bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian disruption via timing of food availability contributes to renal fibrogenesis in male, but not female mice
Authors: Benjamin Jazmine , Pati Paramita , Liu Xiaofen , Luong Tha , Pollock Jennifer , Pollock David 
Published: May 2023

Previous work from our lab showed that restricting food to the lights-on (inactive) period for less than one week causes circadian misalignment blood pressure and kidney excretory rhythms. Since circadian disruption increases risk of cardiometabolic disease, we hypothesized that long-term mistiming of food intake would lead to kidney injury. Male and female 5–7-week-old C57BL6/J mice were placed on the following feeding schedules: ad libitum (AL; 24-h food access), inactive time restricted (iTRF; 12h food access during the lights-on period only), or active time restricted (aTRF; 12h food access during lights-off period only) for 9 weeks. There were no differences in 24-hr food or water intake between the feeding groups. Male iTRF mice demonstrated a significant increase in renal fibrosis with 19.9±1.5% in cortex and 18.3±8.0% area staining positive as compared to AL mice with 8.2±2% and 8.6±1.2% in cortex and medulla, respectively (p < 0.05, n=3/group). In contrast, iTRF in female mice did not result in any discernable increases in renal fibrosis (7.5±2.5% and 8.9±0.3% in cortex and medulla, respectively) compared to AL mice (11.9±2.1% and 8.8±0.0% in cortex and medulla, respectively, (n=3/group). Similarly, pulse wave velocity (PWV), a measure of vascular stiffness (ultrasound) was significantly elevated only in iTRF males compared to either AL or aTRF mice (iTRF 2.4±0.1m/s, ad libitum 1.80.1m/s, aTRF 1.7±0.3m/s, p<0.05, n=3-4/group). To determine whether the observed renal fibrosis and vascular stiffness may be related to blood pressure, mean arterial pressure (MAP) was measured via telemetry in iTRF and aTRF animals. Data for both sexes were similar but combined due to lack of power to test for a sex effect (7/10 female iTRF, 6/11 female aTRF). At 4 weeks of iTRF, we observed a significant interaction of 24-h MAP rhythm between genotypes that was driven by lower MAP during the dark phase of iTRF compared to aTRF mice (Repeated measures 2-way ANOVA; genotype p=0.6793, time of day p<0.0001, interaction p<0.001) Finally, quantitative magnetic resonance revealed no significant differences between groups in body composition regardless of sex, suggesting that circadian disruption by TRF does not result in caloric restriction or weight loss. Together, these data demonstrate that circadian disruption by restricting food access results in significant fibrosis in both kidney and vascular tissues preferentially in male, but not female mice. These changes appear to be independent of changes in blood pressure. PRIME T32 DK116672 (J. Benjamin), AHA Career Development Grant (P. Pati), P01HL136267 (D. Pollock, J. Pollock) 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.
FoxS1 is a Novel Mediator of Hepatic Fibrosis Through Transcriptional Control of the Extracellular Matrix
Authors: Lee Wang-Hsin , Bates Evelyn , Martinez Genesee , Kipp Zachary , Xu Mei , Hinds, Jr Terry 
Published: May 2023

The increasing rates of obesity have led to elevated rates of non-alcoholic fatty liver diseases (NAFLD), which can progress to non-alcoholic steatohepatitis (NASH) and liver fibrosis, liver cirrhosis, and possibly cancer. The hepatic stellate cells (HSCs) have been considered major players in fibrogenesis in liver damage that leads to irreversible scarring. The activation of HSCs occurs as a liver injury signal via transforming growth factor β (TGF-β), which then causes the cells to proliferate and shed their extracellular matrixes. FoxS1, a barely studied transcription factor, was recently found to be increased by tumor growth factor-β (TGF-β) signaling. However, the role of FoxS1 in liver fibrosis has never been demonstrated. Our Real-Time PCR data showed that FoxS1 mRNA was increased in human cirrhotic livers that have significantly higher TGF-β, as well as in a murine model of liver fibrosis. Therefore, we hypothesize that the TGF-β-induction of FoxS1 is an essential process of HSCs activation that leads to hepatic fibrosis and scarring. To test this hypothesis, we created a FoxS1 CRISPR knockout (FoxS1 KO) and scrambled control LX2 cell lines, which are the standard human HSCs used for studying hepatic fibrosis. Then, we performed TGF-β treatments and extracted RNA for RNA sequencing and bioinformatic analysis to determine genes and pathways that are altered by the loss of the FoxS1 transcription factor. Our data demonstrate that FoxS1 regulates genes involved in collagen-containing extracellular matrix pathways, indicating that suppression of FoxS1 might prevent liver scarring. However, more work is needed in animal models to make this determination. In conclusion, these data demonstrate that FoxS1 induces liver fibrosis and plays a critical role in TGF-β-induced human HSC-extracellular matrix production that occurs during hepatic scarring. Based on the findings, FoxS1 may serve as a new therapeutic target for liver fibrosis. 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.
Collagen peptide reduces post-MI inflammatory response
Authors: Olabiyi Ayodeji , Cakir Sirin , de Castro Bras Lisandra 
Published: May 2023

