bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences and the impact of G protein-coupled estrogen receptor deletion in the vascular and renal response to aldosterone
Authors: Leite Ana Paula , Ogola Ben , Visniauskas Bruna , Kilanowski-Doroh Isabella , Horton Alec , Diaz Zaidmara , Lindsey Sarah 
Published: May 2023

We recently showed that the G protein-coupled estrogen receptor (GPER) protects female mice from arterial stiffening, an independent predictor of cardiovascular mortality. Previous work indicates that GPER may directly bind aldosterone and/or dimerize with the mineralocorticoid receptor. Therefore, we hypothesized that GPER may promote aldosterone-induced renal and vascular effects, particularly in male animals where less estrogen is available to activate GPER. Male (M) and female (F) wildtype (wt) and global GPER knockout (ko) mice were used between 6-7 months of age. Aldosterone was delivered to all mice subcutaneously via osmotic mini pumps at a dose of 600 μg/kg/day and drinking water was replaced with saline for 28 days. At the end of the study, tail-cuff systolic blood pressure (SBP) and metabolic cage data were collected. Data were analyzed by 2-way ANOVA followed by Sidak’s test and correlation analysis. In basal conditions, GPER ko increased systolic SBP in males but not females. After aldosterone-salt treatment, SBP was similar in Mwt versus Mko but was significantly higher in Fko versus Fwt (Pinteraction=0.002; 148 ± 12 vs. 108 ± 2 mmHg; P<0.001). Similarly, proteinuria was similar in males but greater in Fko than Fwt (Pinteraction=0.01; 6.0 ± 1.5 vs. 2.4 ± 0.4 mg/day; P=0.04), indicating greater kidney injury. In summary, GPER deletion in females revealed enhanced blood pressure and renal damage in response to an aldosterone-salt challenge. These findings do not support a role for GPER in promoting the impact of aldosterone on vascular and renal damage in either sex. In contrast, GPER protected female mice from the negative impact of aldosterone-salt on blood pressure and kidney function. More studies are needed to understand the interactions of GPER and aldosterone in the kidney of both males and females. This work was supported by the National Institutes of Health (HL133619 and AG071746 to SL, HL155841 to BO) and the American Heart Association (BV and IK) 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.
CD63-Snorkel tagging for isolation of tissue-specific small extracellular vesicles
Authors: Qin Gangjian , Han Chaoshan 
Published: May 2023

Exosomes are important mediators of inter-tissue communications; however, no effective method is available to allow for isolating, thus characterizing, tissue-specific exosomes in vivo. Since CD63 is a reliable marker for exosomes, we have developed a tagging strategy, term “CD63-Snorkel (CD63-SNKL),” in which CD63 at its intracellular C-terminus was fused to a fragment of PDGFRB that contains the transmembrane domain tethered to multiple epitope tags (HA, His, and FLAG) in tandem on the surface. We found that the CD63-SNKL protein has similar subcellular localizations as endogenous CD63 and can be effectively sorted into small EV (sEV), primarily exosomes. Furthermore, sEV secreted from CD63-SNKL–transduced cells can be effectively captured on anti-HA magnetic beads and eluted with HA peptides. Thus, CD63-SNKL may be engineered for isolating and tracking endogenous tissue-specific sEV in vivo. This work was supported by the American Heart Association (Grant# 19TPA34910227 to G.Q., 830472 to C.H., and 19IPLOI34760713 to J.Y.) and Southern University of Science and Technology (startup fund to G.Q.). 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.
Pancreatic islet cell reprogramming into insulin producers: a multi-omics approach
Authors: Monteiro Rodrigues Luis , Farrim Maria , Gomes Andreia , Milenkovic Dragan , Echaniz Regina 
Published: May 2023

