bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of Cardiomyocyte Transcriptome and Chromatin Landscape Demarcates Key Events of Heart Development
Authors: Pawlak Michal , Kedzierska Katarzyna Z. , Migdal Maciej , Abu Nahia Karim , Ramilowski Jordan A. , Bugajski Lukasz , Hashimoto Kosuke , Marconi Aleksandra , Piwocka Katarzyna , Carninci Piero , Winata Cecilia L. 
Published: December 2018

ABSTRACTThe development of an organ involves dynamic regulation of gene transcription and complex multipathway interactions. To better understand transcriptional regulatory mechanism driving heart development and the consequences of its disruption, we isolated cardiomyocytes (CMs) from wild-type zebrafish embryos at 24, 48 and 72 hours post fertilization corresponding to heart looping, chamber formation and heart maturation, and from mutant lines carrying loss-of-function mutations ingata5, tbx5aandhand2, transcription factors (TFs) required for proper heart development. The integration of CM transcriptomics (RNA-seq) and genome-wide chromatin accessibility maps (ATAC-seq) unravelled dynamic regulatory networks driving crucial events of heart development. These networks contained key cardiac TFs including Gata5/6, Nkx2.5, Tbx5/20, and Hand2, and are associated with open chromatin regions enriched for DNA sequence motifs belonging to the family of the corresponding TFs. These networks were disrupted in cardiac TF mutants, indicating their importance in proper heart development. The most prominent gene expression changes, which correlated with chromatin accessibility modifications within their proximal promoter regions, occurred between heart looping and chamber formation, and were associated with metabolic and hematopoietic/cardiac switch during CM maturation. Furthermore, loss of function of cardiac TFs Gata5, Tbx5a, and Hand2 affected the cardiac regulatory networks and caused global changes in chromatin accessibility profile. Among regions with differential chromatin accessibility in mutants were highly conserved non-coding elements which represent putativecisregulatory elements with potential role in heart development and disease. Altogether, our results revealed the dynamic regulatory landscape at key stages of heart development and identified molecular drivers of heart morphogenesis.
Uncovering missed indels by leveraging unmapped reads
Authors: Hasan Mohammad Shabbir , Wu Xiaowei , Zhang Liqing 
Published: December 2018

AbstractIn current practice, Next Generation Sequencing (NGS) applications start with mapping/aligning short reads to the reference genome, with the aim of identifying genetic mutations. While most short reads can be mapped to the reference genome accurately by existing alignment tools, a significant number remain unmapped and excluded from downstream analyses thus potentially discarding important biological information hidden in the unmapped reads. This paper describes Genesis-indel, a computational pipeline that explores the unmapped reads to identify novel indels that are initially missed in the alignment procedure. Genesis-indel is applied to the unmapped reads of 30 Breast Cancer patients from TCGA. Results show that the unmapped reads are conserved between the two subtypes of breast cancer investigated in this study and might contribute to the divergence between the subtypes. Genesis-indel is able to leverage the unmapped reads to identify 72,997 small to large novel high-quality indels previously not found in the original alignments and among them, 16,141 have not been annotated in the widely used mutation database. Statistical analysis shows that these new indels mostly altered the oncogenes and tumor suppressor genes. Functional annotation further reveals that these indels are strongly correlated to pathways of cancer and can have high to moderate impact on protein functions. Additionally, these indels overlap with the genes that are missed in the indels from the originally mapped reads and contribute to the tumorigenesis in multiple carcinomas.
Microstructural and Functional Gradients are Increasingly Dissociated in Transmodal Cortices
Authors: Paquola Casey , Vos De Wael Reinder , Wagstyl Konrad , Bethlehem Richard A.I. , Hong Seok-Jun , Seidlitz Jakob , Bullmore Edward T. , Evans Alan C. , Misic Bratislav , Margulies Daniel S. , Smallwood Jonathan , Bernhardt Boris C. 
Published: December 2018

SummaryWhile the role of cortical microstructure in organising neural function is well established, it remains unclear how structural constraints can give rise to more flexible elements of cognition. While non-human primate research has demonstrated a close structure-function correspondence, the relationship between microstructure and function remains poorly understood in humans, in part because of the reliance onpost mortemanalyses which cannot be directly related to functional data. To overcome this barrier, we developed a novel approach to model the similarity of microstructural profiles sampled in the direction of cortical columns. Our approach was initially formulated based on an ultra-high-resolution 3D histological reconstruction of an entire human brain and then translated to myelin-sensitive MRI data in a large cohort of healthy adults. This novel method identified a system-level gradient of microstructural differentiation traversing from primary sensory to limbic regions that followed shifts in laminar differentiation and cytoarchitectural complexity. Importantly, while microstructural and functional gradients described a similar hierarchy, they became increasingly dissociated in transmodal default mode and fronto-parietal networks. Meta analytic decoding of these topographic dissociations highlighted involvement in higher-level aspects of cognition such as cognitive control and social cognition. Our findings demonstrate a relative decoupling of macroscale functional from microstructural gradients in transmodal regions, which likely contributes to the flexible role these regions play in human cognition.
Functional analyses of the horizontally acquired Phytophaga glycoside hydrolase family 45 (GH45) proteins reveal distinct functional characteristics
Authors: Busch André , Danchin Etienne G.J. , Pauchet Yannick 
Published: December 2018

