bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying biosynthetic network robustness across the human oral microbiome
Authors: Bernstein David B. , Dewhirst Floyd E. , Segrè Daniel 
Published: August 2018

AbstractMetabolic interactions, such as cross-feeding, play a prominent role in microbial communitystructure. For example, they may underlie the ubiquity of uncultivated microorganisms. We investigated this phenomenon in the human oral microbiome, by analyzing microbial metabolic networks derived from sequenced genomes. Specifically, we devised a probabilistic biosynthetic network robustness metric that describes the chance that an organism could produce a given metabolite, and used it to assemble a comprehensive atlas of biosynthetic capabilities for 88 metabolites across 456 human oral microbiome strains. A cluster of organisms characterized by reduced biosynthetic capabilities stood out within this atlas. This cluster included several uncultivated taxa and three recently co-culturedSaccharibacteria(TM7) phylum species. Comparison across strains also allowed us to systematically identify specific putative metabolic interdependences between organisms. Our method, which provides a new way of converting annotated genomes into metabolic predictions, is easily extendible to other microbial communities and metabolic products.
Global cooling & the rise of modern grasslands: Revealing cause & effect of environmental change on insect diversification dynamics
Authors: Davis Katie E. , Bakewell Adam T. , Hill Jon , Song Hojun , Mayhew Peter 
Published: August 2018

AbstractUtilising geo-historical environmental data to disentangle cause and effect in complex natural systems is a major goal in our quest to better understand how climate change has shaped life on Earth. Global temperature is known to drive biotic change over macro-evolutionary time-scales but the mechanisms by which it acts are often unclear. Here, we model speciation rates for Orthoptera within a phylogenetic framework and use this to demonstrate that global cooling is strongly correlated with increased speciation rates. Transfer Entropy analyses reveal the presence of one or more additional processes that are required to explain the information transfer from global temperature to Orthoptera speciation. We identify the rise of C4grasslands as one such mechanism operating from the Miocene onwards. We therefore demonstrate the value of the geological record in increasing our understanding of climate change on macro-evolutionary and macro-ecological processes.
Molecular flexibility of DNA as a key determinant of RAD51 recruitment
Authors: Paoletti Federico , El-Sagheer Afaf , Allard Jun , Brown Tom , Dushek Omer , Esashi Fumiko 
Published: August 2018

AbstractThe timely activation of homologous recombination is essential for the maintenance of genome stability, in which the RAD51 recombinase plays a central role. Biochemically, human RAD51 polymerises faster on single-stranded DNA (ssDNA) compared to double-stranded DNA (dsDNA), raising a key conceptual question: how does it discriminate between them? In this study, we tackled this problem by systematically assessing RAD51 binding kinetics on ssDNA and dsDNA differing in length and flexibility using surface plasmon resonance. By fitting detailed polymerisation models informed by our experimental datasets, we show that RAD51 is a mechano-sensor that exhibits a larger polymerisation rate constant on flexible ssDNA compared to rigid ssDNA or dsDNA. This model presents a new general framework suggesting that the flexibility of DNA, which may increase locally as a result of DNA damage, plays an important role in rapidly recruiting repair factors that multimerise at sites of DNA damage.
Cell Diameter inBacillus subtilisis Determined by the Opposing Actions of Two Distinct Cell Wall Synthetic Systems
Authors: Dion Michael F. , Kapoor Mrinal , Sun Yingjie , Wilson Sean , Ryan Joel , Vigouroux Antoine , Teeffelen Sven van , Oldenbourg Rudolf , Garner Ethan C. 
Published: August 2018

