bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition and potentiation of the mechanoreflex following pharmacological modulation of TRPC6 in male rats
Authors: Ducrocq Guillaume , Anselmi Laura , Stella Salvatore , Copp Steven , Kaufman Marc 
Published: May 2024

We determined the role played by the transient receptor potential canonical 6 (TRPC6) in evoking the mechanical component of the exercise pressor reflex in male decerebrated Sprague-Dawley rats. Quadruple-labelled immunohistochemistry were used in dorsal root ganglion cells to identify the cells that innervate the triceps surae muscles (DiI), the cells that express TRPC6 and the cells that are (Nf200) or are not myelinated (peripherin) (n=4). In addition, static contraction of triceps surae muscles was evoked by electrically stimulating the left tibial nerve before and after injecting into the superficial epigastric artery the TRPC6 antagonists, BI-749327 (n = 11; 12μg.kg−1) or SAR7334 (n = 11; 7μg.kg−1), or the TRPC6 positive modulator, C20 (n = 11; 18μg.kg−1). Similar experiments were conducted while the triceps surae muscles were passively stretched (n = 8 to 12), a maneuver that isolates the mechanical component of the reflex. Blood pressure, tension, renal sympathetic nerve activity (RSNA) and blood flow were recorded throughout the experiments. The neurons innervating the triceps-surae muscles were positive to TRPC6 antigen and co-expressed the neurofilament 200kDa. These cells were not positive for peripherin. While the TRPC6 blockers decreased the pressor response to static contraction (-32 to -42%; P < 0.05) and passive stretch (-35 to 52%; P < 0.05), the positive modulator increased both of these responses (55 to 65%; P < 0.05). In addition, BI-749327 decreased the peak and integrated RSNA responses to both static contraction (-39 to -43%; P < 0.05) and passive stretch (-56 to -62%; P < 0.05) whereas C20 increased these responses to stretch only (55 to 235%; P < 0.05). All of these results were not replicated when the drugs were injected intravenously or when the vehicle of the drug was injected into the superficial epigastric artery. Collectively, our results showed that TRPC6 play a key role in evoking the mechanical component of the exercise pressor reflex in male rats. Supported by NIH grants HL 161160, HL 156594 and HL 156513. 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.
Brief Repetitive Pressure Overload Elicits a Fibrosis-Independent Reduction in Left Ventricular Diastolic Compliance in Swine
Authors: Hudson Emily , Tajlil Arezou , Rolland Tyler , Palka Beth , Young Rebeccah , Canty John , Weil Brian 
Published: May 2024

Objective: We have previously shown that swine subjected to repetitive pressure overload (RPO) via daily 2-hr infusions of phenylephrine (PE) develop a reduction in left ventricular (LV) diastolic compliance that coincides with increased interstitial myocardial fibrosis. The objective of the present study was to determine if brief episodes of RPO produce a similar cardiac phenotype. Methods: Swine (n=6) were subjected to a single 30-min PE infusion (300 μg/min) to determine if brief pressure overload causes myocardial injury (circulating cardiac troponin I; cTnI), inflammation (IL-6), and cardiac dysfunction (echocardiography). A separate group of swine (n=5) were subsequently instrumented with an indwelling venous catheter to enable daily 30-min PE infusions for 2 weeks (“Brief RPO”). LV diastolic compliance (ΔLVEDV/ΔLVEDP during PE) and interstitial fibrosis (picrosirius red staining) were compared to values derived from swine subjected to prolonged RPO (2-hr PE/day; n=8) and age-matched controls (n=8). Results: A single episode of brief pressure overload led to an increase in circulating cTnI (from 22±6 ng/L at baseline to 365±12 ng/L 3-hours post-PE) and IL-6 (from 10±2 to 34±4 pg/mL), along with a transient reduction in LV ejection fraction (from 65±2 to 45±5 %, all p<0.05). Brief RPO led to a significant reduction in LV diastolic compliance (ΔLVEDV/ΔLVEDP: 0.59±0.13 mL/mmHg vs. 1.87±0.12 mL/mmHg in controls; p<0.01) that was nearly identical to that observed after prolonged RPO (0.58±0.17 mL/mmHg, p=0.95). Surprisingly, in contrast to prolonged RPO (10.0±1.4% collagen) the brief RPO-induced reduction in LV compliance was not accompanied by an increase in interstitial fibrosis (5.0±0.3 % collagen vs. 5.0±0.3 % collagen in controls, p=0.95). Conclusion: Brief pressure overload initially causes myocardial injury and inflammation, with repetitive exposure leading to a reduction in LV compliance that is similar to that observed following prolonged RPO. However, the brief RPO-induced reduction in LV compliance occurs in the absence of fibrosis, suggesting that mechanisms of repetitive stretch-induced myocardial stiffening may depend on the duration of episodic pressure overload. Supported by funding from the U.S. Department of Veterans Affairs and National Institutes of Health. 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.
FK506-Binding Protein 51 (FKBP51) Suppresses PPARα Activity and Shifts the Insulin Receptor Alternative Splicing Driving Hepatic Insulin Resistance
Authors: Lee Wang-Hsin , Bates Evelyn , Maharramov Agil , Martinez Genesee , Kipp Zachary , Xu Mei , Hinds Terry 
Published: May 2024

