bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acoustic and Visual Stimulus Parameters Underlying Sound Symbolic Crossmodal Correspondences
Authors: List Sara M. , McCormick Kelly , Lacey Simon , Sathian K. , Nygaard Lynne C. 
Published: January 2019

ABSTRACTIt is often assumed that a fundamental property of language is the arbitrariness of the relationship between sound and meaning. Sound symbolism, which refers to non-arbitrary mapping between the sound of a word and its meaning, contradicts this assumption. Sensitivity to sound symbolism has been studied through crossmodal correspondences (CCs) between auditory pseudowords (e.g. ‘loh-moh’) and visual shapes (e.g. a blob). We used representational similarity analysis to examine the relationships between physical stimulus parameters and perceptual ratings that varied on dimensions of roundedness and pointedness, for a range of auditory pseudowords and visual shapes. We found that perceptual ratings of these stimuli relate to certain physical features of both the visual and auditory domains. Representational dissimilarity matrices (RDMs) of parameters that capture the spatial profile of the visual shapes, such as the simple matching coefficient and Jaccard distance, were significantly correlated with those of the visual ratings. RDMs of certain acoustic parameters of the pseudowords, such as the temporal fast Fourier transform (FFT) and spectral tilt, that reflect spectral composition, as well as shimmer and speech envelope that reflect aspects of amplitude variation over time, were significantly correlated with those of the auditory perceptual ratings. RDMs of the temporal FFT (acoustic) and the simple matching coefficient (visual) were significantly correlated. These findings suggest that sound-symbolic CCs are related to basic properties of auditory and visual stimuli, and thus provide insights into the fundamental nature of sound symbolism and how this might evoke specific impressions of physical meaning in natural language.
A mutation in the endonuclease domain of mouse MLH3 reveals novel roles for MutLγ during crossover formation in meiotic prophase I
Authors: Toledo Melissa , Sun Xianfei , Brieño-Enríquez Miguel A. , Raghavan Vandana , Gray Stephen , Pea Jeffrey , Venkatesh Anita , Patel Lekha , Borst Peter L. , Alani Eric , Cohen Paula E. 
Published: January 2019

ABSTRACTDuring meiotic prophase I, double-strand breaks (DSBs) initiate homologous recombination leading to non-crossovers (NCOs) and crossovers (COs). In mouse, 10% of DSBs are designated to become COs, primarily through a pathway dependent on the MLH1-MLH3 heterodimer (MutLγ). Mlh3 contains an endonuclease domain that is critical for resolving COs in yeast. We generated a mouse (Mlh3DN/DN) harboring a mutation within this conserved domain that is predicted to generate a protein that is catalytically inert.Mlh3DN/DNmales, like fully nullMlh3-/-males, have no spermatozoa and are infertile, yet spermatocytes have normal DSBs and undergo normal synapsis events in early prophase I. UnlikeMlh3-/-males, mutation of the endonuclease domain within MLH3 permits normal loading and frequency of MutLγ in pachynema. However, key DSB repair factors (RAD51) and mediators of CO pathway choice (BLM helicase) persist into pachynema inMlh3DN/DNmales, indicating a temporal delay in repair events and revealing a mechanism by which alternative DSB repair pathways may be selected. WhileMlh3DN/DNspermatocytes retain only 22% of wildtype chiasmata counts, this frequency is greater than observed inMlh3-/-males (10%), suggesting that the allele may permit partial endonuclease activity, or that other pathways can generate COs from these MutLγ-defined repair intermediates inMlh3DN/DNmales. Double mutant mice homozygous for theMlh3DN/DNandMus81-/-mutations show losses in chiasmata that approach levels observed inMlh3-/-males, indicating that the MUS81-EME1-regulated crossover pathway accounts for some of the increased residual chiasmata observed inMlh3DN/DNspermatocytes. Our data demonstrate that mouse spermatocytes bearing the MLH1-MLH3DN/DNcomplex display the proper loading of factors essential for CO resolution (MutSγ, CDK2, HEI10, MutLγ). Despite these functions, mice bearing theMlh3DN/DNallele show defects in the repair of meiotic recombination intermediates and a loss of most chiasmata.SUMMARYThe MLH1-MLH3 complex is essential for crossing over in mammalian meiosis. We generated a mutation in mouse MLH3 that alters its conserved endonuclease domain and show that it disrupts crossing over in a manner distinct from the full nullMlh3mouse, but also results in male infertility.
Efficient estimation and applications of cross-validated genetic predictions
Authors: Mefford Joel , Park Danny , Zheng Zhili , Ko Arthur , Ala-Korpela Mika , Laakso Markku , Pajukanta Päivi , Yang Jian , Witte John , Zaitlen Noah 
Published: January 2019

