bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antisense transcriptional interference mediates condition-specific gene repression in budding yeast
Authors: Nevers Alicia , Doyen Antonia , Malabat Christophe , Néron Bertrand , Kergrohen Thomas , Jacquier Alain , Badis Gwenael 
Published: July 2017

ABSTRACTPervasive transcription generates many unstable non-coding transcripts in budding yeast. The transcription of such noncoding RNAs, in particular antisense RNAs (asRNAs), has been shown in a few examples to repress the expression of the associated mRNAs. Yet, such mechanism is not known to commonly contribute to the regulation of a given class of genes. Using a mutant context that stabilised pervasive transcripts, we observed that the least expressed mRNAs during the exponential phase were associated with high levels of asRNAs. These asRNAs also overlapped their corresponding gene promoters with a much higher frequency than average. Interrupting antisense transcription of a subset of genes corresponding to quiescence-enriched mRNAs restored their expression. The underlying mechanism acts incisand involves several chromatin modifiers. Our results convey that transcription interference represses up to 30% of the 590 least expressed genes, which includes 163 genes with quiescence-enriched mRNAs. We also found that pervasive transcripts constitute a higher fraction of the transcriptome in quiescence relative to the exponential phase, consistent with gene expression itself playing an important role to suppress pervasive transcription. Accordingly, theHIS1asRNA, normally only present in quiescence, is expressed in exponential phase uponHIS1mRNA transcription interruption.
Genome variation and conserved regulation identify genomic regions responsible for strain specific phenotypes in rat
Authors: Martín-Gálvez David , de Segonzac Denis Dunoyer , John Ma Man Chun , Kwitek Anne E , Thybert David , Flicek Paul 
Published: July 2017

AbstractThe genomes of laboratory rat strains are characterised by a mosaic haplotype structure caused by their unique breeding history. These mosaic haplotypes have been recently mapped by extensive sequencing of key strains. Comparison of genomic variation between two closely related rat strains with different phenotypes has been proposed as an effective strategy for the discovery of candidate strain-specific regions involved in phenotypic differences.We developed a method to prioritise strain-specific haplotypes by integrating genomic variation and genomic regulatory data predicted to be involved in specific phenotypes. To identify genomic regions associated with metabolic syndrome, a disorder of energy utilization and storage affecting several organ systems, we compared two Lyon rat strains, LH/Mav which is susceptible to MetS, and LL/Mav, which is susceptible to obesity as an intermediate MetS phenotype, with a third strain (LN/Mav) that is resistant to both MetS and obesity. Applying a novel metric, we ranked the identified strain-specific haplotypes using evolutionary conservation of the occupancy three liver-specific transcription factors (HNF4A, CEBPA, and FOXA1) in five rodents including rat.Consideration of regulatory information effectively identified regions with liver-associated genes and rat orthologues of human GWAS variants related to obesity and metabolic traits. We attempted to find possible causative variants and compared them with the candidate genes proposed by previous studies. In strain-specific regions with conserved regulation, we found a significant enrichment for published evidence to obesity—one of the metabolic symptoms shown by the Lyon strains—amongst the genes assigned to promoters with strain-specific variation.Our results show that the use of functional regulatory conservation is a potentially effective approach to select strain-specific genomic regions associated with phenotypic differences among Lyon rats and could be extended to other systems.
HPCDb: an integrated database of pancreatic cancer
Authors: Tan Yonggang , Tan Yongqiang , Lu Lin , Zhang Heying , Sun Cheng , Liang Yusi , Zeng Juan , Yang Xianghong , Li Dan , Zou Huawei 
Published: July 2017

