bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood
Authors: Qi Ting , Wu Yang , Zeng Jian , Zhang Futao , Xue Angli , Jiang Longda , Zhu Zhihong , Kemper Kathryn , Yengo Loic , Zheng Zhili ,   eQTLGen Consortium, Marioni Riccardo E. , Montgomery Grant W. , Deary Ian J. , Wray Naomi R. , Visscher Peter M. , McRae Allan F. , Yang Jian 
Published: March 2018

AbstractUnderstanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes associated with brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top associated cis-expression (cis-eQTLs or cis-mQTLs) between brain and blood for genes expressed (or CpG sites methylated) in both tissues, while accounting for errors in their estimated effects (rb). Using publicly available data (n = 72 to l,366), we find that the genetic effects of cis-eQTLs (PeQTL < 5×10−8) or mQTLs (PmQTL < 1×10−10) are highly correlated between independent brain and blood samples ( with SE = 0.015 for cis-eQTL and with SE = 0.006 for cis-mQTLs). Using meta-analyzed brain eQTL/mQTL data (n = 526 to 1,194), we identify 61 genes and 167 DNA methylation (DNAm) sites associated with 4 brain-related traits and disorders. Most of these associations are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = l,980 to 14,115). We further find that cis-eQTLs with tissue-specific effects are approximately uniformly distributed across all the functional annotation categories, and that mean difference in gene expression level between brain and blood is almost independent of the difference in the corresponding cis-eQTL effect. Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL or cis-mQTL data with large sample sizes.
The importance of semantic network brain regions in integrating prior knowledge with an ongoing dialogue
Authors: Raykov Petar P. , Keidel James L. , Oakhill Jane , Bird Chris M. 
Published: March 2018

AbstractTo understand a dialogue we need to know the specific topics that are being discussed. This enables us to integrate our knowledge of what was said previously, in order to interpret the current dialogue. Here, we selectively manipulated knowledge about the narrative content of dialogues between two people, presented in short videos. The videos were clips taken from television situation comedies and the speech in the first-half of the clip could either be presented normally (high context) or spectrally rotated in order to render it unintelligible (low context). Knowledge of the preceding narrative boosted memory for the following dialogues as well as increased the inter-subject semantic similarity of recalled descriptions of the dialogues. Sharing knowledge of the preceding narrative across participants had two effects on fMRI markers of neural processing: (1) it strengthened temporal inter-subject correlations in regions including the left angular (AG) and inferior frontal gyri (IFG), and (2) it increased spatial inter-subject pattern similarity in the bilateral anterior temporal lobes (ATL). We argue that these brain regions, which are known to be involved in semantic processing, support the activation and integration of prior knowledge, which helps people to better understand and remember dialogues as they unfold.
High-throughput inference of pairwise coalescence times identifies signals of selection and enriched disease heritability
Authors: Palamara Pier Francesco , Terhorst Jonathan , Song Yun S. , Price Alkes L. 
Published: March 2018

