bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C Virus (HCV) diagnosis, epidemiology and access to treatment in a UK cohort
Authors: Adland Emily , Jesuthasan Gerald , Downs Louise , Wharton Victoria , Wilde Gemma , McNaughton Anna , Collier Jane , Barnes Eleanor , Klenerman Paul , Andersson Monique , Jeffery Katie , Matthews Philippa C. 
Published: November 2017

ABSTRACTBackgroundAs direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial to underpin improvements in delivery of treatment.MethodsWe performed a retrospective study of HCV infection in a UK teaching hospital to evaluate the performance of different diagnostic laboratory tests, to describe the population with active HCV infection, and to determine the proportion of these individuals who access clinical care.ResultsOver a total time period of 33 months between 2013 and 2016, we tested 38,510 individuals for HCV infection and confirmed a new diagnosis of active HCV infection (HCV-Ag+ and/or HCV RNA+) in 359 (positive rate 0.9%). Our in-house HCV-Ab test had a positive predictive value of 87% when compared to repeat HCV-Ab testing in a regional reference laboratory, highlighting the potential for false positives to arise based on a single round of antibody-based screening. Of those confirmed Ab-positive, 70% were HCV RNA positive. HCV-Ag screening performed well, with 100% positive predictive value compared to detection of HCV RNA. There was a strong correlation between quantitative HCV-Ag and HCV RNA viral load (p<0.0001). Among the 359 cases of infection, the median age was 37 years, 85% were male, and 36% were in prison. Among 250 infections for which genotype was available, HCV genotype-1 (n=110) and genotype-3 (n=111) accounted for the majority. 117/359 (33%) attended a clinic appointment and 48 (13%) had curative treatment defined as sustained virologic response at 12 weeks (SVR12).ConclusionsHCV-Ab tests should be interpreted with caution as an indicator of population prevalence of HCV infection, both as a result of the detection of individuals who have cleared infection and due to false positive test results. We demonstrate that active HCV infection is over-represented among men and in the prison population. A minority of patients with a diagnosis of HCV infection access clinical care and therapy; enhanced efforts are required to target diagnosis and providing linkage to clinical care within high risk populations.ABBREVIATIONSDAADirect Acting AntiviralELISAEnzyme linked immunosorbent assayHCVHepatitis C VirusHCV-AbIgG antibody to Hepatitis C virusHCV-AgHepatitis C virus core antigenHCV RNAHepatitis C ribonucleic acid (viral load)MSMmen who have sex with menNATnucleic acid testingPCRpolymerase chain reaction (test for viral load)PPVpositive predictive valuePWIDpeople who inject drugsSDGSustainable Development GoalsSVRsustained virologic responseWHOWorld Health Organisation
DNA methylation estimation using methylation-sensitive restriction enzyme bisulfite sequencing (MREBS)
Authors: Bonora Giancarlo , Rubbi Liudmilla , Morselli Marco , Chronis Constantinos , Plath Kathrin , Pellegrini Matteo 
Published: November 2017

ABSTRACTWhole-genome bisulfite sequencing (WGBS) and reduced representation bisulfite sequencing (RRBS) are widely used for measuring DNA methylation levels on a genome-wide scale(1). Both methods have limitations: WGBS is expensive and prohibitive for most large-scale projects; RRBS only interrogates 6-12% of the CpGs in the human genome(16,19). Here, we introduce methylation-sensitive restriction enzyme bisulfite sequencing (MREBS) which has the reduced sequencing requirements of RRBS, but significantly expands the coverage of CpG sites in the genome. We built a multiple regression model that combines the two features of MREBS: the bisulfite conversion ratios of single cytosines (as in WGBS and RRBS) as well as the number of reads that cover each locus (as in MRE-seq(12)). This combined approach allowed us to estimate differential methylation across 60% of the genome using read count data alone, and where counts were sufficiently high in both samples (about 1.5% of the genome), our estimates were significantly improved by the single CpG conversion information. We show that differential DNA methylation values based on MREBS data correlate well with those based on WGBS and RRBS. This newly developed technique combines the sequencing cost of RRBS and DNA methylation estimates on a portion of the genome similar to WGBS, making it ideal for large-scale projects of mammalian genomes.
A tangled tale of convergence and divergence: archaeal chromosomal proteins and Chromo-like domains in bacteria and eukaryotes
Authors: Kaur Gurmeet , Iyer Lakshminarayan M. , Subramanian Srikrishna , Aravind L. 
Published: November 2017

