bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZFP24 drives SOX9 upregulation and protects tubular epithelial cells during acute kidney injury
Authors: Kim Ji Young , Pabla Navjot 
Published: May 2023

SOX9 is a transcription factor that controls cell-fate determination during embryonic development and adult tissue homeostasis in multiple organs including the kidneys. SOX9 expression is low in the adult kidneys, however, stress conditions can trigger its transcriptional upregulation in tubular epithelial cells. Functionally, SOX9 plays a protective role during the early phase of acute kidney injury (AKI) and facilitates repair during the recovery phase. To identify the upstream transcriptional regulators that drive SOX9 upregulation in tubular epithelial cells, here we have used an unbiased transcription factor screening approach. Our preliminary screening and validation studies show that Zinc finger protein 24 (ZFP24) controls injury induced SOX9 upregulation in tubular epithelial cells. ZFP24, a Cys2-His2 (C2H2) zinc finger protein is essential for oligodendrocyte maturation and myelination, however its role in the kidneys or in SOX9 regulation remains unknown. We find that tubular epithelial ZFP24 gene ablation exacerbates ischemia, rhabdomyolysis, and cisplatin-associated AKI. Importantly, ZFP24 gene deletion results in suppression of SOX9 upregulation in injured tubular epithelial cells. Chromatin immunoprecipitation and promoter luciferase assays confirmed that ZFP24 binds to a specific site in both murine and human SOX9 promoter. Importantly, CRISPR/Cas9 mediated introduction of mutations in the ZFP24 binding site in the SOX9 promoter in vivo led to suppression of SOX9 upregulation during AKI. These findings identify ZFP24 as a critical stress-responsive transcription factor that protects tubular epithelial cells during AKI in part through SOX9 upregulation. The current study was supported by NIDDK 1R01DK132230 grant to N.P. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Can you stomach it? Comparative transcriptomics and biochemistry of the stomachs of prickleback fishes (Stichaeidae) consuming different diets
Authors: German Donovan , Herrera Michelle , Heras Joseph 
Published: May 2023

Despite obvious whole animal, tissue level, and biochemical differences among species with different diets, dietary specialization has molecular underpinnings that are not well understood. In this project, we used comparative transcriptomics of stomach tissues to observe how prickleback fishes (Stichaeidae) achieve dietary-driven differences in stomach function. Xiphister mucosus (herbivore), X. atropurpureus (omnivore), Phytichthys chirus (omnivore) and the carnivorous Anoplarchus purpurescens were harvested from the wild, and fed omnivore and/or carnivore diets in the laboratory. Transcriptomes were sequenced for stomach tissues from two individuals per species and diet treatment. The number of shared orthologs varied with phylogenetic relatedness of the species (i.e., sister-taxa X. mucosus and X. atropurpureus shared the most expressed genes among the species), and differential expression and selection analyses are underway, although hydrogen-potassium ATPase appears to be under positive selection in some species. All four fish species strongly expressed pepsinogen and chitinase genes in their stomachs, yet biochemical activity levels (N ≥ 6 per species and diet treatment) of these two digestive enzymes matched natural diet, with the species consuming the most protein ( A. purpurescens) and chitin ( P. chirus) having the highest pepsin and chitinase activities, respectively. These activities were relatively unaltered by the laboratory diets, suggesting that activity level cannot be changed significantly through a dietary shift. Although intestinal carbohydrases typically show support for the Adaptive Modulation Hypothesis—a match among digestive enzyme activities with concentrations of ingested substrate—this may be one of the first investigations to observe such support for gastric enzymes. Thus, beyond being an important vertebrate innovation, the stomach may also provide digestive benefit depending on natural diet. NSF Grant IOS-1355224 and NSF DBI-1852096 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The gut-microbiome and anxiety in male and female zebrafish
Authors: Lapoint Phoebe , LaPoint Phoebe , Uno Jennifer 
Published: May 2023