AbstractRod shaped bacteria grow by adding material into their cell wall via the action of two spatially distinct enzymatic systems: The Rod system moves around the cell circumference, while the class A penicillin-binding proteins (aPBPs) are unorganized. To understand how the combined action of these two systems defines bacterial dimensions, we examined how each system affects the growth and width ofBacillus subtilis, as well as the mechanical anisotropy and orientation of material within their sacculi. We find that rod diameter is not determined by MreB, rather it depends on the balance between the systems: The Rod system reduces diameter, while aPBPs increase it. RodA/PBP2A can both thin or widen cells, depending on its levels relative to MreBCD. Increased Rod system activity correlates with an increased density of directional MreB filaments, and a greater fraction of directionally moving PBP2A molecules. This increased circumferential synthesis increases the amount of oriented material within the sacculi, increasing their mechanical anisotropy and reinforcing rod shape. Together, these experiments explain how the combined action of the two main cell wall synthetic systems build rods of different widths, a model that appears generalizable:Escherichia colicontaining Rod system mutants show the same relationship between the density of directionally moving MreB filaments and cell width.
Functional dissection of theARGONAUTE7promoter
Authors: Hoyer J. Steen , Pruneda-Paz Jose L. , Breton Ghislain , Hassert Mariah A. , Holcomb Emily E. , Fowler Halley , Bauer Kaylyn M. , Mreen Jacob , Kay Steve A. , Carrington James C. 
Published: August 2018

AbstractARGONAUTES are the central effector proteins of RNA silencing which bind target transcripts in a small RNA-guided manner.Arabidopsis thalianahas tenARGONAUTE(AGO) genes, with specialized roles in RNA-directed DNA methylation, post-transcriptional gene silencing, and antiviral defense. To better understand specialization amongAGOgenes at the level of transcriptional regulation we tested a library of 1497 transcription factors for binding to the promoters ofAGO1, AGO10, andAGO7using yeast 1-hybrid assays. A ranked list of candidate DNA-binding TFs revealed binding of theAGO7promoter by a number of proteins in two families: the miR156-regulated SPL family and the miR319-regulated TCP family, both of which have roles in developmental timing and leaf morphology. Possible functions for SPL and TCP binding are unclear: we showed that these binding sites are not required for the polar expression pattern ofAGO7, nor for the function ofAGO7in leaf shape. NormalAGO7transcription levels and function appear to depend instead on an adjacent 124-bp region. Progress in understanding the structure of this promoter may aid efforts to understand how the conserved AGO7-triggeredTAS3pathway functions in timing and polarity.
Global climate changes will lead to regionally divergent trajectories for ectomycorrhizal communities in North American Pinaceae forests
Authors: Steidinger Brian S. , Bhatnagar Jennifer M. , Vilgalys Rytas , Taylor John W. , Bruns Thomas D. , Peay Kabir G. 
Published: August 2018

AbstractEctomycorrhizal fungi (ECMF) are partners in a globally distributed tree symbiosis that enhanced ecosystem carbon (C)-sequestration and storage. However, resilience of ECMF to future climates is uncertain. We sampled ECMF across a broad climatic gradient in North America, modeled climatic drivers of diversity and community composition, and then forecast ECMF response to climate changes over the next 50 years. We predict ECMF richness will decline over nearly half of North American Pinaceae forests, with median species losses as high as 21%. Mitigation of greenhouse gas emissions can reduce these declines, but not prevent them. Warming of forests along the boreal-temperate ecotone results in projected ECMF species loss and declines in the relative abundance of C demanding, long-distance foraging ECMF species, but warming of eastern temperate forests has the opposite effect. Sites with more ECMF species had higher activities of nitrogen-mineralizing enzymes, suggesting that ECMF species-losses will compromise their associated ecosystem functions.
Decoding semantic predictions from EEG prior to word onset
Authors: Heikel Edvard , Sassenhagen Jona , Fiebach Christian J. 
Published: August 2018

