bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dehydration Decreases Slow Wave Sleep After Heavy Resistance Exercise
Authors: Sekiguchi Yasuki , Jiwan Nigel , Appell Casey , Moya Ruben , Ky Alan , Sekiguchi Jan-Joseph , Keefe Marcos 
Published: May 2024

Purpose: The purpose of this study was to examine the effects of hydration status on sleep and recovery measurement before and after high volume resistance exercise. It was hypothesized that dehydration decreases sleep and recovery measurements following exercise. Methods: Eight resistance-trained men (age, 21±2 years; weight, 82.0±12.6 kg; height, 177.3±6.9 cm) performed a series of bilateral leg press and knee extensions (RE, 5 sets of 10 repetitions at 80% of 1 repetition maximum). Participants completed one trial in a euhydrated state (EUH; urine specific gravity (USG) < 1.020) and the other in a dehydrated state (DEH: USG ≥ 1.020) which was separated by 2 weeks. For the DEH trial, participants were restricted from consuming fluids for 24 hours prior to the RE and were only permitted to drink 1.5 L of water post-exercise for the remainder of the day. For the EUH trial, participants were instructed to consume fluid for 24 hours prior to and 24 hours post RE to maintain euhydration. Sleep and recovery measurements were collected from a wearable sleep device that participants wore the night before (PRE) and after RE (POST). Repeated measures ANOVAs were used to identify the differences between EUH and DEH. Effect size (ES) was calculated with resulting effects identified as either small (0.2-0.49), medium (0.5-0.79), or large (>0.8) effects. Results: Slow wave sleep (SWS) (POST EUH, 1.4±0.5 hr; POST DEH, 1.0±0.5 hr; ES=0.8; p=0.028) and %SWS (POST EUH, 21.8±3.7 %; POST DEH, 14.3±6.4 %; ES=1.4; p=0.016) were greater in DEH compared to EUH at the night following RE. Also, SWS decreased at POST compared to PRE in DEH (PRE DEH, 1.4±0.3hr; ES=1.0; p=0.028), but not in EUH (PRE EUH, 1.2±0.6 hr; p=0.061). Sleep duration, sleep effciency, sleep disturbance, sleep deprivation, rapid eye movement sleep (REM), %REM, light sleep, resting heart rate, and heart rate variability were not different between EUH and DEH ( p>0.05). Conclusion: Dehydration decreases slow wave sleep following heavy RE, which potentially impairs recovery from exercise as SWS is important for physiological recovery. Therefore, it is critical to maintain euhydration to maximize recovery following an acute bout of RE. This study was funded by National Strength and Conditioning Association (NSCA). 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.
Overwintering Induces Ischemia-Tolerance of Synaptic Function in the Forebrain of Bullfrogs
Authors: Bueschke Nikolaus , Santin Joseph 
Published: May 2024