AbstractCellulose, a major polysaccharide of the plant cell wall, consists of β-1,4-linked glucose moieties forming a molecular network recalcitrant to enzymatic breakdown. Although cellulose is potentially a rich source of energy, the ability to degrade it is rare in animals and was believed to be present only in cellulolytic microbes. Recently, it has become clear that some animals encode endogenous cellulases belonging to several glycoside hydrolase families (GHs), including GH45. GH45s are distributed patchily among the Metazoa and, in insects, are encoded only by the genomes of Phytophaga beetles. This study aims to understand both the enzymatic properties and the evolutionary history of GH45s in these beetles. To this end, we tested the enzymatic abilities of 37 GH45s derived from five species of Phytophaga beetles and learned that beetle-derived GH45s degrade three different substrates: amorphous cellulose, xyloglucan and glucomannan. Our phylogenetic and gene structure analyses indicate that at least one gene encoding a putative cellulolytic GH45 was present in the last common ancestor of the Phytophaga, and that GH45 xyloglucanases evolved several times independently in these beetles. The most closely related clade to Phytophaga GH45s contained fungal sequences, suggesting this GH family was acquired by horizontal gene transfer from fungi. Other than in insects, arthropod GH45s do not share a common origin and appear to have emerged at least three times independently.
Global increase in circRNA levels in myotonic dystrophy
Authors: Czubak Karol , Taylor Katarzyna , Piasecka Agnieszka , Sobczak Krzysztof , Kozlowska Katarzyna , Philips Anna , Sedehizadeh Saam , Brook J. David , Wojciechowska Marzena , Kozlowski Piotr 
Published: December 2018

AbstractSplicing aberrations induced as a consequence of the sequestration of MBNL splicing factors on the DMPK transcript, which contains expanded CUG repeats, present a major pathomechanism of myotonic dystrophy type 1 (DM1). As MBNLs may also be important factors involved in the biogenesis of circular RNAs (circRNAs), we hypothesized that the level of circRNAs would be decreased in DM1. To test this hypothesis, we selected twenty well-validated circRNAs and analyzed their levels in several experimental systems (e.g., cell lines, DM muscle tissues, and a mouse model of DM1) using droplet digital PCR assays. We also explored the global level of circRNAs using two RNA-Seq datasets of DM1 muscle samples. Contrary to our original hypothesis, our results consistently showed a global increase in circRNA levels in DM1 and we identified numerous circRNAs that were increased in DM1. We also identified many genes (including muscle-specific genes) giving rise to numerous (>10) circRNAs. Thus, this study is the first to show an increase in global circRNA levels in DM1. We also provided preliminary results showing the association of circRNA level with muscle weakness and alternative splicing changes that are biomarkers of DM1 severity.Author SummaryRecently, a great deal of interest has been focused on a new class of RNA molecules called circular RNAs (circRNAs). To date, thousands of circRNAs have been found in different human cells/tissues. Although the function of circRNAs remains mostly unknown, circRNAs have emerged as an important component of the RNA-RNA and RNA-protein interactome. Thus, intensive efforts are being made to fully understand the biology and function of circRNAs, especially their role in human diseases. As an important role in the biogenesis of circRNA may be played by MBNL splicing factors, in this study we used DM1 (to a lesser extent, DM2) as a natural model in which the level of MBNLs is decreased. In contrast to the expected effect, our results consistently showed a global increase in circRNA levels in DM1. As a consequence, whole genome transcriptome analysis revealed dozens of circRNAs with significantly altered (mostly increased) levels in DM1. Furthermore, we observed that the circRNA levels were in many cases strongly associated with DM1 severity.
Extensive genetic differentiation between recently evolved sympatric Arctic charr morphs
Authors: Guðbrandsson Jóhannes , Kapralova Kalina H. , Franzdóttir Sigríður R. , Bergsveinsdóttir Þóra Margrét , Hafstað Völundur , Jónsson Zophonías O. , Snorrason Sigurður S. , Pálsson Arnar 
Published: December 2018

