Cell phone-based dating applications (apps) are increasingly popular in the USA. However, there is a paucity of research regarding dating app use among young heterosexual adults. This study examined ...the prevalence of dating application use and its connections with sexual behavior among young heterosexual adults. Five hundred nine heterosexual cisgender undergraduate students aged 18–25 completed an online survey assessing trait impulsivity, dating app use and motivations for using dating apps, sexual behavior, and demographics. 39.5% of the participants reported using dating apps. Individuals who used dating apps had higher rates of sexual risk behaviors in the past 3 months, including sex after using drugs or alcohol, and unprotected sex (anal or vaginal), and more lifetime sexual partners. When controlling for demographics and impulsivity, individuals who used dating applications were twice as likely to have had unprotected sex in the past 3 months, but were not significantly more likely to have had multiple partners within the past 3 months. In an exploratory analysis controlling for demographics and impulsivity, dating app use predicted the number of lifetime sexual partners. This study documented an association between dating app use and sexual risk behaviors among young heterosexual adults. Results suggest potential targets for intervention, including interventions that address sexual health information, and the dissemination of sexual health information through dating apps themselves.
Fructose consumption is now recognised as a major risk factor in the development of metabolic diseases, such as hyperlipidaemia, diabetes, non-alcoholic fatty liver disease and obesity. In addition ...to environmental, social, and genetic factors, an unfavourable intrauterine environment is now also recognised as an important factor in the progression of, or susceptibility to, metabolic disease during adulthood. Developmental trajectory in the short term, in response to nutrient restriction or excessive nutrient availability, may promote adaptation that serves to maintain organ functionality necessary for immediate survival and foetal development. Consequently, this may lead to decreased function of organ systems when presented with an unfavourable neonatal, adolescent and/or adult nutritional environment. These early events may exacerbate susceptibility to later-life disease since sub-optimal maternal nutrition increases the risk of non-communicable diseases (NCDs) in future generations. Earlier dietary interventions, implemented in pregnant mothers or those considering pregnancy, may have added benefit. Although, the mechanisms by which maternal diets high in fructose and the vertical transmission of maternal metabolic phenotype may lead to the predisposition to adult disease are poorly understood. In this review, we will discuss the potential contribution of excessive fructose intake during pregnancy and how this may lead to developmental reprogramming of mitochondrial function and predisposition to metabolic disease in offspring.
Many intracellular pathogens exploit host secretory trafficking to support their intracellular cycle, but knowledge of these pathogenic processes is limited. The bacterium Brucella abortus uses a ...type IV secretion system (VirB T4SS) to generate a replication-permissive Brucella-containing vacuole (rBCV) derived from the host ER, a process that requires host early secretory trafficking. Here we show that the VirB T4SS effector BspB contributes to rBCV biogenesis and Brucella replication by interacting with the conserved oligomeric Golgi (COG) tethering complex, a major coordinator of Golgi vesicular trafficking, thus remodeling Golgi membrane traffic and redirecting Golgi-derived vesicles to the BCV. Altogether, these findings demonstrate that Brucella modulates COG-dependent trafficking via delivery of a T4SS effector to promote rBCV biogenesis and intracellular proliferation, providing mechanistic insight into how bacterial exploitation of host secretory functions promotes pathogenesis.
Display omitted
•The Brucella Type IV effector BspB promotes rBCV biogenesis and bacterial replication•BspB targets the COG complex to redirect vesicular traffic to the rBCV•COG-dependent membrane traffic is required for optimal bacterial replication
How bacterial pathogens exploit host secretory functions to achieve their intracellular cycle remains poorly understood. Miller et al. show here that Brucella abortus delivers into macrophages a type IV-secretion effector that remodels Golgi-associated membrane traffic to promote biogenesis of the Brucella replicative vacuole and bacterial proliferation.