ABSTRACTLarge-scale cohorts with combined genetic and phenotypic data, coupled with methodological advances, have produced increasingly accurate genetic predictors of complex human phenotypes called polygenic risk scores (PRS). In addition to the potential translational impacts of identifying at-risk individuals, PRS are being utilized for a growing list of scientific applications including causal inference, identifying pleiotropy and genetic correlation, and powerful gene-based and mixed model association tests. Existing PRS approaches rely on external large-scale genetic cohorts that have also measured the phenotype of interest. They further require matching on ancestry and genotyping platform or imputation quality. In this work we present a novel reference-free method to produce PRS that does not rely on an external cohort. We show that naive implementations of reference-free PRS either result in substantial over-fitting or prohibitive increases in computational time. We show that our algorithm avoids both of these issues, and can produce informative in-sample PRS over any existing cohort without over-fitting. We then demonstrate several novel applications of reference-free PRS including detection of pleiotropy across 246 metabolic traits and efficient mixed-model association testing.
Cancer Classification from Healthy DNA
Authors: Jain Siddharth , Mazaheri Bijan , Raviv Netanel , Bruck Jehoshua 
Published: January 2019

ABSTRACTThe genome is traditionally viewed as atime-independentsource of information; a paradigm that drives researchers to seek correlations between the presence of certain genes and a patient’s risk of disease. This analysis neglectsgenomic temporal changes, which we believe to be a crucial signal for predicting an individual’s susceptibility to cancer. We hypothesize that each individual’s genome passes through anevolution channel(The termchannelis motivated by the notion of communication channel introduced by Shannon1 in 1948 and started the area ofInformation Theory), that is controlled by hereditary, environmental and stochastic factors. This channel differs among individuals, giving rise to varying predispositions to developing cancer. We introduce the concept ofmutation profilesthat are computed without any comparative analysis, but by analyzing the short tandem repeat regions in asingle healthy genomeand capturing information about the individual’s evolution channel. Using machine learning on data from more than 5,000 TCGA cancer patients, we demonstrate that thesemutation profilescan accurately distinguish between patients with various types of cancer. For example, the pairwise validation accuracy of the classifier between PAAD (pancreas) patients and GBM (brain) patients is 93%. Our results show that healthy unaffected cells still contain a cancer-specific signal, which opens the possibility of cancer prediction from a healthy genome.
Comparative genomics identified a genetic locus in plant-associated Pseudomonas spp. that is necessary for induced systemic susceptibility
Authors: Beskrovnaya Polina , Melnyk Ryan A. , Liu Zhexian , Liu Yang , Higgins Melanie A. , Song Yi , Ryan Katherine , Haney Cara H. 
Published: January 2019

AbstractPlant root-associated microbes promote plant growth and induce systemic resistance (ISR) to foliar pathogens. In an attempt to find novel growth-promoting and ISR-inducing strains, we previously identified strains of root-associated Pseudomonas spp. that promote plant growth but unexpectedly induced systemic susceptibility (ISS) rather than ISR to foliar pathogens. Here we demonstrate that the ISS-inducing phenotype is common among root-associated Pseudomonas spp. Using comparative genomics, we identified a single P. fluorescens locus that is unique to ISS strains. We generated a clean deletion of the 11-gene ISS locus and found that it is necessary for the ISS phenotype. Although the functions of the predicted genes in the locus are not apparent based on similarity to genes of known function, the ISS locus is present in diverse bacteria and a subset of the genes have previously been implicated in pathogenesis in animals. Collectively these data show that a single bacterial locus contributes to modulation of systemic plant immunity.ImportanceMicrobiome-associated bacteria can have diverse effects on health of their hosts, yet the genetic and molecular basis of these effects have largely remained elusive. This work demonstrates that a novel bacterial locus can modulate systemic plant immunity. Additionally, this work demonstrates that growth promoting strains may have unanticipated consequences on plant immunity and this is critical to consider when engineering the plant microbiome for agronomic improvement.
Artificial Dendritic Neurons Enable Self-Supervised Temporal Feature Extraction
Authors: Asabuki Toshitake , Fukai Tomoki 
Published: January 2019