Progressive adverse remodeling of the left ventricle (LV) after myocardial infarction (MI) includes persistent inflammation and degradation of the extracellular matrix that can lead to the dilation of LV and eventually congestive heart failure. Previously, we reported a collagen derived peptide – p1159 – to reduce LV dilation and adverse LV remodeling post-MI. This study evaluates the effect of p1159 in the post-MI acute inflammatory response. We hypothesize p1159 reduces LV dilation by mitigating the inflammatory response. Two groups of mice (C57BI/9; n=4/group) consisting of saline (vehicle) and p1159 treatments, same sex (female, 3- 6 months old), were used in this study. We performed baseline echocardiography followed by surgery to induce a permanent occlusion MI model. Three hours post-MI, mice received a randomized osmotic mini-pump to continuously deliver p1159 (14μg/day/kg body weight) or vehicle (saline, 0.9%). The LV was harvested on day three (D3) after a final echocardiographic assessment. Infarct size measurements (2,3,5- triphenyl tetrazolium chloride ‘TTC’ staining and strain analysis) were performed followed by gene array against 84 inflammatory markers using only the infarcted tissues. Infarct sizes were similar between groups, indicating same level of initial injury. Compared to vehicle controls, p1159 treatment markedly reduced levels of pro-inflammatory chemokines that associate with lymphocyte and leukocyte infiltration. Specifically, levels of both CCL22, a Th2-/Treg type chemokine known to increase in ischemic heart disease, and CCL24, which has been implicated in activation of fibrogenic pathways, were significantly reduced by p1159. Our data supports that p1159 treatment mitigates the inflammatory response post-MI, which in turn results in reduced adverse LV remodeling. This work was supported by the NIH/NHLBI (grant HL152297). 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.
A Rejuvenation Signature in Skeletal Muscle That Is Mediated By Late-Life Exercise
Authors: Jones Ronald , Dimet-Wiley Andrea , Haghani Amin , Morena da Silva Francielly , Brightwell Camille , Lim Seongkyun , Khadgi Sabin , Wen Yuan , Dungan Cory , Brooke Robert , Greene Nicholas , Peterson Charlotte , McCarthy John , Horvath Steve , Watowich Stanley , Fry Christopher , Murach Kevin 
Published: May 2023

