bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional studies of the RBPJ-SHARP complex reveal conserved corepressor binding site
Authors: Yuan Zhenyu , VanderWielen Bradley D. , Giaimo Benedetto Daniele , Pan Leiling , Collins Courtney E. , Turkiewicz Aleksandra , Hein Kerstin , Oswald Franz , Borggrefe Tilman , Kovall Rhett A. 
Published: May 2018

AbstractThe Notch pathway is a conserved signaling mechanism that is essential for cell fate decisions during pre and postnatal development. Dysregulated signaling underlies the pathophysiology of numerous human diseases, most notably T-cell acute lymphoblastic leukemia. Receptor-ligand interactions result in changes in gene expression, which are regulated by the transcription factor CSL. CSL forms a complex with the intracellular domain of the Notch receptor and the transcriptional coactivator Mastermind, which is required to activate transcription of all Notch target genes. CSL can also function as repressor by interacting with corepressor proteins, e.g. SHARP in mammals and Hairless in Drosophila melanogaster; however, its role as a transcriptional repressor is not well understood. Here we determine the high-resolution structure of RBPJ, the mouse CSL ortholog, bound to the corepressor SHARP and DNA, which reveals a new mode of corepressor binding to CSL and an interesting example for how ligand binding sites evolve in proteins. Based on the structure, we designed and tested a number of mutants in biophysical, biochemical, and cellular assays to characterize the role of RBPJ as a repressor of Notch target genes. Our cellular studies clearly demonstrate that RBPJ mutants that are deficient for binding SHARP are incapable of repressing transcription from genes responsive to Notch signaling. Altogether, our structure-function studies of the RBPJ-SHARP corepressor complex bound to DNA provide significant insights into the repressor function of RBPJ and identify a new binding pocket on RBPJ that could be targeted for therapeutic benefit.
Extensive and deep sequencing of the Venter/HuRef genome for developing and benchmarking genome analysis tools
Authors: Zhou Bo , Arthur Joseph G. , Ho Steve S. , Pattni Reenal , Huang Yiling , Wong Wing H. , Urban Alexander E. 
Published: May 2018

ABSTRACTWe produced an extensive collection of deep re-sequencing datasets for the Venter/HuRef genome using the Illumina massively-parallel DNA sequencing platform. The original Venter genome sequence is a very-high quality phased assembly based on Sanger sequencing. Therefore, researchers developing novel computational tools for the analysis of human genome sequence variation for the dominant Illumina sequencing technology can test and hone their algorithms by making variant calls from these Venter/HuRef datasets and then immediately confirm the detected variants in the Sanger assembly, freeing them of the need for further experimental validation. This process also applies to implementing and benchmarking existing genome analysis pipelines. We prepared and sequenced 200 bp and 350 bp short-insert whole-genome sequencing libraries (sequenced to 100x and 40x genomic coverages respectively) as well as 2 kb, 5 kb, and 12 kb mate-pair libraries (49x, 122x, and 145x physical coverages respectively). Lastly, we produced a linked-read library (128x physical coverage) from which we also performed haplotype phasing.
Connecting the dots between computational tools to analyse soil-root water relations
Authors: Passot Sixtine , Couvreur Valentin , Meunier Félicien , Draye Xavier , Javaux Mathieu , Leitner Daniel , Pagès Loïc , Schnepf Andrea , Vanderborght Jan , Lobet Guillaume 
Published: May 2018

AbstractIn the recent years, many computational tools, such as image analysis, data management, process-based simulation and upscaling tools, were developed to help quantify and understand water flow in the soil-root system, at multiple scales (tissue, organ, plant and population). Several of these tools work together or, at least, are compatible. However, for the un-informed researcher, they might seem disconnected, forming a unclear and disorganised succession of tools.In this article, we present how different pieces of work can be further developed by connecting them to analyse soil-root-water relations in a comprehensive and structured network. This “explicit network of soil-root computational tools” informs the reader about existing tools and help them understand how their data (past and future) might fit within the network. We also demonstrate the novel possibilities of scale-consistent parameterizations made possible by the network with a set of case studies from the literature. Finally, we discuss existing gaps in the network and how we can move forward to fill them.HighlightsMany computational tools exist to quantify water flow in the soil-root system. These tools can be arranged in a comprehensive network that can be leveraged to better interpret experimental data.
Finding informative neurons in the brain using Multi-Scale Relevance
Authors: Cubero Ryan John , Marsili Matteo , Roudi Yasser 
Published: May 2018

