bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Anti–HIV-1 Antibodies in Oral and Nasal Compartments of Volunteers From 3 Different Populations
Authors: Bergin Philip J. , Langat Robert , Omosa-Manyonyi Gloria , Farah Bashir , Ouattara Gina , Park Harriet , Coutinho Helen , Laufer Dagna , Fast Pat , Verlinde Carl , Bizimana Jean , Umviligihozo Gisele , Nyombayire Julien , Ingabire Rosine , Kuldanek Kristin , Cox Josephine , McMorrow Martin , Fidler Sarah , Karita Etienne , Gilmour Jill , Anzala Omu 
Published: May 2016

Abstract:
In this study, we assessed the feasibility of collecting standardized nasal and salivary samples at centers in Nairobi (Kenya), Kigali (Rwanda), and London (United Kingdom) using different collection devices and media (synthetic absorptive matrices versus flocked swabs, and Salimetrics oral swabs versus whole oral fluid collection). We detected anti-Gag (p24) and envelope (gp140) antibodies in both nasal fluid and salivary collections from all HIV-infected individuals, and cross-reactive anti-p24 antibodies were detected in 10% of HIV-uninfected individuals enrolled at one site. Collections from the nasal turbinates were comparable with samples collected deeper in the nasopharyngeal tract, and the yield of anti-p24 IgA in the whole oral fluid samples was higher than in samples collected from the parotid gland. We noted a trend toward reduced levels of anti-HIV antibody in the volunteers receiving anti-retroviral therapy. Levels of antibodies were stable over multiple collection visits. Overall, this study shows that nasal and salivary samples can be collected in a standardized manner over repeated visits in both low- and high-resource settings. These methods may be used in support for future HIV vaccine clinical trials.
IPC - Isoelectric Point Calculator
Authors: Kozlowski Lukasz P. 
Published: May 2016

ABSTRACTAccurate estimation of the isoelectric point (pI) based on the amino acid sequence can be useful for many biochemistry and proteomics techniques such as 2-D polyacrylamide gel electrophoresis, or capillary isoelectric focusing used in combination with high-throughput mass spectrometry. Here, I present the Isoelectric Point Calculator, a web service for the estimation ofpIusing different sets of dissociation constant (pKa) values, including two new, computationally optimizedpKasets. According to the presented benchmarks, IPC outperform previous algorithms by at least 14.9% for proteins and 0.9% for peptides (on average, 22.1% and 59.6%, respectively), which corresponds to an average error of thepIestimation equal to 0.87 and 0.25 pH units for proteins and peptides, respectively. Peptide and protein datasets used in the study and the precalculatedpIfor PDB, SwissProt databases are available for large-scale analysis and future development. The IPC can be accessed athttp://isoelectric.ovh.org.
Signatures of personality on dense 3D facial images
Authors: Hu Sile , Xiong Jieyi , Fu Pengcheng , Qiao Lu , Tan Jingze , Jin Li , Tang Kun 
Published: May 2016

AbstractIt has long been speculated that there exist cues on human face that allow observersto make reliable judgments of others’personality traits. However, direct evidences ofassociation between facial shapes and personality are missing. This study assessed thepersonality attributes for 834 Han Chinese volunteers (405 males and 429 females) utilizing the five-factor personality model (the ‘Big Five’ model), and collected their neutral 3D facial images. Dense anatomical correspondence was established across the 3D facial images to allow high-dimensional quantitative analyses on the face phenotypes. Two different approaches, Composite Partial Least Square Component(CPLSC) and principle component analysis (PCA) were used to test the associations between the self-testedpersonality scores and the dense 3D face image data. Among the fivepersonality factors, Agreeableness and Conscientiousness in male, and Extraversion in female were significantly associated to specific facial patterns. The personality-related facial patterns were extracted and their effects were extrapolated on simulated 3Dfacial models.
Aequatus: An open-source homology browser
Authors: Thanki Anil S. , Soranzo Nicola , Herrero Javier , Haerty Wilfried , Davey Robert P. 
Published: May 2016

