Transceptors, solute transporters that facilitate intracellular entry of molecules and also initiate intracellular signaling events, have been primarily studied in lower-order species. Ammonia, a cytotoxic endogenous metabolite, is converted to urea in hepatocytes for urinary excretion in mammals. During hyperammonemia, when hepatic metabolism is impaired, nonureagenic ammonia disposal occurs primarily in skeletal muscle.
View Article and Find Full Text PDFBackground & Aims: Single-cell RNA sequencing (scRNA) has empowered many insights into gastrointestinal microenvironments. However, profiling human biopsies using droplet-based scRNA (D-scRNA) is challenging since it requires immediate processing to minimize epithelial cell damage. In contrast, picowell-based (P-scRNA) platforms permit short-term frozen storage before sequencing.
View Article and Find Full Text PDFHypoxia-inducible factor (HIF)-1α is continuously synthesized and degraded in normoxia. During hypoxia, HIF1α stabilization restricts cellular/mitochondrial oxygen utilization. Cellular stressors can stabilize HIF1α even during normoxia.
View Article and Find Full Text PDFImmunoglobulin A (IgA) is an important factor in maintaining homeostasis at mucosal surfaces, yet luminal IgA levels vary widely. Total IgA levels are thought to be driven by individual immune responses to specific microbes. Here, we found that the prebiotic, pectin oligosaccharide (pec-oligo), induced high IgA levels in the small intestine in a T cell-dependent manner.
View Article and Find Full Text PDFPerturbed metabolism of ammonia, an endogenous cytotoxin, causes mitochondrial dysfunction, reduced NAD /NADH (redox) ratio, and postmitotic senescence. Sirtuins are NAD -dependent deacetylases that delay senescence. In multiomics analyses, NAD metabolism and sirtuin pathways are enriched during hyperammonemia.
View Article and Find Full Text PDFNocturnal hypoxaemia, which is common in chronic obstructive pulmonary disease (COPD) patients, is associated with skeletal muscle loss or sarcopenia, which contributes to adverse clinical outcomes. In COPD, we have defined this as prolonged intermittent hypoxia (PIH) because the duration of hypoxia in skeletal muscle occurs through the duration of sleep followed by normoxia during the day, in contrast to recurrent brief hypoxic episodes during obstructive sleep apnoea (OSA). Adaptive cellular responses to PIH are not known.
View Article and Find Full Text PDFSkeletal muscle generation of ammonia, an endogenous cytotoxin, is increased during exercise. Perturbations in ammonia metabolism consistently occur in chronic diseases, and may blunt beneficial skeletal muscle molecular responses and protein homeostasis with exercise. Phosphorylation of skeletal muscle proteins mediates cellular signaling responses to hyperammonemia and exercise.
View Article and Find Full Text PDFObjective: Fibrosis is a common feature of Crohn's disease (CD) which can involve the mesenteric fat. However, the molecular signature of this process remains unclear. Our goal was to define the transcriptional signature of mesenteric fibrosis in CD subjects and to model mesenteric fibrosis in mice to improve our understanding of CD pathogenesis.
View Article and Find Full Text PDFAligning short-read sequences is the foundational step to most genomic and transcriptomic analyses, but not all tools perform equally, and choosing among the growing body of available tools can be daunting. Here, in order to increase awareness in the research community, we discuss the merits of common algorithms and programs in a way that should be approachable to biologists with limited experience in bioinformatics. We will only in passing consider the effects of data cleanup, a precursor analysis to most alignment tools, and no consideration will be given to downstream processing of the aligned fragments.
View Article and Find Full Text PDFAre touchscreen devices a public health risk for the transmission of pathogenic bacteria, especially those that are resistant to antibiotics? To investigate this, we embarked on a project aimed at isolating and identifying bacteria that are resistant to antibiotics from the screens of smartphones. Touchscreen devices have become ubiquitous in society, and it is important to evaluate the potential risks they pose towards public health, especially as it pertains to the harboring and transmission of pathogenic bacteria that are resistant to antibiotics. Sixteen bacteria were initially isolated of which five were unique (four species and one species).
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