AbstractInterest in reconstructing demographic histories has motivated the development of methods to estimate locus-specific pairwise coalescence times from whole-genome sequence data. We developed a new method, ASMC, that can estimate coalescence times using only SNP array data, and is 2-4 orders of magnitude faster than previous methods when sequencing data are available. We were thus able to apply ASMC to 113,851 phased British samples from the UK Biobank, aiming to detect recent positive selection by identifying loci with unusually high density of very recent coalescence times. We detected 12 genome-wide significant signals, including 6 loci with previous evidence of positive selection and 6 novel loci, consistent with coalescent simulations showing that our approach is well-powered to detect recent positive selection. We also applied ASMC to sequencing data from 498 Dutch individuals (Genome of the Netherlands data set) to detect background selection at deeper time scales. We observed highly significant correlations between average coalescence time inferred by ASMC and other measures of background selection. We investigated whether this signal translated into an enrichment in disease and complex trait heritability by analyzing summary association statistics from 20 independent diseases and complex traits (averageN=86k) using stratified LD score regression. Our background selection annotation based on average coalescence time was strongly enriched for heritability (p = 7×10−153) in a joint analysis conditioned on a broad set of functional annotations (including other background selection annotations), meta-analyzed across traits; SNPs in the top 20% of our annotation were 3.8x enriched for heritability compared to the bottom 20%. These results underscore the widespread effects of background selection on disease and complex trait heritability.
Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control
Authors: Chilloux Julien , Brial Francois , Everard Amandine , Smyth David , Andrikopoulos Petros , Zhang Liyong , Plovier Hubert , Myridakis Antonis , Hoyles Lesley , Moreno-Navarrete José Maria , Luque Jèssica Latorre , Casagrande Viviana , Menghini Rosella , Ahmetaj-Shala Blerina , Blancher Christine , Martinez-Gili Laura , Gencer Selin , Fearnside Jane F. , Barton Richard H. , Neves Ana Luisa , Rothwell Alice R. , Gérard Christelle , Calderari Sophie , Williamson Mark J. , Fuchs Julian E. , Govada Lata , Boulangé Claire L. , Patel Saroor , Scott James , Thursz Mark , Chayen Naomi , Glen Robert C. , Gooderham Nigel J. , Nicholson Jeremy K. , Federici Massimo , Fernández-Real José-Manuel , Gauguier Dominique , Liu Peter P. , Cani Patrice D. , Dumas Marc-Emmanuel 
Published: March 2018

AbstractThe global type 2 diabetes epidemic is a major health crisis and there is a critical need for innovative strategies to fight it. Although the microbiome plays important roles in the onset of insulin resistance (IR) and low-grade inflammation, the microbial compounds regulating these phenomena remain to be discovered. Here, we reveal that the microbiome inhibits a central kinase, eliciting immune and metabolic benefits. Through a series ofin vivoexperiments based on choline supplementation, blocking trimethylamine (TMA) production then administering TMA, we demonstrate that TMA decouples inflammation and IR from obesity in the context of high-fat diet (HFD) feeding. Throughin vitrokinome screens, we reveal TMA specifically inhibits Interleukin-1 Receptor-associated Kinase 4 (IRAK4), a central kinase integrating signals from various toll-like receptors and cytokine receptors. TMA blunts TLR4 signalling in primary human hepatocytes and peripheral blood monocytic cells, and improves mouse survival after a lipopolysaccharide-induced septic shock. Consistent with this, genetic deletion and chemical inhibition of IRAK4 result in similar metabolic and immune improvements in HFD. In summary, TMA appears to be a key microbial compound inhibiting IRAK4 and mediating metabolic and immune effects with benefits upon HFD. Thereby we highlight the critical contribution of the microbial signalling metabolome in homeostatic regulation of host disease and the emerging role of the kinome in microbial–mammalian chemical crosstalk.
The effect of strain level diversity on robust inference of virus-induced mortality
Authors: Beckett Stephen J. , Weitz Joshua S. 
Published: March 2018

AbstractInfection and lysis of phytoplankton by viruses affects population dynamics and nutrient cycles within oceanic microbial communities. However, estimating the quantitative rates of viral-induced lysis remains challenging in situ. The modified dilution method is the most commonly utilised empirical approach to estimate virus-induced killing rates of phytoplankton. The lysis rate estimates of the modified dilution method are based on models of virus-host interactions involving only a single virus and a single host population. Here, using modelling approaches, we examine the robustness of the modified dilution method in multi-strain, complex communities. We assume that strains differ in their life history traits, including growth rates (of hosts) and lysis rates (by viruses). We show that trait differences affect resulting experimental dynamics such that lysis rates measured using the modified dilution method may be driven by the fastest replicating strains; which are not necessarily the most abundant in situ. We discuss the implications of using the modified dilution method and alternative dilution-based approaches for estimating viral-induced lysis rates in marine microbial communities.
Layer 3 dynamically coordinates columnar activity according to spatial context
Authors: Plomp Gijs , Larderet Ivan , Fiorini Matilde , Busse Laura 
Published: March 2018