AbstractBackgroundPhylogenetic information inferred from the study of homologous genes helps us to understand the evolution of genes and gene families, including the identification of ancestral gene duplication events as well as regions under positive or purifying selection within lineages. Gene family and orthogroup characterisation enables the identification of syntenic blocks, which can then be visualised with various tools. Unfortunately, currently available tools display only an overview of syntenic regions as a whole, limited to the gene level, and none provide further details about structural changes within genes, such as the conservation of ancestral exon boundaries amongst multiple genomes.FindingsWe present Aequatus, a standalone web-based tool that provides an in-depth view of gene structure across gene families, with various options to render and filter visualisations. It relies on pre-calculated alignment and gene feature information typically held in, but not limited to, the Ensembl Compara and Core databases. We also offer Aequatus.js, a reusable JavaScript module that fulfils the visualisation aspects of Aequatus, available within the Galaxy web platform as a visualisation plugin, which can be used to visualise gene trees generated by the GeneSeqToFamily workflow.AvailabilityAequatus is an open-source tool freely available to download under the MIT license athttps://github.com/TGAC/Aequatus. A demo server is available athttp://aequatus.earlham.ac.uk/. A publicly available instance of the GeneSeqToFamily workflow to generate gene tree information and visualise it using Aequatus is available on the Galaxy EU server athttps://usegalaxy.eu.ContactsAnil.Thanki@earlham.ac.ukandRobert.Davey@earlham.ac.uk
Analysis of behavioral variables across domains and skin phenotypes in zebrafish: Role of brain monoamines
Authors: Lima Monica Gomes , Herculano Anderson Manoel , Maximino Caio 
Published: May 2016

AbstractImportant neurochemical variations between strains or linages which correlate with behavioral differences have been identified in different species. Here, we report neurochemical and behavioral differences in four common zebrafish wild-type phenotypes (blue shortfin, longfin stripped, leopard and albino). Leopad zebrafish have been shown to display increased scototaxis in relation to the other strains, while both albino and leopard zebrafish show increased geotaxis. Moreover, leopard displayed increased nocifensive behavior, while albino zebrafish showed increased neophobia in the novel object task. Longfin zebrafish showed decreased turn frequency in both the novel tank and light/dark tests, and habituated faster in the novel tank, as well as displaying increased 5-HT levels. Leopard zebrafish showed decreased brain 5-HT levels and increased 5-HT turnover than other strains, and albino had increased brain DA levels. Finally, specific behavioral endpoints co-varied in terms of the behavioral and neurochemical differences between strains, identifying cross-test domains which included response to novelty, exploration-avoidance, general arousal, and activity.
Genomic dimensions of Su(H)-targeted regulatory belts inDrosophila
Authors: Stroebele Elizabeth , Fuqua Timothy , Warren Madelyn , Herrig Danielle , Noblett Christian , Yuan Xin , Erives Albert 
Published: May 2016

AbstractAsymmetric Notch signaling promotes divergent fates in select cells throughout metazoan development. In the receiving cell, signaling results in cleavage of the Notch intracellular domain and its import into the nucleus, where it binds Suppressor of Hairless [Su(H)] to promote gene expression in conjunction with contextual cues in the surrounding DNA sequence. To investigate the nature of this contextual logic, we identify 1344 Su(H)-site containing regulatory belts that are conserved across theDrosophilagenus. Each Su(H)-type regulatory belt (SUH-RB) is a 0.6-1.0 kb chain of conservation peaks consistent with a transcriptional enhancer or core promoter. These regulatory belts contain one or more canonical binding sites for Su(H) along with ~15-30 other binding sites. SUH-RBs are densely clustered in certain chromosomal regions such as the E(spl)-complex, theWntgene complex, and genes encoding Notch receptor ligands (Delta and Serrate). SUH-RBs overlap most known Su(H)/Notch-target enhancers and others, including non-embryonic enhancers that are not identified by embryonic ChIP-seq peaks. Thus, SUH-RBs overcome the stage-specific nature of embryonic ChIP-seq peaks and suggest a pervasive role for contextual tissue-specific pioneer and/or enhancer-licensing factors. SUH-RBs also delineate false positive ChIP-seq peaks, which do not overlap SUH-RBs, are missing even the weakest Su(H)-binding sequences, and have the shortest ChIP peak widths. Last, we characterize several novel enhancers including Su(H)-dependent enhancers atNotchandDelta, intestinal enhancers atA2bp1andhedgehog, and distinct enhancers atroughest,E2f1, andescargot.
Accurate prediction of single-cell DNA methylation states using deep learning
Authors: Angermueller Christof , Lee Heather J. , Reik Wolf , Stegle Oliver 
Published: May 2016

