Differential gene expression analysis in blood of first episode psychosis patients

Background Psychosis is a condition influenced by an interaction of environmental and genetic factors. Gene expression studies can capture these interactions; however, studies are usually performed in patients who are in remission. This study uses blood of first episode psychosis patients, in order to characterise deregulated pathways associated with psychosis symptom dimensions. Methods Peripheral blood from 149 healthy controls and 131 first episode psychosis patients was profiled using Illumina HT-12 microarrays. A case/control differential expression analysis was performed, followed by correlation of gene expression with positive and negative syndrome scale (PANSS) scores. Enrichment analyses were performed on the associated gene lists. We test for pathway differences between first episode psychosis patients who qualify for a Schizophrenia diagnosis against those who do not. Results A total of 978 genes were differentially expressed and enriched for pathways associated to immune function and the mitochondria. Using PANSS scores we found that positive symptom severity was correlated with immune function, while negative symptoms correlated with mitochondrial pathways. Conclusions Our results identified gene expression changes correlated with symptom severity and showed that key pathways are modulated by positive and negative symptom dimensions

Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth

This is the final version. Available on open access from Nature Research via the DOI in this record. Data availability: Individual cohorts contributing to the meta-analysis should be contacted directly as each cohort has different data access policies. GWAS summary statistics from this study are available via the EGG website (https://egg-consortium.org/placental-weight-2023.html, https://www.ebi.ac.uk/gwas/), as well as the GWAS catalog (https://www.ebi.ac.uk/gwas/, accession numbers GCST90275189, GCST90275190, GCST90275191, GCST90275192, GCST90275193, GCST90275194, GCST90275195, GCST90275196, GCST90275197, GCST90275198, GCST90275199). Access to personal-level information from Gen3G (including methylation array data) is subject to controlled access according to participants’ consent concerning sharing of personal data. Request for conditions of access and for data access should be addressed to Center Hospitalier Universitaire de Sherbrooke institutional ethics committee: [email protected] availability: Analysis code is available from https://github.com/EarlyGrowthGenetics/placental_weight_codeA well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.Wellcome Trus

Proliferation of Listeria monocytogenes L-form cells by formation of internal and external vesicles

L-forms are cell wall-deficient bacteria that divide through unusual mechanisms, involving dynamic perturbations of the cellular shape and generation of vesicles, independently of the cell-division protein FtsZ. Here we describe FtsZ-independent mechanisms, involving internal and external vesicles, by which Listeria monocytogenes L-forms proliferate. Using micromanipulation of single cells and vesicles, we show that small vesicles are formed by invagination within larger intracellular vesicles, receive cytoplasmic content, and represent viable progeny. In addition, the L-forms can reproduce by pearling, that is, generation of extracellular vesicles that remain transiently linked to their mother cell via elastic membranous tubes. Using photobleaching and fluorescence recovery, we demonstrate cytoplasmic continuity and transfer through these membranous tubes. Our findings indicate that L-forms' polyploidy and extended interconnectivity through membranous tubes contribute to the generation of viable progeny independently of dedicated division machinery, and further support L-forms as models for studies of potential multiplication mechanisms of hypothetical primitive cells

Perceived Access Problems Among Patients with Diabetes in Two Public Systems of Care

OBJECTIVE: We examined the prevalence of access problems among public clinic patients after participating in trials of automated telephone disease management with nurse follow-up. DESIGN: Randomized trial. SETTING: General medicine clinics of a county health care system and a Veterans Affairs (VA) health care system. PARTICIPANTS: Five hundred seventy adults with diabetes using hypoglycemic medication were enrolled and randomized; 520 (91%) provided outcome data at 12 months. INTERVENTION: Biweekly automated telephone assessments with telephone follow-up by diabetes nurse educators. MEASUREMENTS AND MAIN RESULTS: At follow-up, patients reported whether in the prior 6 months they had failed to obtain each of six types of health services because of a financial or nonfinancial access problem. Patients receiving the intervention were significantly less likely than patients receiving usual care to report access problems (adjusted odds ratio [AOR], 0.61; 95% confidence interval [CI], 0.43 to 0.97). The risk of reporting access problems was greater among county clinic patients than VA patients even when adjusting for their experimental condition, and socioeconomic and clinical risk factors (AOR, 1.61; 95% CI, 1.02 to 2.53). County patients were especially more likely to avoid seeking care because of a worry about the cost (AOR, 2.82; 95% CI, 1.48 to 5.37). CONCLUSIONS: Many of these public sector patients with diabetes reported that they failed to obtain health services because they perceived financial and nonfinancial access problems. Automated telephone disease management calls with telephone nurse follow-up improved patients' access to care. Despite the impact of the intervention, county clinic patients were more likely than VA patients to report access problems in several areas