AbstractSpatial integration is a fundamental, context-dependent neural operation that involves extensive neural circuits across cortical layers of V1. To better understand how spatial integration is dynamically coordinated across layers we recorded single- and multi-unit activity and local field potentials across V1 layers of awake mice, and used dynamic Bayesian model comparisons to identify when laminar activity and inter-laminar functional interactions showed surround suppression, the hallmark of spatial integration. We found that surround suppression is strongest in layer 3 (L3) and L4 activity, showing rapidly sharpening receptive fields and increasing suppression strength. Importantly, we also found that specific directed functional connections were strongest for intermediate stimulus sizes and suppressed for larger ones, particularly for the L3->L5 and L3->L1 connections. Taken together, the results shed light on the different functional roles of cortical layers in spatial integration and show how L3 dynamically coordinates activity across a cortical column depending on spatial context.
Dynamic virulence-related regions of the fungal plant pathogen Verticillium dahliae display remarkably enhanced sequence conservation
Authors: Depotter Jasper R.L. , Shi-Kunne Xiaoqian , Missonnier Hélène , Liu Tingli , Faino Luigi , van den Berg Grardy C.M. , Wood Thomas A. , Zhang Baolong , Jacques Alban , Seidl Michael F. , Thomma Bart P.H.J. 
Published: March 2018

ABSTRACTSelection pressure impacts genomes unevenly, as different genes adapt with differential speed to establish an organism’s optimal fitness. Plant pathogens co-evolve with their hosts, which implies continuously adaption to evade host immunity. Effectors are secreted proteins that mediate immunity evasion, but may also typically become recognized by host immune receptors. To facilitate effector repertoire alterations, in many pathogens, effector genes reside in dynamic genomic regions that are thought to display accelerated evolution, a phenomenon that is captured by the two-speed genome hypothesis. The genome of the vascular wilt pathogen Verticillium dahliae has been proposed to obey to a similar two-speed regime with dynamic, lineage-specific regions that are characterized by genomic rearrangements, increased transposable element activity and enrichment in in planta-induced effector genes. However, little is known of the origin of, and sequence diversification within, these lineage-specific regions. Based on comparative genomics among Verticillium spp. we now show differential sequence divergence between core and lineage-specific genomic regions of V. dahliae. Surprisingly, we observed that lineage-specific regions display markedly increased sequence conservation. Since single nucleotide diversity is reduced in these regions, host adaptation seems to be merely achieved through presence/absence polymorphisms. Increased sequence conservation of genomic regions important for pathogenicity is an unprecedented finding for filamentous plant pathogens and signifies the diversity of genomic dynamics in host-pathogen co-evolution.
Comprehensive peptide quantification for data independent acquisition mass spectrometry using chromatogram libraries
Authors: Searle Brian C. , Pino Lindsay K. , Egertson Jarrett D. , Ting Ying S. , Lawrence Robert T. , Villén Judit , MacCoss Michael J. 
Published: March 2018

ABSTRACTData independent acquisition (DIA) mass spectrometry is a powerful technique that is improving the reproducibility and throughput of proteomics studies. We introduce a new experimental workflow that uses this technique to construct chromatogram libraries that capture fragment ion chromatographic peak shape and retention time for every detectable peptide in an experiment. These coordinates calibrate information in spectrum libraries or protein databases to a specific mass spectrometer and chromatography setup, and enable sensitive peptide detection in quantitative experiments. We also present EncyclopeDIA, a software tool for generating and searching chromatogram libraries, and demonstrate the performance of our workflow by quantifying proteins in human and yeast cells. We find that by exploiting calibrated retention time and fragmentation specificity in chromatogram libraries, EncyclopeDIA can detect and quantify >50% more peptides from DIA experiments than with DDA-based spectrum libraries alone.
Genetic and environmental influence on the human functional connectome
Authors: Reineberg Andrew E. , Hatoum Alexander S. , Hewitt John K. , Banich Marie T. , Friedman Naomi P. 
Published: March 2018

