Physiological Genomics

Epigenetic alterations such as dysregulation of microRNAs (miRNAs) have been reported to play important roles in interactions between genetic and environmental factors. In this study, we tested the hypothesis that induction of lung inflammation by inhaled allergens triggers a sex-specific miRNA regulation that is dependent on chromosome complement and hormonal milieu. We challenged the four core genotypes (FCG) model through intranasal sensitization with a house dust mite (HDM) solution (or PBS as a control) for 5 weeks...

Heart failure is a major clinical problem, with treatments involving medication, devices, and emerging neuromodulation therapies such as vagus nerve stimulation (VNS). Considering the ongoing interest in using VNS to treat cardiovascular disease it is important to understand the genetic and molecular changes developing in the heart in response to this form of autonomic neuromodulation. This experimental animal (rat) study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity using an optogenetic approach...

Background PANoptosis is an inflammatory programmed cell death (PCD) regulated by multifaceted PANoptosome complexes with major features of pyroptosis, apoptosis and/or necroptosis that cannot be accounted for by any of these PCD pathways alone. This study was aim to investigate the role of PANoptosis on the occurrence and development of abdominal aortic aneurysm (AAA). Methods Clinical samples of AAA patients, angiotensin II (Ang II)-induced AAA mouse model, and Ang II-induced vascular smooth muscle cells (VSMCs) in vitro model were used for investigation on PANoptosis features...

Sex differences in allergic inflammation have been reported, but the mechanisms underlying these differences remain unknown. Contributions of both sex hormones and sex-related genes to these mechanisms have been previously suggested in clinical and animal studies. Here, Four Core Genotypes (FCG) mouse model was used to study the inflammatory response to house dust mite (HDM) challenge and identify differentially expressed genes (DEGs) and regulatory pathways in lung tissue. Briefly, adult mice (8-10 weeks old) of the FCG (XXM, XXF, XYM, XYF) were challenged intranasally with 25μg of HDM or vehicle (PBS-control group) 5 days/week for 5 weeks (n=3/10group)...

BACKGROUND: High cardiorespiratory fitness (CRF) is associated with a reduced risk of metabolic disease and is linked to superior mitochondrial respiratory function. This study investigated how intrinsic CRF affects bioenergetics and metabolic health in adulthood and early life. METHODS: Adult rats selectively bred for low (LCR) and high (HCR) running capacity underwent metabolic phenotyping before mating. Weanlings were evaluated at 4-6 weeks of age, and whole-body energetics and behavior were assessed using metabolic cages...

Exercise is beneficial for obesity, partially through increased mitochondrial activity and raised nicotinamide adenine dinucleotide, a coenzyme critical for mitochondrial function and metabolism. Recent work has shown that increasing the availability of nicotinamide adenine dinucleotide through pharmacological means improves metabolic health in rodent models of diet induced obesity, and that the effect of these supplements when administered orally may be modulated by the gut microbiome. The gut microbiome is altered by both diet and exercise, and is thought to contribute to some aspects of high-fat diet-induced metabolic dysfunction...

Endothelial cells (ECs) adapt to the unique needs of their resident tissue and metabolic perturbations, such as obesity. We sought to understand how obesity affects EC metabolic phenotypes, specifically mitochondrial gene expression. We investigated the mesenteric and adipose endothelium because these vascular beds have distinct roles in lipid homeostasis. Initially we performed bulk RNA-seq on ECs from mouse adipose and mesenteric vasculatures after a normal chow (NC) or high fat diet (HFD) and found higher mitochondrial gene expression in adipose ECs compared to mesenteric ECs in both NC and HFD mice...

The microenvironment and cell populations within the myometrium play crucial roles in maintaining uterine structural integrity and protecting the fetus during pregnancy. However, the specific changes occurring at the single-cell level in the human myometrium between non-pregnant (NP) and term pregnant (TP) states remain unexplored. In this study, we utilized single-cell RNA sequence (scRNA-seq) and spatial transcriptomics (ST) to construct a transcriptomic atlas of individual cells in the myometrium of NP and TP women...

The mammary glands are dynamic tissue affected by pregnancy-related hormones during pregnancy-lactation cycle. Collagen production and its dynamics are essential to the remodeling of the mammary glands. Alterations of mammary microenvironment and stromal cells during the pregnancy-lactation cycle is important for understanding the physiology of mammary gland and development of breast tumor. In this study, we performed the evaluation of collagen dynamics in the mammary fat pad during the pregnancy-lactation cycle...

Salt sensitivity impacts a significant portion of the population and is an important contributor to the development of chronic kidney disease. One of the significant early predictors of salt-induced damage is albuminuria, which reflects the deterioration of the renal filtration barrier - the glomerulus. Despite significant research efforts, there is still a gap in knowledge regarding the molecular mechanisms and signaling networks contributing to instigating and/or perpetuating salt-induced glomerular injury...