AbstractWe propose a metric – called Multi-Scale Relevance (MSR) – to score neurons for their prominence in encoding for the animal’s behaviour that is being observed in a multi-electrode array recording experiment. The MSR assumes that relevant neurons exhibit a wide variability in their dynamical state, in response to the external stimulus, across different time scales. It is a non-parametric, fully featureless indicator, in that it uses only the time stamps of the firing activity, without resorting to any a priori covariate or invoking any specific tuning curve for neural activity. We test the method on data from freely moving rodents, where we found that neurons having low MSR tend to have low mutual information and low firing sparsity across the correlates that are believed to be encoded by the region of the brain where the recordings were made. In addition, neurons with high MSR contain significant information on spatial navigation and allow to decode spatial position or head direction as efficiently as those neurons whose firing activity has high mutual information with the covariate to be decoded.
The Complete Chloroplast Genome of Dendrobium nobile, an endangered medicinal orchid from Northeast India and its comparison with related chloroplast genomes of Dendrobium species
Authors: Konhar Ruchishree , Debnath Manish , Bhattacharjee Atanu , Sundar Durai , Tandon Pramod , Dash Debasis , Biswal Devendra Kumar 
Published: May 2018

AbstractThe medicinal orchid genus Dendrobium belonging to the Orchidaceae family is the largest genus comprising about 800-1500 species. To better illustrate the species status in the genus Dendrobium, a comparative analysis of 33 newly sequenced chloroplast genomes retrieved from NCBI Refseq database was compared with that of the first complete chloroplast genome of D. nobile from north-east India based on next-generation sequencing methods (Illumina HiSeq 2500-PE150). Our results provide comparative chloroplast genomic information for taxonomical identification, alignment-free phylogenomic inference and other statistical features of Dendrobium plastomes, which can also provide valuable information on their mutational events and sequence divergence.
Effects of Xiantao sewage treatment on microbial community structure of shallow groundwater in wetland
Authors: Song Shu-Fen , Gao Xiu-Fang , Yang Fan 
Published: May 2018

AbstractIn order to solve the problem of urban domestic sewage treated by semi natural wetland method with high connectivity between surface water and underground water in the flood diversion channel, Whether there is a blank study on the pollution of shallow groundwater. The community structure and abundances of CODCr, total nitrogen, total phosphorus and microorganism were added to the surface water. Environmental factors such as CODCr, TN, TP, NH4+-N and microbial community and abundance indices were monitored through surface water and groundwater. In this study, physical and chemical indicators, microbial diversity and community structure of 12 water samples from Xiantao artificial wetland were studied by using the Illumina Miseq sequencing technique and the resulting microbial data were statistically analyzed in combination with environmental variables. The results showed that CODCr concentration had a very significant positive correlation with total microbial communities (r=0.530, P<0.01), NH4+-N and TN were significantly positively correlated (r=0.337 and 0.325, P<0.05). In addition, CODCr concentration was highly positively correlated with abundant groups (r=0.520, P<0.05), NH4+-N and TN were significantly positively correlated (r=0.325 and 0.304, P<0.05). For rare taxa, they might be more sensitive to the environment than their abundant groups. The relative abundance of the rare group is 0 at the depth of 10m, so we should carefully evaluate microbial reaction (rare group) environmental conditions in the future.
Epidemiology, Microbiology and Therapeutic Consequences of Chronic Osteomyelitis in Northern China: A Retrospective Analysis of 255 Patients
Authors: Ma Xianzhi , Han Shengshou , Ma Jun , Chen Xiaotao , Bai Wenbin , Yan Wenqi , Wang Kai 
Published: May 2018