AbstractThe Chromo-like superfamily of SH3-fold β-barrel domains recognize epigenetic marks in eukaryotic proteins. Their provenance has been placed either in archaea, based on apparent structural similarity to chromatin-compacting Sul7d and Cren7 proteins, or in bacteria based on the presence of sequence homologs. Using sequence and structural evidence we establish that the archaeal Cren7/Sul7 proteins emerged from a zinc ribbon (ZnR) ancestor. Further, we show that the ancestral eukaryotic Chromo-like domains evolved from bacterial precursors acquired from early endosymbioses, which already possessed an aromatic cage for recognition of modified amino-groups. These bacterial versions are part of a radiation of secreted SH3-fold domains, which spawned both chromo-like domains and classical SH3 domains in the context of peptide-recognition in the peptidoglycan. This establishes that Cren7/Sul7 converged to a "SH3”-like state from a ZnR precursor via the loss of metal-chelation and acquisition of stronger hydrophobic interactions; it is unlikely to have participated in the evolution of the chromo-like domains. We show that archaea possess several Cren7/Sul7-related proteins with intact Zn-chelating ligands, which we predict to play previously unstudied roles in cell-division comparable to the PRC barrel.
Recurrent network model for learning goal-directed sequences through reverse replay
Authors: Haga Tatsuya , Fukai Tomoki 
Published: November 2017

ABSTRACTReverse replay of hippocampal place cells occurs frequently at rewarded locations, suggesting its contribution to goal-directed pathway learning. Symmetric spike-timing dependent plasticity (STDP) in CA3 likely potentiates recurrent synapses for both forward (start to goal) and reverse (goal to start) replays during sequential activation of place cells. However, how reverse replay selectively strengthens forward pathway is unclear. Here, we show computationally that firing sequences bias synaptic transmissions to the opposite direction of propagation under symmetric, but not asymmetric, STDP in the co-presence of short-term synaptic plasticity. We demonstrate that a significant bias can be created in biologically realistic simulation settings, and that this bias enables reverse replay to enhance goal-directed spatial memory on a T-maze. Our model for the first time provides the mechanistic account for the way reverse replay contributes to hippocampal sequence learning for reward-seeking spatial navigation.
Feed-forward inhibition conveys time-varying stimulus information in a collision detection circuit
Authors: Wang Hongxia , Dewell Richard B. , Zhu Ying , Gabbiani Fabrizio 
Published: November 2017

SummaryFeed-forward inhibition is ubiquitous as a motif in the organization of neuronal circuits. During sensory information processing, it is traditionally thought to sharpen the responses and temporal tuning of feed-forward excitation onto principal neurons. As it often exhibits complex time-varying activation properties, feed-forward inhibition could also convey information used by single neurons to implement dendritic computations on sensory stimulus variables. We investigated this possibility in a collision detecting neuron of the locust optic lobe that receives both feed-forward excitation and inhibition. We identified a small population of neurons mediating feed-forward inhibition, with wide visual receptive fields and whose responses depend both on the size and speed of moving stimuli. By studying responses to simulated objects approaching on a collision course, we determined that they jointly encode the angular size of expansion of the stimulus. Feed-forward excitation on the other hand encodes a function of the angular velocity of expansion and the targeted collision detecting neuron combines these two variables non-linearly in its firing output. Thus, feed-forward inhibition actively contributes to the detailed firing rate time course of this collision detecting neuron, a feature critical to the appropriate execution of escape behaviors. These results suggest that feed-forward inhibition could similarly convey time-varying stimulus information in other neuronal circuits.
Presence of Atopy Increases the Risk of Asthma Relapse
Authors: Teoh Laurel , Mackay Ian , Van Asperen Peter P , Acworth Jason , Hurwitz Mark , Upham John W , Siew Weng Hou , Wang Claire YT , Sloots Theo P , Neeman Teresa , Chang Anne B 
Published: November 2017

AbstractObjectivesIn children with hospitalised and non-hospitalised asthma exacerbations, to: (a) describe the point prevalence of respiratory viruses/atypical bacteria using polymerase chain reaction (PCR) and; (b) evaluate the impact of respiratory viruses/atypical bacteria and atopy on acute severity and clinical recovery.DesignThis was a prospective study performed during 2009-2011.SettingThe study was performed in the Emergency Departments of 2 hospitals.Patients244 children aged 2-16 years presenting with acute asthma to the Emergency Departments were recruited. A nasopharyngeal aspirate and allergen skin prick test were performed.Main outcome measuresThe outcomes were divided into (a) acute severity outcomes [Australian National Asthma Council assessment, hospitalisation, Functional Severity Scale, acute asthma score, asthma quality of life questionnaires for parents (PACQLQ) on presentation, asthma diary scores (ADS) on presentation and length of hospitalisation] and (b) recovery outcomes (PACQLQ for 21 days, ADS for 14 days and representation for asthma for 21 days).ResultsPCR for viruses/atypical bacteria was positive in 81.7% of children (75.1% human rhinovirus, co-detection in 14.2%).M. pneumoniaeandC. pneumoniaewere rarely detected. The presence of micro-organisms had little impact on acute asthma or recovery outcomes. Children with atopy were significantly more likely to relapse and represent for medical care by day-14 (OR 1.11, 95%CI 1.00,1.23).ConclusionsThe presence of any viruses is associated with asthma exacerbations but does not appear to influence asthma recovery. In contrast, atopy is associated with asthma relapse.M. pneumoniaeandC. pneumoniaeare rare triggers of acute asthma in young children.
Multi-Omics factor analysis - a framework for unsupervised integration of multi-omic data sets
Authors: Argelaguet Ricard , Velten Britta , Arnol Damien , Dietrich Sascha , Zenz Thorsten , Marioni John C. , Huber Wolfgang , Buettner Florian , Stegle Oliver 
Published: November 2017

AbstractMulti-omic studies promise the improved characterization of biological processes across molecular layers. However, methods for the unsupervised integration of the resulting heterogeneous datasets are lacking. We present Multi-Omics Factor Analysis (MOFA), a computational method for discovering the principal sources of variation in multi-omic datasets. MOFA infers a set of (hidden) factors that capture biological and technical sources of variability. It disentangles axes of heterogeneity that are shared across multiple modalities and those specific to individual data modalities. The learnt factors enable a variety of downstream analyses, including identification of sample subgroups, data imputation, and the detection of outlier samples. We applied MOFA to a cohort of 200 patient samples of chronic lymphocytic leukaemia, profiled for somatic mutations, RNA expression, DNA methylation and ex-vivo drug responses. MOFA identified major dimensions of disease heterogeneity, including immunoglobulin heavy chain variable region status, trisomy of chromosome 12 and previously underappreciated drivers, such as response to oxidative stress. In a second application, we used MOFA to analyse single-cell multiomics data, identifying coordinated transcriptional and epigenetic changes along cell differentiation.
Use-dependent plasticity in human primary motor hand area: Synergistic interplay between training and immobilisation
Authors: Raffin Estelle , Siebner Hartwig Roman 
Published: November 2017

AbstractTraining and immobilization are powerful drivers of use-dependent plasticity in human primary motor hand area (M1HAND). Here we used transcranial magnetic stimulation to clarify how training and immobilisation of a single finger interact within M1HAND. Healthy volunteers trained to track a moving target with a finger for one week. The tracking skill acquired with the trained finger was transferred to a non-trained finger of the same hand. The cortical representations of the trained and non-trained finger muscle converged in proportion with skill transfer. Finger immobilisation alone attenuated the corticomotor representation and pre-existing tracking skill of the immobilized finger. The detrimental effects of finger immobilization were blocked by concurrent training of the non-immobilized finger. Conversely, immobilization of the non-trained fingers accelerated learning during the first two days of training. The results provide novel insight into use-dependent cortical plasticity, revealing synergistic rather than competitive interaction patterns within M1HAND.
Natural genetic variation inC. elegansreveals genomic loci controlling metabolite levels
Authors: Gao Arwen W. , Sterken Mark G. , Bos Jelmi uit de , Creij Jelle van , Kamble Rashmi , Snoek Basten L. , Kammenga Jan E. , Houtkooper Riekelt H. 
Published: November 2017