The loss of β-cell mass is a common pathological process of type 1 and type 2 diabetes and α- to β-cell-like transdifferentiation has gained attention as a potential strategy to increase insulin production.This study used powerful integrative multi-omics bioinformatic tools to scrutinize and perform integrated analyses of publicly available diabetes-associated “omics” data to unveil novel molecular targets associated with α- to β-cell-like transdifferentiation. To achieve this goal, a comprehensive search on PubMed for human studies on gene expression alterations associated with diabetes was conducted Ninety-eight entries were retrieved from which 8 studies reporting microarray data, RNAseq and single-cell RNAseq (scRNAseq) were selected for the in-dept bioinformatic analysis. Each dataset was analyzed individually to identify differently expressed genes (DEG) (p < 0.05). DEGs were obtained using GEO2R tool available at Gene Expression Omnibus (GEO) repository or the supplementary data of the respective studies. Pathway enrichment analyses of DEGs were conducted using GeneTrail as a platform to access KEGG and WIKI pathways databases. Potential transcription factors were identified with Enrichr as a platform to TRRUST and TRANSFAC. For non-coding differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), targets were identified using the MIENTURNET27 and LncRRIsearch28 tools, respectively. Comparison of genes among studies reporting microarray data showed 808 common genes (3 studies in total). Pathways enrichment analysis pointed out cell signaling, endocrine system (insulin resistance and insulin secretion) and metabolism as common to at least two studies. A similar analysis was conducted for 5 studies reporting diabetes-related alterations of mRNA levels in RNAseq/scRNAseq analyses, further supporting these data. The extracted transcriptomic data was then used to search for potential transcription factors modulating specific diabetes-related regulons, which revealed the transcription factors RXRA, ELK1, CTCF, and AR in common to two or more studies.Regarding the non-coding RNAs, we identified 101 miRNAs in 5 studies from which 22 were common between 2 or more studies, together with 10 common lncRNAs among 3 or more studies. Bioinformatic analyses are ongoing to pinpoint the targets and pathways of these regulatory molecules in particular targeting α- to β-cell-like transdifferentiation. This research is funded by Fundação Ciência Tecnologia (FCT) by grant UIDB/04567/2020. R. Menezes is supported by the Science Employment Stimulus program from FCT. 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.
Dietary pattern, body composition, metabolic markers, and skin physiology
Authors: Monteiro Rodrigues Luis , Menezes Regina , Andrade Sergio , Fontes Tatiana , Lopes Sofia , Ferreira-Pego Cintia 
Published: May 2023

Dietary patterns have been linked to differences in cardiovascular physiology, metabolic markers, and ahealthy skin condition.. However, published evidence on these issues is still insufficient and often controversial. This study aimed to identify differences in total body composition, biochemical markers, and skin physiology among omnivorous (OM) and vegetarian (VG) individuals. Participants (n=176, both sexes, mean age 31yo) included 115 OM and 61 VG. Body composition was assessed by absorptiometry (DXA Lunar-GE Healthcare®) and metabolic markers measured from capillary blood sampling (LINX DUO, Menarini). Skin physiology, regarded as an indicator of health, was assessed by transepidermal water loss (TEWL, Tewameter® CK electronics), hydration (Moisturemeter® DTec), and biomechanics (Cutometer® CK electronics) in five anatomical sites (forehead, cheek, neck, hand, and leg). No significant differences were observed between groups for any body composition variables although VG participants showed higher levels of Visceral (VAT) and Subcutaneous Adipose Tissue (SAT). The OM group presented significantly higher levels of total cholesterol, LDL cholesterol, and non-HDL cholesterol, and VAT was positively correlated (p<0.05) with all the biomarkers evaluated. Meanwhile, in the VG group (a) higher levels of fat mass were statistically correlated with higher levels of Hemoglobin A1c, LDL-cholesterol, and Non-HDL-cholesterol; (b) VAT was positively correlated with triglycerides/HDL ratio, Non-HDL-cholesterol, and systolic blood pressure; and (c) SAT was negatively correlated with HDL-cholesterol, and positively correlated with LDL-cholesterol and non-HDL-cholesterol. Prospective (10 year) cardiovascular risk calculations were considerably higher in OM participants compared to VG (2.17 vs. 1.06 points). Noteworthy, the VG participants were more active physically than the OM, and reported diets of lower energetic density, protein, saturated fat, and cholesterol, with higher contents of fiber and complex carbohydrates and sugars. VG participants have shown a higher TEWL, hydration, elasticity, and skin carotenoid content. Correlation analysis regarding VAT, SAT, and skin parameters showed a significant positive correlation between TEWL, hydration, and skin elasticity, and a negative correlation with skin retraction (after creep). These results suggest that some composition features, cardiovascular risk, and skin physiology differ between VG and OM individuals and might be related to their dietary patterns. This research is funded by Fundação Ciência Tecnologia (FCT) by grant UIDB/04567/2020. C.F.-P. and R.M. are supported by the Science Employment Stimulus program from FCT. 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 potential role of matrix metalloproteinases on reducing small artery stiffness and improving vasodilation in old spontaneously hypertensive rats
Authors: Augenreich Marc , Jurrissen Thomas , Ramirez-Perez Francisco , Castorena-Gonzalez Jorge , Morales-Quinones Mariana , Foote Christopher , Nourian Zahra , Lateef Olubodun , Sun Luke , Hill Michael , Meininger Gerald , Padilla Jaume , Martinez-Lemus Luis 
Published: May 2023