In the years following the September 11, 2001 terrorist attacks in New York (USA), otherwise known as 9/11, first responders and recovery workers began experiencing a range of physical and mental ...health challenges. Publications documenting these provide an important evidence-base identifying exposure-related health challenges associated with environmental exposures from the World Trade Center (WTC) site and describe the key lessons learned regarding both physical and mental health challenges (including symptoms and defined conditions) from the 9/11 disaster response.
A systematic literature review was conducted using the MEDLINE, PubMed, CINAHL, and PsychInfo databases (September 11, 2001 to September 11, 2018) using relevant search terms, truncation symbols, and Boolean combination functions. Publications were limited to journal articles that documented the physical or mental health challenges of 9/11 on first responders or recovery workers.
A total of 156 publications were retrieved by the search strategy. The majority (55%) reported a quantitative methodology, while only seven percent reported the use of a qualitative research methodology. Firefighters were the group of responders most frequently reported in the literature (35%), while 37% of publications reported on research that included a mix of first responders and recovery workers. Physical health was the focus of the majority of publications (57%). Among the challenges, respiratory issues were the physical health condition most frequently reported in publications, while posttraumatic stress disorder (PTSD) was the most frequent mental health condition reported on. Publications were published in a broad range of multi-disciplinary journals (n = 75).
These findings will go some way to filling the current gap in the 9/11 evidence-base regarding the understanding of the long-term health challenges for first responders and recovery workers.
Induced pluripotent stem cells (iPSCs) are an established cellular system to study the impact of genetic variants in derived cell types and developmental contexts. However, in their pluripotent ...state, the disease impact of genetic variants is less well known. Here, we integrate data from 1,367 human iPSC lines to comprehensively map common and rare regulatory variants in human pluripotent cells. Using this population-scale resource, we report hundreds of new colocalization events for human traits specific to iPSCs, and find increased power to identify rare regulatory variants compared with somatic tissues. Finally, we demonstrate how iPSCs enable the identification of causal genes for rare diseases.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data ...to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.
Invasive microbial pathogens often disrupt epithelial barriers, yet the mechanisms used to dismantle tight junctions are poorly understood. Here, we show that the obligate pathogen Chlamydia ...trachomatis uses the effector protein TepP to transiently disassemble tight junctions early during infection. TepP alters the tyrosine phosphorylation status of host proteins involved in cytoskeletal regulation, including the filamentous actin-binding protein EPS8. We determined that TepP and EPS8 are necessary and sufficient to remodel tight junctions and that the ensuing disruption of epithelial barrier function promotes secondary invasion events. The genetic deletion of EPS8 renders epithelial cells and endometrial organoids resistant to TepP-mediated tight junction remodeling. Finally, TepP and EPS8 promote infection in murine models of infections, with TepP mutants displaying defects in ascension to the upper genital tract. These findings reveal a non-canonical function of EPS8 in the disassembly of epithelial junctions and an important role for Chlamydia pathogenesis.
Display omitted
•C. trachomatis transiently disrupts epithelial tight junctions•The effector TepP interacts with EPS8 and recruits it to nascent inclusions•TepP repurposes EPS8 to disrupt tight junctions and promote Chlamydia entry•TepP and EPS8 promote infection in mouse models of Chlamydia infection
Dolat et al. show that the obligate intracellular pathogen, Chlamydia trachomatis, disrupts epithelial tight junctions to promote infection. The authors identify a role for the C. trachomatis-secreted effector TepP in repurposing the host actin-binding protein EPS8 to dismantle tight junctions and promote the invasion of polarized epithelia.