AbstractThe study aimed to explore the epidemiology and clinical characteristics of chronic osteomyelitis observed in a northern China hospital. Clinical data of 255 patients with chronic osteomyelitis from January 2007 to January 2014 were collected and analyzed, including general information, disease data, treatment and follow-up data. Chronic osteomyelitis is more common in males and in the age group from 41-50 years of age. Common infection sites are the femur, tibiofibular, and hip joint. More g+ than g- bacterial infections were observed, with S. aureus the most commonly observed pathogenic organism. The positive detection rate from debridement bacterial culture is 75.6%. The detection rate when five samples are sent for bacterial culture is 90.6%, with pathogenic bacteria identified in 82.8% of cases. The two-stage debridement method (87.0%) has higher first curative rate than the one-stage debridement method (71.2%). To improve detection rate using bacterial culture, at least five samples are recommended. Treatment of chronic osteomyelitis with two-stage debridement, plus antibiotic-loaded polymethylmethacrylate (PMMA) beads provided good clinical results in this study and is therefore recommended.
Sarek: A portable workflow for whole-genome sequencing analysis of germline and somatic variants
Authors: Garcia Maxime , Juhos Szilveszter , Larsson Malin , Olason Pall I. , Martin Marcel , Eisfeldt Jesper , DiLorenzo Sebastian , Sandgren Johanna , de Ståhl Teresita Diaz , Wirta Valtteri , Nistér Monica , Nystedt Björn , Käller Max 
Published: May 2018

AbstractSummaryWhole-genome sequencing (WGS) is a cornerstone of precision medicine, but portable and reproducible open-source workflows for WGS analyses of germline and somatic variants are lacking. We present Sarek, a modular, comprehensive, and easy-to-install workflow, combining a range of software for the identification and annotation of single-nucleotide variants (SNVs), insertion and deletion variants (indels), structural variants, tumor sample heterogeneity, and karyotyping from germline or paired tumor/normal samples. Sarek is implemented in a bioinformatics workflow language (Nextflow) with Docker and Singularity compatible containers, ensuring easy deployment and full reproducibility at any Linux based compute cluster or cloud computing environment. Sarek supports the human reference genomes GRCh37 and GRCh38, and can readily be used both as a core production workflow at sequencing facilities and as a powerful stand-alone tool for individual research groups.AvailabilitySource code and instructions for local installation are available at GitHub (https://github.com/SciLifeLab/Sarek) under the MIT open-source license, and we invite the research community to contribute additional functionality as a collaborative open-source development project.
Improved estimation of macroevolutionary rates from fossil data using a Bayesian framework
Authors: Silvestro Daniele , Antonelli Alexandre , Salamin Nicolas , Meyer Xavier 
Published: May 2018

AbstractThe estimation of origination and extinction rates and their temporal variation is central to understanding diversity patterns and the evolutionary history of clades. The fossil record provides the most direct evidence of extinction and biodiversity changes through time and has long been used to infer the dynamics of diversity changes in deep time. The software PyRate implements a Bayesian framework to analyze fossil occurrence data to estimate the rates of preservation, origination and extinction while incorporating several sources of uncertainty. This fully probabilistic approach allows us to explicitly assess the statistical support of alternative macroevolutionary hypotheses and to infer credible intervals around parameter estimates. Here, we present a major update of the software, which implements substantial methodological advancements, including more complex and realistic models of preservation, a reversible jump Markov chain Monte Carlo algorithm to estimate origination and extinction rates and their temporal variation, and a substantial boost in performance. We demonstrate the new functionalities through extensive simulations and with the analysis of a large dataset of Cenozoic marine mammals. We identify several significant shifts in origination and extinction rates of marine mammals, underlying a late Miocene diversity peak and a subsequent 50% diversity decline towards the present. Our analyses indicate that explicit statistical model testing, which is often neglected in fossil-based macroevolutionary analyses, is crucial to obtain accurate and robust results. PyRate provides a flexible, statistically sound analytical framework, which we think can serve as a useful toolkit for many future studies in paleobiology.
Chronic starvation induces non-canonical pro-death stress granules
Authors: Reineke Lucas C. , Cheema Shebna A. , Dubrulle Julien , Neilson Joel R. 
Published: May 2018