Healthy brain function requires the continuous delivery of oxygen and glucose to nerve cells. Interruptions result in rapid cessation of normal circuit function in most vertebrates. The American bullfrog ( Lithobates catesbeianus) is an interesting model, as we have shown that brainstem synapses increase their capacity to function during hypoxia and ischemia by roughly 20-30 fold following aquatic overwintering (cold-acclimated, CA) compared to control conditions (warm-acclimated, WA). Here, we tested the hypothesis that other synapses, specially those in the forebrain, also improve their function to determine if extreme metabolic plasticity is specific to the brainstem, or a generalized response throughout the central nervous system. We used the synapse that carries thalamic input to dorsal pallium, which is involved in sensory processing and associative memory. To measure synaptic function, we stimulated thalamic axons and recorded evoked excitatory postsynaptic currents (eEPSCs) in the medial dorsal pallium, the proposed homolog to the mammalian hippocampus, in normoxic conditions and in oxygen and glucose deprivation (OGD). eEPSC amplitude at a baseline frequency of 0.5 Hz was depressed at OGD onset in WA frogs (paired t-test, p=0.0002, n=12) but not in CA animals (paired t-test, p=0.1602, n=6). This suggests that unlike WA frogs, overwintering allows maintained synaptic function in OGD within the forebrain, as well as the brainstem. Mechanistically, the maintenance of synaptic function in OGD appeared to be associated with dynamic increase in the probability of neurotransmitter release. Paired-pulse experiments to assess dynamics in neurotransmitter release in response to high-frequency stimulus pairs showed that synapses depressed in normoxic conditions in both WA (9 of 11 cells) and CA (4 out of 6 cells) groups. In OGD, synaptic depression was maintained in WA frogs (paired t-test, p=0.9192); however, synaptic depression reversed, whereby paired-pulse stimulation instead led to synaptic facilitation in 5 out of 6 neurons (paired t-test, p=0.0113). This suggests that synapses may alter the probability of glutamate release to act as a countermeasure to maintain forebrain function during energetic stress associated with emergence. Overall, these results show that metabolic plasticity to restart critical behaviors in hypoxia following hibernation is preserved across the brain and that altered synaptic dynamics may play a role in this response. This research was funded by the National Institutes of Health (R01NS114514, R15NS112920-01A1). 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.
Leptin Induces Evidence of Placental Mitochondrial Dysfunction in a Mouse Model of Preeclampsia
Authors: Mellott Elisabeth , Schibalski Ryan , Cherezova Alena , Moronge Desmond , Ogbi Safia , Ilatovskaya Daria , Faulkner Jessica 
Published: May 2024

Preeclampsia (PE) affects 5-10% of pregnancies worldwide that increase maternal and fetal morbidity and mortality. PE is often characterized by hypertension, endothelial dysfunction, and restriction of intrauterine fetal growth. Our lab established that mid-gestation leptin infusion in pregnant mice induces a model of PE, notably reducing fetal growth in late gestation. Clinical studies indicate that PE patients demonstrate elevated levels of leptin compared to healthy pregnancies as well as present with evidence of placental mitochondrial dysfunction. Therefore, we hypothesize that mid-late gestation leptin infusion induces placental mitochondrial dysfunction in pregnant mouse placenta. We infused timed-pregnant C57/Bl6 mice with saline (sham) or leptin (0.9 mg/kg/day) via s.c. osmotic minipump from gestation day (GD)11-18 (n=4-8). We collected placentas on GD18 for analysis. We isolate mitochondria from mouse placenta via differential centrifugation, after douncing pulverized tissue. From the isolated mitochondria, we assessed morphology via electron microscopy (EM) and performed amplex red assay for reactive oxygen species (ROS) measurements and tetramethyl rhodamine methyl ester (TMRM) dye was used to measure membrane potential. Pairwise comparisons were by student’s t-test. Our data indicates that leptin decreased membrane potential in placenta mitochondria compared to the sham placentas (1466±16.42 sham vs 1353±32.48 leptin A.U./mg of protein, **p<0.01). In comparison, there were no differences in H2O2 production between the sham and leptin-infused placental mitochondrial isolations (7381±125.2 leptin vs 7311±180.3 sham A.U./mg of protein). EM analysis of one sham and one leptin placenta indicated an increase in mitophagy in the leptin-infused placenta slices as well as decreased mitochondrial circularity, suggesting that leptin increases mitochondrial death. In summary, these data indicate that leptin induces mitochondrial dysfunction which in turn may contribute to placental dysfunction and reduced uteroplacental fetal growth in PE. 1R01HL169576, 4R00HL146948. 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.
Calcineurin mediates the inhibitory effects of TNF on NKCC2 phosphorylation
Authors: Hao Shoujin , Lasaracina Anna Pia , Epps Jarred , Ferreri Nicholas 
Published: May 2024

