bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Time-Course and Magnitude of Cardiorespiratory Responses to Superimposed Surgical Masks or N95 Respirators during 20-min Treadmill Walking
Authors: Galeos Angela , Isakovich Rodion , Cates Valerie , Marullo Anthony , Strzalkowski Nicholas , Day Trevor 
Published: May 2024

Wearing medical barriers has recently expanded from healthcare to public settings, and could increase dead space and facilitate rebreathing of expired air resulting in heat accumulation, hypercapnia, and hypoxia, particularly during physical activity. We recently showed that participants wearing surgical masks (SM) and N95 respirators (N95) over 60-min during seated rest had mild and immediately reversible (a) increases face microclimate temperature, (b) increases in the pressure of end-tidal (PET)CO2, (c) decreases in PETO2, but (d) no differences in peripheral oxygen saturation (SpO2). Previous publications showed conflicting results of superimposed barrier wearing during physical activity, and there are limited studies that assessed face microclimate temperature and end-tidal gases, particularly comparing superimposed SM and N95. We hypothesized that participants wearing SM and N95 will experience mild face microclimate hyperthermia, hypoxia, and hypercapnia during 3mph treadmill walking. Participants (n=18; 8F) randomly wore (a) no barrier (NB), (b) SM or (c) N95 during a 10-min standing baseline, 20-min treadmill walking (3 mph), and a 10-min standing recovery. We continuously measured face microclimate temperature (thermistor), end tidal gases (PETCO2, PETO2; oro-nasal cannula), SpO2 (peripheral pulse oximeter). Average 20-min PETCO2 (higher; p<0.0001, P=0.0001) and PETO2 (lower; P=0.0003, P=0.0178) were significantly from baseline for both SM and N95, respectively. The delta between the 20-min average compared to the baseline data was not statistically significant for PETCO2 or PETO2 in all three conditions, except for ΔPETCO2 NB vs. N95 (higher; P=0.0344). Additionally, there was no difference in SpO2 across all barrier conditions during exercise. These mild physiological effects may account for qualitative reports of shortness of breath and increased perceived exertion while wearing barriers during physical activity. However, these effect-magnitudes are not physiologically-meaningful, and are immediately reversed upon cessation of exercise and/or barrier removal. NSERC. This is the full abstract presented at the American Physiology Summit 2024 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.
B1AR regulation of the Cav1.2 via the SAP97 complex
Authors: Salemme Victoria , Xu Bing , Bahriz Sherif , Zhu Chaoqun , Zhao Meimi , Wang Ying , Xiang Yang k 
Published: May 2024

Beta adrenergic (BAR) signaling is stimulated by the catecholamines norepinephrine (NE) and epinephrine (EPI) to control cardiac contractility. The beta-1-AR (B1AR) is the major cardiac subtype. B1AR signals canonically through the Gas subunit, leading to increases in cAMP and PKA; however, it can also signal via the Gai subunit, leading to increased NOS1, cGMP, and PKG levels. B1AR-NOS1 signaling leads to increased contractility and calcium cycling in cardiomyocytes. We found a novel complex within cardiomyocytes in which the B1AR, Cav1.2, and NOS1 proteins are held in proximity by the membrane scaffolding protein SAP97. In heart failure, there is a decrease in SAP97 expression and impaired B1AR signaling. Cardiac-specific deletion of SAP97 disrupts this complex. In the SAP97-cKO mice, there are minimal changes in B1AR-Gas; however, B1AR-Gai signaling is decreased, with a loss of B1AR-NOS1 signaling. Furthermore, we see a decrease in whole cell calcium currents and cardiac contractility. In mice lacking the NOS1, we see the same decrease in calcium currents. We hypothesize SAP97 is necessary to maintain B1AR modulation of Cav1.2 in cardiomyocytes. Using electrophysiology and biochemical techniques, we aim to elucidate the role of SAP97 in B1AR modulation of Cav1.2 and how this is impacted by the impairment of B1AR-Gai signaling. T32HL086350 RO1-HL147263. This is the full abstract presented at the American Physiology Summit 2024 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.
Myocardial Blood Flow in Newly Diagnosed Breast Cancer Patients at Rest and During Exercise
Authors: Heinonen Ilkka , Koivula Tiia , Uurasmaa Tytti-Maria , Han Chunlei , Maaniitty Teemu , Latifi Shiva , Lempiäinen Salla 
Published: May 2024

