cas-bioinf/genexpi-stan.
A deep learning approach to pattern recognition for short DNA sequences
Authors: Busia Akosua , Dahl George E. , Fannjiang Clara , Alexander David H. , Dorfman Elizabeth , Poplin Ryan , McLean Cory Y. , Chang Pi-Chuan , DePristo Mark 
Published: June 2018

AbstractMotivationInferring properties of biological sequences--such as determining the species-of-origin of a DNA sequence or the function of an amino-acid sequence--is a core task in many bioinformatics applications. These tasks are often solved using string-matching to map query sequences to labeled database sequences or via Hidden Markov Model-like pattern matching. In the current work we describe and assess an deep learning approach which trains a deep neural network (DNN) to predict database-derived labels directly from query sequences.ResultsWe demonstrate this DNN performs at state-of-the-art or above levels on a difficult, practically important problem: predicting species-of-origin from short reads of 16S ribosomal DNA. When trained on 16S sequences of over 13,000 distinct species, our DNN achieves read-level species classification accuracy within 2.0% of perfect memorization of training data, and produces more accurate genus-level assignments for reads from held-out species thank-mer, alignment, and taxonomic binning baselines. Moreover, our models exhibit greater robustness than these existing approaches to increasing noise in the query sequences. Finally, we show that these DNNs perform well on experimental 16S mock community dataset. Overall, our results constitute a first step towards our long-term goal of developing a general-purpose deep learning approach to predicting meaningful labels from short biological sequences.AvailabilityTensorFlow training code is available through GitHub (https://github.com/tensorflow/models/tree/master/research). Data in TensorFlow TFRecord format is available on Google Cloud Storage (gs://brain-genomics-public/research/seq2species/).Contactseq2species-interest@google.comSupplementary informationSupplementary data are available in a separate document.
A Continuous-Time Semi-Markov Model for Animal Movement in a Dynamic Environment
Authors: Johnson Devin S. , Pelland Noel A. , Sterling Jeremy T. 
Published: June 2018

AbstractWe consider an extension to discrete-space continuous-time models animal movement that have previously be presented in the literature. The extension from a continuous-time Markov formulation to a continuous-time semi-Markov formulation allows for the inclusion of temporally dynamic habitat conditions as well as temporally changing movement responses by animals to that environment. We show that with only a little additional consideration, the Poisson likelihood approximation for the Markov version can still be used within the multiple imputation framework commonly employed for analysis of telemetry data. In addition, we consider a Bayesian model selection methodology with the imputation framework. The model selection method uses a Laplace approximation to the posterior model probability to provide a computationally feasible approach. The full methodology is then used to analyze movements of 15 northern fur seal (Callorhinus ursinus) pups with respect to surface winds, geostrophic currents, and sea surface temperature. The highest posterior model probabilities belonged to those models containing only winds and current, SST did not seem to be a significant factor for modeling their movement.
A systems view of spliceosomal assembly and branchpoints with iCLIP
Authors: Briese Michael , Haberman Nejc , Sibley Christopher R. , Chakrabarti Anob M. , Wang Zhen , König Julian , Perera David , Wickramasinghe Vihandha O. , Venkitaraman Ashok R. , Luscombe Nicholas M. , Smith Christopher W. , Curk Tomaž , Ule Jernej 
Published: June 2018

AbstractStudies of spliceosomal interactions are challenging due to their dynamic nature. Here we employed spliceosome iCLIP, which immunoprecipitates SmB along with snRNPs and auxiliary RNA binding proteins (RBPs), to map human spliceosome engagement with snRNAs and pre-mRNAs. This identified over 50,000 branchpoints (BPs) that have canonical sequence and structural features. Moreover, it revealed 7 binding peaks around BPs and splice sites, each precisely overlapping with binding profiles of specific splicing factors. We show how the binding patterns of these RBPs are affected by the position and strength of BPs. For example, strong or proximally located BPs preferentially bind SF3 rather than U2AF complex. Notably, these effects are partly neutralized during spliceosomal assembly in a way that depends on the core spliceosomal protein PRPF8. These insights exemplify spliceosome iCLIP as a broadly applicable method for transcriptomic studies of splicing mechanisms.
A Moment-Based Maximum Entropy Model for Fitting Higher-Order Interactions in Neural Data
Authors: Cayco-Gajic N. Alex , Zylberberg Joel , Shea-Brown Eric 
Published: June 2018