AbstractThe availability of diverse ecological niches can promote adaptation of trophic specializations and related traits, as has been repeatedly observed in evolutionary radiations of freshwater fish. The role of genetics, environment and history in ecologically driven divergence and adaptation, can be studied on adaptive radiations or populations showing ecological polymorphism. Salmonids, especially theSalvelinusgenus, are renowned for both phenotypic diversity and polymorphism. Arctic charr (Salvelinus alpinus) invaded Icelandic streams during the glacial retreat (about 10,000 years ago) and exhibits many instances of sympatric polymorphism. Particularly well studied are the four morphs in Lake Þingvallavatn in Iceland. The small benthic (SB), large benthic (LB), planktivorous (PL) and piscivorous (PI) charr differ in many regards, including size, form and life history traits. To investigate relatedness and genomic differentiation between morphs we identified variable sites from RNA-sequencing data from three of those morphs, and verified 22 variants in population samples. The data reveal genetic differences between the morphs, with the two benthic morphs being more similar and the PL-charr more genetically different. The markers with high differentiation map to all linkage groups, suggesting ancient and pervasive genetic separation of these three morphs. Furthermore, GO analyses suggest differences in collagen metabolism, odontogenesis and sensory systems between PL-charr and the benthic morphs. Genotyping in population samples from all four morphs confirms the genetic separation and indicates that the PI-charr are less genetically distinct than the other three morphs. The genetic separation of the other three morphs indicates certain degree of reproductive isolation. The extent of gene flow between the morphs and the nature of reproductive barriers between them remain to be elucidated.
Reduced Resting-State Connectivity in the Precuneus is correlated with Apathy in Patients with Schizophrenia
Authors: Forlim Caroline Garcia , Klock Leonie , Bächle Johanna , Stoll Laura , Giemsa Patrick , Fuchs Marie , Schoofs Nikola , Montag Christiane , Gallinat Jürgen , Kühn Simone 
Published: December 2018

AbstractA diagnosis of schizophrenia is associated with a heterogeneous psychopathology including positive and negative symptoms. The disconnection hypothesis, an early pathophysiological framework conceptualizes the diversity of symptoms as a result from disconnections in neural networks. In line with this hypothesis, previous neuroimaging studies of patients with schizophrenia reported alterations within the default mode network (DMN), the most prominent network at rest.Aim of the present study was to investigate the functional connectivity during rest in patients with schizophrenia and healthy individuals and explore whether observed functional alterations are related to the psychopathology of patients. Therefore, functional magnetic resonance images at rest were recorded of 35 patients with schizophrenia and 41 healthy individuals. Independent component analysis (ICA) was used to extract resting state networks.Comparing ICA results between groups indicated alterations only within the network of the DMN. More explicitly, reduced connectivity in the precuneus was observed in patients with schizophrenia compared to healthy controls. Connectivity in this area was negatively correlated with the severity of negative symptoms, more specifically with the domain of apathy.Taken together, the current results provide further evidence for a role DMN alterations might play in schizophrenia and especially in negative symptom such as apathy.
Metacommunity-scale biodiversity regulation and the self-organized emergence of macroecological patterns
Authors: O’Sullivan Jacob D. , Knell Robert J. , Rossberg Axel G. 
Published: December 2018

AbstractThere exist a number of key macroecological patterns whose ubiquity suggests the spatio-temporal structure of ecological communities is governed by some universal mechanisms. The nature of these mechanisms, however, remains poorly understood. Here we probe spatio-temporal patterns in species richness and community composition using a simple metacommunity assembly model. Despite making noa prioriassumptions regarding biotic spatial structure or the distribution of biomass across species, model metacommunities self-organize to reproduce well documented patterns including characteristic species abundance distributions, range size distributions and species area relations. Also in agreement with observations, species richness in our model attains an equilibrium despite continuous species turnover. Crucially, it is in the neighbourhood of the equilibrium that we observe the emergence of these key macroecological patterns. Biodiversity equilibria in models occur due to the onset of ecological structural instability, a population-dynamical mechanism. This strongly suggests a causal link between local community processes and macroecological phenomena.Should this manuscript be accepted all simulation data supporting the results will be archived in a public repository and the data DOI will be included at the end of the article
Sound source localization with varying amount of visual information in virtual reality
Authors: Ahrens Axel , Lund Kasper Duemose , Marschall Marton , Dau Torsten 
Published: December 2018