FK506-binding protein-51 (FKBP51) is a molecular chaperone protein that has great potential to serve as a treatment target for non-alcoholic fatty liver disease (NAFLD) and type II diabetes (T2DM). FKBP51 has been known to regulate nuclear receptors such as glucocorticoid receptor (GR) and peroxisome proliferator-activated receptor γ (PPARγ). However, the connections between FKBP51 and other PPAR family members, such as peroxisome proliferator-activated receptor α (PPARα), are yet to be identified. FKBP51 can also inhibit protein kinase B (AKT) activation, which may impact the insulin receptor signaling pathway. It has been reported that FKBP51 knockout mice presented less adiposity, reduced liver steatosis, and increased insulin sensitivity and insulin clearance, indicating that FKBP51 plays a role in insulin resistance and fatty liver development. However, how FKBP51 regulates insulin resistance, especially in the liver, still needs to be unveiled. It has been shown that insulin receptor (IR) alternative splicing is associated with insulin sensitivity and that PPARα activation is critical in reducing insulin resistance. Thus, we hypothesize that FKBP51 can regulate hepatic insulin resistance through insulin receptor alternative splicing and PPARα suppression. To test this hypothesis, we developed an FKBP51 knockout mouse hepatocyte cell line, 51KO AML12, and treated the cells with insulin for 1hr. We measured RNA and protein expressions in the cells through RT-PCR and western blotting and found that 51KO AML12 had increased phospho-AKT Ser473 (pAKT S473) and IR isoform B (IR-B), indicating increased insulin signaling activity. We also found increased IR isoform A (IR-A) and IR-B expression in 51KO AML12. In addition, we found an increased ratio of IR-B: IR-A in 51KO AML12 treated with insulin. These data indicate a great potential for FKBP51 to be a novel treatment target for hepatic insulin resistance and T2DM. This research is supported by the National Institute of Health R01DK121797 (T.D.H.), R01DA058933 (T.D.H.), and Start-Up funds from the University of Kentucky (T.D.H.). 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.
The Role of GLP-1 Affects Fate of Astrocytes Following Ischemic Stroke in Mice
Authors: Lu Hsuan-Yu , Li Su-Ying , Yang Jenq-Lin 
Published: May 2024

Stroke is one of the leading causes of physical and intellectual disability and mortality in adults of most of the developed countries. The most of studies in ischemic stroke focus on neuronal pathological mechanisms and neuronal death trying to rescue neurons via stopping the detrimental pathological processes or enhancing neuronal viability. Although astrocytes are the most abundant cells and in mammal central nervous system (CNS), they were ignored for period of time but are return to spotlight in recent years. Astrocyte play multiple roles in maintain normal function of central nervous system and respond to all kinds of CNS injury and disease. Responses of astrocytes to CNS damage lead to both detrimental and beneficial consequences. Previous studies have reported that astrocyte inflammatory responses to ischemic stroke may devastate the ischemic lesion, but other astrocytic responses lead to anti-excitotoxicity, secreting neurotrophic factors, neurogenesis, synaptogenesis, axonal remodeling, and angiogenesis promoting neuroprotective effects. Glucagon-like peptide-1 (GLP-1) have been intensively studied on beneficial effects of neurons, but not many studies work on effects of GLP-1 to astrocytes. Our early study has found that activation of GLP-1 receptors prevented ischemia-induced brain cell death and observed newly neuronal progenitor cells were from astrocyte-lineage in penumbral area of 3-day post-ischemic mouse brains by immunohistochemistry (IHC). RT-PCR, immunoblotting, and immunofluorescent results also clearly indicated the astrocytes expressed GLP-1 receptors. Furthermore, Western blotting results showed administration of GLP-1 analogue, exendin-4 (EX-4), suppressed expression of pro-inflammatory proteins in oxygen-glucose deprivation (OGD) treated mouse primary astrocytes. Interestingly, we also observed that infarct site obtained sever DNA damage and less GFAP positive astrocytes, on contrary, the penumbral area had more GFAP positive astrocytes and less DNA damage in IHC images of stroke brains. The results implied that A1 and A2 astrocytes play certain roles in ischemic brains and recovery. The goal of this study is to determine the mechanisms of GLP-1 involving in astrocytic fate decision and approach on minimizing detrimental effects and amplifying the beneficial effects, which possibly develop innovative therapies for ischemic stroke. The study is supported by 108-2320-B-182A-005-MY3 and 112-2320-B-182A-003- from Taiwan National Science and Technology Council. 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.
Effects of inspiratory muscle warm-up on perceptual, physiological, and performance outcomes during high-intensity exercise in normoxia and hypoxia
Authors: Gabler Mikaela , Martin Bruce , Johnson Blair , Schlader Zachary , Chapman Robert 
Published: May 2024