Recent research from the CDC indicates that 41.5% of adults in the US classify themselves as anxious or depressed. Interestingly, anxiety disorders are disproportionately more prevalent in women than men. It is well established that the microbiome greatly influences stress responses, mood states, and other aspects of brain health including anxiety disorders. It is also known that the microbial composition differs in males and females. This study aims to determine the similarities and differences between the male and female zebrafish microbiome and identify if these differences impact anxiety. Zebrafish were treated with amoxicillin to decrease the total intestinal bacterial abundance. The zebrafish were then subjected to an acute stress protocol or a chronic stress protocol. For acute stress, fish were net stressed for three minutes, followed by 3 minutes of acclimation. Chronic stress was induced over 8 days with fish being stressed daily prior to the three minute net stress. Fish behavior and anxiety were assessed using the EthoVision tracking system and software. We observed a 48% and 67% decrease in bacterial abundance in males and females respectively treated with amoxicillin (p<0.05, n= 5). Interestingly both males and females treated with antibiotics showed significantly fewer right and left crosses following acute stress exposure- no significant differences were observed between male and female fish (p<0.05, n=10). In chronically stressed fish, no differences were seen in anxiety-like behavior in control or antibiotic-treated fish regardless of sex. These results support current research indicating the overall role of the microbiome in anxiety and depression however, the differences between intestinal bacteria in males and females behavior remains unclear. Elon University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Differential Expression of miRNAs by Anti-Obesity Treatment Sulforaphane in Skeletal Muscle of Diet-Induced Obesity in Mice
Authors: Rizk Nasser , Mohamed Omnia , Alasmar Dima 
Published: May 2023

Background: Skeletal muscles comprise 40–60% of the body's total weight and 30% of the metabolic rate at rest. As the primary site for glucose uptake into tissues by insulin induction, it is crucial for metabolic homeostasis in the body. The natural isothiocyanate compound sulforaphane primarily functions as an antioxidant, but numerous studies have revealed that it also has anti-obesity properties. Recent studies have demonstrated that miRNAs are essential in controlling skeletal muscle dysfunction. The objective is to investigate the miRNA expression profile in the skeletal muscles of DIO mice given SFN and to ascertain their function by identifying the metabolic pathways and gene ontologies involved. Methods: Male mice of CD1 strain were randomized at age four weeks and fed a high fat diet to induce diet-induced obesity (DIO) followed by SFN and vehicle treatment for four weeks. Total RNA was extracted from the skeletal muscles of DIO mice, and small RNA sequencing was utilized to identify the microRNA expression profiles. In addition, pathway mapping and gene ontology (GO) tools were used to evaluate the biological processes and signaling pathways affected by the differentially expressed microRNAs. Results: Body weight, food intake, plasma glucose, and leptin levels were all significantly lower in the SFN-treated group compared to the control group. Furthermore, in SFN-treated DIO mice, eight differentially expressed miRNAs were detected, five upregulated (mmu-miR-150-5p, mmu-miR-486a-3p, mmu-miR-126b-5p, mmu-miR-140-3p, mmu-miR-92a-3p) and three of which were downregulated (mmu-miR-101a-3p, mmu-miR-29c-3p, mmu-miR-3074-5p). Furthermore, SFN treatment alters miRNAs that regulate genes involved in insulin signaling, MAPK, and PI3K/Akt signaling pathways, all essential regulators of skeletal muscle metabolism, including insulin resistance and obesity. Conclusion: SFN induced a change in the expression profiles of microRNAs in the skeletal muscle of DIO mice, which regulate gene targets of miRNAs involved in a variety of biological processes that combat obesity. This study was supported by the Qatar National Research Foundation grant (NPRP9-351-3-075) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Cardiac Adaptions to Exercise Training in Mice Lacking Adiponectin
Authors: Asher Andy , Medarev Steven , Faal Madikay , Smith Cole , Qasim Muhammad , Belenko Jasen , Mitchell Logan , Ojah-Maharaj Jayden , Hendrickson Dylan , Faynberg Victor , Morales Paula , Garcia Michelle , Pinto Jose , Muller-Delp Judy 
Published: May 2023