AbstractTo achieve accurate spatial auditory perception, subjects typically require personal head-related transfer functions (HRTFs) and the freedom for head movements. Loudspeaker-based virtual sound environments allow for realism without individualized measurements. To study audio-visual perception in realistic environments, the combination of spatially tracked head mounted displays (HMDs), also known as virtual reality glasses, and virtual sound environments may be valuable. However, HMDs were recently shown to affect the subjects’ HRTFs and thus might influence sound localization performance. Furthermore, due to limitations of the reproduction of visual information on the HMD, audio-visual perception might be influenced. Here, a sound localization experiment was conducted both with and without an HMD and with a varying amount of visual information provided to the subjects. Furthermore, interaural time and level difference errors (ITDs and ILDs) as well as spectral perturbations induced by the HMD were analyzed and compared to the perceptual localization data. The results showed a reduction of the localization accuracy when the subjects were wearing an HMD and when they were blindfolded. The HMD-induced error in azimuth localization was found to be larger in the left than in the right hemisphere. Thus, the errors in ITD and ILD can only partly account for the perceptual differences. When visual information of the limited set of source locations was provided, the localization error induced by the HMD was found to be negligible. Presenting visual information of hand-location, room dimensions, source locations and pointing feedback on the HMD revealed similar effects as previously shown in real environments.
A quantitative inventory of yeast P body proteins reveals principles of composition and specificity
Authors: Xing Wenmin , Muhlrad Denise , Parker Roy , Rosen Michael K. 
Published: December 2018

ABSTRACTP bodies are archetypal biomolecular condensates that concentrate proteins and RNA without a surrounding membrane. While dozens of P body proteins are known, the concentrations of components in the compartment have not been measured. We used live cell imaging to generate a quantitative inventory of the major proteins in yeast P bodies. Only 7 proteins are highly concentrated in P bodies (5.1-15 uM); the 24 others examined are appreciably lower (most ≤ 2.6 uM). P body concentration correlates inversely with cytoplasmic exchange rate. Sequence elements driving Dcp2 concentration into P bodies are distributed across the protein and act cooperatively. Our data indicate that P bodies, and probably other condensates, are biochemically simpler than suggested by proteomic analyses, with implications for specificity, reconstitution and evolution.
Bayesian decision theoretic design of two-founder experimental crosses given diallel data
Authors: Keele Gregory R. , Maurizio Paul L. , Oreper Daniel , Valdar William 
Published: December 2018

ABSTRACTIn designing experimental crosses of inbred strains of model organisms, researchers must make a number of decisions. These include the selection of the appropriate strains, the cross design (eg. F2 intercross), and the number of progeny to collect (sample size). These decisions strongly influence the potential for a successful quantitative trait locus (QTL) mapping experiment; good design decisions will lead to efficient and effective science. Thus experimental design deserves careful consideration and planning. Experimental outcomes can be quantified through utility functions using a Bayesian decision theoretic approaches. For QTL mapping experiments, the power to map a QTL is an appealing utility function to maximize. Using any utility function to aid in experimental design will be dependent on assumptions, such as the QTL effect size in the case of power. Rather than arbitrarily selecting QTL effect size values, they can be estimated from pilot data using a Bayesian hierarchical model. The information in the pilot data can be propagated to the utility function, using Markov Chain Monte Carlo (MCMC) to sample from the posterior distribution. Key features of this approach include: 1) distributional summaries of utility, which are preferable to point estimates, and 2) a comprehensive search of the experimental space of crosses of inbred lines for well-designed experiments. We evaluate this Bayesian theoretic approach using diallel crosses as the pilot data. We present results from simulations as well as present examples from both Mendelian and complex traits in the founder strains of the mouse Collaborative Cross. All analyses were performed using our R package, DIDACT (Diallel-Informed Decision theoretic Approach for Crosses Tool), developed to perform Bayesian cross selection based on diallel pilot data.
MitoZ: A toolkit for mitochondrial genome assembly, annotation and visualization
Authors: Meng Guanliang , Li Yiyuan , Yang Chentao , Liu Shanlin 
Published: December 2018

AbstractMitochondrial genome (mitogenome) plays important roles in evolutionary and ecological studies. It becomes routine to utilize multiple genes on mitogenome or the entire mitogenomes to investigate phylogeny and biodiversity of focal groups with the onset of High Throughput Sequencing technologies. We developed a mitogenome toolkit MitoZ, consisting of independent modules ofde novoassembly, findMitoScaf, annotation and visualization, that can generate mitogenome assembly together with annotation and visualization results from HTS raw reads. We evaluated its performance using a total of 50 samples of which mitogenomes are publicly available. The results showed that MitoZ can recover more full-length mitogenomes with higher accuracy compared to the other available mitogenome assemblers. Overall, MitoZ provides a one-click solution to construct the annotated mitogenome from HTS raw data and will facilitate large scale ecological and evolutionary studies. MitoZ is free open source software distributed under GPLv3 license and available athttps://github.com/linzhi2013/MitoZ.