Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis.

Background: The neutral amino acid transporter SLC7A8 (LAT2) has been described as a key regulator of metabolic adaptation. LAT2 mutations in human populations have been linked to the early onset of age-related hearing loss and cataract growth. As LAT2 was previously found to be highly expressed in skeletal muscle, here we characterised its role in the regulation of skeletal muscle amino acid flux and metabolic adaptation to fasting.

Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens.

Background: Heightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load ("blips") during ART are associated with increases in inflammation.

The molecular landscape of sepsis severity in infants: enhanced coagulation, innate immunity, and T cell repression.

Introduction: Sepsis remains a major cause of mortality and morbidity in infants. In recent years, several gene marker strategies for the early identification of sepsis have been proposed but only a few have been independently validated for adult cohorts and applicability to infant sepsis remains unclear. Biomarkers to assess disease severity and risks of shock also represent an important unmet need.

Differential Regulation of Immune-Related Genes in the Developing Heart.

In many congenital heart defects, it can be difficult to ascertain primary pathology from secondary consequences from altered flow through the developing heart. The molecular differences between the growing right and left ventricles (RV and LV, respectively) following the completion of septation and the impact of sex on these mechanisms have not been investigated. We analyzed RNA-seq data derived from twelve RV and LVs, one with Hypoplastic Left Heart Syndrome (HLHS), to compare the transcriptomic landscape between the ventricles during development.

Virome Analysis and Association of Positive Coxsackievirus B Serology during Pregnancy with Congenital Heart Disease.

Background: We have previously shown coxsackievirus B (CVB) to be a potent inducer of congenital heart disease (CHD) in mice. The clinical relevance of these findings in humans and the roles of other viruses in the pathogenesis of CHD remain unknown.

Methods: We obtained plasma samples, collected at all trimesters, from 89 subjects (104 pregnancies), 73 healthy controls (88 pregnancies), and 16 with CHD-affected birth (16 pregnancies), from the Perinatal Family Tissue Bank (PFTB).

The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice.

Modulation of individual macronutrients or caloric density is known to regulate host resistance to infection in mice. However, the impact of diet composition, independent of macronutrient and energy content, on infection susceptibility is unclear. We show that two laboratory rodent diets, widely used as standard animal feeds and experimental controls, display distinct abilities in supporting mice during influenza infection.

A Case of Persistent Human Pegivirus Infection in Two Separate Pregnancies of a Woman.

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique attributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two pregnancies, which occurred 4 years apart and without evidence of human immunodeficiency virus or hepatitis C virus infection.

A 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell.

The sense of smell helps us navigate the environment, but its molecular architecture and underlying logic remain understudied. The spatial location of odorant receptor genes (Olfrs) in the nose is thought to be independent of the structural diversity of the odorants they detect. Using spatial transcriptomics, we create a genome-wide 3D atlas of the mouse olfactory mucosa (OM).

Transcriptomic profile investigations highlight a putative role for NUDT16 in sepsis.

Sepsis is an aberrant systemic inflammatory response mediated by the acute activation of the innate immune system. Neutrophils are important contributors to the innate immune response that controls the infection, but harbour the risk of collateral tissue damage such as thrombosis and organ dysfunction. A better understanding of the modulations of cellular processes in neutrophils and other blood cells during sepsis is needed and can be initiated via transcriptomic profile investigations.

SysInflam HuDB, a Web Resource for Mining Human Blood Cells Transcriptomic Data Associated with Systemic Inflammatory Responses to Sepsis.

Sepsis develops after a dysregulated host inflammatory response to a systemic infection. Identification of sepsis biomarkers has been challenging because of the multifactorial causes of disease susceptibility and progression. Public transcriptomic data are a valuable resource for mechanistic discoveries and cross-studies concordance of heterogeneous diseases.

Transcriptome and Literature Mining Highlight the Differential Expression of ERLIN1 in Immune Cells during Sepsis.

Sepsis results from the dysregulation of the host immune system. This highly variable disease affects 19 million people globally, and accounts for 5 million deaths annually. In transcriptomic datasets curated from public repositories, we observed a consistent upregulation (3.

Immunomodulatory Effects of Vitamin D Supplementation in a Deficient Population.