Hypoadiponectinemia is associated with development of cardiovascular disease. We have previously reported that exercise-induced adaptations of the heart are impaired in mice with germline deletion of adiponectin. To determine a direct role for acute deletion of adiponectin in cardiac adaptations to exercise training, we exercise trained young adult mice with normal circulating adiponectin (wild type, WT) and mice in which adiponectin was acutely deleted (Cre-Lox conditional knockout system induced with Tamoxifen chow, AdipoKO) before undergoing 8 weeks of exercise training. Sedentary WT and AdipoKO mice were housed under similar cage conditions for 8 weeks. Lean mass and fat mass were assessed bi-weekly with Echo-MRI during the training and sedentary periods. Exercise tolerance, and cardiac function were assessed before and after completion of the 8 weeks training/sedentary period. Exercise training reduced fat mass and increased lean muscle mass in both WT mice and AdipoKO mice. Exercise training increased exercise tolerance in both WT mice and AdipoKO mice. Fractional shortening increased in WT mice, both sedentary and exercise trained, over the 8-week period, whereas fractional shortening tended to decrease in both sedentary and exercise trained AdipoKO mice. At the end of the 8-week exercise training/sedentary period, fractional shortening was significantly higher in WT mice compared to AdipoKO mice. At the end of the 8-week exercise training/sedentary period, ejection fraction was significantly higher in WT mice as compared to AdipoKO. Eight weeks of exercise training increased cardiac output in WT mice and cardiac output was higher in WT mice as compared to AdipoKO mice at the end of the 8-week exercise training/sedentary period. These data suggest that central cardiovascular adaptation is an important contributor to the increase in exercise tolerance that occurs in response to exercise training in WT mice. In contrast, in mice lacking adiponection, peripheral changes in metabolism and oxygen utilization are more likely contributors to the increase in exercise tolerance that occurs in response to exercise training. NIH R56AG068156 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
4-octyl itaconate ameliorate cognitive impairment in 3xTg mouse model of Alzheimer's Disease
Authors: Behera Jyotirmaya , Nasme Fariha , Zhang Yu-Ting , Smolenkova Irina , Tyagi Neetu 
Published: May 2023

The most prevalent form of dementia, Alzheimer's disease (AD), is characterized by abnormal amyloid-(A) plaque accumulation, neuroinflammation, and neuronal loss. A cell-permeable derivative of itaconate called 4-octyl itaconate (OI) has recently been shown to reduce inflammation. However, the impact of OI in the 3xTg transgenic mouse model of AD is still unclear. We administered OI or saline to 3xTg-AD mice. According to our findings, OI improved cognitive functions. OI also significantly decreased brain Aβ deposition and Aβ levels, inhibited cell apoptosis, decreased hippocampal and cortical neuronal damage. Additionally, we discovered that OI decreased the levels of proinflammatory cytokines, cell apoptosis, and cognitive decline in the brains of 3xTg-AD mice while increasing the expression of the Nrf2/HO-1 signaling pathway in 3xTg-AD mice, suggesting that OI might be recognized as a promising candidate for the treatment of AD. TPA 971566-AHA This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Systemic Mapping of Organ Plasma Extravasation Post Myocardial Infarction
Authors: Kitzerow Oliver , Suber Paul , Mohanad Shukry , Zucker Irving , Wang Hanjun 
Published: May 2023

Chronic Heart failure (CHF) is a highly prevalent disease that leads to significant morbidity and mortality. Diffuse vasculopathy is a common feature of the morbidity associated with CHF. Increased vascular permeability leading to plasma extravasation (PEx) occurs in surrounding tissues following endothelial dysfunction. Such micro- and macro-vascular complications develop over time and lead to edema, inflammation, and multi-organ dysfunction in CHF. However, a systemic examination of PEx in vital organs among different time windows of CHF has never been performed before. In the present study, we investigated time-dependent PEx in several major visceral organs including heart, lung, liver, spleen, kidney, duodenum, ileum, cecum and pancreas between sham-operated and CHF rats induced by myocardial infarction (MI). Plasma extravasation was determined by evaluating Evans Blue concentrations calorimetrically at fluorescence excitation wavelength of 620 nm (bandwidth 10 nm) and an emission wavelength of 680 nm (bandwidth 40 nm) at 3 days, 8-10 weeks and 4 months following MI. Data show that heart PEx level was initially high at day 3 post MI and then gradually decreased but still remained at a moderately high level at 8-10 weeks and 4 months post MI. Lung PEx began at day 3 and remained significantly high at both 8-10 weeks and 4 months post MI. Spleen PEx level was significantly high at 8-10 weeks and 4 months but not day 3 post MI. Liver PEx occurs early at day 3 and remain significantly high at 8-10 weeks and 4 months post MI. For the gastrointestinal (GI) organs including Duodenum, ileum and cecum, there was a general trend that PEx level gradually increased following MI and reached a statistical significance at 4 months post MI. Different with GI PEx, renal PEx level was initially high at day 3 but back to normal level at 8-10 weeks post MI. However, renal PEx was significantly elevated again at 4 months post MI. In summary, we found that MI generally incites a time-dependent PEx of multiple visceral organs. However, the PEx time window for individual organ in response to the MI challenge was different, suggesting that different mechanisms might be involved in the pathogenesis of PEx in these vital organs during CHF. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Epicore Discovery Patch® sweat collection system to assess sweat proteomics-based biomarker discovery in exercise-heat stress and acclimation
Authors: Mahoney Kyle , Chon Ki , Ghaffari Roozbeh , Minnis Mike , Huggins Robert , Lee Elaine 
Published: May 2023