AbstractCorrelations in neural activity have been demonstrated to have profound consequences for sensory encoding. To understand how neural populations represent stimulus information, it is therefore necessary to model how pairwise and higher-order spiking correlations between neurons contribute to the collective structure of population-wide spiking patterns. Maximum entropy models are an increasingly popular method for capturing collective neural activity by including successively higher-order interaction terms. However, incorporating higher-order interactions in these models is difficult in practice due to two factors. First, the number of parameters exponentially increases as higher orders are added. Second, because triplet (and higher) spiking events occur infrequently, estimates of higher-order statistics may be contaminated by sampling noise. To address this, we extend previous work on the Reliable Interaction class of models [1] to develop a normalized variant that adaptively identifies the specific pairwise and higher-order moments that can be estimated from a given dataset for a specified confidence level. The resulting “Reliable Moment” model is able to capture cortical-like distributions of population spiking patterns. Finally, we show that, compared with the Reliable Interaction model, the Reliable Moment model infers fewer strong spurious higher-order interactions and is better able to predict the frequencies of previously unobserved spiking patterns.
Yeast replicative aging leads to permanent cell cycle arrest in G1 effectuated by the start repressor Whi5
Authors: Yang Jing , Wang Ziwei , Liu Xili , Li Hao , Ouyang Qi 
Published: June 2018

AbstractYeast replicative aging has been a canonical model for aging research. Since replicative aging eventually leads to permanent cell cycle arrest, a fundamental question is how cells sense the signals from aging and communicate that to the cell cycle control machineries. Using microfluidic devices to track individual mother cells labeled by two different cell cycle markers Whi5-tdTomato and Myo1-EGFP, we measured the length of different cell cycle phases as a function of age and the distribution of cell death in different cell cycle phases. We found that the majority of the cells died in the G1 phase, and their G1 cell cycle length increased drastically in the last few cell divisions. This increase of G1 length correlates with the increase of the nuclear concentration of Whi5, which is a major transcriptional suppressor of the cell cycle start check point. Interestingly, this correlation is apparent only above a threshold concentration of Whi5. We show that in response to external stress, Whi5 concentration increases and cell growth slows down in a Whi5 dependent manner, and that Whi5 deletion significantly extends the lifespan. Together these data suggest the existence of a programmed control to arrest cell cycle in G1 in response to stress signals due to aging, and that Whi5 is a major mediator of this process. Our findings may have important implications in understanding senescence and cancer in mammalian cells, which have a parallel G1/S control system with Rb (a well known tumor suppressor) as the analog of Whi5.Significance statementIn this work, we used microfluidic devices to track individual mother cells labeled by two cell cycle markers Whi5-tdTomato and Myo1-EGFP. We found that aging leads to significant lengthening of G1 phase in old cells and the eventual permanent cell cycle arrest in G1, and Whi5 plays an important role in implementing such a program. We show that oxidative stress can lead to the increase of Whi5 expression and the slow-down of cell division. Furthermore, Whi5 deletion significantly extends the lifespan. The result suggest the existence of a programmed control to arrest cell cycle in G1 in response to stress signals due to aging, and that Whi5 is a major mediator of this process.
Cross-platform meta-analysis reveals common matrisome variation associated with tumor genotypes and immunophenotypes in human cancers
Authors: Bin Lim Su , Jin Tan Swee , Lim Wan-Teck , Lim Chwee Teck 
Published: June 2018

AbstractBackgroundRecent sequencing efforts unveil genomic landscapes of the tumor microenvironment. Yet, little is known about the extent to which matrisome pattern is conserved in progressive tumors across diverse cancer types, and thus its clinical impact remains largely unexplored.FindingsUsing a newly generated, unified data resource, we conducted cross-platform assessment of a measure of altered extra-cellular matrix (ECM) composition and remodeling associated with tumor progression, termed as the matrisome index (TMI). Parallel analyses with TCGA in over 30,000 patient-derived biopsies revealed that TMI is closely associated with mutational load, tumor histopathology, and predictive of patient outcomes. We found an enrichment of specific tumor-infiltrating immune cell populations, signatures predictive of immunotherapy resistance, and several immune checkpoints in tumors with high TMI, suggesting potential role of ECM interaction with immunophenotyes and tumor immune escape mechanisms. Both epithelial cancer cells and carcinoma-associated fibroblasts are potential cellular contributors of such deregulated matrisome.ConclusionsDespite wide spectrum of genetic heterogeneity and dynamic nature, matrisome abnormalities are integral to disease progression. Our resource of a curated compendium of 8,386 genome-wide profiles, molecular and clinical associations, and matrisome-tumor genotype-immunophenotype relationships identify potentially actionable immune targets that may guide personalized immunotherapy.
Local adaptation and sexual selection drive intra-island diversification in a songbird lineage: differential divergence in autosomes and sex chromosomes
Authors: Bourgeois Yann XC , Bertrand Joris AM , Delahaie Boris , Holota Hélène , Thébaud Christophe , Milá Borja 
Published: June 2018

