bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel sensory pathway from bone marrow to ventrolateral periaqueductal gray regulates blood pressure in the hypertensive rat
Authors: Koutsikou Stella , Zubcevic Jasenka 
Published: May 2023

Introduction: A range of pathophysiological conditions present with dysfunctional immune and autonomic nervous system (ANS), including hypertension. Here, we present new data from a hypertensive rodent model that demonstrate an altered afferent communication between the bone marrow (BM), a major hematopoietic organ, and midbrain autonomic regions that regulate blood pressure. Considering that BM is pro-inflammatory in hypertension, we propose a dysfunctional BM-brain communication will be present in hypertensive rodents. Methods: Male adult (12-14wo) spontaneously hypertensive rats (SHR) and their age-matched normotensive controls, the Wistar-Kyoto (WKY) rats, were used in this study. Rats were anesthetized with isoflurane (1.5%) and mean arterial pressure (MAP) and heart rate (HR) were monitored in real time via a femoral arterial catheter and ECG leads in Spike2 (CED UK). Electrical stimulation (100 square pulses, 20Hz; 5mA, 500us) was applied inside the femoral bone cavity for stimulation of BM afferents, before and after a unilateral bicuculline (BIC) microinjection (100nl, 0.4mM) in the dorsolateral, lateral, or ventrolateral periaqueductal gray (PAG) separately. Results: Electrical BM stimulation produced an immediate stimulation-dependent decrease in MAP and HR that was of similar amplitude in the WKY versus SHR (WKY, from baseline: ΔMAP=-8±1mmHg, ΔHR=-1± 4bpm; SHR, from baseline: ΔMAP=-9±2mmHg, ΔHR=-6±4bpm; P=0.5 ANOVA). However, these responses were significantly enhanced in the SHR, but not the WKY, immediately following an injection of BIC in the ventrolateral PAG (vlPAG; WKY, from baseline: ΔMAP=-9±1mmHg; SHR, from baseline: ΔMAP=-31±3mmHg; ****P<0.0001 ANOVA). Conclusion: We demonstrate a novel BM-vlPAG afferent neural pathway in regulation of blood pressure. This neuronal circuitry may be dampened in hypertension due to elevated GABA signaling in the vlPAG. 1) University of Kent Deputy Vice-Chancellor's Partnership Fund to SK and JZ; 2) The Physiological Society UK to SK; 3) NIH R01 HL152162 to JZ 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.
Core temperature decline prior to sleep onset is associated with nocturnal heart rate variability
Authors: Cleveland Emily , Bigalke Jeremy , Barkstrom Elyse , Nicevski Jennifer , Tikkanen Anne , Carter Jason 
Published: May 2023

Impaired thermoregulation is associated with poor sleep and autonomic dysfunction. Previous studies demonstrate an association between core body temperature (CBT) dipping and an increase in heart rate variability (HRV) prior to sleep onset. However, the relationship between the rate of CBT decline prior to sleep onset and nocturnal HRV has not been established. The purpose of this study was to investigate the relationship between the rate of CBT decline prior to sleep onset and nocturnal HRV in objectively poor sleepers. We hypothesized a blunted pre-sleep CBT decline would correspond to reduced nocturnal HRV. Fifteen participants (9 males, 6 females; age, 33±4 years; BMI 27±1 kg/m2) underwent an 8-hour overnight sleep opportunity with continuous polysomnography (PSG) and 2-lead electrocardiogram monitoring. A temperature monitoring pill (CoreTempTM, HQ Inc., Palmetto, FL) was ingested with a standardized dinner to record CBT every 10 seconds throughout the sleep period. Core temperature was sampled every 5 minutes from the core temperature tracing one hour prior to sleep onset until final awakening. The rate of CBT decline prior to sleep onset was measured as the slope of CBT values from 1 hour prior to lights out until PSG sleep onset. Nocturnal HRV measures including the root mean squared of successive differences (RMSSD), percentage of R-R intervals (RRI) varying by greater than 50 ms (pNN50), and the high frequency (HF) power of the RRI were determined across the night in stage 2 (N2), stage 3 (SWS), and rapid eye movement (REM) sleep stages. Bivariate correlations were performed to assess the association between CBT rate of decline and nocturnal HRV measures. An inverse correlation was observed between the rate of CBT prior to sleep onset and the RRI in N2 (R= -0.743, p=0.002), SWS (R = -0.730, P = 0.002), and REM (R = -0.708, P = 0.003). Additionally, the rate of pre-sleep CBT decline was inversely correlated with time domain HRV measures in N2 (pNN50: R= -0.598, p= 0.019; RMSSD: R = -0.557, P = 0.031) and SWS (pNN50: R = -0.542, P = 0.037; RMSSD: R = -0.591, P = 0.020). A blunted rate of CBT was further correlated to decreased HFlog10 in N2 (R= -0.592, p= 0.020) and REM (R= -0.602, p= 0.018). Our results indicate an association between blunted core temperature decline prior to sleep onset and reduced nocturnal HRV. These findings suggest that adequate thermoregulation prior to sleep onset may have lasting associations with nocturnal cardiac autonomic function. Support is provided by the National Institutes of Health (AA-024892, U54GM115371; P20GM103474). 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.
Store-operated calcium entry inhibition ameliorates Ang II induced podocyte apoptosis and mitochondria respiratory dysfunction
Authors: Tao Yu , Parisa Yazdizadeh Shotorban , Ma Rong , Inman Denise 
Published: May 2023