AbstractMetabolic homeostasis is sustained by complex biological networks responding to nutrient availability. Disruption of this equilibrium involving intricate interactions between genetic and environmental factors can lead to metabolic disorders, including obesity and type 2 diabetes. To identify the genetic factors controlling metabolism, we applied a quantitative genetic strategy using aCaenorhabditis eleganspopulation consisting of 199 recombinant inbred lines (RILs) originally derived from crossing parental strains Bristol N2 and Hawaii CB4856. We focused on the genetic factors that control metabolite levels and measured fatty acid (FA) and amino acid (AA) composition in the 199 RILs using targeted metabolomics. For both FA and AA profiles, we observed large variation in metabolite levels with 32-82% heritability between the RILs. We performed metabolite-metabolite correlation analysis and detected strongly co-correlated metabolite clusters. To identify natural genetic variants responsible for the observed metabolite variations, we performed QTL mapping and detected 36 significant metabolite QTL (mQTL). We focused on the mQTL that displayed high significant linkage and heritability, including an mQTL for the FA C14:1 on chromosome I, and another mQTL for the FA C18:2 on chromosome IV. Using introgression lines (ILs) we were able to narrow down both mQTL to a 1.4 Mbp and a 3.6 Mbp region, respectively. Overall, this systems approach provides us with a powerful platform to study the genetic basis ofC. elegansmetabolism. It also allows us to investigate additional interventions, such as nutrients and stresses that maintain or disturb the regulatory network controlling metabolic homeostasis, and identify gene-by-environment interactions.
Acute fluoxetine differently affects aggressive display in zebrafish phenotypes
Authors: Barbosa Hellen Pereira , Lima Monica Gomes , Maximino Caio 
Published: November 2017

AbstractZebrafish have been introduced as a model organism in behavioral neuroscience and biological psychiatry, increasing the breadth of findings using fish to study the neurobiology of aggression. Phenotypic differences between leopard and longfin zebrafish were exploited in order to elucidate the role of phasic serotonin in aggressive displays on this species. The present study revealed differences in aggressive display between leopard and longfin zebrafish, and a discrepant effect of acute fluoxetine in both populations. In mirror-induced aggression, leopard animals showed higher display latencies than longfin, as well as lower display duration and frequency (Experiment 1). Moreover, 2.5 mg/kg fluoxetine decreased the duration and frequency of display in longfin, but not leopard; and 5 mg/kg fluoxetine increased display frequency in leopard, but not longfin (Experiment 2). It is suggested that zebrafish from the longfin phenotype show more aggressive motivation and readiness in the mirror-induced aggression test that leopard, and that acute fluoxetine increases aggression in leopard and decreased it in longfin zebrafish.
Hidden variation in polyploid wheat drives local adaptation
Authors: Gardiner Laura-Jayne , Joynson Ryan , Omony Jimmy , Rusholme-Pilcher Rachel , Olohan Lisa , Lang Daniel , Bai Caihong , Hawkesford Malcolm , Salt David , Spannagl Manuel , Mayer F.X.Klaus , Kenny John , Bevan Michael , Hall Neil , Hall Anthony 
Published: November 2017

AbstractWheat has been domesticated into a large number of agricultural environments and has a remarkable ability to adapt to diverse environments. To understand this process, we survey genotype, repeat content and DNA methylation across a bread wheat landrace collection representing global genetic diversity. We identify independent variation in methylation, genotype and transposon copy number. We show that these, so far unexploited, sources of variation have had a massive impact on the wheat genome and that ancestral methylation states become preferentially ‘hard coded’ as SNPs via 5-methylcytosine deamination. These mechanisms also drive local adaption, impacting important traits such as heading date and salt tolerance. Methylation and transposon diversity could therefore be used alongside single nucleotide polymorphism (SNP) based markers for breeding.
Minerva: An Alignment and Reference Free Approach to Deconvolve Linked-Reads for Metagenomics
Authors: Danko David C. , Meleshko Dmitry , Bezdan Daniela , Mason Christopher , Hajirasouliha Iman 
Published: November 2017