AbstractThe brain identifies potentially salient features within continuous information streams to appropriately process external and internal temporal events. This requires the compression or abstraction of information streams, for which no effective information principles are known. Here, we propose conditional entropy minimization learning as the fundamental principle of such temporal processing. We show that this learning rule resembles Hebbian learning with backpropagating action potentials in dendritic neuron models. Moreover, networks of the dendritic neurons can perform a surprisingly wide variety of complex unsupervised learning tasks. Our model not only accounts for the mechanisms of chunking of temporal inputs in the human brain but also accomplishes blind source separation of correlated mixed signals, which cannot be solved by conventional machine learning methods, such as independent-component analysis.One Sentence SummaryNeurons use soma-dendrite interactions to self-supervise the learning of characteristic features of various temporal inputs.
Recent origin of an XX/XY sex-determination system in the ancient plant lineageGinkgo biloba
Authors: Zhang He , Zhang Rui , Yang Xianwei , Gu Kai-Jie , Chen Wenbin , Chang Yue , Xu Qiwu , Liu Qun , Qin Yating , Hong Xiaoning , Yin  , Seim Inge , Lin Han-Yang , Li Wen-Hao , Tian Jinfu , Li Shanshan , Liu  , Liu Junnian , Liu Shanshan , Su Xiaoshan , Wang Congyan , Zhang Fu-Ming , Ge Song , Fu Cheng-Xin , Lee Simon Ming-Yuen , Xia Yiji , Wang Jian , Yang Huanming , Fan Guangyi , Xu Xun , Zhao Yun-Peng , Xin  
Published: January 2019

ABSTRACTSexual dimorphism like dioecy (separate male and female individuals) have evolved in diverse multicellular eukaryotes while the molecular mechanisms underlying the development of such a key biological trait remains elusive (1). The living fossilGinkgo bilobarepresents an early diverged lineage of land plants with dioecy. However, its sex-determination system and molecular basis have long been controversial or unknown. In the present research, we assembled the first and largest to date chromosome-level genome of a non-model tree species using Hi-C data. With this reference genome, we addressed both questions using genome resequencing data gathered from 97 male and 265 female trees of ginkgo, as well as transcriptome data from three developmental stages for both sexes. Our results support vertebrate-like XY chromosomes for ginkgo and five potential sex-determination genes, which may originate ~14 million years ago. This is the earliest diverged sex determination region in all reported plants as yet. The present research resolved a long-term controversy, lay a foundation for future studies on the origin and evolution of plant sexes, and provide genetic markers for sex identification of ginkgo which will be valuable for both nurseries and field ecology of ginkgo.
Integrating past, present and future wheat research with Pretzel
Authors: Keeble-Gagnère Gabriel , Isdale Don , Suchecki Rados-ław , Kruger Alex , Lomas Kieran , Carroll David , Li Sean , Whan Alex , Hayden Matthew , Tibbits Josquin 
Published: January 2019

AbstractMotivationMajor advances have been made in the assembly of complex genomes such as wheat. Remaining challenges include linking these new resources to legacy research, as well as lowering the bar to entry for members of the research community who may lack specific bioinformatics skills.ResultsPretzel aims to solve these problems by providing an interactive, online environment for data visualisation and analysis which, when loaded with appropriately curated data, can enable researchers with no bioinformatics training to exploit the latest genomic resources. We demonstrate that Pretzel can be used to answer common questions asked by researchers as well as for advanced curation of pseudomolecule structure.AvailabilityPretzel is implemented in JavaScript and is freely available under a GPLv3 license online at: https://github.com/plantinformatics/pretzel.Contactgabriel.keeble-gagnere@ecodev.vic.gov.au
A Note on Computing Interval Overlap Statistics
Authors: Sarmashghi Shahab , Bafna Vineet 
Published: January 2019