AbstractDetailed mapping of genetic and environmental influences on the functional connectome is a crucial step toward developing intermediate phenotypes between genes and clinical diagnoses or cognitive abilities. We analyze resting-state data from two, adult twin samples - 390 twins from the Colorado Longitudinal Twin Sample and 422 twins from the Human Connectome Project - to examine genetic and environmental influence on all pairwise functional connections between 264 brain regions (~35,000 functional connections). Non-shared environmental influence was high, genetic influence was moderate, and shared environmental influence was weak-to-moderate across the connectome. The brain’s genetic organization is diverse and not as one would expect based solely on structure evident in non-genetically informative data or lower-resolution data. As follow-up, we make novel classifications of functional connections and examine highly-localized connections with particularly strong genetic influence. This high-resolution genetic taxonomy of brain connectivity will be useful in understanding genetic influences on brain disorders.
Spatial and Temporal Changes in Habitat Heterogeneity Promote Partition of Resources of Small Mammals in a Midlatitude Temperate Forest
Authors: De la Cruz-Arguello Ivan M. , Castro-Campillo Alondra , Zavala-Hurtado Alejandro , Salame-Méndez Arturo , Ramírez-Pulido José 
Published: March 2018

AbstractOne of the basics and fundamentals problems in ecology is understand the factors that shape the spatial patterns in the distribution of the species and the coexistence of close relatives species. Among the most important factors governing the distributions and the coexistence of species are the spatiotemporal changes occurring in the microhabitat heterogeneity. Here, we assessed the heterogeneity of microhabitats and how they have an effect in the spatial segregation of two species of small mammals (i. e.,Peromyscus difficilisandP. melanotis), which coexist in a temperate, mixed forest. We evaluated the microhabitat heterogeneity through multivariate statistics, using onto 23 habitat variables for vertical-horizontal habitat structure along pluvial seasons. To detect specific microdistribution changes and habitat preferences by two species of small mammals, we used second order spatial statistics and general linear models. According to their respective morphology and locomotive adaptations, the middle sized, midscansorialP. difficiliswas resident all year long and preferred microhabitats with a high log ground cover, while the opportunistic, small sized, cursorialP. melanotischanged its occupancy area, depending on density of herbaceous and woody plants cover. Under the more benign microhabitat conditions of rainy season (denser plant coverage, milder temperature), both species showed closer microdistribution patterns; while these became repulsive at the less benign conditions of dry season (scarcer plant cover, colder temperature). Thus, we could confirm that seasonal changes of microhabitat heterogeneity promotedPeromyscuscoexistence, through dispersion patterns reflecting partition of microhabitat resources.
Influence of microbial adherence on corrosion of UNS 1008 carbon steel and hybrid nano-structured coatings
Authors: Diaz De Rienzo Mayri Alejandra , Aguirre Ramirez Marisela , Martin Peter J. , Galicia Garcia Monica 
Published: March 2018

Purpose
Microbes that are able to grow on different surfaces can cause the deterioration of the underlying layers because of their metabolic activity. The purpose of this study is report the ability of fungi-bacteria consortium (FBC) in anaerobic media, and marine strain bacteria, to attach onto UNS 1008 carbon steel and zinc epoxy coats.

Design/methodology/approach
Impedance analysis, scanning electronic microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) were used to evaluate the adherence, biofilm formation and corrosion effect of FBC and marine bacteria onto UNS1008 carbon steel in anaerobic and aired conditions, respectively. In a similar way, the anticorrosive performance of hybrid coats on UNS 1008 carbon steel against marine bacteria.