Heart depends critically on continuous supply of blood, but it is unknown whether cancer, without any treatments, affects myocardial blood flow (MBF) at rest or during exercise. This study therefore aimed at measuring MBF in cancer patients and control subjects and it was hypothesized that MBF is affected by cancer. The study included recently-diagnosed breast cancer patients (n=18) who had not started their oncologic treatments and age-matched female control participants (n=32). Controls were women referred to cardiac diagnostic testing but who were by this testing judged to be free of obstructive coronary artery disease. MBF was quantified with [15O]H2O positron emission tomography (PET) at rest in both groups and additionally during 10-min supine bicycling exercise in the breast cancer patients. Furthermore, cardiac morphological changes were analyzed with a breast cancer mice-model four weeks after the inoculation of 13TC mammary tumor cells. Respective mice without tumors served as controls. Resting heart rate (HR) and rate pressure product (RPP) correlated positively with resting MBF, but were similar in both groups resulting also in similar resting MBF in cancer patients and controls. MBF increased significantly from rest during exercise in breast cancer patients (p<0.0001) and exercising MBF correlated positively with the histologic grade of cancer (r=0.54, p=0.021). However, cancer grade did not associate with exercise intensity measures such as HR, RPP or HR percentage from age-predicted maximal HR. In the mouse model, the breast cancer did not affect heart weight, cardiomyocyte size, myocardial capillary density, or capillary-to-myocyte size ratio. In conclusion, resting MBF in humans or myocardial capillarity in mice appear not to be affected by breast cancer. However, the more severe is the histologic grade of cancer, the higher is the MBF during exercise in patients with breast cancer, independently of the intensity of the exercise suggesting dysregulation of myocardial blood supply with cancer. This novel finding requires further investigations. This study was financially supported by Academy of Finland and Hospital District of South-West Finland. This is the full abstract presented at the American Physiology Summit 2024 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.
Clock and Bmal1 inhibit expression of Sglt1 in mouse Kidneys and glucose reabsorption
Authors: Stevenson Matthew , Mowdawalla Cyrus , Wong Bokey , Chu Alexander , Ragolia Louis , Vallon Volker , Hussain M.Mahmood 
Published: May 2024

Aberrantly elevated sodium/glucose cotransporter 1 (Sglt1) expression and increased glucose reabsorption contribute to obesity or lean-associated metabolic complications, however, the precise mechanisms underlying the high expression of Sglt1 and increased glucose absorption are unclear. Clock (circadian locomotor output cycles kaput protein) is known as the master clock gene; Bmal1 (basic helix-loop-helix arnt like 1) is a known heterodimer of Clock that is a critical regulator of circadian metabolism and has the potential for regulating obesity-related diseases. We examined whether circadian clock genes involving Clock/Bmal1 and the orphan nuclear receptor Shp (the small heterodimer partner) regulate the expression of Sglt1 to maintain glucose reabsorption and glucose homeostasis. Renal Sglt1 levels were increased in Clock-mutant or Bmal1-knockout (KO) mice and were decreased by activation of Bmal1 in an SHP-dependent manner. Mechanistically, the transactivation of Sglt1 by HNF1α (hepatic nuclear factor 1 alpha) was inhibited by SHP. In wild-type mice fed a western diet, activation of Shp by Nobiletin reduced Sglt1 levels and improved glucose reabsorption and glucose handling, but these beneficial effects were not seen in Clock−mutant and Bmal1 KO mice. These results demonstrate that normal inhibition of Sglt1 by Clock/Bmal1-SHP is defective in obesity, resulting in increased Sglt1 levels, glucose reabsorption, and renal steatosis. This Clock/Bmal1-SHP-Sglt1 pathway may present novel targets for treating obesity. This work was supported in part by National Institutes of Health (NIH) grant R56 HL137912 and American Heart Association Scientist Development Grant 2300158 and Grant-in-Aid 16GRNT30960027 to XP; by U.S. NIH grants DK121490, HL137202, HL158054 and HD094778, and VA Merit Award BX004113 to MMH; and NIH grants R01DK112042, R01HL142814, RF1AG061296, the UAB/UCSD O’Brien Center of Acute Kidney Injury NIH-P30DK079337, and the Department of Veterans Affairs to V Vallon. This is the full abstract presented at the American Physiology Summit 2024 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.
Examining the Role of the Gut-Brain Axis in Alcohol Use Disorder in Zebrafish
Authors: Ramirez Samuel , Uno Jennifer K. 
Published: May 2024