AbstractWe consider the following problem: Let I and If each describe a collection of n and m non-overlapping intervals on a line segment of finite length. Suppose that k of the m intervals of If are intersected by some interval(s) in I. Under the null hypothesis that intervals in I are randomly arranged w.r.t If, what is the significance of this overlap? This is a natural abstraction of statistical questions that are ubiquitous in the post-genomic era. The interval collections represent annotations that reveal structural or functional regions of the genome, and overlap statistics can provide insight into the correlation between different structural and functional regions. However, the statistics of interval overlaps have not been systematically explored. In this manuscript, we formulate a statistical significance problem which considers the length and structure of intervals. We describe a combinatorial algorithm for a constrained interval overlap problem that can accurately compute very small p-values. We also propose a fast approximate method to facilitate problems consisted of very large number of intervals. These methods are all implemented in a tool, iStat. We applied iStat to simulated interval data to obtain precise estimates of low p-values, and characterize the performance of our methods. We also test iStat on real datasets from previous studies, and compare iStat results with the reported p-values using basic permutation or parametric tests. The iStat software is made publicly available on https://github.com/shahab-sarmashghi/ISTAT.git
Phylogenomics resolves major relationships and reveals significant diversification rate shifts in the evolution of silk moths and relatives
Authors: Hamilton CA , St Laurent RA , Dexter K , Kitching IJ , Breinholt JW , Zwick A , Timmermans MJTN , Barber JR , Kawahara AY 
Published: January 2019

AbstractBackgroundThe silkmoths and their relatives constitute the ecologically and taxonomically diverse superfamily Bombycoidea, which includes some of the most charismatic species of Lepidoptera. Despite displaying some of the most spectacular forms and ecological traits among insects, relatively little attention has been given to understanding their evolution and the drivers of their diversity.ResultsTo begin to address this problem, we created a new Bombycoidea-specific Anchored Hybrid Enrichment (AHE) probe set and sampled up to 571 loci for 117 taxa across all major lineages of the Bombycoidea, producing a well-supported phylogeny. The tree was overall consistent with prior morphological and molecular studies, although some taxa (e.g.,ArotrosSchaus) were misplaced in the Bombycidae and here formally transferred to Apatelodidae. We identified important evolutionary patterns (e.g., morphology, biogeography, and differences in speciation and extinction), and our analysis of diversification rates highlights the stark increases that exist within the Sphingidae (hawkmoths) and Saturniidae (wild silkmoths).ConclusionsWe postulate that these rate shifts are due to the well-documented bat-moth “arms race” and differences in selective pressures from insectivorous bats. The study establishes a backbone for future evolutionary, comparative, and taxonomic studies, and presents a modified DNA extraction protocol that allows Lepidoptera specimens to be readily sequenced from pinned natural history collections, succeeding in samples up to 30 years old. Our research highlights the flexibility of AHE to generate genomic data from a wide range of museum specimens, both age and preservation method, and will allow researchers to tap into the wealth of biological data residing in natural history collections around the globe.
Complex-Traits Genetics Virtual Lab: A community-driven web platform for post-GWAS analyses
Authors: Cuellar-Partida Gabriel , Lundberg Mischa , Kho Pik Fang , D’Urso Shannon , Gutierrez-Mondragon Luis F. , Hwang Liang-Dar 
Published: January 2019

AbstractBackgroundGenome-wide association studies (GWAS) are an important method for mapping genetic variation underlying complex traits and diseases. Tools to visualize, annotate and analyse results from these studies can be used to generate hypotheses about the molecular mechanisms underlying the associations.FindingsThe Complex-Traits Genetics Virtual Lab (CTG-VL) integrates over a thousand publicly-available GWAS summary statistics, a suite of analysis tools, visualization functions and diverse data sets for genomic annotations. CTG-VL also makes available results from gene, pathway and tissue-based analyses from over 1,500 complex-traits allowing to assess pleiotropy not only at the genetic variant level but also at the gene, pathway and tissue levels. In this manuscript, we showcase the platform by analysing GWAS summary statistics of mood swings derived from UK Biobank. Using analysis tools in CTG-VL we highlight hippocampus as a potential tissue involved in mood swings, and that pathways including neuron apoptotic process may underlie the genetic associations. Further, we report a negative genetic correlation with educational attainment rG = −0.41 ± 0.018 and a potential causal effect of BMI on mood swings OR = 1.01 (95% CI = 1.00–1.02). Using CTG-VL’s database, we show that pathways and tissues associated with mood swings are also associated with neurological traits including reaction time and neuroticism, as well as traits such age at menopause and age at first live birth.ConclusionsCTG-VL is a platform with the most complete set of tools to carry out post-GWAS analyses. The CTG-VL is freely available at https://genoma.io as an online web application.
Srs2 helicase prevents the formation of toxic DNA damage during late prophase I of yeast meiosis
Authors: Sasanuma Hiroyuki , Sakurai Hana Subhan M. , Furihata Yuko , Challa Kiran , Palmer Lira , Gasser Susan M. , Shinohara Miki , Shinohara Akira 
Published: January 2019