Some evidence shows that an inspiratory muscle warm-up (IMW) could enhance exercise performance; however, the mechanistic basis is unclear. PURPOSE: To examine how IMW affects the sensory and affective components of dyspnea, exercise performance, and locomotor muscle oxygenation. METHODS: Thirteen recreationally active individuals (23 ± 5 yr, 5 women) performed a cycling time to exhaustion test (~80-85% VȮ2max) preceded by either IMW (2x30 breaths, 40% maximal inspiratory pressure) or SHAM (2x30 breaths, 15% maximal inspiratory pressure) in normoxic (FIO2 = 0.21) and hypoxic (FIO2 = 0.16) conditions (i.e., 4 trials total). NIRS, dyspnea (i.e., breathing intensity and breathing unpleasantness), and cardiorespiratory parameters were measured throughout. Cardiorespiratory variables were analyzed using the individual isotime method. RESULTS: There were no differences in mean dyspnea responses between IMW and SHAM ( p > 0.05). Mean Δ tissue saturation index (TSI) did not reach statistical significance between IMW and SHAM in normoxia ( p = 0.110) or hypoxia ( p = 0.07). Mean performance was not different in normoxia ( p = 0.636) or hypoxia ( p = 0.512). In normoxia, V̇E ( p = 0.059) and fB ( p = 0.056) approached significance with IMW values greater compared to SHAM in the third isotime. CONCLUSION: Group improvements in dyspnea, performance, and ΔTSI were not seen following IMW. However, the degree of select individual responses suggest this intervention has interindividual applicability that should not be overlooked. No external funding was received for this work. 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.
Physical activity alleviates obesity-associated mesenteric arterial endothelial dysfunction: Role of adiponectin receptor
Authors: Park Yoonjung , Lee Junghoon , Lee Jonghae 
Published: May 2024

Introduction: A strong association between cardiovascular disease and obesity has been reported. However, the role of adiponectin in the effect of physical activity on mesenteric circulation and its underlying mechanism has been unknown. We investigated the protective effect of voluntary wheel running (EX) on endothelial function in the mesenteric artery of obese mice and its underlying mechanisms. Methods: C57BL/6J male mice were randomly divided into four groups: (1) control low-fat diet (LF), (2) LF diet with free access to a voluntary running wheel (LF-EX), (3) high-fat diet (HF; 45% of calories from fat), and (4) HF-EX. The protein expressions of total-endothelial nitric oxide synthase (t-eNOS), adiponectin receptors 1 and 2, AMPK, Ob (leptin), inflammatory markers, and proteins regulating apoptosis were quantified by Western blot analysis. Statistical comparisons between groups were performed with two-way ANOVA with Fisher’s LSD test. Results: The protein expressions of t-eNOS, adiponectin receptors 1 and 2, and p-AMPK in HF were lower compared to LF, but EX increased the protein levels ( P < 0.05). Ob in HF was higher compared to LF, but EX decreased it ( P < 0.05). IL-1β, TNF-α, and Caspase-1 in HF were higher compared to LF, but EX decreased the protein levels ( P < 0.05). There was no difference in expressions of AMPK, CHOP, Bcl-2, and GADD153 between groups. Conclusion: Voluntary wheel running alleviates e-NOS-mediated endothelial dysfunction in the mesenteric artery of obese mice possibly via increased adiponectin receptors and decreased inflammation. 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.
Cab39 is the major scaffolding protein for SPAK-mediated NCC activation in the mouse kidney
Authors: Ferdaus Mohammed , Koumangoye Rainelli , Welling Paul , Delpire Eric 
Published: May 2024