Purpose and hypothesis: Podocyte injury induced by Angiotensin II (Ang II) is the key factor contributing to proteinuria and glomerulopathy in many kidney diseases including diabetic nephropathy and hypertensive kidney disease. Recent studies suggest that mitochondria dysfunction mediates Ang II-induced podocyte injury. However, the mechanism for Ang II-induced podocyte mitochondria damage is poorly understood. Store-operated Ca2+ entry (SOCE) has multiple functions in both excitable and non-excitable cells. Ang II can activate SOCE by releasing endoplasmic reticulum Ca2+ through generation of IP3. In addition, Ang II also activates Transient Receptor Potential Conventional Member 6 (TRPC6) channel through diacylglycerol (DAG). Our previous study demonstrated that enhanced SOCE mediated high glucose-induced podocyte cytoskeleton remodeling. However, the role of SOCE in podocyte injury by Ang II is not clear. The present study was carried out to test the hypothesis that enhanced SOCE contributed to Ang II-induced podocyte apoptosis and mitochondria respiration dysfunction. Methods: All experiments were carried out using cultured immortalized human podocytes. BTP2 (4 μM) was used to inhibit SOCE. SAR 7334 (100 nM) was used to block TRPC6 channel. Podocyte apoptosis was determined by flow cytometry using Annexin V/Propidium iodide (PI) staining. The conventional whole-cell patch-clamp was performed to measure store-operated Ca2+ channel (SOC) currents. Mitochondrial respiration function and mitochondria ATP production were evaluated by oxygen consumption rate (OCR) using seahorse analysis. Results: Ang II (1 μM) evoked inward currents, which were significantly blunted by BTP2 (10 μM), an SOC channel blocker. Ang II (1 μM) treatments for 24 hours significantly increased podocyte apoptosis and reduced podocyte basal OCR, maximal OCR, spare capacity and mitochondria ATP production. All these responses were significantly blunted by BTP2. However, Ang II treatment for 30 min did not induce a significant response of OCR, but significantly reduced maximal respiration and spare capacity. These responses were also significantly inhibited by BTP2 (10 μM), but not by SAR 7334 (100 nM). Conclusion: SOCE contributed to Ang II-induced podocyte apoptosis and mitochondria respiratory dysfunction. Translational Project Award from American Heart Association (20TPA35500045, to RM); National Institute of Diabetes and Digestive and Kidney Disease (DK115424-01, to RM); Predoctoral Fellowship from American Heart Association (903925, to YT). 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.
Real-Life Scenario Blended Teaching Approach for Nurturing Inquisitive Learning of Central Nervous System in Medical Students
Authors: Narayanan Sareesh , Merghani Tarig 
Published: May 2023

Among the various systems taught in the preclinical phases, the nervous system is more challenging to learn than other systems. In this report, a novel teaching methodology, ‘real-life scenario (RLS) blended teaching’ is described and its effectiveness in facilitating inquisitive learning in undergraduate medical students was evaluated. This mixed-method study was conducted among three groups (Group 1; n=83, Group 2; n=85, and Group 3; n=79) of undergraduate medical students (18-20 years) in the neurology and behavioral sciences module. RLS was presented to students in the form of demonstrations, role-plays, videos, and group activities. Group-1 students underwent traditional teaching-learning sessions. Group-2 students underwent RLS blended sessions and were provided with multiple mini-assignments in a vignette format. Group-3 students received RLS blended sessions, multiple mini-assignments, peer discussions, multiple formative assessments, and facilitator feedback sessions. The student performances on different exams were compared in terms of their Group, and their perceptions of RLS were documented. Students exposed to RLS sessions blended with multiple assignments, peer discussions, multiple formative assignments, and facilitator feedback sessions performed well in the final summative assessments (67.87%) compared to those exposed to RLS sessions and assignments (50.21%) or exposed to traditional teaching alone (50.34%). RLS sessions increased students’ curiosity and motivated them to learn the subject well. RLS sessions stimulated student interest and facilitated their learning. RLS along with effective use of multiple assignments, formative assessments and/or feedback sessions significantly improved student learning. This demonstrates the effectiveness of this active method in teaching various subjects with appropriate modifications. No funding was received for this research work. The data presented in this abstract is from the original work carried out at the Department of Physiology, Ras Al Khaimah Medical and Health Sciences University, UAE and a manuscript containing the same data is under consideration for publication in Advances in Physiology Education journal. 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.
Approximate entropy showed greater tidal volume and breathing frequency variability during steady state exercise in healthy adolescents compared to adults
Authors: Welch Ryan , Casey Sarah , Kolbe John , Kevin Ellyett 
Published: May 2023