AbstractProper repair of double-strand breaks (DSBs) is key to ensure proper chromosome segregation. In this study, we found that the deletion of the SRS2 gene, which encodes a DNA helicase necessary for the control of homologous recombination, induces aberrant chromosome segregation during budding yeast meiosis. This abnormal chromosome segregation in srs2 cells accompanies the formation of a novel DNA damage induced during late meiotic prophase-I. The damage may contain long stretches of single-stranded DNAs (ssDNAs), which lead to aggregate formation of a ssDNA binding protein, RPA, and a RecA homolog, Rad51, as well as other recombination proteins inside of the nuclei. The Rad51 aggregate formation in the srs2 mutant depends on the initiation of meiotic recombination and occurs in the absence of chromosome segregation. Importantly, as an early recombination intermediate, we detected a thin bridge of Rad51 between two Rad51 foci or among the foci in the srs2 mutant, which is rarely seen in wild type. These might be cytological manifestation of the connection of two DSB ends and multi-invasion. The DNA damage with Rad51 aggregates in the srs2 mutant is passed through anaphase-I and -II, suggesting the absence of DNA damage-induced cell-cycle arrest after the pachytene stage. We propose that Srs2 helicase resolves early protein-DNA recombination intermediates to suppress the formation of aberrant lethal DNA damage during late prophase-I.
In vitro synergy between Sodium Deoxycholate and Furazolidone against Enterobacteria via Inhibition of Multidrug Efflux Pumps
Authors: Le Vuong Van Hung , Olivera Catrina , Spagnuolo Julian , Davies Ieuan , Rakonjac Jasna 
Published: January 2019

AbstractAntimicrobial combinations have been proven to be a promising approach in the confrontation with multi-drug resistant bacterial pathogens, owing to enhancement of antibacterial efficacy, deceleration of resistance development rate and mitigation of side effects by lowering the doses of two drugs. In the present study, we report that combination of furazolidone (FZ) and other nitrofurans with a secondary bile salt, Sodium Deoxycholate (DOC), generates a profound synergistic effect on growth inhibition and lethality in enterobacteria, including Escherichia coli, Salmonella, Citrobacter gillenii and Klebsiella pneumoniae. Taking E. coli as the model organism to study the mechanism of DOC-FZ synergy, we found that the synergistic effect involves FZ-mediated inhibition of efflux pumps that normally remove DOC from bacterial cells. We further show that the FZ–mediated nitric oxide production contributes to the synergistic effect. This is to our knowledge the first report of nitrofuran-DOC synergy against Gram-negative bacteria.
Eurotium cristatum, a new fungi probiotic from Fuzhuan brick tea, alleviated obesity in mice by modulating gut microbiota
Authors: Kang Dingding , Su Meng , Duan Yanwen , Huang Yong 
Published: January 2019

AbstractObesity is one of the major public health problems worldwide, mainly resulting from unhealthy lifestyles and diet. Gut microbiota dysbiosis may also lead to obese humans and animals. Modulating gut bacteria through fecal transplantation, the use of probiotics or certain dietary supplements, could normalize gut microbiota and subsequently alleviate obesity. Daily consumption of Fuzhuan brick tea (FBT) or its extracts have been observed to alleviate obesity in humans and experimental animals. In this study, high-fat diet-induced dysbiosis of gut microbiota in C57BL/6J mice was partially reversed by consumption of Eumtium cristatum, the dominant fungi during the manufacturing and storage of FBT. E. cristatum was able to modulate both gut fungi and bacteria composition, based on the analysis of microbiota composition of mice fecal samples. E. cristatum increased acetate and butyrate-producing bacteria in mice gut, and produced five times more butyrate than both obese and normal mice. Our results suggested that E. cristatum may be used as a fungi probiotic to beneficially modulate gut microbiota and to alleviate obesity in humans.