AbstractRecently diverged taxa showing marked phenotypic and ecological diversity are optimal systems to test the relative importance of two major evolutionary mechanisms, adaptation to local ecological conditions by natural selection, or mechanisms of reproductive isolation such as assortative mating mediated by sexually selected mating signals or post-zygotic incompatibilities. Whereas local adaptation is expected to affect many loci throughout the genome, traits acting as mating signals are expected to be located on sex chromosomes and have a simple genetic basis. We used genome-wide markers to test these predictions in Reunion Island’s gray-white eye (Zosterops borbonicus), which has recently diversified into five distinct plumage forms. Two of them correspond to a polymorphic highland population that is separated by a steep ecological gradient from three distinct lowland forms that show narrow contact zones in plumage color traits, yet no association with environmental variables. An analysis of population structure using genome-wide SNP loci revealed two major clades corresponding to highland and lowland forms, respectively, with the latter separated further into three independent lineages corresponding to plumage forms. Coalescent tests of alternative demographic scenarios provided support for divergence of highland and lowland lineages with an intensification of gene flow in the last 60,000 years. Landscapes of genomic variation revealed that signatures of selection associated with elevation are found at multiple regions across the genome, whereas most loci associated with the lowland forms are located on the Z sex chromosome. A gene ontology analysis identified TYRP1, a Z-linked color gene, as a likely candidate locus underlying color variation among lowland forms. Our results are consistent with the role of natural selection in driving the divergence of locally adapted highland populations, and the role of sexual selection in differentiating lowland forms through reproductive isolation mechanisms, showing that both modes of lineage divergence can take place at very small geographic scales in birds.
The Effect of Aldehyde Dehydrogenase Activator, Alda-1®, on the Ethanol-induced Brain Damage in a Rat of Binge Ethanol Intoxication
Authors: Kim Changsun , Hwang Sejin , Choi Hyuk Joong , Lim Tae Ho , Kang Ju-seop 
Published: June 2018

ABSTRACTAimsThis study aimed to investigate whether an aldehyde dehydrogenase (ALDH) activator (Alda-1®) reduces neuronal damage in a rat model of binge ethanol exposure.MethodsThirty-six adolescent male rats (130-150 g) were randomly assigned into three groups: sham, ethanol-only group (25% ethanol intragastrically thrice daily for four days, approximately 10 g/kg/day) and ethanol with Alda-1®group (10 mg/kg thrice daily for four days). The ALDH activity at baseline and 90 min after the last infusion in each group was measured. Brain damage was investigated using Luxol fast blue-Cresyl violet staining in the hippocampus, CA1 and CA2/3. The activation of astrocytes and microglia was examined using immunohistochemistry for antiglial fibrillary acidic protein (GFAP) and anti-ionized calcium-binding adapter molecule 1 (Iba-1).ResultsAfter a four-day binge, the ALDH activity level was doubled in the ethanol with Alda-1®group (mean: 7.87, SD: 0.67), whereas the levels in the sham group (mean: 4.07, SD: 0.53) and ethanol-only group (mean: 3.77, SD: 0.36) were slightly decreased. More significant neuronal shrinkage, fewer neurons, and loss of Nissl in the hippocampus were observed in the ethanol-only group compared to the ethanol with Alda-1®group. Astrocytosis and microgliosis of the hippocampus also showed increased activation in the ethanol only group compared with the ethanol with Alda-1®group.ConclusionAlda-1®administration reduces cytotoxic damage to the hippocampus in adolescent rats with binge ethanol exposure.
Over 2.5 million COI sequences in GenBank and growing
Authors: Porter Teresita M. , Hajibabaei Mehrdad 
Published: June 2018

AbstractThe increasing popularity of cytochrome c oxidase subunit 1 (COI) DNA metabarcoding warrants a careful look at the underlying reference databases used to make high-throughput taxonomic assignments. The objectives of this study are to document trends and assess the future usability of COI records for metabarcode identification. Over 2.5 million COI sequences were found in GenBank, half of which were fully identified to the species rank. From 2003 to 2017, the number of COI Eukaryote records deposited has grown by two orders of magnitude representing a nearly 42-fold increase in unique species. For fully identified records, 92% are at least 500 bp in length, 74% have a country annotation, and 51% have latitude-longitude annotations. To ensure the future usability of COI records in GenBank we suggest: 1) Improving the geographic representation of COI records 2) Improving the cross-referencing of COI records in the Barcode of Life Data System and GenBank to facilitate consolidation and incorporation into existing bioinformatic pipelines, 3) Adherence to the minimum information about a marker gene sequence guidelines, and 4) Integrating metabarcodes from eDNA and mixed community studies with existing sequences. COI metabarcoders are normally considered consumers of taxonomic data. Here we discuss the potential for taxonomists to reverse this pattern and instead mine metabarcode data to guide species discovery. The growth of COI reference records over the past 15 years has been substantial and is likely to be a resource across many fields for years to come.
Defending the Undefendable: Male Territorial Behaviour and Mating System in Monogamous Primates
Authors: Dunbar R.I.M. 
Published: June 2018