AbstractStress granules (SGs) assemble under stress-induced conditions that inhibit protein synthesis, including eIF2α phosphorylation, inhibition of the RNA helicase eIF4a, or inactivation of mTORC1. Classically defined SGs are composed of translation initiation factors, 40S ribosomes, RNA binding proteins, and poly(A)+ mRNAs, and as such represent an important compartment for storage of mRNAs and regulation of their translation. Emerging work on SGs indicates they may play important roles in cancer, neurodegenerative disease, and viral infection, often promoting survival. Yet much previous work on SGs formation and function has employed acute stress conditions, which may not accurately reflect the chronic stresses that manifest in human disease. We used prolonged nutrient starvation to investigate SG formation and function during chronic stress. Surprisingly, SGs that form under chronic nutrient starvation lack 40S ribosomes, do not actively exchange their constituent components with cytoplasmic pools, and promote cell death. These results imply that SG assembly and function in the context of prolonged nutrient starvation stress differ significantly from what has been described for acute stress conditions.Summary StatementThis work characterizes the mechanisms of formation of a novel type of stress granule that is induced in response to long-term starvation, and unlike previously described stress granules, functions in a pro-death capacity.
Unexpected versatility in the metabolism and ecophysiology of globally relevant nitrite-oxidizingNitrotogabacteria
Authors: Boddicker Andrew M. , Mosier Annika C. 
Published: May 2018

ABSTRACTNitrite-oxidizing bacteria (NOB) play a critical role in the mitigation of nitrogen pollution from freshwater systems by metabolizing nitrite to nitrate, which is removed via assimilation, denitrification, or anammox. Recent studies revealed that NOB are phylogenetically and metabolically diverse, yet most of our knowledge of NOB comes from only a few cultured representatives. Using enrichment methods and genomic sequencing, we identified four novelCandidatusNitrotoga NOB species from freshwater sediments and water column samples in Colorado, USA. Genome assembly revealed highly conserved 16S rRNA gene sequences, but a surprisingly broad metabolic potential including genes for nitrogen, sulfur, hydrogen, and organic carbon metabolism. Genomic predictions suggest thatNitrotogacan metabolize in low oxygen or anaerobic conditions, which may support a previously unrecognized environmental niche. An array of antibiotic and metal resistance genes likely allowsNitrotogato withstand environmental pressures in impacted systems. Phylogenetic analyses reveal a deeply divergent nitrite oxidoreductase alpha subunit (NxrA) not represented in any other NOB, suggesting a novel evolutionary trajectory forNitrotoga.Nitrotoga-like 16S rRNA gene sequences were prevalent in globally distributed environments. This work considerably expands our knowledge of theNitrotogagenus and improves our understanding of their role in the global nitrogen cycle.
Easily phylotyping E. coli via the EzClermont web app and command-line tool
Authors: Waters Nicholas R. , Abram Florence , Brennan Fiona , Holmes Ashleigh , Pritchard Leighton 
Published: May 2018

SummaryThe Clermont PCR method of phylotyping Escherichia coli has remained a useful classification scheme despite the proliferation of higher-resolution sequence typing schemes. We have implemented an in silico Clermont PCR method as both a web app and as a command-line tool to allow researchers to easily apply this phylotyping scheme to genome assemblies easily.Availability and ImplementationEzClermont is available as a web app at http://www.ezclermont.org. For local use, EzClermont can be installed with pip or installed from the source code at https://github.com/nickp60/ezclermont. All analysis was done with version 0.4.0.Contactn.waters4@nuigalway.ie, leighton.pritchard@strath.ac.ukSupplementary informationTable S1: test dataset; S2: validation dataset; S3: results.
A legacy role for DNA binding of Lon protects against genotoxic stress
Authors: Zeinert Rilee D. , Ogdahl Justyne L. , Liu Jing , Yang Qiyuan , Du Yunguang , Barros Benjamin B. , Freddolino Peter L. , Haynes Cole M. , Chien Peter 
Published: May 2018

