Predictors of sleep quality: stress exposure and the additive influence of six serotonergic polymorphisms

Sleep is critical for physical and mental health and peak cognitive performance (Watson et al., 2015). While main effects of genetic and environmental factors, including stress, on sleep quality are well-established, the influence of gene-environment interactions on sleep merits further study. The present research evaluated the relationship between serotonergic genetic variation, exposure to recent perceived life stress, and sleep quality outcomes among a sample of emerging adults. Given the polygenic influences underlying sleep processes, the cumulative effect of single nucleotide polymorphisms (SNPs) in and near several serotonin system genes was examined. A genetic profile score was constructed using a sum of alleles hypothesized to confer risk for sleep disruption. Undergraduate participants provided DNA samples, wore wrist-actigraphs to record sleep-wake patterns over three nights, and completed daily diary entries for two weeks. Diaries included assessments of sleep quality and exposure to daily hassles, a form of life stress. Using hierarchical linear modeling, we evaluated the hypotheses that 1) daily hassles would be associated with poorer quality of sleep in main effect and 2) genetic profile scores would significantly moderate the relationship between hassles and sleep, such that higher genetic risk scores would predict poorer quality of sleep in the context of increased daily hassles. Findings indicated that interpersonal and non-interpersonal daily hassles did not predict self-reported or actigraph-measured sleep outcomes in main effect, and the interaction of hassles and serotonergic MLP score did not predict sleep outcomes. Results suggested that the study sample exhibited relatively healthy sleep patterns and reported relatively few hassles. The findings suggest avenues for future research, including exploration of the roles of additional forms of stress in sleep disruption

Development and psychometric validation of the chronic life stress questionnaire : a multidomain measure of chronic stress exposure

Chronic life stress—ongoing, non-acute strain—is implicated in physical and psychiatric disease pathways, including depression, but is understudied. Critically, the absence of psychometrically sound, valid, and efficient measures for comprehensively assessing chronic stress exposure represents a barrier to its further study. The present study developed and evaluated the psychometric properties of the Chronic Life Stress Questionnaire (CLSQ), which is based on the well-regarded UCLA Life Stress Interview (LSI). The CLSQ’s properties, including its reliability, factor structure, and validity, were examined using the classical test theory framework. Analyses drew on data collected from four diverse samples of young adults (N = 787) at three academic institutions. The final CLSQ contained 107 items assessing chronic stress in ten life domains. Results indicated that the large majority of CLSQ scales showed good internal consistency and test-retest reliability. Confirmatory factor analysis with a two-factor structure yielded mixed evidence of acceptable model fit. However, factor analytic findings shed light on forms of chronic stress—namely family relationship and academic stress—that were associated with chronic stress in multiple life domains; these findings may guide future research efforts into stress spillover mechanisms among young adults. Analyses examining construct, criterion, and discriminant validity of the CLSQ scales also yielded promising results. Findings suggest future avenues for iterative development and for empirical investigation using the CLSQ, which provides a viable, efficient avenue for comprehensively assessing chronic stress exposure in young adults

Campylobacter jejuni Demonstrates Conserved Proteomic and Transcriptomic Responses When Co-cultured With Human INT 407 and Caco-2 Epithelial Cells

Major foodborne bacterial pathogens, such as Campylobacter jejuni, have devised complex strategies to establish and foster intestinal infections. For more than two decades, researchers have used immortalized cell lines derived from human intestinal tissue to dissect C. jejuni-host cell interactions. Known from these studies is that C. jejuni virulence is multifactorial, requiring a coordinated response to produce virulence factors that facilitate host cell interactions. This study was initiated to identify C. jejuni proteins that contribute to adaptation to the host cell environment and cellular invasion. We demonstrated that C. jejuni responds to INT 407 and Caco-2 cells in a similar fashion at the cellular and molecular levels. Active protein synthesis was found to be required for C. jejuni to maximally invade these host cells. Proteomic and transcriptomic approaches were then used to define the protein and gene expression profiles of C. jejuni co-cultured with cells. By focusing on those genes showing increased expression by C. jejuni when co-cultured with epithelial cells, we discovered that C. jejuni quickly adapts to co-culture with epithelial cells by synthesizing gene products that enable it to acquire specific amino acids for growth, scavenge for inorganic molecules including iron, resist reactive oxygen/nitrogen species, and promote host cell interactions. Based on these findings, we selected a subset of the genes involved in chemotaxis and the regulation of flagellar assembly and generated C. jejuni deletion mutants for phenotypic analysis. Binding and internalization assays revealed significant differences in the interaction of C. jejuni chemotaxis and flagellar regulatory mutants. The identification of genes involved in C. jejuni adaptation to culture with host cells provides new insights into the infection process

Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.

International audienceThe mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection

Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

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