AbstractWe have established a database of Human Pancreatic Cancer (HPCDb) through effectively mining, extracting, analyzing, and integrating PC-related genes, single-nucleotide polymorphisms (SNPs), and microRNAs (miRNAs), now available online athttp://www.pancancer.org/. Data were extracted from established databases, ≥5 published literature (PubMed), and microarray chips (screening of differentially expressed genes using limma package in R, |log2fold change (FC)| > 1). Further, protein–protein interactions (PPIs) were investigated through the Human Protein Reference Database. miRNA–target relationships were also identified using the online software TargetScan. Currently, HPCDb contains 3284 genes, 120 miRNAs, 589 SNPs, 10,139 PPIs, and 3904 miRNA–target pairs. The detailed information on PC-related genes (e.g., gene identifier (ID), symbol, synonyms, full name, chip sets, expression alteration, PubMed ID, and PPIs), miRNAs (e.g., accession number, chromosome location, related disease, PubMed ID, and miRNA–target interactions), and SNPs (e.g., SNP ID, allele, gene, PubMed ID, chromosome location, and disease) is presented through user-friendly query interfaces or convenient links to NCBI GEO, NCBI PubMed, NCBI Gene, NCBI dbSNP, and miRBase. Overall, HPCDb provides biologists with relevant information on human PC-related molecules at multiple levels, helping to generate new hypotheses or identify candidate markers.
Very low depth whole genome sequencing in complex trait association studies
Authors: Gilly Arthur , Southam Lorraine , Suveges Daniel , Kuchenbaecker Karoline , Moore Rachel , Melloni Giorgio E.M. , Hatzikotoulas Konstantinos , Farmaki Aliki-Eleni , Ritchie Graham , Schwartzentruber Jeremy , Danecek Petr , Kilian Britt , Pollard Martin O. , Ge Xiangyu , Tsafantakis Emmanouil , Dedoussis George , Zeggini Eleftheria 
Published: July 2017

AbstractMotivationVery low depth sequencing has been proposed as a cost-effective approach to capture low-frequency and rare variation in complex trait association studies. However, a full characterisation of the genotype quality and association power for very low depth sequencing designs is still lacking.ResultsWe perform cohort-wide whole genome sequencing (WGS) at low depth in 1,239 individuals (990 at 1x depth and 249 at 4x depth) from an isolated population, and establish a robust pipeline for calling and imputing very low depth WGS genotypes from standard bioinformatics tools. Using genotyping chip, whole-exome sequencing (WES, 75x depth) and high-depth (22x) WGS data in the same samples, we examine in detail the sensitivity of this approach, and show that imputed 1x WGS recapitulates 95.2% of variants found by imputed GWAS with an average minor allele concordance of 97% for common and low-frequency variants. In our study, 1x further allowed the discovery of 140,844 true low-frequency variants with 73% genotype concordance when compared to high-depth WGS data. Finally, using association results for 57 quantitative traits, we show that very low depth WGS is an efficient alternative to imputed GWAS chip designs, allowing the discovery of up to twice as many true association signals than the classical imputed GWAS design.Supplementary DataSupplementary Data are appended to this manuscript.
A Framework to Simulate Cortical microtubule Dynamics in Arbitrary Shaped Plant Cells
Authors: Chakrabortty Bandan , Scheres Ben , Mulder Bela 
Published: July 2017

AbstractPlant morphogenesis is strongly dependent on the directional growth and the subsequent oriented division of individual cells. It has been shown that the plant cortical microtubule array plays a key role in controlling both these processes. This ordered structure emerges as the collective result of stochastic interactions between large numbers of dynamic microtubules. To elucidate this complex self-organization process a number of analytical and computational approaches to study the dynamics of cortical microtubules have been proposed. To date, however, these models have been restricted to 2D planes or geometrically simple surfaces in 3D, which strongly limits their applicability as plant cells display a wide variety of shapes. This limitation is even more acute, as both local as well as global geometrical features of cells are expected to influence the overall organization of the array. Here we describe a framework for efficiently simulating microtubule dynamics on triangulated approximations of arbitrary three dimensional surfaces. This allows the study of microtubule array organization on realistic cell surfaces obtained by segmentation of microscopic images. We validate the framework against expected or known results for the spherical and cubical geometry. We then use it to systematically study the individual contributions of global geometry, edge-induced catastrophes and cell face-induced stability to array organization in a cuboidal geometry. Finally, we apply our framework to analyze the highly non-trivial geometry of leaf pavement cells ofNicotiana benthamianaandHedera helix.We show that our simulations can predict multiple features of the array structure in these cells, revealing, among others, strong constraints on the orientation of division planes.
Redesigning chromosomes for optimized Hi-C assay provides insights on loop formation and homologs pairing during meiosis
Authors: Héloïse Muller , Vittore Scolari F. , Guillaume Mercy , Nicolas Agier , Piazza Aurèle , Luciana Lazar-Stefanita , Stephane Descorps-Declere , Olivier Espeli , Bertrand Llorente , Gilles Fischer , Julien Mozziconacci , Romain Koszul 
Published: July 2017

AbstractIn all chromosome conformation capture based experiments the accuracy with which contacts are detected varies considerably because of the uneven distribution of restriction sites along genomes. In addition, repeated sequences as well as homologous, large identical regions remain invisible to the assay because of the ambiguities they introduce during the alignment of the sequencing reads along the genome. As a result, the investigation of homologs during meiosis prophase through 3C studies has been limited. Here, we redesigned and reassembled in yeast a 145kb region with regularly spaced restriction sites for various enzymes. Thanks to this Syn-3C design, we enhanced the signal to noise ratio and improved the visibility of the entire region. We also improved our understanding of Hi-C data and definition of resolution. The redesigned sequence is now distinguishable from its native homologous counterpart in an isogenic diploid strain. As a proof of principle, we track the establishment of homolog pairing during meiotic prophase in a synchronized population. This provides new insights on the individualization and pairing of homologs, as well as on their internal restructuration into arrays of loops during meiosis prophase. Overall, we show the interest of redesigned genomic regions to explore complex biological questions otherwise difficult to address.
Efficient hydrogen-dependent carbon dioxide reduction byEscherichia coli
Authors: Roger Magali , Brown Fraser , Gabrielli William , Sargent Frank 
Published: July 2017

ABSTRACTThe formate hydrogenlyase (FHL) complex ofEscherichia coliis normally produced under anaerobic fermentative conditions when its physiological role is to oxidise formate to carbon dioxide and couple that reaction directly to the reduction of protons to molecular hydrogen. This forward reaction is the major route of hydrogen production byE. coliand the physiology, genetics and biochemistry of this process are reasonably well understood. However, studies of the reverse reaction - hydrogen-dependent carbon dioxide reduction – have been rather less extensive. Harnessing the alternative reverse reaction has the potential to unlock FHL as a carbon dioxide cycling enzyme, or could potentially lead to the development of bio-based carbon capture technologies. In this work, it is established that FHL can operate as a highly efficient CO2reductase. A controllable pressure system was designed with the intention of maximising substrate availability to the FHL enzyme. By placing gaseous CO2and H2are under pressure (up to 10 bar), and by using a compartmentalised intact whole cell approach where the produced formate is excreted, the optimised experimental system was observed to convert 100 % of gaseous CO2to formic acid and generate >500 mM formate in solution at an initial rate of 1.2 g formateperlitreperhour.
riboWaltz: optimization of ribosome P-site positioning in ribosome profiling data
Authors: Lauria Fabio , Tebaldi Toma , Bernabò Paola , Groen Ewout J.N. , Gillingwater Thomas H. , Viero Gabriella 
Published: July 2017

ABSTRACTRibosome profiling is a powerful technique used to study translation at the genome-wide level, generating unique information concerning ribosome positions along RNAs. Optimal localization of ribosomes requires the proper identification of the ribosome P-site in each ribosome protected fragment, a crucial step to determine trinucleotide periodicity of translating ribosomes, and draw correct conclusions concerning where ribosomes are located. To determine the P-site within ribosome footprints at nucleotide resolution, the precise estimation of its offset with respect to the protected fragment is necessary. Here we present riboWaltz, an R package for calculation of optimal P-site offsets, diagnostic analysis and visual inspection of data. Compared to existing tools, riboWaltz shows improved accuracies for P-site estimation and neat ribosome positioning in multiple case studies.Availability and ImplementationriboWaltz was implemented in R and is available athttps://github.com/LabTranslationalArchitectomics/RiboWaltzContactgabriella.viero@cnr.itorfabio.lauria@unitn.it
Mechanistic view and genetic control of DNA recombination during meiosis
Authors: Marsolier-Kergoat Marie-Claude , Khan Md Muntaz , Schott Jonathan , Zhu Xuan , Llorente Bertrand 
Published: July 2017