Purpose: To optimize sample processing workflow, test the hypothesis that sweat proteome expression is expansive and stress-specific, and to discover novel sweat biomarkers able to detect heat stress exposure and acclimation state. Methods: Men and women (n=5, 25.7±4.5 yrs, 66.7±10.5 kg, 69±4 inches, VO2max 49.5±4 ml×kg-1 ×min-1) completed 7 bouts of exercise in hot and humid conditions (40°C, 40% relative humidity). Parallel sweat samples (thigh) were collected on days 1 and 7 (HE1 and HE7, respectively) using the Epicore Discovery Patch® system and using gauze confined to the skin using Tegaderm. A subset of sweat samples were processed immediately vs. frozen for at least 24 hours prior to processing. ~30 ug of protein in 2% SDS in 0.1 M Tris HCl, pH 8 were reduced and alkylated (5 mM dithiothreitol, 20 mM iodoacetamide), acidified (2.5% (v/v) phosphoric acid), and subjected to the S-Trap protocol (ProtiFi, LLC) and digestion with porcine modified sequencing grade trypsin (Promega). Eluted peptides were dried, desalted, and submitted to mass spectrometry for proteomics analyses. Differential expression analyses were conducted with Scaffold and R. Results: Proteomics verified that immediately processed sweat samples yielded 213 more uniquely expressed proteins, but 188 shared proteins (vs. frozen >24 h) in presence/absence analyses, but only 1 significantly expressed protein (FDR<0.05) different between the two sample preservation protocols. In the exercise-heat stress experiments, 1,922 unique peptide sequences were detected for 2,774 unique spectra. Presence/absence analysis revealed 6 proteins uniquely present in HE1, 172 mutually present in both time points and 45 uniquely present in HE7. Based on the quantitative profile (p<0.05) of the 223 unique proteins, 13 were significantly expressed in HE7, including CD59 glycoprotein, heat shock-related 70 kDa protein 2, and aspartate aminotransferase, which have been previously linked to heat stress, although never in sweat. Conclusion: Protocol optimization reveals unique stability of Epicore Discovery Patch® sweat collection quantifiable by highly sensitive proteomics assays. Specific to a physiological heat acclimation over 7 days, stress response proteins such as various histone family members, and unique biomarkers such as CD59 glycoprotein, HSP72 and aspartate aminotransferase appeared in sweat samples. Our novel observations regarding sweat composition complexity and specific supports ongoing work with diverse subject populations and other stress conditions. ONR, DoD, Faculty IDC This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
High fat-high sugar diet induces sex-dependent effects on the small intestine
Authors: Osborne Sarah , Rubin Maxwell , Ahlert John , Smith Emma , St Aubin Chaheyla , Miller Kyle , Al-Nakkash Layla 
Published: May 2023

Background: Metabolic syndrome includes a plethora of symptoms ultimately leading to obesity and type 2 diabetes. Obesity has been linked to chronic gastrointestinal dysfunction (constipation, or diarrhea) and specifically females with high BMI have been associated with increased prevalence of diarrhea. We aimed to better understand the influence of high fat-high sugar diet (Western diet) on small intestinal function and to assess sex-dependent effects. Methods: We measured transepithelial short circuit current (Isc) a measure of chloride secretory function, across freshly isolated segments of jejunum from male and female C57Bl/6J mice fed a high fat high sugar diet (HFS) for 12 weeks, compared to lean controls. At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions and senescence. Intestinal morphology was assessed. Serum cytokine assays were performed. Results: Basal Isc was significantly decreased 70% ( P<0.05) in HFS both females and males versus leans. In females, the HFS-induced decrease in Isc was attributed to a significant loss of CLC2, NKCC1 and CFTR expression whereas in males the decrease in Isc was due to a significant loss of Na/K-ATPase, KCa and NKCC1 expression (indicating interesting sex-dependent etiology). A2BR levels were also dysregulated in HFS fed male and female mice. Inflammatory state and shadowed body weight changes with feeding a western diet. Assessment of intestinal morphology and metabolic profile is being further evaluated. Conclusions: Our data suggests that the reduced basal jejunal Isc in HFS mice is attributed to sex-dependent mechanisms. Improved understanding of Western diet-induced intestinal dysfunctions may provide improved drug targets to treat gastrointestinal disturbances in obesity and diabetes. Midwestern Arizona Alzheimer’s Consortium and Diabetes Action Research and Education Foundation This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.