14.5 million people struggle with Alcohol Use Disorder (AUD), characterized by uncontrolled drinking and withdrawal. Both chronic and acute alcohol use are known to disrupt the intestinal microbiome and are associated with mood disorders. The gut-brain axis is a bidirectional communication pathway between the brain and the intestines. Probiotic modulation has already been shown to alter brain chemistry in zebrafish. Recent research indicates the gut-brain axis is involved in the behavior modifications associated with AUD, however the mechanism by which it does so remains unknown. The objective of this study is to examine the impact that alcohol has on the gut-brain axis. We hypothesize that a reduced intestinal diversity will lead to heightened behavioral responses and alter biomarkers associated with chronic alcohol exposure. In order to examine this hypothesis, zebrafish (Danio rerio) were exposed to amoxicillin and erythromycin for fifteen days to clear their microbiome. Following treatment, fish were immersed in 0.50% ethanol for one hour and in escalating dosage up to 0.25% for two weeks to mimic acute and chronic alcohol exposure. Fish were recorded for 10 minutes following treatment to analyze behavioral patterns. Bacterial populations were significantly knocked down following treatment in both groups (n= 6, p < 0.05). Behavioral results from the acute ethanol treatment indicate fish exposed to ethanol displayed reduced vertical and horizontal transitions in both antibiotic and control groups, with more pronounced shifts in antibiotic-ethanol- treated group (n= 6). This reduction was not observed in the chronically treated fish, suggesting an adaptation effect. In order to further assess cognitive function, levels of NMDA Glut1 receptor mRNA were assessed, we observed no significant changes in receptor gene expression in the brains of zebrafish in the treatment groups relative to control groups. Collectively these results indicate that acute alcohol induced behavior correlates to changes in the microbiome, though this correlation is not observed in chronic alcohol exposure. Future studies are needed to better understand what role the gut brain axis plays in alcohol mediated-behavioral observations. Glen Raven Endowed Grant, Elon University. This is the full abstract presented at the American Physiology Summit 2024 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.
Interleukins expression by lymphocytes of rats exposed to chronic intermittent normobaric hypoxia
Authors: Moraga Fernando , Calderon-Jofré Rodrigo , Bernal-Dosseto Giuliano , Moraga Daniel 
Published: May 2024

Hypoxia acute and chronic modulates the expression of inflammatory mediators such as cytokines. However, studies in chronic and intermittent hypobaric or normobaric hypoxia similar to described in miner’s population are scares o absent. In regards with this we propose evaluated the effect of chronic intermittent normobaric hypoxia (CINH) on the hematological, cardiovascular response and expression of lymphocyte’s cytokines such as IL-1b, IL-2, IL6 and IL-10 in rats. A total of 20 Sprague-Dawley rats were divided in two groups: a) CINH of FiO2 10% (n=10) and normoxic rats (n=10) were used as controls. Blood samples were obtained from both groups for hematological studies, systolic arterial pressure and heart rate was measured in tail-cuff sensor, and expression of cytokines obtained from lymphocytes was determined by RT-PCR. Hematocrit, hemoglobin, platelet count and hematological constant are elevated however leucocyte count decrease. A significant increase of systolic arterial pressure (over 50%). In vitro expression of cytokines from lymphocytes shown that IL-10, IL-2 and IL6 increase 35%, 64% and 16% respectively, while that of IL-1bdecreases by 18%. CINH could be activate an inflammatory response mediated by IL-2, however this response could be attenuated due to the increase in the expression of IL-10, a known anti-inflammatory cytokine, and the decrease in the expression of IL-1β and IL6 suggesting a mechanism of adaptation to CINH. Innova-Corfo Project 07CN13ISM-152. This is the full abstract presented at the American Physiology Summit 2024 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.
CXCL10 regulates pressure overload-induced heart failure
Authors: Souza-Neto Fernando , Le Preston , Alamgir Ashab , van Berlo Jop H. 
Published: May 2024