AbstractRecent technological advances have enabled assaying DNA methylation at single-cell resolution. Current protocols are limited by incomplete CpG coverage and hence methods to predict missing methylation states are critical to enable genome-wide analyses. Here, we report DeepCpG, a computational approach based on deep neural networks to predict DNA methylation states from DNA sequence and incomplete methylation profiles in single cells. We evaluated DeepCpG on single-cell methylation data from five cell types generated using alternative sequencing protocols, finding that DeepCpG yields substantially more accurate predictions than previous methods. Additionally, we show that the parameters of our model can be interpreted, thereby providing insights into the effect of sequence composition on methylation variability.
Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters
Authors: Chen Yun , Pai Athma A. , Herudek Jan , Lubas Michal , Meola Nicola , Järvelin Aino I. , Andersson Robin , Pelechano Vicent , Steinmetz Lars M. , Heick Jensen Torben , Sandelin Albin 
Published: May 2016

AbstractMammalian transcriptomes are complex and formed by extensive promoter activity. In addition, gene promoters are largely divergent and initiate transcription of reverse-oriented promoter upstream transcripts (PROMPTs). Although PROMPTs are commonly terminated early, influenced by polyadenylation sites, promoters often cluster so that the divergent activity of one might impact another. Here, we find that the distance between promoters strongly correlates with the expression, stability and length of their associated PROMPTs. Adjacent promoters driving divergent mRNA transcription support PROMPT formation, but due to polyadenylation site constraints, these transcripts tend to spread into the neighboring mRNA on the same strand. This mechanism to derive new alternative mRNA transcription start sites (TSSs) is also evident at closely spaced promoters supporting convergent mRNA transcription. We suggest that basic building blocks of divergently transcribed core promoter pairs, in combination with the wealth of TSSs in mammalian genomes, provides a framework with which evolution shapes transcriptomes.
Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution
Authors: van Iterson Maarten , van Zwet Erik ,   the BIOS Consortium, Slagboom P. Eline , Heijmans Bastiaan T. 
Published: May 2016

ABSTRACTAssociation studies on omic-level data other then genotypes (GWAS) are becoming increasingly common, i.e., epigenome-and transcriptome-wide association studies (EWAS/TWAS). However, a tool box for the analysis of EWAS and TWAS studies is largely lacking and often approaches from GWAS are applied despite the fact that epigenome and transcriptome data have vedifferent characteristics than genotypes. Here, we show that EWASs and TWASs are prone not only to significant inflation but also bias of the test statistics and that these are not properly addressed by GWAS-based methodology (i.e. genomic control) and state-of-the-art approaches to control for unmeasured confounding (i.e. RUV, sva and cate). We developed a novel approach that is based on the estimation of the empirical null distribution using Bayesian statistics. Using simulation studies and empirical data, we demonstrate that our approach maximizes power while properly controlling the false positive rate. Finally, we illustrate the utility of our method in the application of meta-analysis by performing EWASs and TWASs on age and smoking which highlighted an overlap in differential methylation and expression of associated genes. An implementation of our new method is available fromhttp://bioconductor.org/packages/bacon/.
Convergent evolution of genes controlling mitonuclear balance in annual fishes
Authors: Sahm Arne , Bens Martin , Platzer Matthias , Cellerino Alessandro 
Published: May 2016

AbstractComplexes of the respiratory chain are formed in a complex process where nuclearly-and mitochondrially-encoded components are assembled and inserted into the inner mitochondrial membrane. The coordination of this process is named mitonuclear balance and experimental manipulations of mitonuclear balance can increase longevity of laboratory species.Here, we investigated the pattern of positive selection in annual (i.e. short-lived)and non-annual (i.e. long-lived) African killifishes to identify a genomic substrate for evolution of annual life history (and reduced lifespan).We identified genes under positive selection in all mitonuclear balance: mitochondrial (mt) DNA replication, transcription from mt promoters, processing and stabilization of mt RNAs, mt translation, assembly of respiratory chain complexes and electron transport chain. Signs of convergent evolution are observed in four out of five steps. This strongly indicates that these genes are preferential genetic targets for the evolution of short lifespan and annual life cycle
Adapting Genotyping-by-Sequencing for Rice F2 Populations
Authors: Furuta Tomoyuki , Ashikari Motoyuki , Jena Kshirod K. , Doi Kazuyuki , Reuscher Stefan 
Published: May 2016