Findings
In aerobic conditions, the outer layer shows a micro-crack appearance and several semi-sphere products that could be because of spore formation. In anaerobic conditions, evidence of iron sulfide surrounded by a mixture of sulfur-containing extracellular polymer substance was observed by SEM images and EDS analysis. The presence of hybrid coats (zinc epoxy with carbon nanotubes CNT content) affected the level of microbial adherence and the concentration of corrosion products (Fe2O3, Fe(OH)2 and FeS); the cell attachment was lower when the steel surface was coated with Zn/CNTs.

Originality/value
This study opens a window for further evaluations of CNTs associated with metals as active materials to assess the corrosion on extreme corrosive environments, like in oil and gas industries the microorganisms play an important role either to increase or reduce the corrosion processes.
Is there discrimination against the agricultural sector in the credit rationing behavior of commercial banks in Ghana?
Authors: Sackey Frank Gyimah 
Published: March 2018

Purpose
The purpose of this paper is to examine if credit rationing persists even in the era of financial liberalization, the extent to which individual, firm and loan characteristics influence the rationing behavior of commercial banks and whether the agricultural sector is discriminated against in the commercial bank credit market.

Design/methodology/approach
The study employed a probit model with marginal effects and a generalized Blinder-Oaxaca decomposition estimation on a randomly selected data of 1,239 entrepreneurs from eight commercial banks’ credit records about their individual, firm and loan characteristics.

Findings
The study revealed that credit rationing persists and that applying for a relatively longer payment period, providing collateral and guarantor, being illiterate, being relatively older and being in the agricultural sector increases the likelihood of being credit rationed, while having some relationship with the bank, having non-mandatory savings and applying from a bank with relatively high interest rates reduce the likelihood of being credit rationed. The study also revealed a credit gap of 17.77 percent and a positive discrimination against borrowers in the agricultural sector as the gap was largely being influenced by unexplained factors.

Research limitations/implications
The research was intended to cover a large number of commercial banks in Ghana. However, most of the banks were unwilling to provide such information about their borrowers; hence, the research was limited to only eight commercial banks who provided the author with the information needed for the study.

Practical implications
The study concludes that policies that enhance human capital, women, and older access to credit and agricultural-oriented financial services and others, will go a long way to reduce rationing and increase access to credit, especially to the agricultural sector.

Social implications
The research proposes the use of group lending as a form of collateral and monitoring to ease risks and default, and hence supports sustainable funding to increase access and outreach.

Originality/value
The paper looks at the comprehensive way about the various factors determining credit rationing in that it considers not only the individual, economic/firm and loan characteristics but also the extent to which discrimination toward the agricultural sector exists in the commercial banks credit market.
Managing dramaturgical dilemmas: youth drinking and multiple identities
Authors: Cocker Hayley , Piacentini Maria , Banister Emma 
Published: March 2018

Purpose
This paper aims to understand how young people manage the dramaturgical dilemmas related to drinking alcohol and performing multiple identities.

Design/methodology/approach
Drawing on qualitative data collected with 16-18-year olds, the authors adopt Goffman’s dramaturgical perspective to examine youth alcohol consumption in relation to multiple identities.

Findings
Young people continuously and skilfully juggle multiple identities across multiple contexts, where identities overflow and audiences and interactions overlap. Techniques of audience segregation, mystification and misrepresentation and justification are used to perform and manage multiple identities in a risky health behaviour context.

Research limitations/implications
The approach may facilitate some over- and under-claiming. Future studies could observe young people’s performances of self across multiple contexts, paying particular attention to how alcohol features in these performances.

Practical implications
Social marketing campaigns should demonstrate an understanding of how alcohol relates to the contexts of youth lives beyond the “night out” and engage more directly with young peoples’ navigation between different identities, contexts and audiences. Campaigns could tap into the secretive nature of youth alcohol consumption and discourage youth from prioritising audience segregation and mystification above their own safety.

Originality/value
Extant work has argued that consumers find multiplicity unmanageable or manage multiple identities through internal dialogue. Instead, this paper demonstrates how young people manage multiple identities through interaction and performance. This study challenges the neat compartmentalisation of identities identified in prior literature and Goffman’s clear-cut division of performances into front and back stage.