ABSTRACTMeiotic recombination is essential for fertility and allelic shuffling. Canonical recombination models fail to capture the observed complexity of meiotic recombinants. Here we revisit these models by analyzing meiotic heteroduplex DNA tracts genome-wide in combination with meiotic DNA double-strand break (DSB) locations. We provide unprecedented support to the synthesis-dependent strand annealing model and establish estimates of its associated template switching frequency and polymerase processivity. We show that resolution of double Holliday junctions (dHJs) is biased toward cleavage of the pair of strands containing newly synthesized DNA near the junctions. The suspected dHJ resolvase Mlh1-3 as well as Mlh1-2, Exo1 and Sgs1 promote asymmetric positioning of crossover intermediates relative to the initiating DSB and bidirectional conversions. Finally, we show that crossover-biased dHJ resolution depends on Mlh1-3, Exo1, Msh5 and to a lesser extent on Sgs1. These properties are likely conserved in eukaryotes containing the ZMM proteins, which includes mammals.
The nucleoid as a scaffold for the assembly of bacterial signaling complexes
Authors: Moine Audrey , Espinosa Leon , Martineau Eugenie , Yaikhomba Mutum , Jazleena P J , Byrne Deborah , Biondi Emanuele G. , Notomista Eugenio , Brilli Matteo , Molle Virginie , Gayathri Pananghat , Mignot Tâm , Mauriello Emilia M.F. 
Published: July 2017

ABSTRACTThe FrzCD chemoreceptor from the gliding bacteriumMyxococcus xanthusforms cytoplasmic clusters that occupy a large central region of the cell body also occupied by the nucleoid. In this work, we show that FrzCD directly binds to the nucleoid with its N-terminal positively charged tail and recruits active signaling complexes at this location. The FrzCD binding to the nucleoid occur in a DNA-sequence independent manner and leads to the formation of multiple distributed clusters that explore constrained areas. This organization might be required for cooperative interactions between clustered receptors as observed in membrane-bound chemosensory arrays.AUTHOR SUMMARYIn this work, we show that the cytoplasmic chemoreceptor of the Frz chemosensory system, FrzCD, does not bind the cytoplasmic membrane like most MCPs but bind the bacterial nucleoid directly, thus forming distributed protein clusters also containing the Frz kinase.In vitroandin vivoexperiments show that DNA-binding is not sequence-specific and is mediated by a basic aminoacid sequence of the FrzCD N-terminal domain. The deletion of this motif abolishes FrzCD DNA-binding and cooperativity in the response to signals. This work shows the importance of the nucleoid in the organization and functioning of cytoplasmic signaling systems in bacteria.
Intrinsically photosensitive retinal ganglion cell mediated pupil function is impaired in Parkinson’s disease
Authors: Joyce Daniel S. , Feigl Beatrix , Kerr Graham , Roeder Luisa , Zele Andrew J. 
Published: July 2017

AbstractParkinson’s disease is characterised by non-motor symptoms including sleep and circadian disruption, but the underlying aetiology is not well understood. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals from the eye to brain areas controlling circadian rhythms and the pupil light reflex. Here we evaluate the hypothesis that these non-motor symptoms in people with Parkinson’s disease may be linked to ipRGC dysfunction. Using chromatic pupillometry, we measured intrinsic (melanopsin-mediated) ipRGC and extrinsic (rod/cone photoreceptor-mediated) inputs to the pupil control pathway in a group of optimally medicated participants with a diagnosis of Parkinson’s disease (PD,n= 17) compared to controls (n= 12). Autonomic tone was evaluated by measuring pupillary unrest in darkness. The PD participants underwent additional clinical assessments using the Unified Parkinson’s disease Rating Scale (UPDRS) and the Hoehn and Yahr scale (H&Y).Compared to controls, the PD group demonstrated an attenuated pupil constriction amplitude in response to long wavelength pulsed stimulation, and reduced post-illumination pupil response (PIPR) amplitude in response to both short wavelength pulsed and sinusoidal stimulation. In the PD group, PIPR amplitude did not correlate with measures of sleep quality, retinal nerve fibre layer thickness, UPDRS or H&Y score, or medication dosage. Both groups exhibited similar pupillary unrest in darkness.We show that melanopsin and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage Parkinson’s disease. Given that the deficits are independent of clinical assessment severity and are observed despite optimal medication, the melanopsin-mediated PIPR may be a biomarker for the detection of Parkinson’s disease and its continued monitoring in both medicated and unmedicated individuals.
RNA structure inference through chemical mapping after accidental or intentional mutations
Authors: Cheng Clarence Y. , Kladwang Wipapat , Yesselman Joseph , Das Rhiju 
Published: July 2017