Rationale: Heart failure involves tissue inflammation with elevated serum levels of CXCL9 and CXCL10, which are CXCR3 receptor ligands. Both chemokines are expressed by cardiac fibroblasts and myeloid cells in mice subjected to pressure overload induced by transverse aortic constriction (TAC) surgery. Although it is known that CXCR3−/− animals are protected from cardiac remodeling induced by TAC, the role of CXCL10 is unknown. The present study was undertaken to test the hypothesis that CXCL10 is crucial in the cardiac remodeling response to pressure overload induced by TAC in mice. Methods: We subjected wild-type and CXCL10−/− mice to TAC surgery, resulting in 4 experimental groups: WT Sham, WT TAC, CXCL10−/− Sham and CXCL10−/− TAC. WGA was used to analyze the cross-sectional area of cardiomyocytes. To analyze total collagen deposition, PicroSirius Red was used. Immunohistochemistry was performed to measure the number of CD64, CD3g and CD45 positive cells. Echocardiography was used to analyze cardiac function. Results are presented as the mean and standard error of the mean. Comparisons between means were made using two-way variance analysis (ANOVA), as well as Tukey's post hoc test for parametric comparisons, or Kruskal-Wallis and Dunn‘s post hoc test for non-parametric data. Differences with p<0.05 were considered significant. Results: After 1 week, the CXCL10−/− mice showed the same level of cardiac hypertrophy and similar changes in echocardiography parameters, when compared to wild-type mice. However, after 6 weeks, we observed that the CXCL10−/− mice showed an attenuation of heart weight with a reduction in the total collagen deposition compared with wild-type TAC mice. At the cellular level, the genetic deletion of CXCL10 prevented the TAC-induced increase in the cross-sectional area of cardiomyocytes. Moreover, we observed that TAC increased the number of CD3+ T-cells in the heart quantified from stained cross sections of both wild type and CXCL10−/− mice, while no differences were observed for the total number of macrophages. Importantly, echocardiographic changes, including dilation and cardiac dysfunction, induced by pressure overload in wild animals were blunted in CXCL10−/− mice. Corroborating this, the genetic deletion of CXCL10 prevented the increase in lung weight induced by TAC. Conclusion: CXCL10 regulates cardiac hypertrophy and fibrosis induced by pressure overload in mice, as well as the functional changes that characterize heart failure. We are currently unraveling the mechanism through which CXCL10 can accelerate the development of heart failure in response to cardiac pressure overload. Interaction between T cells and macrophages are likely mediating these effects. R01HL155993. This is the full abstract presented at the American Physiology Summit 2024 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.
Contractile pericyte-mediated cerebrovascular deficits in a mouse model of CADASIL
Authors: Vigderman Abigail , Hariharan Ashwini , Weir Nick , Xiang Liuruimin , Longden Thomas 
Published: May 2024