ABSTRACTThe outstanding speed of language comprehension necessitates a highly efficient implementation of cognitive-linguistic processes. The domain-general theory of Predictive Coding suggests that our brain solves this problem by continuously forming linguistic predictions about expected upcoming input. The neurophysiological implementation of these predictive linguistic processes, however, is not yet understood. Here, we use EEG (human participants, both sexes) to investigate the existence and nature of online-generated, category-level semantic representations during sentence processing. We conducted two experiments in which some nouns – embedded in a predictive spoken sentence context – were unexpectedly delayed by 1 second. Target nouns were either abstract/concrete (Experiment 1) or animate/inanimate (Experiment 2). We hypothesized that if neural prediction error signals following (temporary) omissions carry specific information about the stimulus, the semantic category of the upcoming target word is encoded in brain activity prior to its presentation. Using time-generalized multivariate pattern analysis, we demonstrate significant decoding of word category from silent periods directly preceding the target word, in both experiments. This provides direct evidence for predictive coding during sentence processing, i.e., that information about a word can be encoded in brain activity before it is perceived. While the same semantic contrast could also be decoded from EEG activity elicited by isolated words (Experiment 1), the identified neural patterns did not generalize to pre-stimulus delay period activity in sentences. Our results not only indicate that the brain processes language predictively, but also demonstrate the nature and sentence-specificity of category-level semantic predictions preactivated during sentence comprehension.STATEMENT OF SIGNIFICANCEThe speed of language comprehension necessitates a highly efficient implementation of cognitive-linguistic processes. Predictive processing has been suggested as a solution to this problem, but the underlying neural mechanisms and linguistic content of such predictions are only poorly understood. Inspired by Predictive Coding theory, we investigate whether the meaning of expected, but not-yet heard words can be decoded from brain activity. Using EEG, we can predict if a word is, e.g., abstract (as opposed to concrete), or animate (vs. inanimate), from brain signals preceding the word itself. This strengthens predictive coding theory as a likely candidate for the principled neural mechanisms underlying online processing of language and indicates that predictive processing applies to highly abstract categories like semantics.
Gene silencing by double-stranded RNA fromC. elegansneurons reveals functional mosaicism of RNA interference
Authors: Ravikumar Snusha , Devanapally Sindhuja , Jose Antony M 
Published: August 2018

ABSTRACTDelivery of double-stranded RNA (dsRNA) into animals can silence genes of matching sequence in diverse cell types through mechanisms that have been collectively called RNA interference. In the nematodeC. elegans, dsRNA from multiple sources can trigger the amplification of silencing signals. Amplification occurs through the production of small RNAs by two RNA-dependent RNA polymerases (RdRPs) that are thought to be tissue-specific - EGO-1 in the germline and RRF-1 in somatic cells. Here we analyze instances of silencing in somatic cells that lack RRF-1. By varying dsRNA sources and target genes, we find that silencing in the absence of RRF-1 is most obvious when dsRNA from neurons is used to silence genes in intestinal cells. This silencing requires EGO-1, but the lineal identity of cells that can use EGO-1 varies. This variability could be because random sets of cells can either receive different amounts of dsRNA from the same source or use different RdRPs to perform the same function. As a result, all cells appear similarly functional despite underlying differences that vary from animal to animal. This functional mosaicism cautions against the use of a few molecules as proxies for predicting the behavior of a cell.Graphical AbstractRandom sets of cells can either receive different amounts of double-stranded RNA from neurons or use different RdRPs – RRF-1 only versus RRF-1 or EGO-1 – to perform the same function.
The perils of intralocus recombination for inferences of molecular convergence
Authors: Mendes Fábio K. , Livera Andrew , Hahn Matthew W. 
Published: August 2018

AbstractAccurate inferences of convergence require that the appropriate tree topology be used. If there is a mismatch between the tree a trait has evolved along and the tree used for analysis, then false inferences of convergence (“hemiplasy”) can occur. To avoid problems of hemiplasy when there are high levels of gene tree discordance with the species tree, researchers have begun to construct tree topologies from individual loci. However, due to intralocus recombination even locus-specific trees may contain multiple topologies within them. This implies that the use of individual tree topologies discordant with the species tree can still lead to incorrect inferences about molecular convergence. Here we examine the frequency with which single exons and single protein-coding genes contain multiple underlying tree topologies, in primates and Drosophila, and quantify the effects of hemiplasy when using trees inferred from individual loci. In both clades we find that there are most often multiple diagnosable topologies within single exons and whole genes, with 91% of Drosophila protein-coding genes containing multiple topologies. Because of this underlying topological heterogeneity, even using trees inferred from individual protein-coding genes results in 25% and 38% of substitutions falsely labeled as convergent in primates and Drosophila, respectively. While constructing local trees can reduce the problem of hemiplasy, our results suggest that it will be difficult to completely avoid false inferences of convergence. We conclude by suggesting several ways forward in the analysis of convergent evolution, for both molecular and morphological characters.
FastqCleaner: an interactive Bioconductor application for quality-control, filtering and trimming of FASTQ files
Authors: Roser Leandro Gabriel , Agüero Fernán , Sánchez Daniel Oscar 
Published: August 2018