In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (>80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen prescribed and the potential factors affecting an individual's response to vitamin D supplementation are not well characterized.

Distinct antibody repertoires against endemic human coronaviruses in children and adults.

Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these "common cold" viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage immunoprecipitation sequencing.

A literature-based approach for curating gene signatures in multifaceted diseases.

Background And Aims: The task of identifying a representative and yet manageable target gene list for assessing the pathogenesis of complicated and multifaceted diseases is challenging. Using Inflammatory Bowel Disease (IBD) as an example, we conceived a bioinformatic approach to identify novel genes associated with the various disease subtypes, in combination with known clinical control genes.

Methods: From the available literature, we used Acumenta Literature Lab (LitLab), network analyses, and LitLab Gene Retriever to assemble a gene pool that has a high likelihood of representing immunity-related subtype-specific signatures of IBD.

Differential regulation of the immune system in a brain-liver-fats organ network during short-term fasting.

Objective: Fasting regimens can promote health, mitigate chronic immunological disorders, and improve age-related pathophysiological parameters in animals and humans. Several ongoing clinical trials are using fasting as a potential therapy for various conditions. Fasting alters metabolism by acting as a reset for energy homeostasis, but the molecular mechanisms underlying the beneficial effects of short-term fasting (STF) are not well understood, particularly at the systems or multiorgan level.

A curated collection of transcriptome datasets to investigate the molecular mechanisms of immunoglobulin E-mediated atopic diseases.

Prevalence of allergies has reached ~20% of population in developed countries and sensitization rate to one or more allergens among school age children are approaching 50%. However, the combination of the complexity of atopic allergy susceptibility/development and environmental factors has made identification of gene biomarkers challenging. The amount of publicly accessible transcriptomic data presents an unprecedented opportunity for mechanistic discoveries and validation of complex disease signatures across studies.

Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency.

Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function allele.

A multi-omic approach to elucidate low-dose effects of xenobiotics in zebrafish (Danio rerio) larvae.

Regulatory-approved toxicity assays such as the OECD Fish Embryo Toxicity Assay (TG236) allow correlation of chemical exposure to adverse morphological phenotypes. However, these assays are ineffective in assessing sub-lethal (i.e.

Xenobiotics Produce Distinct Metabolomic Responses in Zebrafish Larvae (Danio rerio).

Sensitive and quantitative protocols for characterizing low-dose effects are needed to meet the demands of 21st century chemical hazard assessment. To test the hypothesis that xenobiotic exposure at environmentally relevant concentrations produces specific biochemical fingerprints in organisms, metabolomic perturbations in zebrafish (Danio rerio) embryo/larvae were measured following 24 h exposures to 13 individual chemicals covering a wide range of contaminant classes. Measured metabolites (208 in total) included amino acids, biogenic amines, fatty acids, bile acids, sugars, and lipids.

Delayed effects of methylmercury on the mitochondria of dopaminergic neurons and developmental toxicity in zebrafish larvae (Danio rerio).

Methylmercury (MeHg) is a known neurotoxicant affecting the central nervous system but effects on dopaminergic (DA) neurons are not well understood. Wild-type zebrafish (Danio rerio) and two transgenic lines: Tg(dat:eGFP) expressing enhanced green fluorescent protein (eGFP) in DA neuron clusters and Tg(dat:tom20 MLS-mCherry) expressing red fluorescence (mCherry) targeted to mitochondria of DA neurons were used to evaluate the effects of micromolar MeHg exposure on DA neuron and whole animal motor function during early development. Three-day-old larvae were exposed to micromolar concentrations of MeHg (0.

Effect of dietary selenomethionine on growth performance, tissue burden, and histopathology in green and white sturgeon.

A comparative examination of potential differences in selenium (Se) sensitivity was conducted on two sturgeon species indigenous to the San Francisco Bay-Delta. Juvenile green (Acipenser medirostris), recently given a federally threatened status, and white sturgeon (Acipenser transmontanus) were exposed to one of four nominal concentrations of dietary l-selenomethionine (SeMet) (0 (control), 50, 100, or 200 mg SeMet/kg diet) for 8 weeks. Mortality, growth performance, whole body composition, histopathology, and Se burdens of the whole body, liver, kidneys, gills, heart, and white muscle were determined every 2 to 4 weeks.