Small vessel disease (SVD) of the brain underlies 25% of stroke cases and is the most common cause of vascular cognitive impairment. The most common monogenic form of SVD is CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), caused by mutations of the NOTCH3 protein which is widely expressed in mural cells (vascular smooth muscle cells [SMCs] and pericytes). Cerebral blood flow (CBF) deficits present early in CADASIL, attributable in part to NOTCH3-mediated extracellular matrix dysregulation, which alters heparin-binding epidermal growth factor-like (HB-EGF) signaling in SMCs and endothelial cells (ECs). Pericytes also robustly express NOTCH3 and are a relatively underexplored cell type in the context of CADASIL. Pericytes proximal to the penetrating arteriole (PA), known as contractile pericytes, express α-smooth muscle actin (αSMA) and can contract to rapidly regulate capillary diameter and thus blood flow in the downstream capillary tree. We conducted two-photon laser scanning microscopy (2PLSM) of blood flow and pericyte contractile responses with CADASIL Notch3R169C transgenic and control mice. Our data indicates that contractile pericyte-mediated control of blood flow is impaired prior to other known CBF deficits, thus raising the tantalizing possibility that these pericytes could be a target for early clinical intervention in CADASIL. While PA responses to stimulation of capillary electrical signaling remain intact, both blood flow as well as capillary diameter of contractile pericyte-covered vessels are diminished. Taken together, this work will establish pericytes as a novel site of dysfunction and provide a new candidate mechanism by which CBF is diminished early in CADASIL pathogenesis for potential therapeutic intervention. 5T32GM008181-33 (AV), 1DP2OD02944801 (TL), 1R01AG066645 (TL), 5R01NS115401 (TL). This is the full abstract presented at the American Physiology Summit 2024 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.
Antigen Presenting Cell activator protein 1 (AP-1) complex contributes to Salt-sensitive Blood Pressure
Authors: Ahmad Taseer , Saleem Mohammad , Pitzer Mutchler Ashley , Ertuglu lale , Kirabo Annet 
Published: May 2024

Salt-sensitivity of blood pressure (SSBP) affects 50% of the hypertensive and 25% of the normotensive population and is a major independent risk factor for cardiovascular morbidity and mortality. We previously found that SSBP is associated with activation of the NLRP3 inflammasome in antigen presenting cells (APCs) via increased oxidated stress and isolevuglandin (IsoLG) formation, but the underlying mechanisms are unknown. The activator protein 1 (AP-1) (FOS/JUN) has been implicated in activation of the NLRP3 inflammasome but its role in SSBP is not known. We hypothesized that AP-1 transcription factor in APCs senses elevated sodium and contributes to SSBP. We further hypothesize that antioxidant flavonoid, diosmetin prevents AP-1 activation and SSBP. Using bulk RNA-sequencing in human monocytes, we found elevated sodium increases expression of the AP-1 gene family when compared to normal sodium concentration, including cFOS (2378.18 ± 480.7 vs 6494.09 ± 945.55, p= 0.0009), FOSB (53.63 ± 17. 55 vs 131.06 ± 10.30, p= 0.397), cJUN (7313.90 ± 984.93 vs 11370.09 ± 1286.35, p= 0.2563) JUNB (4218.4.36 ± 199.17 vs 570.45 ± 200.91, p= 0.0445) and JUND (3309. 63 ± 270.64 vs 8057.90 ± 1043.05, p= 0.00006). In additional experiments, we enrolled people with hypertension and phenotype them for SSBP using an established in-patient protocol of salt-loading/depletion and performed single-cell transcriptomic analyses in vivo on peripheral blood mononuclear cells (PBMCs). We found that expression of the FOSB and JUNB genes are more sensitive in concert with blood pressure in salt-sensitive (SS) but not salt-resistant (SR) humans. Moreover, diosmetin attenuated high salt-induced hypertension, 123.5 ± 4.1 vs 146.8 ± 2.5 mm Hg in controls, **p< 0.01). In addition, diosmetin also reduced high salt-induced inflammation including APC production of IsoLG-protein adducts, IL-1β, and NLRP3 inflammasome expression. These findings reveal a role for immune cell AP-1 (FOS/JUN) signaling in salt-sensitive hypertension and diosmetin may provide a potential therapeutic target for treatment of SSBP. 1R01HL144941-01A1. This is the full abstract presented at the American Physiology Summit 2024 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.