Introduction: During incremental exercise breathing frequency (Bf) and tidal volume (VT) increase to ensure that minute ventilation (VE) meets the metabolic demands of exercise. The control of exercise ventilation, which comprises of feedback and feedforward mechanisms, is challenged during adolescence by physiological changes in respiratory system characteristics. Our previous work showed that healthy adolescents demonstrate unstable ventilation during incremental exercise compared to the relatively stable breathing patterns of healthy adults. However, we were unable to objectively quantify these breathing patterns due to the increasing workload profile of incremental exercise. Approximate entropy (ApEn) is a non-linear method which can be used to quantify the unpredictability of ventilatory data. Aim/hypothesis: The objective of this study was to apply ApEn analysis to quantify and compare breathing patterns during steady state exercise in healthy physically active adolescent and adult subjects. We hypothesised that ApEn would be greater (i.e. more variable) in adolescent compared to adult subjects. Method: Two groups were recruited: the adolescent group (n=12, 5M:7F) aged 12-14 years and the adult group (n=9, 4M:5F) aged 25-35 years. Participants performed 20-minutes of steady state exercise on a cycle ergometer at a workload of 1 W·kg-1 of body weight. ApEn was performed for VT, Bf and VE over the final 15-minutes of exercise to ensure steady-state exercise breathing patterns were adopted. The Mann-Whitney U test compared the between group ApEn results. Results: Significantly greater ApEn results were observed in the adolescent group compared to the adult group for VT (1.28 ± 0.05 vs. 1.12 ± 0.11, p<0.05) and Bf (1.31 ± 0.07 vs. 1.19 ± 0.11, p<0.01) but not VE (1.25 ± 0.13 vs. 1.03 ± 0.23). Conclusion: Using ApEn we showed greater variability of VT and Bf for healthy adolescents compared to healthy adults. This supports the results of our previous studies of maximal exercise. We suggest that the greater variability of breathing patterns observed in the adolescent group likely reflects the normal development and maturation of ventilatory control and should not be viewed as abnormal. This research was supported by an award from The Green Lane Research and Education Fund Board. 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.
Proteinuria observed post-uninephrectomy stems from partial suppression of protein endocytosis along the proximal tubule
Authors: Edwards Aurelie , Ralph Donna , Lei Hillmin , Priver Taylor , McDonough Alicia 
Published: May 2023

Living kidney donors are at higher risk of developing proteinuria, yet few studies have addressed the etiology. To investigate whether post-uninephrectomy (UNX) proteinuria was due to increased filtration and/or reduced endocytosis/reabsorption along the proximal tubule (PT), we compared renal function, morphology, and PT endocytic machinery in male Sprague Dawley rats before and after UNX.At 12 wk post-UNX, the weight of the remnant kidney rose by 50%, PT diameters by 30%, and single nephron GFR by 50% (based on 26% fall in creatinine clearance and 50% decrease in the number of nephrons). Urinary albumin excretion increased 10-fold post-UNX. Since the filtered load of proteins decreases in parallel with GFR post-UNX, increased albumin excretion likely reflects decreased endocytosis along the PT, a notion supported by a 50% reduction in abundance of albumin and plasminogen in renal cortex homogenates from remnant versus explant kidneys. We tested the hypothesis that the protein endocytic machinery was reduced following UNX. Immunoblot assays of renal cortex revealed decreased abundance of megalin and Dab2, two key mediators of protein endocytosis along the PT, and no change in cubilin abundance. Immunohistochemistry confirmed a 50% fall in megalin along the PT apical membrane.Mathematical modeling predicted that albumin uptake per nephron increases post-UNX, owing to higher single nephron GFR and PT hypertrophy, but is attenuated by the decrease in megalin abundance; moreover, modeling predicts that if the endocytic machinery were not partly suppressed, overall albumin excretion would remain at pre-UNX levels.In addition to albumin, urinary plasminogen and angiotensinogen were similarly increased post-UNX, while uromodulin (synthesized and secreted distally) was decreased post-UNX. Urinary biomarkers of renal injury, RBP4 and KIM-1, were increased post-UNX likely reflecting the impact of the increased endocytosis of albumin which can carry bound toxic lipids into the PT.Taken together, our findings suggest that the blunting of albumin endocytosis post-UNX, apparent as increased albuminuria, may serve to protect PT cells from albumin-induced cytotoxicity. DK083785; Keck School of Medicine Dean’s Pilot Funding 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.
Maintaining Cerebral-Endothelial Integrity and Permeability Guard Against Uremic Toxins Induced Cognitive Impairment
Authors: Yang Jenq-Lin 
Published: May 2023