AbstractIt has been suggested that monogamy evolves when females forage alone and are overdispersed, such that males cannot defend more than one female at a time. I test the underlying assumption that the females of monogamous anthropoid primates are overdispersed in three different ways, and compare the results with data for several polygynous primate genera. First, I show that monogamous primates do not have per capita territories that are significantly larger than those of polygynous taxa. Second, given their day journey length and the Mitani-Rodman equation (Mitani & Rodman 1979), males of most monogamous species could easily defend areas large enough to allow them to monopolise 5-6 females. Finally, I use a model of male mate searching strategies to show that, unlike the males of polygynous species, the males of monogamous species would sire more offspring by adopting a roving male form of polygyny when females are dispersed. The opportunity cost that monogamous males incur is typically more than five times the reproductive success they have by being obligately monogamous, suggesting that the selection pressure preventing them from pursuing a roving male strategy is very considerable. Given that biparental care always follows the adoption of monogamy in primate evolution, the only viable explanation for monogamy would seem to be either high predation risk or high infanticide risk.
STK25 directly activates LATS1/2 independent of MST/MAP4Ks
Authors: Lim Sanghee , Hermance Nicole , Mudianto Tenny , Mustaly Hatim M. , Mauricio Ian Paolo Morelos , Vittoria Marc A. , Quinton Ryan J. , Howell Brian W. , Cornils Hauke , Manning Amity L. , Ganem Neil J. 
Published: June 2018

AbstractThe Hippo pathway maintains tissue homeostasis by negatively regulating the oncogenic transcriptional co-activators YAP and TAZ. Though functional inactivation of the Hippo pathway is common in tumors, mutations in core pathway components are rare. Thus, understanding how tumor cells inactivate Hippo signaling remains a key unresolved question. Here, we identify the kinase STK25 as a novel activator of Hippo signaling. We demonstrate that loss of STK25 promotes YAP/TAZ activation and enhanced cellular proliferation, even under normally growth-suppressive conditions. We reveal that STK25 activates LATS via a previously unobserved mechanism, in which STK25 directly phosphorylates the LATS activation loop. This represents a new paradigm in Hippo activation and distinguishes STK25 from all other identified kinase activators of LATS. STK25 is significantly focally deleted across a wide spectrum of human cancers, suggesting STK25 loss may represent a common mechanism by which tumor cells functionally impair the Hippo tumor suppressor pathway.
Draft Genome Sequence of the Asian Pear Scab Pathogen, Venturia nashicola
Authors: Johnson Shakira , Jones Dan , Thrimawithana Amali H. , Deng Cecilia H. , Bowen Joanna K. , Mesarich Carl H. , Ishii Hideo , Won Kyungho , Bus Vincent G.M. , Plummer Kim M. 
Published: June 2018

AbstractVenturia nashicola, which causes scab disease of Asian pear, is a host-specific, biotrophic fungus, with a sexual stage that occurs during saprobic growth. V. nashicola is endemic to Asia and is regarded as a quarantine threat to Asian pear production outside of this continent. Currently, fungicide applications are routinely used to control scab disease. However, fungicide resistance in V. nashicola, as in other fungal pathogens, is an ongoing challenge and alternative control or prevention measures that include, for example, the deployment of durable host resistance, are required. A close relative of V. nashicola, V. pirina, causes scab disease of European pear. European pear displays non-host resistance (NHR) to V. nashicola and Asian pears are non-hosts of V. pirina. It is anticipated that the host specificity of these two fungi is governed by differences in their effector arsenals, with a subset responsible for activating NHR. The Pyrus-Venturia pathosystems provide a unique opportunity to dissect the underlying genetics of non-host interactions and to understand coevolution in relation to this potentially more durable form of resistance. Here, we present the first V. nashicola draft whole genome sequence (WGS), which is made up of 40,800 scaffolds (totalling 45 Mb) and 11,094 predicted genes. Of these genes, 1,232 are predicted to encode a secreted protein by SignalP, with 273 of these predicted to be effectors by EffectorP. The V. nashicola WGS will enable comparison to the WGSs of other Venturia spp. to identify effectors that potentially activate NHR in the pear scab pathosystems.