ABSTRACTRapid and cost-effective genotyping of large mapping populations can be achieved by sequencing a reduced representation of the genome of every individual in a given population and using that information to generate genetic markers. A customized genotyping-by-sequencing (GBS) pipeline was developed to genotype a rice F2 population from a cross ofOryza sativassp.japonicacv. Nipponbare and the African wild rice speciesOryza longistaminata. While most GBS pipelines aim to analyze mainly homozygous populations we attempted to genotype a highly heterozygous F2 population. We show how species-and population-specific improvements of established protocols can drastically increase sample throughput and genotype quality. Using as few as 50,000 reads for some individuals (134,000 reads on average) we were able to generate up to 8,154 informative SNP markers in 1,081 F2 individuals. Additionally, the effects of enzyme choice, read coverage and data post-processing are evaluated. Using GBS-derived markers we were able to assemble a genetic map of 1,536 cM. To demonstrate the usefulness of our GBS pipeline we determined QTL for the number of tillers. We were able to map four QTLs to chromosomes 1, 3, 4 and 8 and confirm their effects using introgression lines. We provide an example of how to successfully use GBS with heterozygous F2 populations. By using the comparatively low-cost MiSeq platform we show that the GBS method is flexible and cost-effective even for smaller laboratories
PIPI: PTM-Invariant Peptide Identification Using Coding Method
Authors: Yu Fengchao , Li Ning , Yu Weichuan 
Published: May 2016

AbstractIn computational proteomics, identification of peptides with an unlimited number of post-translational modification (PTM) types is a challenging task. The computational cost increases exponentially with respect to the number of modifiable amino acids and linearly with respect to the number of potential PTM types at each amino acid. The problem becomes intractable very quickly if we want to enumerate all possible modification patterns. Existing tools (e.g., MS-Alignment, ProteinProspector, and MODa) avoid enumerating modification patterns in database search by using an alignment-based approach to localize and characterize modified amino acids. This approach avoids enumerating all possible modification patterns in a database search. However, due to the large search space and PTM localization issue, the sensitivity of these tools is low. This paper proposes a novel method named PIPI to achieve PTM-invariant peptide identification. PIPI first codes peptide sequences into Boolean vectors and converts experimental spectra into real-valued vectors. Then, it finds the top 10 peptide-coded vectors for each spectrum-coded vector. After that, PIPI uses a dynamic programming algorithm to localize and characterize modified amino acids. Simulations and real data experiments have shown that PIPI outperforms existing tools by identifying more peptide-spectrum matches (PSMs) and reporting fewer false positives. It also runs much faster than existing tools when the database is large.
Rapid emergence of HCMV drug resistance in immunocompromised paediatric patients detected using target enrichment and deep sequencing
Authors: Houldcroft Charlotte , Bryant Josephine M. , Depledge Daniel P. , Margetts Ben K. , Simmonds Jacob , Nicolaou Stephanos , Tutill Helena , Williams Rachel , Worth Austen , Marks Stephen D. , Veys Paul , Whittaker Elizabeth , Breuer Judith ,   the PATHSEEK condortium
Published: May 2016

AbstractBackgroundCytomegalovirus can cause fatal disease in immunocompromised patients. With the advent of new anti-HCMV drugs there is interest in using virus sequence data to monitor resistance and identify new mutations.MethodsWe used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed paediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1-27 weeks. Changes in consensus sequence and resistance mutations were analysed for three ORFs targeted by anti-HCMV drugs and the frequencies of drug resistance mutations monitored.ResultsTargeted-enriched sequencing of clinical material detected mutations occurring at frequencies of 2%. Seven patients showed no evidence of drug resistance mutations. Four patients developed drug resistance mutations a mean of 16 weeks after starting treatment. In two patients, multiple resistance mutations accumulated at frequencies of 20% or less, including putative resistance mutations P522Q (UL54) and C480F (UL97). In one patient, resistance was detected 14 days earlier than by PCR. Phylogenetic analysis suggested recombination or superinfection in one patient.ConclusionsDeep sequencing of HCMV enriched from clinical samples excluded resistance in 7 of eleven subjects and identified resistance mutations earlier than conventional PCR-based resistance testing in 2 patients. Detection of multiple low level resistance mutations was associated with poor outcome.
α4-containing GABAAreceptors on dopamine D2 receptor-expressing neurons mediate instrumental responding for conditioned reinforcers, and its potentiation by cocaine
Authors: Macpherson Tom , Dixon Claire I , Janak Patricia H. , Belelli Delia , Lambert Jeremy J. , Stephens David N. , King Sarah 
Published: May 2016