Arterial stiffening is a major risk factor for cardiovascular disease development and progression. Both hypertension and aging are associated with presence of microcirculation endothelial dysfunction, hypercontractility, and vascular stiffening. Reports suggest that while hypertension results in inward remodeling, aging is associated with either no changes in internal diameter or outward remodeling with or without increases in wall thickness. Herein, we hypothesized that small arteries from old spontaneously hypertensive rats (SHR) would be inwardly remodeled and stiffer than old normotensive Wistar Kyoto (WKY) rats due to aggravated endothelial dysfunction, hypercontractility, and an increased presence of vascular smooth muscle stress fibers and collagen to elastin ratios. We further hypothesized that these characteristics would be associated with reduced expression of matrix metalloproteinases (MMPs). These hypotheses were tested in mesenteric arteries isolated from 88-week-old SHR and WKY rats. All reported differences are significant at P<0.05. SHRs had increased mean arterial pressure (P), pulse P, and heart weight normalized to body weight vs WKY rats. No differences in small mesenteric artery responses to phenylephrine or acetylcholine were observed between the rat strains. However, responses to the sodium nitroprusside were greater in SHR than in WKY isolated arteries. SHR arteries also had increased wall thickness and wall to lumen ratios, in addition to reduced cross-sectional compliance at 5-40 mmHg intraluminal P and lesser incremental modulus of elasticity at 80-120 mmHg. No differences in content of the extracellular matrices, collagen or elastin, were observed between arteries from either strain, whereas smooth muscle F-actin stress fibers were more abundant in the SHR arteries and MMP-2 and -9 expression were increased in the SHR arteries. In conclusion, these data suggest the interaction of age and hypertension in SHRs is associated with hypertrophic remodeling and increased responsiveness to nitric oxide likely due to increased MMP activity and reduced arterial stiffness. NIH HL-088105-02 to LAM-L 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.
Furosemide rescues hypercalciuria in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis model
Authors: Mutig Kerim , Kriuchkova Natalia , Breiderhoff Tilman , Müller Dominik , Yilmaz Duygu , Demirci Hasan , Drewell Hoora , Günzel Dorothee , Himmerkus Nina , Bleich Markus , Persson Pontus 
Published: May 2023