STE20/SPS1-related proline/alanine-rich kinase (SPAK) phosphorylates the sodium-chloride cotransporter (NCC) to stimulate sodium reabsorption in the Distal Convoluted Tubule (DCT) for K+ homeostasis and blood pressure. The scaffold proteins, Calcium-binding protein 39 (Cab39) and Cab39-like (Cab39l) activate SPAK in a Xenopus oocyte expression system. Still, it has not been determined whether Cab39 or Cab39-like are required for NCC phosphorylation in the DCT. Here, we developed DCT-specific Cab39 knockout (KO), global Cab39l-KO, and Cab39/Cab39l double knockout (DKO) mice to assess the role of the two adaptor proteins in the Kidney. The SPAK-NCC signaling axis was evaluated by Western Blot and immunofluorescence microscopy. Physiological consequences of altered signaling were evaluated with blood and urine electrolyte measurements. Cab39-KO mice had significantly lower total NCC (tNCC) and phosphorylated NCC (pNCC) abundance than wild-type mice. Phospho-activation of NCC with low K+ diet was also blunted in the Cab39 KO mice. By contrast, the Cab39l-KO mice did not show differences in total or phosphorylated NCC signals. However, when Cab39 was eliminated on the Cab39l KO background (DKO), pNCC abundance further decreased to almost undetectable levels. Remarkably, the DKO did not affect the phospho-activation of SPAK. Instead, SPAK failed to move to the apical membrane and accumulated into cytoplasmic puncta in the DKO mice. In summary, these data indicate that Cab39 and Cab39l act as major and minor regulators of SPAK-NCC signaling, providing an adaptor for translocating SPAK to the apical membrane for NCC interaction and phosphorylation. NIH grant R01DK093501 to Professor Eric Delpire and Professor Paul Welling, The Leducq Foundation grant 17CVD05 to Professor Eric Delpire and Professor Paul Welling, and a Crawford Long Innovation grant to Professor Eric Delpire. 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.
Creatively Reflecting About Human Function
Authors: Petzold Andrew 
Published: May 2024

Non-traditional methods of evaluating student knowledge have been gaining traction in non-scientific fields for a number of years. These multi-media based expositions of knowledge, colloquially as the “unessay,” serve to not only showcase a student’s true knowledge of a subject but also a self-awareness that is not commonly examined in science classes. We provided students with various methods of displaying their knowledge in physiology that was coupled with self-reflection. Specifically, students were asked not only to reflect on a topic that struck them as important, exciting or notable, but they were also asked to relay that information to an audience of their choosing. By combining a reflection on their own learning with a review of content knowledge, students could carefully consider information that stuck out to them as being relevant to their own lives and reflect upon that meaning fostering metacognition regarding their own learning. 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.
Effects of Exercise Intensities on Changes in Pro-/Anti-inflammatory Cytokines following 8-weeks of Aerobic Exercise Training
Authors: Beltran Gerardo , Park Kyung-Shin , Arellano Jocelynn , Reyes Sergio , Park Jeffrey , Cho Seong Kwan 
Published: May 2024

Inflammatory cytokines are useful biomarkers in predicting the development of metabolic and cardiovascular diseases and may be positively affected by physical activity and weight loss. Despite much interest in chronic low-level inflammation in the obese population, effects of aerobic training intensity on inflammatory cytokines remain elusive. PURPOSE: The purpose of this study was to investigate effects of 8-week aerobic exercise training at high and low intensities on changes in pro-/anti-inflammatory cytokines. Methods: Fifty three inactive obese Hispanic females (mean BMI = 34.5 kg/m2, aged 34-46 years) were divided into one of three groups: low intensity training group (LT: walking at 55% VO2max, n=16), high intensity training group (HT: running at 70% VO2max, n=18), and control group (CON: no intervention, n=19). LT and HT performed aerobic exercises three times per week at the given intensities. Exercise volume for two exercise groups was equated relative to kilograms of body weight by adjusting duration of exercise session (approximately 60 minutes for LT and 40 minutes for HT per session). Blood samples were collected before and after 8 weeks of intervention to measure levels of adiponectin, C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α). Two-way repeated measures ANOVA and Tukey post hoc tests were used for data analysis. Results: Level of adiponectin showed no significant change in any groups after 8 weeks of aerobic exercise intervention. A significant decrease in CRP was observed in the HT group only (4.12 ±.26mg/L mean±SE → 3.89±.37, P=.041), but levels of TNF-a were significantly decreased in both LT (4.57±.24pg/mL → 4.14±.31, P=.019) and HT (4.54±.25 → 4.02±.41, P=.011). No changes were observed in CON. CONCLUSIONS: Significant decreases in CRP and TNF-a were found following high intensity aerobic exercise training while low intensity training reduced TNF-a only. The greater changes of pro-inflammatory cytokines in HT indicates high intensity aerobic exercise training may be more beneficial than low intensity training. Specifically, for controlling low-grade inflammation and immune function in obese Hispanic females. This study confirmed results of previous studies suggesting that longer period of exercise training with distinct fat loss may be required to induce significant changes in adiponectin in obese adults. TAMIU university research grant. 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.