AbstractDNA binding proteins are essential for cellular life, but persistently bound complexes have toxic consequences. Here we show that the proteotoxic responsive bacterial protease Lon clears proteins from DNA to promote genotoxic stress resistance. Purified Lon binds DNA and degrades neighboring bound proteins, while a fully active DNA-blind Lon variant does not. This variant can degrade substrates as normal during unstressed growth, complements pleotropic phenotypes of Δlon, including proteotoxic resilience, but remains sensitive to genotoxic stresses and fails to degrade proteins efficiently during DNA damage. Transposon sequencing reveals that Δlonis vulnerable to loss of protein-DNA eviction factors and we use dynamic nucleoid occupancy profiling to show that chromosome-wide protein turnover relies on Lon DNA binding. Finally, disrupting Lon binding to mitochondria genomes also results in genotoxic stress sensitivity, consistent with the bacterial ancestry of this organelle. We propose that clearance of persistent proteins from DNA by Lon originated in free-living α-proteobacteria and maintained during the evolution of mitochondria.SummaryDNA binding by the Lon protease protects against genotoxic damage in a manner preserved from bacteria to mitochondria.
How Much Information is Provided by Human Epigenomic Data? An Evolutionary View
Authors: Gulko Brad , Siepel Adam 
Published: May 2018

ABSTRACTHere, we ask the question, “How much information do available epigenomic data sets provide about human genomic function, individually or in combination?” We consider nine epigenomic and annotation features across 115 cell types and measure genomic function by using signatures of natural selection as a proxy. We measure information as the reduction in entropy under a probabilistic evolutionary model that describes genetic variation across ∼50 diverse humans and several nonhuman primates. We find that several genomic features yield more information in combination than they do individually, with DNase-seq displaying particularly strong synergy. Most of the entropy in human genetic variation, by far, reflects mutation and neutral drift; the genome-wide reduction in entropy due to selection is equivalent to only a small fraction of the storage requirements of a single human genome. Based on this framework, we produce cell-type-specific maps of the probability that a mutation at each nucleotide will have fitness consequences (FitCons scores). These scores are predictive of known functional elements and disease-associated variants, they reveal relationships among cell types, and they suggest that ∼8% of nucleotide sites are constrained by natural selection.
N-terminal degradation activates the Nlrp1b inflammasome
Authors: Chui Ashley J. , Okondo Marian C. , Rao Sahana D. , Gai Kuo , Griswold Andrew R. , Vittimberga Brooke A. , Bachovchin Daniel A. 
Published: May 2018

AbstractIntracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptotic cell death. The anthrax lethal factor metalloprotease and small molecule DPP8/9 inhibitors both activate the Nlrp1b inflammasome, but the molecular mechanism of Nlrp1b activation is not known. Here, we used genome-wide CRISPR/Cas9 knockout screens to identify genes required for Nlrp1b-mediated pyroptosis, and discovered that lethal factor induces cell deathviathe N-end rule proteasomal degradation pathway. Lethal factor directly cleaves Nlrp1b, which induces the N-end rule-mediated degradation of the Nlrp1b N-terminus and thereby frees the Nlrp1b C-terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the Nlrp1b N-terminus, but, in contrast, not through the N-end rule pathway. Overall, these data reveal that N-terminal degradation is the common mechanism for activation of this innate immune sensor protein.One Sentence SummaryProteasome-mediated degradation of the Nlrp1b N-terminus releases the Nlrp1b C-terminus to activate caspase-1 and induce pyroptotic cell death.