Aim: Impaired calcium homeostasis limits life expectancy and quality in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC). This rare disease is caused by loss-of-function mutations in CLDN16 or CLDN19 genes leading to impaired paracellular reabsorption of divalent cations along the cortical thick ascending limb (cTAL). The ensuing late distal nephron and collecting duct system partially compensate for the defect in cTAL by increased transcellular Ca2+ reabsorption via the luminal transient receptor potential channel V5 (TRPV5), as well as basolateral plasma membrane calcium ATPase (PMCA) and sodium-potassium exchanger (NCX1). The loop diuretic furosemide induces compensatory activation in these distal segments due to blockade of NaCl and divalent cation reabsorption in the preceeding TAL. Although furosemide enhances urinary calcium excretion via inhibition of the aforementioned cTAL in general population, this effect is not expected in FHHNC patients with already severely impaired Ca2+ transport in the cTAL. The present study follows the hypothesis that furosemide may alleviate hypercalciuria in this disease by activation of the distal transcellular Ca2+ transport proteins. Methods: Cldn16-deficient mice (Cldn16-/- ) served as a FHHNC model. Wild-type (WT) and Cldn16-/- mice were treated with furosemide (7 days of 40 mg/kg bw) or vehicle. We assessed renal electrolyte handling (metabolic cages) and key divalent transport proteins. Results: Cldn16-/- mice show increased Ca2+ excretion than WT and compensatory stimulation of Cldn2 in the proximal tubule, as well as of TRPV5, and NCX1 in the distal nephron at baseline. Furosemide reduced hypercalciuria in Cldn16-/- mice and enhanced TRPV5 and PMCA levels in Cldn16-/- but not in WT mice. Conclusions: Furosemide alleviated hypercalciuria in a mouse FHHNC model, likely via stimulation of transcellular luminal and basolateral Ca2+ transport systems in the distal nephron and collecting duct. These results may have a clinical implication in FHHNC patients. No conflict of interests 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.
Assessment of Functional Characteristics of Small Arterioles and Capillaries Using an Intact Dura Mater Preparation
Authors: Arnold Amanda , Sprouse-Blum Adam , Nelson Mark , Klug Nicholas 
Published: May 2023

The dura mater, a protective layer surrounding the brain and spinal cord, plays a crucial role in maintaining homeostatic function of the central nervous system. The large arteries and veins of the dura mater are relatively sparse and have been extensively studied with respect to their contribution to pain sensation, with unclear and controversial contributions to headache and migraine pathology. Small arterioles and capillaries exhibit nearly ubiquitous coverage of the entire dura, yet their physiological and pathophysiological functions remain largely unexplored. Here, using ex vivo mouse dura, we examined the electrical (membrane potential recordings), Ca2+ signaling properties (GCaMP or Cal-520 AM imaging), and vasomotor behavior (pressurized dura vessels with diameter measurement) of these exquisitely small vessels. Furthermore, we show electrical and Ca2+ responses in smooth muscle and pericytes in response to calcitonin gene-related peptide (CGRP) receptor and transient receptor potential V1 (TRPV1) channel activation, which are two principal targets in headache and migraine pathology. Last, we highlight unique anatomical interactions between nerves and arterioles in the dura mater using immunostaining techniques. In conclusion, we hypothesize that microvessels consisting of arterioles and capillaries are a logical and unexplored region for studying homeostatic and pathological roles of the dura mater. Funding Provided by the Totman Medical Trust 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.
Comparing amount of mechanical work and metabolic cost between two kettlebell swing protocols
Authors: Vencel Daniel , Crecelius Anne , Beerse Matthew 
Published: May 2023