The objectives of this study were to measure to what extent exercise stimulates partial molecular reprogramming in skeletal muscle. We hypothesized that exercise training, beyond its known functional improvements in aged tissues, could recapitulate some of the same effects that are seen with in vivo partial reprogramming by Yamanaka factors. Using transcriptome profiling from 1) a skeletal muscle-specific in vivo Oct3/4, Klf4, Sox2, and Myc (OKSM) reprogramming-factor expression murine model, 2) an in vivo inducible muscle-specific Myc induction murine model, 3) a translatable high-volume hypertrophic exercise training approach in aged mice, and 4) human exercise muscle biopsies, we collectively defined exercise-induced genes common to partial reprogramming. Late-life exercise training lowered murine DNA methylation age according to several contemporary muscle-specific clocks. A comparison of the murine soleus transcriptome after late-life exercise training to the soleus transcriptome after OKSM induction revealed an overlapping signature. Within this signature, downregulation of specific mitochondrial and muscle-enriched genes was conserved in skeletal muscle of long-term exercise-trained humans; among these was muscle-specific Abra/Stars. Myc is the OKSM factor most induced by exercise in muscle and was elevated following exercise training in aged mice. A pulse of MYC rewired the global soleus muscle methylome, and the transcriptome after a MYC pulse partially recapitulated OKSM induction. A common signature also emerged in the murine MYC-controlled and exercise adaptation transcriptomes, including lower muscle-specific Melusin and reactive oxygen species-associated Romo1. With Myc, OKSM, and exercise training in mice as well habitual exercise in humans, the complex I accessory subunit Ndufb11 was lower; low Ndufb11 is linked to longevity in rodents. Our data collectively suggest: 1) a biological age-mitigating effect on the epigenetic landscape by late-life exercise-training in murine skeletal muscle, 2) a common gene expression signature of partial reprogramming by OKSM and exercise training in muscle of humans and aged mice, and 3) that Myc is an exercise-responsive factor that contributes to a rewired molecular profile at the transcriptome and methylome levels. National Institutes of Health: Kevin A. Murach, AG063994; American Federation for Aging Research (AFAR): Kevin A. Murach, Junior Investigator Grant 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.
Role of PPAR gamma in Acute Renal Failure
Authors: Yousefipour Zivar , Newaz Mohammad 
Published: May 2023

Objective: Acute Renal failure (ARF) is a common sequel to chronic diseases such as hypertension and Diabetes Mellitus. Understanding the mechanism involved in damaging the glomerular membrane at the molecular level is of significant importance since this will allow us to prevent molecular changes before they attain a level of irreversibility.Oxidative stress and nitric oxide (NO) play a significant role in the maintenance of renal tubular and glomerular function in health and illness. Enzymes responsible for either ROS generation or NO production are controlled by transcription factors such as peroxisome proliferator activated receptor gamma (PPARγ). Here, we hypothesized that oxidative stress during chronic disease process reduced PPARγ gene expression and therefore, NAD(P)H oxidase NO production. Design and method: We used a glycerol model of ARF in male Sprague-Dawly rats, divided in control and treated groups. ARF was induced using the standard method involving administration of 50% glycerol (v/v, 8 mL/kg, i.m). After 21 days of study period, the required amount of glycerol was administered as a deep intramuscular injection equally distributed to both hind legs. Rats were deprived of food and water for 24 hours after glycerol administration. After injecting glycerol, rats were placed in metabolic cages, and 24 hr urine was collected. Blood was collected via cardiac puncture under pentobarbital anesthesia (Na pentobarbital 50 mg/kg; i.p). Kidneys were processed for isolation of renal microvessels and subsequent biochemical and molecular biology analysis. Results: Our results indicated reduced PPARγ mRNA and protein expression and activity in ARF. Addition of PPARg inducer, Ciglitazone, increased PPARγ mRNA and protein expression and activity in ARF. Ciglitazone improved renal vascular reactivity that was exaggerated in ARF. We observed ~100% increase in 8-isoprostane level in the plasma of ARF rats compared control. Ciglitazone abolished the increase in free-radical generation significantly. Conclusion: Based on our data we are concluding that reduced PPARg has a definitive role in the kidney function. This work was supported by an Innovation grant from Texas Southern 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.
Preliminary Characterization of Facial and Oral Microbiomes of Three Bat Species Commonly Occurring in Northwest Kansas
Authors: Miller Sarah , Kobayashi Yass 
Published: May 2023

Various bat species are at risk due to White-Nose Syndrome, a disease rapidly spreading throughout the United States. Metagenomic research on the microbiome of bats’ mouths and noses may provide helpful information to characterize how bats’ microbiomes interact with White-Nose Syndrome so that this disease may be mitigated. However, minimal research has been conducted in characterizing bats’ oral and facial microbial populations. To address this issue, we analyzed the oral and facial microbiomes of bat species commonly occurring in Northwestern Kansas. Oral and facial swabs were taken from Tricolor, Big Brown, and Evening bat (n=1 per species). Bacterial DNA was isolated from swabs, and the V3/V4 region of the 16s DNA was amplified using polymerase chain reactions (PCR). The PCR products were purified and sequenced. Sequencing data was then analyzed using Galaxy bioinformatics software. Results showed that the majority of bacteria present in facial swabs was Alteromonas, reflecting the high mineral content in the water source that bats use. Oral bacterial population profiles of Tricolor and Big Brown bats were more diverse than their respective facial samples. In contrast, oral and facial swabs from the Evening bat had similar bacterial population profiles. Our preliminary study showed that the oral samples appeared more diverse in bacterial populations than in facial. Therefore, our future studies should investigate the difference between oral and facial bacteria population profiles in more detail by investigating a larger sample and increasing bat species diversity. Further research should also include the seasonal effects on bacterial populations. The College of St. Scholastica Summer Undergraduate Research Fellowship 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.
Contribution of cervical sympathetic nerve activity during swallowing following CIH exposure
Authors: Karlen-Amarante Marlusa , Huff Alyssa , Oliveira Luiz , Ramirez Jan-Marino 
Published: May 2023

Swallowing is a vital behavior that is coordinated with breathing involving rhythmogenic networks in the medulla, the preBötzinger complex (PreBötC) and postinspiratory complex (PiCo). These networks are critical for generating inspiratory and postinspiratory activity, respectively. Both areas also interact with neurons involved in autonomic control, which contributes to increased sympathetic drive after chronic intermittent hypoxia exposure (CIH) exposure.Prior studies have demonstrated that CIH, an experimental model of obstructive sleep apnea, has been associated with dysphagia. However, the contribution of the sympathetic activity to swallow function is unknown in both healthy and diseased models. In this study we investigated the cervical sympathetic response to water swallow stimulation as well as optogenetic stimulation of the brainstem in an in vivo mouse preparation under control and CIH conditions for 21 days (5% O2 – 80 bouts/day). Recordings of diaphragm (DIA), submental and laryngeal muscles complex, hypoglossal (HN), vagus (cVN), and cervical sympathetic nerves (cSN) were performed in spontaneously breathing, anaesthetized (Urethane 1.5mg/kg) adult mice in baseline conditions and during swallow stimulation by injecting 0.1cc of water into the mouth. We found that baseline cSN is enhanced after CIH exposure due to a blunted respiratory-sympathetic coupling. During swallow stimulation, cSN activity was increased in both groups, which was further increased in the CIH group, suggesting swallow triggers an excitatory vasomotor sympathetic pathway. In order to understand the mechanistic underpinning of these findings, we use optogenetic stimulation of PreBötC and PiCo neurons to explore the effects on sympathetic activity modulation during swallow-breathing coordination. NIH Grants: P01 HL090554, R01 HL126523, R01 HL144801, R01 HL151389 and FY22 24050162. 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.
No impact of biological sex on nitric oxide contribution to cutaneous vascular response to 39ºC local heating
Authors: Williams Auni , Dillon Gabrielle , Wolf S. , Kenney W , Alexander Lacy 
Published: May 2023

Purpose: The contribution of endothelial nitric oxide (NO) to vasodilation (%NO contribution) is a significant indicator of risk of cardiovascular disease development. Local skin heating to either 42 ºC or 39 ºC is used to determine mechanisms of vasodilation in health and disease, specifically to investigate %NO contribution. Women have lower %NO contribution in the cutaneous vasculature than men in the early follicular phase of the menstrual cycle, when the circulating vasoactive reproductive hormones are at their lowest concentration. However, this phase represents only a brief portion of the menstrual cycle. We aimed to determine the overall impact of biological sex on %NO contribution to cutaneous vasodilation utilizing a 39ºC local heating protocol, which better isolates the endothelial NO-synthase pathway. We tested women randomly during any phase of the menstrual cycle. We hypothesized that women would demonstrate greater NO-dependent cutaneous vasodilation than men in response to 39ºC local heating. Methods: Data are represented as mean(SD). An intradermal microdialysis fiber was placed in the ventral forearms of 12 men and 13 women [24.2(4.6) years]. Local heaters and laser-Doppler flowmetry probes were used to measure red blood cell flux (perfusion units, PU). Cutaneous vascular conductance (CVC) was calculated as laser-Doppler PU/mean arterial pressure. A standard 39ºC local heating protocol was conducted wherein PU was continuously collected at rest (10 minutes), then the local temperature was increased to 39ºC. After PU reached a steady plateau (~40 minutes), the NO synthase inhibitor 15 mM NG-nitro-L-arginine methyl ester (L-NAME) was perfused. Maximal vasodilation was induced by heating to 43ºC and perfusing 28 mM sodium nitroprusside and normalized to %CVCmax. %NO contribution was calculated as the absolute percentage difference between %CVCmax of 39ºC plateau and %CVCmax of L-NAME steady-state. We compared both CVC and %CVCmax between groups with two-way ANOVA and the %NO contribution with unpaired t-tests. Results: The %NO contribution was not different between sexes [men 48(23)%, women 39(17)%; P = 0.26]. There was no effect of sex on either absolute CVC [men 0.717(0.29) PU, women 0.73(0.48) PU at 39ºC phase] or %CVCmax [men 69(31)%, women 54(20)% at 39ºC phase] at any stage of the 39ºC local heating protocol (main effects P ≥ 0.08). Conclusion: These data indicate there is no impact of biological sex on the vasodilatory response of the cutaneous vasculature to 39ºC local heating in young healthy adults when women are tested at random across the menstrual cycle. Funding: National Institutes of Health Grant T-32-5T32AG049676 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.
Associations between Aortic Stiffness, Cerebral Artery Resistance and White Matter Integrity in Women with a History of Preeclampsia
Authors: Nuckols Virginia , Magnotta Vincent , Hoth Karin , Santillan Mark , Pierce Gary 
Published: May 2023

Purpose: Preeclampsia is a pregnancy complication characterized by new-onset hypertension and systemic organ dysfunction. Women with a history of preeclampsia (hxPE) have a greater cerebral white matter ischemic damage burden and a three-fold elevated risk of vascular dementia later in life compared with healthy pregnancy independent of traditional cardiovascular risk factors. Aortic stiffness promotes the transmission of deleterious pulsatile pressure to the distal cerebral circulation, resulting in increased cerebrovascular resistance (CVR) that contributes to compromised brain blood flow and structure. We hypothesized that young women with hxPE would have greater aortic stiffness and CVR compared to healthy pregnancy, and CVR would be related to lower cerebral white matter microstructural integrity (WMI). Methods: Women with hxPE (N=10) were matched with healthy pregnancy controls (N=11) by age (28-42 years), educational attainment, body mass index, and postpartum duration (1-5 years). Aortic stiffness was quantified as carotid-femoral pulse wave velocity (CFPWV). 4D flow and diffusion tensor magnetic resonance images were acquired to evaluate internal carotid and middle cerebral artery (MCA) blood flow velocity and WMI (fractional anisotropy), respectively (3T MRI, GE). CVR index was calculated as the ratio of central mean arterial pressure to regional flow velocity. Results: Women with hxPE tended to exhibit higher CFPWV compared with controls (6.3±0.8 vs 5.6±0.7 m/s, P=0.09 adjusted for mean arterial pressure). CVR did not differ at the internal carotid artery (2.2±0.4 vs 2.0±0.3 mmHg s cm-1, P=0.30) but was higher at the MCA among women with hxPE (2.4±0.3 vs 2.1±0.4 mmHg s cm-1, P=0.08). In the entire group, CFPWV was associated with greater CVR at the internal carotid (r=0.41, P=0.07) and MCA (r=0.48, P=0.03). Although WMI did not differ between groups, greater MCA CVR was related to lower WMI overall (r=-0.45, P=0.049) and in select white matter tracts (corpus callosum genu, r=-0.53, P=0.02; cingulum hippocampus, r=-0.43, P=0.06; superior frontooccipital fasciculus, r=-0.46, P=0.04). Conclusions: Women with hxPE had elevated aortic stiffness that was associated with greater CVR. Greater CVR was related to lower WMI in subcortical watershed regions susceptible to reduced perfusion. These findings indicate that aortic stiffness may contribute to early declines in WMI via CVR in women with hxPE. Supported by AHA Transformational Project Award (969732) to GLP and NIH grant 1S10OD025025-01 to VM 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.