Obesity and major depressive disorder (MDD) are both significant health issues that have been increasing in prevalence and are associated with multiple comorbidities. Obesity and MDD have been shown to be bi-directionally associated, and they are both influenced by genetics and environmental factors. However, the molecular mechanisms that link these two diseases are not yet fully understood. It is possible that these diseases are connected through the actions of the cAMP/PKA pathway. Within this pathway, Adenylate cyclase 3 (Adcy3) has emerged as a key player in both obesity and MDD...

Recently, we identified a recessive mutation, an abnormal coat appearance in BXH6 strain, a member of the HXB/BXH set of recombinant inbred (RI) strains. The RI strains were derived from the SHR (spontaneously hypertensive rat) and BN- Lx (Brown Norway rat) progenitors. Whole genome sequencing of the mutant rats identified the 195875980 G/A mutation in the Tuft1 (tuftelin 1) gene on chromosome 2, which resulted in a premature stop codon. Compared to wild-type BXH6 rats, BXH6- Tuft1 mutant rats exhibited lower body weight due to reduced visceral fat and ectopic fat accumulation in the liver and heart...

Oocyte maturation is accompanied by changes in abundances of thousands of mRNAs, many degraded and many preferentially stabilized. mRNA stability can be regulated by diverse features including GC content, codon bias, and motifs within the 3' untranslated region (UTR) interacting with RNA binding proteins (RBPs) and miRNAs. Many studies identified factors participating in mRNA splicing, bulk mRNA storage and translational recruitment in mammalian oocytes, but the roles of potentially hundreds of expressed factors, how they regulate cohorts of thousands of mRNAs, and to what extent their functions are conserved across species has not been determined...

Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in chronic stable angina (CSA) and acute coronary syndrome (ACS) patients compared to healthy controls. Bacterial alpha diversity in stool from ACS or CSA patients was comparable to healthy controls at both baseline and follow-up visits...

Congenital heart disease (CHD) is one of the most prevalent neonatal congenital anomalies. To catalog the putative candidate CHD risk, we collected 16,349 variants (single nucleotide variants (SNVs) and Indels) impacting 8,308 genes in 3,166 CHD cases for a comprehensive meta-analysis. Using ACMG guidelines we excluded the 0.1% of benign/likely benign variants and resulting data set consisted of 83% predicted loss of function variants and 17% missense variants. Seventeen percent were de novo variants. A stepwise analysis identified 90 variant-enriched CHD genes, of which six ( GPATCH1, NYNRIN, TCLD2, CEP95, MAP3K19 and TTC36) were novel candidate CHD genes...

Epigenetic modifications, particularly DNA methylation, have emerged as regulators of gene expression and are implicated in various biological processes and disease states. Understanding the factors influencing the epigenome is essential for unravelling its complexity. In this study, we aimed to identify how the methylome of buccal epithelial cells, a non-invasive and easily accessible tissue, is associated with demographic and health-related variables commonly used in clinical settings, such as age, sex, blood immune composition, hemoglobin levels, and others...

Lysine is an essential amino acid that serves as a building block in protein synthesis. Beside this, lysine's metabolic activity has only recently been unraveled. Lysine metabolism is tissue specific and is linked to several renal, cardiovascular and endocrinological diseases through human metabolomics datasets. As a free molecule, lysine takes part in antioxidant response, engages in protein modifications and its chemistry shapes both proteome and metabolome. In the proteome, it is an acceptor for a plethora of posttranslational modifications...

Obesity- and type 2 diabetes mellitus-induced changes in the expression of protein-coding genes in human skeletal muscle were extensively examined at baseline (after an overnight fast). We aimed to compare the early transcriptomic response to a typical single meal in skeletal muscle of metabolically healthy subjects and obese individuals without and with type 2 diabetes. Transcriptomic response (RNA-seq) to a mixed meal (nutritional drink, ∼25 kJ/kg of body mass) was examined in the vastus lateralis muscle (1 h after a meal) in 7 healthy subjects and 14 obese individuals without or with type 2 diabetes...

In this study, post-smolt male Atlantic salmon, previously identified as low (LR) or high responders (HR) based on post-stress cortisol levels, had their head kidney and liver sampled at 12 and 20°C prior to injection (time 0) and after (i.e., at 12 and 24 hpi, respectively) they were injected with either Forte Micro (a multi-valent vaccine containing bacterin, to capture peak antibacterial responses) or an equal volume of phosphate-buffered saline (PBS). Real-time quantitative polymerase chain reaction (qPCR) was then used to measure the expression of 15 biomarker genes in the head kidney and 12 genes in the liver at each temperature/sampling point...

Augmented vagal signaling may be therapeutic in hypertension. Most studies to date employed stimulation of the cervical vagal branches. Here, we investigated the effects of chronic intermittent electric stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on long term blood pressure (BP), immune markers, and gut microbiota in the spontaneously hypertensive rat (SHR), a rodent model of hypertension characterized by vagal dysfunction, gut dysbiosis and low-grade inflammation. We evaluated the effects of sdVNS on transcriptional networks in the nucleus of the solitary tract (NTS), a major cardioregulatory brain region with direct gut vagal projections...