Abstract:Extrasynaptic GABAAreceptors (GABAARs) composed of α4, β and δ subunits mediate GABAergic tonic inhibition and are pertinent molecular targets in the modulation of behavioural responses to drugs of abuse, including ethanol and cocaine. These GABAARs are highly expressed within the nucleus accumbens (NAc) where they influence the excitability of the medium spiny neurons (MSNs). Here we explore their role in modulating behavioural responses to reward-conditioned cues and the behaviour-potentiating effects of cocaine. α4-subunit constitutive knockout mice (α4-/-) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen following viral knockdown of GABAAR α4 subunits within the NAc. Local infusion of the δ-GABAAR-preferring agonist, THIP, into the NAc had no effect on responding when given alone, but reduced cocaine potentiation of responding for conditioned reinforcers in wildtype but not α4-/- mice. Finally, specific deletion of α4-subunits from dopamine D2-, but not D1-receptor-expressing neurons, mimicked the phenotype of the constitutive knockout, potentiating CRf responding and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that α4-GABAAR mediated inhibition of dopamine D2 receptor-expressing neurons reduces instrumental-responding for a conditioned reinforcer, and its potentiation by cocaine, and emphasise the potential importance of GABAergic signalling within the NAc in mediating cocaine’s effects.
Population structure of UK Biobank and ancient Eurasians reveals adaptation at genes influencing blood pressure
Authors: Galinsky Kevin J. , Loh Po-Ru , Swapan Mallick , Patterson Nick J. , Price Alkes L. 
Published: May 2016

AbstractAnalyzing genetic differences between closely related populations can be a powerful way to detect recent adaptation. The very large sample size of the UK Biobank is ideal for detecting selection using population differentiation, and enables an analysis of UK population structure at fine resolution. In analyses of 113,851 UK Biobank samples, population structure in the UK is dominated by 5 principal components (PCs) spanning 6 clusters: Northern Ireland, Scotland, northern England, southern England, and two Welsh clusters. Analyses with ancient Eurasians show that populations in the northern UK have higher levels of Steppe ancestry, and that UK population structure cannot be explained as a simple mixture of Celts and Saxons. A scan for unusual population differentiation along top PCs identified a genome-wide significant signal of selection at the coding variant rs601338 inFUT2(p= 9.16 × 10−9). In addition, by combining evidence of unusual differentiation within the UK with evidence from ancient Eurasians, we identified new genome-wide significant (p< 5 × 10−8) signals of recent selection at two additional loci:CYP1A2/CSKandF12. We detected strong associations to diastolic blood pressure in the UK Biobank for the variants with new selection signals atCYP1A2/CSK(p= 1.10 × 10−19)) and for variants with ancient Eurasian selection signals in theATXN2/SH2B3locus (p= 8.00 × 10−33), implicating recent adaptation related to blood pressure.
Rapidly evolving homing CRISPR barcodes
Authors: Kalhor Reza , Mali Prashant , Church George M. 
Published: May 2016

AbstractWe present here an approach for engineering evolving DNA barcodes in living cells. The methodology entails using a homing guide RNA (hgRNA) scaffold that directs the Cas9-hgRNA complex to target the DNA locus of the hgRNA itself. We show that this homing CRISPR-Cas9 system acts as an expressed genetic barcode that diversifies its sequence and that the rate of diversification can be controlled in cultured cells. We further evaluate these barcodes in cultured cell populations and show that they can record lineage history and and that their RNA can be assayed as single moleculesin situ. This integrated approach will have wide ranging applications, such as in deep lineage tracing, cellular barcoding, molecular recording, dissecting cancer biology, and connectome mapping.