The kettlebell swing has been touted as having both cardiovascular-driven metabolic and strength benefits which several studies have investigated. However, to the authors’ knowledge, none have researched the work economy of the exercise by capturing both mechanical work and metabolic cost. Here, we implement a commonly studied kettlebell swing protocol consisting of short intervals of 20 reps and 30 seconds of rest and compare it to longer intervals of 60 reps followed by 90 seconds of rest. Work-rest ratio was 1:1 for both protocols based on a consistent cadence (short: 36.75 ± 2.12 vs. long: 37.08 ± 1.66 reps/min) total volume was the same. A group of 6 healthy young adults, familiar with the kettlebell swing, performed both protocols in a counterbalanced order and separated by 20 minutes of rest. To calculate total mechanical work performed (J/kg), we used the Noraxon motion capture system with inertial measurement units (IMUs) and conducted a segmental analysis of the feet, shanks, thigh, pelvis, trunk, upper arms, forearms, hands, and head. Oxygen consumption (VO2) and other metabolic variables were captured using a metabolic cart (Parvo). We hypothesized that longer intervals might challenge form due to muscle fatigue, thereby changing economy despite matched work-rest ratios and total volume. Contrary to our hypothesis, there is no statistical significance in total mechanical work (short: 1043 ± 261 J/kg vs long: 1159 ± 334 J/kg, paired t-test: p = 0.49) between the two protocols. Similarly, total VO2 (short: 121 ± 14 vs long: 126 ± 15 vs long: mL/kg; paired t-test: p = 0.62) was not significantly different and as a result the total work economy, total VO2 divided by total work, was also not significantly different (short: 0.122 ± 0.031 ml/J vs long: 0.118 ± 0.043 ml/J; paired t-test: p = 0.34). The present findings suggest that protocols of the same work-rest ratios for the kettlebell swing elicit similar work, metabolic responses and therefore economy, even with different duration intervals. University of Dayton University Honors Program, Berry Summer Thesis Institute 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.
Exercise pressor response in healthy Hispanic Adults
Authors: Dalve Ashlesha , Perez Justo , Liu Randy , Nyarko Ruby , Appiah Crystal , Van Wagoner Tyler , Kaur Jasdeep 
Published: May 2023

Hispanic adults (HA) have the highest prevalence of type 2 diabetes and obesity compared to any other ethnic/racial group in the United States. Given that hypertension is a common comorbidity in diabetic patients, this further increases the cardiovascular risk in HA. In fact, recent data indicate an increased mortality attributable to hypertension in HA. Despite accumulating evidence of health disparities in the HA population, studies investigating the mechanism are lacking. Previous studies have demonstrated an exaggerated exercise pressor response in patients with hypertension and type 2 diabetes, two common risk factors highly prevalent in HA. In this study, we investigated whether young, healthy HA exhibit an augmented pressor response during exercise compared to the age-matched non-Hispanic White (NHW) adults. In 5 Hispanic (age 21±1 years; BMI 23±1 kg/m2; MVC= 76±5kg) and 6 NHW adults (age 22±2 years; BMI 24±1 kg/m2; MVC=75±5 kg), blood pressure (finger photoplethysmography) and heart rate (ECG) were measured at rest and during 2 min of static handgrip exercise performed at 30% and 40% of their maximal voluntary contraction (MVC). Muscle metaboreflex was isolated by post-exercise ischemia (PEI; supra-systolic cuff inflation of the exercising arm) for 2 min. A cold pressor test (CPT) was also performed as a generalized sympatho-excitatory stimulus. Resting mean arterial pressure was similar in both the groups (HA=77±2 mmHg vs. NHW=79±7 mmHg, p=0.79). The increase in blood pressure during exercise was not different between HA and NHW (ΔMAP: 40% MVC; HW=44±9 mmHg vs NHW=40±3 mmHg; p=0.74). Similarly, MAP during isolation of muscle metaboreflex did not reach statistical significance when compared between HA and NHW (ΔMAP: 40% MVC PEI, HW=42±7.3 vs NHW=34±1.6 mmHg; p=0.16). During CPT, HA had a significantly higher increase in blood pressure compared to NHW (ΔMAP: HW=30±6 mmHg vs NHW=20±2 mmHg; p=0.09). These preliminary data suggest that while exercise pressor reflex is not augmented in young, healthy HA, the heightened pressor response to a non-exercise stimulus potentially indicates exaggerated sympathetic reactivity in this population. Supported by Kinesiology and Health Education UT Austin Start-up Account 19-2635-91 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.