ABSTRACTDespite the critical roles RNA structures play in regulating gene expression, sequencing-based methods for experimentally determining RNA base pairs have remained inaccurate. Here, we describe a multidimensional chemical mapping method called M2-seq (mutate-and-map read out through next-generation sequencing) that takes advantage of sparsely mutated nucleotides to induce structural perturbations at partner nucleotides and then detects these events through dimethyl sulfate (DMS) probing and mutational profiling. In special cases, fortuitous errors introduced during DNA template preparation and RNA transcription are sufficient to give M2-seq helix signatures; these signals were previously overlooked or mistaken for correlated double DMS events. When mutations are enhanced through error-prone PCR,in vitroM2-seq experimentally resolves 33 of 68 helices in diverse structured RNAs including ribozyme domains, riboswitch aptamers, and viral RNA domains with a single false positive. These inferences do not require energy minimization algorithms and can be made by either direct visual inspection or by a new neural-net-inspired algorithm called M2-net. Measurements on the P4-P6 domain of theTetrahymenagroup I ribozyme embedded inXenopusegg extract demonstrate the ability of M2-seq to detect RNA helices in a complex biological environment.SIGNIFICANCE STATEMENTThe intricate structures of RNA molecules are crucial to their biological functions but have been difficult to accurately characterize. Multidimensional chemical mapping methods improve accuracy but have so far involved painstaking experiments and reliance on secondary structure prediction software. A methodology called M2-seq now lifts these limitations. Mechanistic studies clarify the origin of serendipitous M2-seq-like signals that were recently discovered but not correctly explained and also provide mutational strategies that enable robust M2-seq for new RNA transcripts. The method detects dozens of Watson-Crick helices across diverse RNA foldsin vitroand within frog egg extract, with low false positive rate (< 5%). M2-seq opens a route to unbiased discovery of RNA structuresin vitroand beyond.
Image velocimetry and spectral analysis enable quantitative characterization of larval zebrafish gut motility
Authors: Ganz Julia , Baker Ryan P. , Hamilton M. Kristina , Melancon Ellie , Diba Parham , Eisen Judith S. , Parthasarathy Raghuveer 
Published: July 2017

Summary StatementWe present a new image analysis technique using image velocimetry and spectral analysis that returns quantitative measures of gut contraction strength, frequency, and wave speed that can be used to study gut motility and other cellular movements.AbstractNormal gut function requires rhythmic and coordinated movements that are affected by developmental processes, physical and chemical stimuli, and many debilitating diseases. The imaging and characterization of gut motility, especially regarding periodic, propagative contractions driving material transport, are therefore critical goals. Whereas previous image analysis approaches have successfully extracted properties related to temporal frequency of motility modes, robust measures of contraction magnitude remain elusive. We developed a new image analysis method based on image velocimetry and spectral analysis that reveals temporal characteristics such as frequency and wave propagation speed, while also providing quantitative measures of the amplitude of gut motions. We validate this approach using several challenges to larval zebrafish, imaged with differential interference contrast microscopy. Both acetylcholine exposure and feeding increase frequency and amplitude of motility. Larvae lacking enteric nervous system gut innervation show the same average motility frequency, but reduced and less variable amplitude compared to wild-types. Our image analysis approach enables insights into gut dynamics in a wide variety of developmental and physiological contexts and can also be extended to analyze other types of cell movements.