Chronic kidney disease (CKD) is with a characterization of progressing loss of renal function; commonly, CKD progression leads to multiple comorbidities, including neurological dysfunction and immune disorders. Our previous study reported that accumulation of uremic toxins, including creatinine, blood urea nitrogen (BUN), indoxyl sulfate (IS), and p-cresol sulfate (PCS), could not only induce neuronal inflammation, but also NLRP3-inflammasome-correlated astrocytic inflammation; both neuronal and astrocytic inflammation significantly contribute to CKD-triggered cognitive impairment. Our study also demonstrated that AST-120, an IS and PCS absorbent, effectively reduced serum and hippocampal IS and PCS levels and hippocampal inflammation as well as reversed the cognitive function in CKD mice. The current study aims to understand how IS and PCS passing through endothelial cells and affecting endothelial physiology, consequently, compromises cerebral-endothelial and blood-brain-barrier (BBB) function. The results of Evans blue assay and Western blotting of this study have shown that 5/6 nephrectomy CKD mice occurred leakage of BBB and IS treatment could trigger NLRP3 inflammasome-mediated endothelial inflammation respectively. Moreover, Western blotting assay also indicated expression of endothelial tight-junction proteins was altered by IS and immunocytochemistry images showed that the aryl hydrocarbon receptor (AhR) was activated and relocated to nuclei of endothelial cells. Furthermore, images of immunocytochemistry revealed that the organic anion transporter (OAT) inhibiters, chloroquine and hydroxychloroquine, prohibit IS-induced AhR relocation to endothelial nuclei. Therefore, we postulated that IS and PCS pass through endothelial membrane via certain types of OATs/OATPs and activate AhRs relocating to nuclei, subsequently, induce endothelial inflammation, alter expression of tight-junction proteins, and dysregulate permeability of BBB. The goal of our study is to decipher mechanisms of aromatic uremic toxins, specially IS and PCS, induced cognitive impairment and find out possible treatments via blocking IS/PCS endothelial transcytosis, suppressing endothelial AhR activity, preventing endothelial inflammation, and maintaining endothelial permeability. The study is funded by National Science and Technology Committee of Taiwan, grant number 111-2320-B-128A-004 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.
Swallowing disrupts tongue-jaw coordination during chewing in a rat model of Parkinson's disease
Authors: Gould Francois , Palhang Meejan , Charles Nicole 
Published: May 2023

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in isolation in a rat model of Parkinson’s disease. Four adult Lewis rats were treated with daily IP injections of rotenone for 7 days to induce Parkinsonian symptoms. Prior to injections radio opaque markers were implanted into the tongue and jaw. Animals were filmed using high speed (2oofps) videofluoroscopy before the first injection and on injection day 7. Markers in the tongue and jaw were tracked to measure chew cycle duration and tongue-jaw coordination. Swallows times were identified from videofluoroscopic recordings. We tested whether chews occurring before, during, or after a swallow were longer, and whether tongue jaw coordination changed in rats before and after treatment using linear mixed models and post hoc pairwise contrasts. Chews that co-occur with swallows are significantly longer after treatment than before (p=0.006), whereas the lengths of pre and post swallow chews do not changes. Tongue jaw coordination after treatment is different in post chew swallows (p=0.016). The effects of Parkinsonian neurodegeneration on chewing are most pronounced when chewing and swallowing co-occur, which is in line with expectation given the role of the basal ganglia in coordinating motor functions. Lingering impacts on tongue–jaw coordination after the swallow suggest that return to baseline function is also impaired. The coordination of overlapping motor functions in feeding is affected in Parkinson’s disease, with potential implications for feeding difficulties and dysphagia. Funding source: Rowan School of Osteopathic Medicine 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.