AbstractBackgroundExploration and processing of FASTQ files are the first steps in state-of-the-art data analysis workflows of Next Generation Sequencing (NGS) platforms. The large amount of data generated by these technologies has put a challenge in terms of rapid analysis and visualization of sequencing information. Recent integration of the R data analysis platform with web visual frameworks has stimulated the development of user-friendly, powerful, and dynamic NGS data analysis applications.ResultsThis paper presents FastqCleaner, a Bioconductor visual application for both quality-control (QC) and pre-processing of FASTQ files. The interface shows diagnostic information for the input and output data and allows to select a series of filtering and trimming operations in an interactive framework. FastqCleaner combines the technology of Bioconductor for NGS data analysis with the data visualization advantages of a web environment.ConclusionsFastqCleaner is an user-friendly, offline-capable tool that enables access to advanced Bioconductor infrastructure. The novel concept of a Bioconductor interactive application that can be used without the need for programming skills, makes FastqCleaner a valuable resource for NGS data analysis.
MyocardialNotch-Rbpjdeletion does not affect heart development or function
Authors: Salguero-Jiménez Alejandro , Grego-Bessa Joaquim , D’Amato Gaetano , Jiménez-Borreguero Luis J. , Pompa José Luis de la 
Published: August 2018

AbstractDuring vertebrate cardiac development NOTCH signaling activity in the endocardium is essential for the crosstalk between endocardium and myocardium that initiates ventricular trabeculation and valve primordium formation. This crosstalk leads later to the maturation and compaction of the ventricular chambers and the morphogenesis of the cardiac valves, and its alteration may lead to disease. Although endocardial NOTCH signaling has been shown to be crucial for heart development, its physiological role in the myocardium has not been clearly established. Here we have used a genetic strategy to evaluate the role of NOTCH in myocardial development. We have inactivated the unique and ubiquitous NOTCH effector RBPJ in the early cardiomyocytes progenitors, and examined its consequences in cardiac development and function. Our results demonstrate that mice withcTnT-Cre-mediated myocardial-specific deletion ofRbpjdevelop to term, with homozygous mutant animals showing normal expression of cardiac development markers, and normal adult heart function. Similar observations have been obtained afterNotch1deletion withcTnT-Cre. We have also deletedRbpjin both myocardial and endocardial progenitor cells, using theNkx2.5-Credriver, resulting in ventricular septal defect (VSD), double outlet right ventricle (DORV), and bicuspid aortic valve (BAV), due to NOTCH signaling abrogation in the endocardium of cardiac valves territories. Our data demonstrate that NOTCH-RBPJ inactivation in the myocardium does not affect heart development or adult cardiac function.
Reducing tau ameliorates behavioural and transcriptional deficits in a novel model of Alzheimer’s disease
Authors: Pickett Eleanor K , Herrmann Abigail G , McQueen Jamie , Abt Kimberly , Dando Owen , Tulloch Jane , Jain Pooja , Dunnett Sophie , Sohrabi Sadaf , Fjeldstad Maria , Calkin Will , Murison Leo , Jackson Rosemary , Tzioras Makis , Stevenson Anna , D’Orange Marie , Hooley Monique , Davies Caitlin , Oren Iris , Rose Jamie , McKenzie Chris-Anne , Allison Elizabeth , Smith Colin , Hardt Oliver , Henstridge Christopher M , Hardingham Giles , Spires-Jones Tara L. 
Published: August 2018

SummaryOne of the key knowledge gaps blocking development of effective therapeutics for Alzheimer’s disease (AD) is the lack of understanding of how amyloid beta (Aβ) and tau cooperate in causing disease phenotypes. Within a mouse tau deficient background, we probed the molecular, cellular and behavioural disruption triggered by wild-type human tau’s influence on human Aβ-induced pathology. We find that Aβ and tau work cooperatively to cause a hyperactivity phenotype and to cause downregulation of gene transcription including many involved in synaptic function. In both our mouse model and in human post-mortem tissue, we observe accumulation of pathological tau in synapses, supporting the potential importance of synaptic tau. Importantly, tau depletion in the mice, initiated after behavioural deficits emerge, was found to correct behavioural deficits, reduce synaptic tau levels, and substantially reverse transcriptional perturbations, suggesting that lowering tau levels, particularly at the synapse, may be beneficial in AD.Highlights- Expression of human familial Alzheimer’s associated mutant amyloid precursor protein and presenillin 1 with wild-type human tau in the absence of endogenous tau in a novel MAPT-AD mouse model results in behavioural deficits and downregulation of genes involved in synaptic function.- Tau is present in pre and postsynaptic terminals in MAPT-AD mice and human AD brain. In mice, lowering synaptic tau levels was associated with improved cognition and recovered gene expression.- These data suggest that Aβ and tau act cooperatively in impairing synaptic function and that lowering tau at synapses could be a beneficial therapeutic approach in AD.
NGseqBasic - a single-command UNIX tool for ATAC-seq, DNaseI-seq, Cut-and-Run, and ChIP-seq data mapping, high-resolution visualisation, and quality control
Authors: Telenius Jelena ,   The WIGWAM Consortium, Hughes Jim R. 
Published: August 2018