AbstractEmerging Linked-Read technologies (aka Read-Cloud or barcoded short-reads) have revived interest in standard short-read technology as a viable way to understand large-scale structure in genomes and metagenomes. Linked-Read technologies, such as the 10X Chromium system, use a microfluidic system and a set of specially designed 3’ barcodes (aka UIDs) to tag short DNA reads which were originally sourced from the same long fragment of DNA; subsequently, these specially barcoded reads are sequenced on standard short read platforms. This approach results in interesting compromises. Each long fragment of DNA is covered only sparsely by short reads, no information about the relative ordering of reads from the same fragment is preserved, and typically each 3’ barcode matches reads from 2-20 long fragments of DNA. However, compared to long read platforms like those produced by Pacific Biosciences and Oxford Nanopore the cost per base to sequence is far lower, far less input DNA is required, and the per base error rate is that of Illumina short-reads.The use of Linked-Reads presents a new set of algorithmic challenges. In this paper, we formally describe one particular issue common to all applications of Linked-Read technology: the deconvolution of reads with a single 3’ barcode into clusters that correspond to a single long fragment of DNA. We introduce Minerva, A graph-based algorithm that approximately solves the barcode deconvolution problem for metagenomic data (where reference genomes may be incomplete or unavailable). Additionally, we develop two demonstrations where the deconvolution of barcoded reads improves downstream results: improving the specificity of taxonomic assignments, and by improving clustering of related sequences. To the best of our knowledge, we are the first to address the problem of barcode deconvolution in metagenomics.
Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What’s behind the scenes?
Authors: Daimi Houria , Khelil Amel Haj , Neji Ali , Hamda Khaldoun Ben , Maaoui Sabri , Aranega Amelia , Chibani Jemni BE , Franco Diego 
Published: November 2017

AbstractBrugada syndrome (BrS) is a rare inherited cardiac arrhythmia associated with a high risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF). BrS is characterized by coved-type ST-segment elevation in the right precordial leads (V1-V3) in the absence of structural heart disease. This pattern is spontaneous, or is unmasked by intravenous administration of Class I antiarrhythmic drugs. The SCN5A-encoded α-subunit of the NaV1.5 cardiac sodium channel has been linked to BrS, and mutations in SCN5A are identified in 15–30% of BrS cases. Genetic testing of BrS patients generally involves sequencing of protein-coding portions and flanking intronic regions of SCN5A, according to recent international guidelines. This excludes the regulatory untranslated regions (5’UTR and 3’UTR) from the routine genetic testing of BrS patients. We here screened the coding sequence, the flanking intronic regions as well as the 5’ and 3’UTR regions of SCN5A gene and further five candidate genes (GPD1L, SCN1B, KCNE3, SCN4B, and MOG1) in a Tunisian family diagnosed with Brugada syndrome.A new Q1000K mutation was identified on the SCN5A gene along with two common polymorphisms (H558R and D1819). Furthermore, multiple genetic variants were identified on the SCN5A 3’UTR, one of which is predicted to create additional microRNA (miRNAs) binding site for miR-1270. Additionally, we identified the hsa-miR-219a rs107822. No relevant coding sequence variant was identified in the remaining studied candidate genes. Although Q1000K is localized in the conserved binding site of MOG1 which predicts a functional consequence, this new mutation along with the additional variants were differentially distributed among the family members without any clear genotype-phenotype concordance. This gives extra evidences about the complexity of the disease and suggests that the occurrence and prognosis of BrS is most likely controlled by a combination of multiple genetic factors and exposures, rather than a single polymorphism/mutation. Most SCN5A polymorphisms were localized in non-coding regions hypothesizing an impact on the miRNA-target complementarities. In this regard, over-expression of miR-1270 led to a significant decrease of luciferase activity suggesting a direct role regulating SCN5A. Therefore, genetic variants that disrupt its binding affinity to SCN5A 3’UTR and/or its expression might cause loss of normal repression control and be associated to BrS.