Publications by authors named "Ryan Musich"

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.

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Background & 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.

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Hypoxia-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.

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Immunoglobulin 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.

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Article Synopsis
  • Patients with acute alcohol-associated hepatitis (AH) exhibit immune dysfunction linked to impaired mitochondrial function, impacting their immune responses and cellular aging processes.
  • A combination of single-cell RNA sequencing and transcriptomics was employed to analyze gene expression related to mitochondrial and telomere function in blood samples from AH patients, healthy controls, and heavy drinkers.
  • Results indicated that AH patients showed reduced mitochondrial respiration and different metabolite profiles compared to healthy individuals, suggesting significant alterations in both mitochondrial function and cellular aging mechanisms in AH.
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Perturbed 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.

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  • Hospitalized patients with SARS-CoV-2 infection are more likely to develop hospital-acquired sacral pressure injuries (HASPI), with a 63% higher incidence rate compared to non-infected patients.
  • COVID-19(+) patients experience more severe HASPIs, requiring more aggressive treatments like debridement, and have a worse overall hospitalization course.
  • Histological examinations of HASPIs in COVID-19(+) patients show significant evidence of thrombotic vasculopathy and an immune response indicating that COVID-19 may disrupt normal skin healing processes, contributing to pressure injuries.
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Nocturnal 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.

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Skeletal 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.

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Objective: 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.

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Aligning 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.

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Article Synopsis
  • Intra-tumoral epigenetic heterogeneity is crucial for understanding tumor behavior and its impact on gene regulation, but existing tools for assessing this have been lacking.
  • The newly developed R/Bioconductor package, epihet, automates the measurement of epigenetic heterogeneity and facilitates related analyses.
  • The package has been successfully applied to acute myeloid leukemia, showing significant differential epigenetic heterogeneity and enabling the construction of relevant biological networks and potential clinical biomarkers.
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Are 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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