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Full-Text Articles in Biochemical Phenomena, Metabolism, and Nutrition

Phosphorylation At S1288 Of Leukemia Associated Rhogef (Larg/Arhgef12) Induces Plasma Membrane Localization And Promotes Binding And Activation Of Rhoa, Won Seok Yang, Neda Z. Ghanem, Steven D. Scahill, Maisel J. Caliva, Hannah Röttig, Annika Fitz, Michelle L. Matter, Joe W. Ramos Dec 2025

Phosphorylation At S1288 Of Leukemia Associated Rhogef (Larg/Arhgef12) Induces Plasma Membrane Localization And Promotes Binding And Activation Of Rhoa, Won Seok Yang, Neda Z. Ghanem, Steven D. Scahill, Maisel J. Caliva, Hannah Röttig, Annika Fitz, Michelle L. Matter, Joe W. Ramos

School of Graduate Studies Faculty Publications

Leukemia-associated RhoGEF (LARG) is a guanine nucleotide exchange factor (GEF) known for its specificity toward Ras homolog family member A (RhoA). LARG plays a crucial regulatory role in various cellular processes such as migration, proliferation, invasion, and metastasis by facilitating the exchange of GDP to GTP on RhoA. Phosphorylation of LARG at S1288 by ribosomal S6 kinase 2 (RSK2) promotes RhoA activation. However, the precise mechanism remains unclear. Here, we demonstrate the essential role and mechanism by which S1288 phosphorylation facilitates LARG-mediated invasiveness in response to epidermal growth factor (EGF). Upon EGF stimulation, RSK2 phosphorylates LARG at S1288, thereby promoting …


Dietary Fiber Modulates Gut Microbiota And Lipid Metabolism Ameliorating Alzheimer's Pathology In 5xfad Mice, Yuhai Zhao, Christopher M. Taylor, Walter J. Lukiw, Nicolas G. Bazan Nov 2025

Dietary Fiber Modulates Gut Microbiota And Lipid Metabolism Ameliorating Alzheimer's Pathology In 5xfad Mice, Yuhai Zhao, Christopher M. Taylor, Walter J. Lukiw, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

The gut-brain axis plays a critical role in maintaining neuronal integrity and influencing the progression of Alzheimer's disease (AD). Here, we investigated how commonly consumed dietary fibers modulate gut microbiota, lipid metabolism, and AD pathology in 5xFAD mice. Male mice were fed either fiber-free (FF) or fiber-plus (FP; 1% cellulose, 2% pectin, 2% inulin) diets for five months, followed by integrated analyses of gut microbiota (16 S rRNA sequencing), fecal lipid metabolites (LC-MS/MS), and neuropathological and behavioral outcomes. FP diets markedly altered microbial composition, characterized by increases in Muribaculaceae, Ileibacterium, and Lachnospiraceae NK4A136 group and reductions in Faecalibaculum and Coriobacteriaceae …


Alcohol And Metabolic Stress Synergize To Dysregulate Mitochondrial Health And Lipid Metabolism; Evidence From A Hepatocyte Spheroid Model, Eden M. Gallegos, Kaitlin Couvillion, Drake Darden, Keishla Rodriguez-Graciani, Patricia E. Molina, Liz Simon Nov 2025

Alcohol And Metabolic Stress Synergize To Dysregulate Mitochondrial Health And Lipid Metabolism; Evidence From A Hepatocyte Spheroid Model, Eden M. Gallegos, Kaitlin Couvillion, Drake Darden, Keishla Rodriguez-Graciani, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease frequently co-occur, manifesting as MetALD. Understanding the hepatocyte-specific effects of alcohol and metabolic stressors is critical to uncovering mechanisms of synergistic injury. This study evaluated the individual and combined effects of ethanol, sugars, and saturated/monounsaturated fats on hepatocyte lipid metabolism, oxidative stress, and mitochondrial function using a 3D human HepaRG spheroid model. HepaRG spheroids were treated with ethanol (50 mm), sugar (glucose and fructose), and fatty acids alone or in combination for 10 d. The combination of ethanol (E) and metabolic (sugar and fat, SF) stressors (ESF) synergistically increased triglyceride content …


Integrated Systems Biology Identifies Disruptions In Mitochondrial Function And Metabolism As Key Contributors To Hfpef, Andrew A. Gibb, Kyle Lapenna, Ryan B. Gaspar, Nadina R. Latchman, Yinfei Tan, Carmen Choya-Foces, Jake E. Doiron, Zhen Li, Huijing Xia, Michael P. Lazaropoulos, Mariell Conwell, Thomas E. Sharp, Traci T. Goodchild, David J. Lefer, John W. Elrod Sep 2025

Integrated Systems Biology Identifies Disruptions In Mitochondrial Function And Metabolism As Key Contributors To Hfpef, Andrew A. Gibb, Kyle Lapenna, Ryan B. Gaspar, Nadina R. Latchman, Yinfei Tan, Carmen Choya-Foces, Jake E. Doiron, Zhen Li, Huijing Xia, Michael P. Lazaropoulos, Mariell Conwell, Thomas E. Sharp, Traci T. Goodchild, David J. Lefer, John W. Elrod

School of Graduate Studies Faculty Publications

Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of HF cases. The ZSF1-obese rat model recapitulates clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and diastolic dysfunction. We utilized a systems-biology approach to define the metabolic and transcriptional signatures to gain mechanistic insight into pathways contributing to HFpEF development. Male ZSF1-obese, ZSF1-lean hypertensive controls, and WKY (wild-type) controls were compared at 14 weeks of age for extensive physiological phenotyping and left ventricle (LV) tissue harvesting for unbiased-metabolomics, RNA-sequencing, and mitochondrial morphology and function. Utilizing ZSF1-lean and WKY controls enabled a distinction between hypertension-driven molecular changes …


Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart Jun 2023

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …