bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelin-1 Contributes to Reduced Endothelial Function in Middle-aged/Older Men with Low Testosterone
Authors: Babcock Matthew , DuBose Lyndsey , Stauffer Brian , Moreau Kerrie 
Published: May 2023

Male aging is associated with a general decline in serum testosterone (T) concentrations. Low endogenous T is associated with increased cardiovascular disease risk, and we recently demonstrated accelerated age-related endothelial dysfunction, measured by brachial artery flow mediated dilation (FMD), in middle-aged/older (MA/O) men with low T compared with age-matched men with normal T. Endothlin-1 (ET-1) is a potent vasoconstrictor that is modulated by sex hormones and contributes to age-associated endothelial dysfunction. However, whether ET-1 contributes to reduced FMD in MA/O men with low T has yet to be determined. PURPOSE: to determine if ET-1 contributes to reduced FMD in MA/O men with low T. HYPOTHESIS: we hypothesized that MA/O men with low T would have higher ET-1 concentrations compared with young and MA/O men with normal T. Additionally, we hypothesized that there would be an inverse relation between ET-1 and FMD. METHODS: 60 men were categorized as either young (18-40 years, T: 400-1000 ng/dL) or MA/O (50-75 years) with low (<300ng/dL) or normal (400-1000 ng/dL) serum total T. T was determined from a venous blood draw using a one-step competitive enzyme linked immunosorbent assay. Endothelial function was determined using brachial artery FMD and ET-1 concentrations were determined using radioimmunoassay from a venous blood sample. RESULTS: T concentrations were significantly lower in MA/O men with low T (269±48 ng/dL) compared to young (500±58 ng/dL; p<0.001) or MA/O men with normal T (512±115, ng/dL; p<0.001). There was no difference in T between MA/O men with normal T and young men (p=0.995). MA/O men were similar in age (low T=59±8, normal T=60±6 years; p=0.996) and older than young men (29±4 years; p<0.001 compared to MA/O with both low and normal T). Age-associated reductions in FMD (young=7.3±1.3 vs. MA/O normal T=5.7±2.2%; p=0.019), were exaggerated in MA/O men with low T (4.0±1.7%; p=0.010 vs. MA/O normal T, p<0.001 vs. young). ET-1 concentrations were similar between young and MA/O men with normal T (young= 5.6±0.9 vs. MA/O normal T=6.0±1.4 pg/mL; p=0.768), and higher in MA/O men with low T (7.7±2.8 pg/mL; p=0.002 vs. young, p=0.016 vs. MA/O normal T). There was a moderate inverse association between FMD and ET-1 (r=-0.374, p=0.003). CONCLUSIONS: These data suggest that the greater age-associated endothelial dysfunction in MA/O men with low T may be related to elevations in ET-1. Future studies should examine the effects of low T on endothelin receptors ETA and ETB, as well as factors that could explain the increase in ET-1 in MA/O men with low T. Supported by NIH Grants R01AG049762, U54AG062319, and T32AG000279-16A1 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.
Single-Cell RNA Sequencing Reveals Roles of Renal Lymphatic Endothelial Cells in Cisplatin Induced Acute Kidney Injury
Authors: Creed Heidi , Rutkowski Joseph 
Published: May 2023

In the United States an estimated 50% of ICU patients develop Acute Kidney Injury (AKI) which is associated with a 50% mortality rate. A single occurrence of AKI predisposes a patient to develop chronic conditions such as Chronic Kidney Disease (CKD). The mechanism of the AKI to CKD transition is still unknown but is likely mediated by the extent and length of the inflammatory response following the initial injury. Lymphatic vessels help to maintain tissue homeostasis through fluid, macromolecule, and immune modulation. Increased lymphatic growth, or lymphangiogenesis, often occurs during inflammation and plays a role in acute and chronic disease processes. We have previously demonstrated that an expanded lymphatic network in KidVD mice increases the CD4:CD8 Tcell ratio and that this may afford protection from an AKI-to-CKD transition. The primary objective of this study was to understand what roles renal lymphatic endothelial cells (LECs) play in AKI recovery and CKD progression, a role which remains largely unknown. To determine if LECs have protective immunomodulatory roles in kidney injury, we utilized male C57/BL6 mice and a single 20 mg/kg Cisplatin dose to induce AKI and isolated renal LECs 72hrs post-injury. Using Seurat, ENRICHR, and STRING protein interaction analyses we defined and identified three LEC populations. Upon Cisplatin injury differences in gene expression revealed alterations in signaling pathway enrichment for (1) immunoregulatory interactions; (2) blood and lymphatic vessel development; and (3) T cell development. These findings illustrate specific differences in immune pathway activation between uninjured and injured renal LECs in regulating the inflammatory response in AKI. Together, this data indicates renal LECs may alter immunological outcomes in injury and uncovers previously unknown molecular roles in kidney injury. NIDDK R01(JMR): 1R01DK119497-01A1, AHA Predoctoral Fellowship (HAC): 916334 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.
An Evolutionarily Conserved Olfactory Receptor Is Required for Sex Differences in Blood Pressure
Authors: Xu Jiaojiao , Choi Rira , Gupta Kunal , Warren Helen , Santhanam Lakshmi , Pluznick Jennifer 
Published: May 2023

Olfactory receptor 558 (Olfr558) is expressed in the kidney where its functional role is unknown. Using RNAScope, we find that Olfr558 localizes to vascular smooth muscle, including the renal afferent arteriole. Thus, we measured blood pressure (BP) in Olfr558 wild-type (WT) and knockout (KO) mice. Systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP) were measured in whole-body Olfr558 wild-type (WT) and knockout (KO) via telemetry. It is known that males have a higher BP than premenopausal females in both humans and mice; indeed, we find Olfr558WT males (M) have higher BP than females (F, n=7-9 per group), including MAP (M:101.0±1.6 vs. F:89.0±0.9 mmHg, p<0.0001), SBP (M:113±2 vs. F:102±1mmHg, p=0.0025), and DBP (M: 89±2 vs. F:75±01mmHg, p<0.0001). However, sex differences in BP are entirely absent in Olfr558 KO (MAP M: 96±2 vs. F: 95±1mmHg; SBP M: 110±2 vs. F: 108±2mmHg; DBP M: 81±2 vs. F: 82±2mmHg). Of note, other sex differences (body weight) are intact in KO, and KO males and females are fertile. To characterize this phenotype, renin expression was analyzed by qPCR, plasma renin activity (PRA) was measured by ELISA, and vasoreactivity was examined ex vivo by wire myography (responses to potassium chloride (KCl), phenylephrine (PE), acetylcholine (Ach), and sodium nitroprusside (SNP) in aortic and mesenteric rings). In male KOs (n=10-12), there was a decrease in kidney renin mRNA (0.4±0.1 vs WT: 1±0.1 p=0.001) and PRA (201±21 vs WT: 402±15, p=0.001); these parameters were unchanged in female KOs. Male KO aortic rings exhibit less constriction to PE, male KO mesenterics exhibit more relaxation to SNP, and female KO aortic rings exhibit more constriction to KCl. In females, pulse wave velocity (PWV) and tensile testing revealed that KO females have increased PWV (KO: 4.6±0.4 vs WT: 3.2±0.2 m/s, p=0.0069, n=8-11), but no changes in tensile testing. The human ortholog of Olfr558, OR51E1, was previously identified as a locus associated with DBP. Using UK Biobank data (N~450k), we find that a rare OR51E1 missense variant has a statistically significant sex interaction effect with DBP ( p=0.015), increasing DBP (+6.28mmHg) in women but decreasing it (-4.77mmHg) in men (similar to the phenotype in M and F Olfr558 KO mice). Finally, we express OR51E1 variants in HEK 293T cells and characterize how two different clinically relevant OR51E1 variants influence OR51E1 signaling. In sum, our findings demonstrate that an evolutionarily conserved olfactory receptor is required for sex differences in BP. Olfr558 regulates BP in males via renin and vascular reactivity, but via arterial stiffness in females. Funding: R56DK107726 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 impact of food insecurity on academic motivation
Authors: Nagorny Katerina , Welch Megan , Rosenberg Lexis , Chowdhury Ushima , Bubis Sabrina , Begdache Lina 
Published: May 2023

Food insecurity is a pressing issue affecting many people nationwide, although it disproportionately affects college students. The association between food insecurity and academic performance has been addressed in the literature; however, its impact on academic motivation has yet to be studied. Food insecurity is defined as the lack of access to reliable and nutritious food. Typically, obtaining enough food is a significant focus for those who are food insecure and may hinder time spent on other responsibilities, such as academics. This study aims to analyze the impact of food insecurity on the motivation to devote time and resources to succeed academically. It is hypothesized that food insecurity is inversely related to academic motivation and diet quality and positively correlated to mental distress. An anonymous survey was administered through social media to individuals over the age of 18. The survey included demographic questions and seven validated scales, including the Food Mood Questionnaire, Brief Resilience Scale, Academic Motivation Scale, Food Insecurity Experience Scale, Perceived Stress Scale, Kessler-6 Psychological Distress Scale, and the Stress Mindset Measure. These scales measured dietary and exercise habits, food insecurity status, academic motivation, stress, resilience, mental distress, and perceived stress. Data from 1005 individuals were analyzed using Spearman’s Rho correlation in IBM SPSS Version 25.0. The results indicate that skipping a meal and not having enough to eat are positively correlated with not having a good reason to go to college (p<0.01), and being hungry but not eating due to lack of money or resources is positively correlated with feeling like time is being wasted in school (p<0.01). Further, it was found that being unable to eat healthy and nutritious food was positively related to eating fast food (p<0.01). Our results suggest that increased food insecurity and a nutritiously deficient diet may negatively impact academic motivation. Further, food insecurity may increase mental distress, negatively impacting academic motivation. Binghamton 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.
Cardiomyocyte-specific GPR22 overexpression ameliorates cardiac injury in mice with acute myocardial infarction
Authors: Leu Steve 
Published: May 2023

The activation of G protein-coupled receptors (GPCR) signaling by external stimuli has been thought to play roles in inducing cardiac stress and stress responses. GPR22 is an orphan GPCR expressed in brains and hearts, while its expression level is associated with cardiovascular damages in diabetes. Previous studies indicated that loss of GPR22 expression increases the susceptibility to heart failure-post ventricular pressure overload, suggesting a protective role of GPR22 in mechanical cardiac stress. However, the participation and underlying signaling of GPR22 in cardiac stress response to ischemic stress remain unknown. In this study, we applied cultured cells and a transgenic mouse model with cardiomyocyte-specific GPR22 overexpression to examine the influence of ischemic stress on GPR22 expression as well as to determine the role of GPR22 in myocardial ischemic injury. To induce acute myocardial infarction (AMI), left coronary artery ligation was performed on eight-week-old male GPR22 transgenic mice, followed by histopathological and biochemical examination four weeks post-induction of AMI. Results showed that GPR22 expressions in H9C2 and RL-14 cells, two cardiomyocyte cell lines, were reduced by cobalt chloride (CoCl2) treatment. Reduced expression of myocardial GPR22 was also observed in mice with acute myocardial infraction (AMI). Histopathological examinations demonstrated the protective role of GPR22 overexpression in ameliorating myocardial infarction in mice with AMI. Furthermore, the myocardial level of Bcl-2 and activation of PI3K-Akt signaling were reduced by ischemic stress and increased by GPR22 over-expression. In conclusion, myocardial ischemic stress reduced the cardiac expression of GPR22, while overexpression of GPR22 in cardiomyocytes upregulated Akt signaling and ameliorated myocardial injury induced by ischemic stress. This research was funded by the Chang Gung Medical Foundation (CMRPG 8K0321) and the National Science and Technology Council, Taiwan (NSC 111-2320-B-182A-005-MY2) 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.
Aging Associated Changes in Autophagy Markers in Mouse Lumbar Motor Neurons
Authors: Jahanian Sepideh , Pareja-Cajiao Miguel , Gransee Heather , Sieck Gary , Mantilla Carlos 
Published: May 2023

Autophagy is a process through which damaged cytoplasmic structures are recycled and degraded within the cell. Aging can affect autophagy regulation in different steps and lead to the accumulation of altered proteins, leading to cell damage and death. Motor neuron (MN) loss is an important contributor to sarcopenia age-dependent motor dysfunction. Understanding the regulatory mechanisms of autophagy can help elucidate the motor dysfunction that occurs with aging and provide a target for developing future therapeutic agents. Previous immunofluorescence imaging studies in phrenic MNs showed an age-dependent increase in key autophagy proteins LC3 and p62, reflecting autophagosome accumulation and autophagy impairment. Accordingly, we hypothesized that aging in lumbar MNs leads to autophagy impairment reflected in regulatory protein expression. The current study assessed autophagy in choline acetyltransferase-positive MNs from spinal levels L1-L6, focused on crural muscles (extensor digitorum longus and soleus), using confocal immunofluorescence imaging. Expression of LC3 and p62 proteins in MNs were determined in male and female C57BL/6 mice at 6-, 18- and 24- months of age. Increased expression of LC3 in lumbar MNs was observed with aging across all three age groups and p62 expression in lumbar MNs was significantly increased by 24- and 18-months compared to 6-months (p<0.001). There was no sex effect observed in LC3, but p62 was significantly higher in lumbar MNs of female mice (p=0.007). Expression of both LC3 and p62 increased diffusely in ventral lumbar gray matter regions with age (p<0.001), an effect that was predominant in male and not female mice. Taken together, the results of this study provide evidence for that age-dependent changes in autophagy markers expression occurs in regions of the spinal cord (motor neurons and ventral horn gray matter). The neuronal mechanisms of aging effects include dysregulation of autophagy. Supported by NIH R01 AG057052. 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.
Ryanodine receptor 3 impacts on the expression of aminopeptidase in mammalian skeletal muscle cells during myogenic differentiation
Authors: Ito Rika , Yokoyama Shingo , Ohashi Kazuya , Hagiwara Arisa , Takeo Yusuke , Egawa Tatsuro , Asakura Atsushi , Goto Katsumasa 
Published: May 2023

In mammalian skeletal muscle, ryanodine receptor (Ryr) expresses in the membrane of sarcoplasmic reticulum (SR), and is known as Ca2+-releasing channel. Ryr in mammalian skeletal muscle consists of 2 isoforms, Ryr1 and Ryr3. Ryr1 is coupled with dihydropyridine receptors (DHPRs) in transverse tubules, and Ca2+ release is a key step for the excitation-contraction coupling (E-C coupling). However, a physiological role of ryr3 is still unclear. Recently, we confirmed that Ryr3 knockdown induces abnormal myotube formation of C2C12 cells. Further, it is reported that the abnormal shape of C2C12 myotubes were observed by the knockdown of puromycin-sensitive aminopeptidase, a selective hydrolyze of amino acid residue from the N-terminus of peptide and proteins. In the present study, we investigated that the molecular mechanisms for the abnormal myotube formation of C2C12 cells following the knockdown of Ryr3. Aggregation of phalloidin-stained actin fibers were observed in Ryr3-knockdown myotubes. On the other hand, a significantly decrease in the mRNA expression level of puromycin-sensitive aminopeptidase and endoplasmic reticulum aminopeptidase 1 was observed in Ryr3-knockdown C2C12 cells (p<0.05). Therefore, Ryr3 may play a crucial role in the quality control of proteins and peptides during myogenic differentiation via the up-regulation of puromycin-sensitive aminopeptidase and endoplasmic reticulum aminopeptidase 1. This study was partially supported by JSPS KAKENHI (18H03160, K.G.; 19K22825, K.G.; 19KK0254, K.G., S.Y., T.E.; 22H03474, K.G., T.E.; 22K19722, K.G., T.E.; 22H03319, K.G., T.E.; 22K18413, K.G., T.E.), a grant from Graduate School of Health Science, Toyohashi SOZO University (K.G.), and a research grant from Toyohashi SOZO university (K.G.). All authors declare that they have no conflicts of interest. 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.
TRPV1 on the endings of thin fiber muscle afferents is not needed to evoke the exercise pressor reflex
Authors: Anselmi Laura , Ruiz-Velasco Victor , Stocker Sean , Higgins Shannon , Ducrocq Guillaume , Kaufman Marc 
Published: May 2023

Laura Anselmi, Victor Ruiz-Velasco, Sean D. Stocker, Shannon P. Higgins, Guillaume P. Ducrocq and Marc P. Kaufman. The role played by the transient receptor potential vallinoid-1 (TRPV1) on the endings of thin fiber muscle afferents in evoking the exercise pressor reflex is controversial. To shed light on this controversy, we used TRPV1-/- rats that were made by a CRISPR-Cas9 deletion to introduce a 26-bp frameshift deletion in exon 3. We compared the magnitude of the reflex between TRPV1 +/+ wild-type rats (WT), TRPV1+/- heterozygous rats (HET), and TRPV1-/- knockout rats (KO). The exercise pressor reflex was evoked by stimulating the tibial nerve (40Hz, 0.01ms, 1.5 times motor threshold) in precollicular decerebrated unanesthetized rats whose femoral arteries were either freely perfused or were occluded for 30 sec before the start of contraction. We found that there was no difference between the magnitude of the reflex in the three groups of rats with freely perfused hindlimbs (p=0.61). Specifically, the exercise pressor reflex averaged 16.4 ± 2.2 mmHg in WT rats (n=9), 21.1 ± 5 mmHg in HET rats (n=9), and 17.7 ± 2.3 mmHg in KO rats (n=9). No difference was also observed among the three groups of rats that received acute femoral artery occlusion (p=0.79). Specifically, the peak exercise pressor reflex averaged 15.3 ± 2.2 mmHg in WT rats (n=4), 19.8 ± 4.7 mmHg in HET rats (n=6), and 19 ± 8 mmHg in KO rats (n=3). Stimulation of the tibial nerve after paralysis of the rats with pancuronium (iv) had trivial effects on arterial pressure indicating that the pressor responses to contraction were not caused by electrical stimulation within the axon of the tibial nerve. Intra-carotid arterial injection of the TRPV1 agonist, capsaicin (0.5 mg), evoked a significant pressor response in the WT rats (34.7 ± 9.2 mmHg) and in the HET rats (36.3 ± 7.2 mmHg), but not in the KO rats (3.2 ± 0.4 mmHg). In electrophysiological studies of dorsal root ganglion cells innervating the gastrocnemius muscles, capsaicin evoked inward currents in the WT and HET rats, but not in the KO rats. Moreover, immunofluorescence revealed the presence of TRPV1 in the DRG of WT, but not in the DRG of KO rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex either in rats whose femoral arteries were either freely perfused or were occluded. These results are consistent with our previous finding that pharmacological antagonism of TRPV1 had no effect on the exercise pressor reflex. Supported by HL156594 and HL 156513 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.