Cardiovascular disease (CVD) is the leading cause of death worldwide. Recent genome-wide association (GWA) studies have pinpointed many loci associated with CVD risk factors in adults. It is unclear, ...however, if these loci predict trait levels at all ages, if they are associated with how a trait develops over time, or if they could be used to screen individuals who are pre-symptomatic to provide the opportunity for preventive measures before disease onset. We completed a genome-wide association study on participants in the longitudinal Bogalusa Heart Study (BHS) and have characterized the association between genetic factors and the development of CVD risk factors from childhood to adulthood. We report 7 genome-wide significant associations involving CVD risk factors, two of which have been previously reported. Top regions were tested for replication in the Young Finns Study (YF) and two associations strongly replicated: rs247616 in CETP with HDL levels (combined P = 9.7 x 10(-24)), and rs445925 at APOE with LDL levels (combined P = 8.7 x 10(-19)). We show that SNPs previously identified in adult cross-sectional studies tend to show age-independent effects in the BHS with effect sizes consistent with previous reports. Previously identified variants were associated with adult trait levels above and beyond those seen in childhood; however, variants with time-dependent effects were also promising predictors. This is the first GWA study to evaluate the role of common genetic variants in the development of CVD risk factors in children as they advance through adulthood and highlights the utility of using longitudinal studies to identify genetic predictors of adult traits in children.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The C. elegans eat-3 gene encodes a mitochondrial dynamin family member homologous to Opa1 in humans and Mgm1 in yeast. We find that mutations in the C. elegans eat-3 locus cause mitochondria to ...fragment in agreement with the mutant phenotypes observed in yeast and mammalian cells. Electron microscopy shows that the matrices of fragmented mitochondria in eat-3 mutants are divided by inner membrane septae, suggestive of a specific defect in fusion of the mitochondrial inner membrane. In addition, we find that C. elegans eat-3 mutant animals are smaller, grow slower, and have smaller broodsizes than C. elegans mutants with defects in other mitochondrial fission and fusion proteins. Although mammalian Opa1 is antiapoptotic, mutations in the canonical C. elegans cell death genes ced-3 and ced-4 do not suppress the slow growth and small broodsize phenotypes of eat-3 mutants. Instead, the phenotypes of eat-3 mutants are consistent with defects in oxidative phosphorylation. Moreover, eat-3 mutants are hypersensitive to paraquat, which promotes damage by free radicals, and they are sensitive to loss of the mitochondrial superoxide dismutase sod-2. We conclude that free radicals contribute to the pathology of C. elegans eat-3 mutants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genome-wide association studies (GWAS) have identified multiple common variants associated with body mass index (BMI). In this study, we tested 23 genotyped GWAS-significant SNPs (p-value<5*10-8) for ...longitudinal associations with BMI during childhood (3-17 years) and adulthood (18-45 years) for 658 subjects. We also proposed a heuristic forward search for the best joint effect model to explain the longitudinal BMI variation. After using false discovery rate (FDR) to adjust for multiple tests, childhood and adulthood BMI were found to be significantly associated with six SNPs each (q-value<0.05), with one SNP associated with both BMI measurements: KCTD15 rs29941 (q-value<7.6*10-4). These 12 SNPs are located at or near genes either expressed in the brain (BDNF, KCTD15, TMEM18, MTCH2, and FTO) or implicated in cell apoptosis and proliferation (FAIM2, MAP2K5, and TFAP2B). The longitudinal effects of FAIM2 rs7138803 on childhood BMI and MAP2K5 rs2241423 on adulthood BMI decreased as age increased (q-value<0.05). The FTO candidate SNPs, rs6499640 at the 5 '-end and rs1121980 and rs8050136 downstream, were associated with childhood and adulthood BMI, respectively, and the risk effects of rs6499640 and rs1121980 increased as birth weight decreased. The best joint effect model for childhood and adulthood BMI contained 14 and 15 SNPs each, with 11 in common, and the percentage of explained variance increased from 0.17% and 9.0*10(-6)% to 2.22% and 2.71%, respectively. In summary, this study evidenced the presence of long-term major effects of genes on obesity development, implicated in pathways related to neural development and cell metabolism, and different sets of genes associated with childhood and adulthood BMI, respectively. The gene effects can vary with age and be modified by prenatal development. The best joint effect model indicated that multiple variants with effects that are weak or absent alone can nevertheless jointly exert a large longitudinal effect on BMI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
