301 research outputs found
Breaking the Silence: The role of gossip in organizational culture
From the early 1980s, the number of studies pertaining to organizational culture expanded considerably to the point where it could reasonably be argued that the field had reached a level of maturity. Perhaps indicative of this maturity was the publication of the first handbook of organizational culture and climate (Ashkanasy et al. 2000). The commencement of academic interest in the topic of organizational culture generally coincided with the publication of two books mainly aimed at practitionersâPeters and Watermanâs, In search of excellence (1982) and Deal and Kennedyâs, Corporate cultures: the rites and rituals of corporate life (1982). This is not to suggest that these books account exclusively for the intellectual curiosity generated in the function and purpose of culture for an organization as there were well-known examples which had earlier sought to address the issue of organizational cultures (e.g. Pettigrew 1979). Nonetheless, these tomes were influential in raising interest in, and scope for, research on organizational culture
A characterization of cis- and trans-heritability of RNA-Seq-based gene expression
Insights into individual differences in gene expression and its heritability (h2) can help in understanding pathways from DNA to phenotype. We estimated the heritability of gene expression of 52,844 genes measured in whole blood in the largest twin RNA-Seq sample to date (1497 individuals including 459 monozygotic twin pairs and 150 dizygotic twin pairs) from classical twin modeling and identity-by-state-based approaches. We estimated for each gene h2 total, composed of cis-heritability (h2 cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h2 res, the residual variance explained by all other genome-wide variants). Mean h2 total was 0.26, which was significantly higher than heritability estimates earlier found in a microarray-based study using largely overlapping (>60%) RNA samples (mean h2 = 0.14, p = 6.15 Ă 10â258). Mean h2 cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, Ï = 0.76, p < 10â308) and with estimates from earlier RNA-Seq-based studies. Mean h2 res was 0.20 and correlated with the beta of the corresponding trans-eQTL (Ï = 0.04, p < 1.89 Ă 10â3) and was significantly higher for genes involved in cytokine-cytokine interactions (p = 4.22 Ă 10â15), many other immune system pathways, and genes identified in genome-wide association studies for various traits including behavioral disorders and cancer. This study provides a thorough characterization of cis- and trans-h2 estimates of gene expression, which is of value for interpretation of GWAS and gene expression studies
Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution
We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate. We illustrate the utility of our method in large-scale EWAS and TWAS meta-analyses of age and smoking.</p
Detection of inadequate anastomotic perfusion with handheld vital microscopy in two patients during colorectal surgery
Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted
Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution
Everyday Secrecy:Boundaries of Confidential Gossip
Gossip is an everyday part of organizational life and has been increasingly researched. However, some gossip has a particular character, whereby it is to some degree secret. Drawing on studies of both gossip and secrecy, in this paper we explore this âconfidential gossipâ via a participant observation case study. This was based on an internship with Quinza, a British media company, and had a covert element which is discussed and justified. Specifically, we show how the boundaries around confidential gossip are marked in organizational interactions. The paper contributes to existing knowledge about organizational gossip by showing the particular significance of secrecy which makes confidential gossip a more potent source of group inclusion and exclusion
Refining Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Genetic Loci by Integrating Summary Data From Genome-wide Association, Gene Expression, and DNA Methylation Studies
Background: Recent genome-wide association studies (GWASs) identified the first genetic loci associated with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The next step is to use these results to increase our understanding of the biological mechanisms involved. Most of the identified variants likely influence gene regulation. The aim of the current study is to shed light on the mechanisms underlying the genetic signals and prioritize genes by integrating GWAS results with gene expression and DNA methylation (DNAm) levels. Methods: We applied summary-dataâbased Mendelian randomization to integrate ADHD and ASD GWAS data with fetal brain expression and methylation quantitative trait loci, given the early onset of these disorders. We also analyzed expression and methylation quantitative trait loci datasets of adult brain and blood, as these provide increased statistical power. We subsequently used summary-dataâbased Mendelian randomization to investigate if the same variant influences both DNAm and gene expression levels. Results: We identified multiple gene expression and DNAm levels in fetal brain at chromosomes 1 and 17 that were associated with ADHD and ASD, respectively, through pleiotropy at shared genetic variants. The analyses in brain and blood showed additional associated gene expression and DNAm levels at the same and additional loci, likely because of increased statistical power. Several of the associated genes have not been identified in ADHD and ASD GWASs before. Conclusions: Our findings identified the genetic variants associated with ADHD and ASD that likely act through gene regulation. This facilitates prioritization of candidate genes for functional follow-up studies
Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms
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