ABSTRACTWith decreasing cost of next-generation sequencing (NGS), we are observing a rapid rise in the volume of ‘big data’ in academic research, healthcare and drug discovery sectors. The present bottleneck for extracting value from these ‘big data’ sets is data processing and analysis. Considering this, there is still a lack of reliable, automated and easy to use tools that will allow experimentalists to assess the quality of the sequenced libraries and explore the data first hand, without the need of investing a lot of time of computational core analysts in the early stages of analysis.NGseqBasic is an easy-to-use single-command analysis tool for chromatin accessibility (ATAC, DNaseI) and ChIP sequencing data, providing support to also new techniques such as low cell number sequencing and Cut-and-Run. It takes in fastq, fastq.gz or bam files, conducts all quality control, trimming and mapping steps, along with quality control and data processing statistics, and combines all this to a single-click loadable UCSC data hub, with integral statistics html page providing detailed reports from the analysis tools and quality control metrics. The tool is easy to set up, and no installation is needed. A wide variety of parameters are provided to fine-tune the analysis, with optional setting to generate DNase footprint or high resolution ChIP-seq tracks. A tester script is provided to help in the setup, along with a test data set and downloadable example user cases.NGseqBasic has been used in the routine analysis of next generation sequencing (NGS) data in high-impact publications 1,2. The code is actively developed, and accompanied with Git version control and Github code repository. Here we demonstrate NGseqBasic analysis and features using DNaseI-seq data from GSM689849, and CTCF-ChIP-seq data from GSM2579421, as well as a Cut-and-Run CTCF data set GSM2433142, and provide the one-click loadable UCSC data hubs generated by the tool, allowing for the ready exploration of the run results and quality control files generated by the tool.AvailabilityDownload, setup and help instructions are available on the NGseqBasic web site http://userweb.molbiol.ox.ac.uk/public/telenius/NGseqBasicManual/external/Bioconda users can load the tool as library “ngseqbasic”. The source code with Git version control is available in https://github.com/Hughes-Genome-Group/NGseqBasic/releases.Contactjelena.telenius@imm.ox.ac.uk
Saccharomyces cerevisiae displays a stable transcription start site landscape in multiple conditions
Authors: Börlin Christoph S. , Cvetesic Nevena , Holland Petter , Bergenholm David , Siewers Verena , Lenhard Boris , Nielsen Jens 
Published: August 2018

ABSTRACTOne of the fundamental processes that determine cellular fate is regulation of gene transcription. Understanding these regulatory processes is therefore essential for understanding cellular responses to changes in environmental conditions. At the core promoter, the regulatory region containing the transcription start site (TSS), all inputs regulating transcription are integrated. Here, we used Cap Analysis of Gene Expression (CAGE) to analyze the pattern of transcription start sites at four different environmental conditions (limited in ethanol, limited in nitrogen, limited in glucose and limited in glucose under anaerobic conditions) using the Saccharomyces cerevisiae strain CEN.PK113-7D. With this experimental setup we were able to show that the TSS landscape in yeast is stable at different metabolic states of the cell. We also show that the shape index, a characteristic feature of each TSS describing the spatial distribution of transcription initiation events, has a surprisingly strong negative correlation with the measured expression levels. Our analysis supplies a set of high quality TSS annotations useful for metabolic engineering and synthetic biology approaches in the industrially relevant laboratory strain CEN.PK113-7D, and provides novel insights into yeast TSS dynamics and gene regulation.