We previously showed that TNF inhibits NKCC2 activity and phosphorylation along the TAL, however, the mechanism has not yet been defined. As calcineurin (CN) activity in synoviocytes was increased by proinflammatory cytokines such as IL-1 and TNF, we tested the hypothesis that induction of CN activity and expression of CN isoforms is part of a pathway by which TNF inhibits NKCC2 phosphorylation. In this study, we found that CN activity increased by approximately 2-fold in primary cultures of medullary thick ascending limb (mTAL) cells that were maintained at 37oC/5%CO2 then challenged with mouse recombinant TNF (1 nM) for 60 min. Similarly, TNF induced a 3-fold increase in CN activity when mTAL cells were exposed to hypertonic media (400 mOsm/Kg H2O), an effect that was prevented by cyclosporine A (CsA). In contrast, silencing TNF production in mTAL cells using lentivirus (U6-TNF-ex4) significantly reduced CN activity by approximately 56% in cells exposed to 400 mOsm/Kg H2O for 1 h. CN activity also was inhibited in cells pretreated with CsA for 30 min followed by incubation in 400 mOsm/Kg H2O. Our data indicate that NKCC2 phosphorylation was significantly decreased in cultured mTAL cells challenged with TNF (1 nM) for 4 hr while inhibition of CN activity with CsA increased pNKCC2 expression. Analysis of qRT-PCR experiments showed that mTAL cells express the calcineurin A subunit (CNA) isoforms a (Sequence ID: NM_001293622.1) and b (sequence ID: NM_001310426.1). However, only the mRNA abundance of the CNAb isoform increased when mTAL cells were incubated with TNF (1 nM) for 4 hr under NS or HS (400 mOsm/Kg H2O) conditions as TNF had no effect on the a isoform of CNA. In vivo, both TNF and CNAb expression increased in outer medulla (OM) from mice given 1% NaCl in the drinking water (HS) for 7 days while intrarenal silencing of TNF with the U6-TNF-ex4 lentivirus reduced expression of CNAb under NS or HS conditions. Similarly, intrarenal injection of a lentivirus construct that specifically silenced CNAb in the kidney (U6-CNAb-ex6) reduced expression of CNAb in mice ingesting HS for 7 days. Interestingly, co-administration of U6-CNAb-ex6 with U6-TNF-ex4 increased pNKCC2 expression by approximately 63% in the OM from mice compared with silencing of TNF alone. Collectively, these data are the first to demonstrate that TNF increases CN activity as well as specific isoform expression in the kidney. Since NKCC2 has been identified as a target of the CNAb isoform, which is increased by TNF, these data demonstrate that a calcineurin-dependent signaling pathway is part of the mechanism by which TNF inhibits the phosphorylation of NKCC2. NIH grants R01 HL133077 and HL153525. 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.
Decreased inhibition of ventral brainstem liver-related neurons in high-fat diet fed mice
Authors: Gao Hong , Zsombok Andrea , Derbenev Andrei 
Published: May 2024

Pre-sympathetic liver-related neurons in the ventrolateral and ventromedial medulla (VLM/VMM) participate in the regulation of hepatic carbohydrate and lipid metabolism. Increased sympathetic activity observed in diet-induced obese mice likely contributes to excessive hepatic glucose production, and thus to the development, and/or progression of type 2 diabetes mellitus. At the cellular level, change in neuronal activity and/or synaptic balance is one of the underlying mechanisms that can lead to increased sympathetic outflow. In this study, we tested the hypothesis that high-fat diet (HFD) diminishes glycinergic inhibition of liver-related neurons in the VLM/VMM. We crossed heterozygous glycine transporter 2 Cre (GlyT2Cre) mice with floxed channelrhodopsin 2 (ChR2-EYFP) mice to generate GlyT2-ChR2 expressing mice (GlyT2ChR2/EYFP). Liver-related neurons were identified in the VLM/VMM with a retrograde viral tracer and patch-clamp recordings were conducted. Whole-cell recordings from pre-sympathetic, liver-related neurons revealed that spontaneous inhibitory postsynaptic currents (sIPSCs) are mediated by GABA and glycine. Our data showed that increasing the activity of inhibitory inputs leads to increased glycine release. Next, light stimulation was used to trigger glycine release in GlyT2ChR2/EYFP mice. Light stimulation of ChR2-expressing glycinergic fibers triggered evoked IPSCs (eIPSCs) generated by co-release of GABA and glycine with identical time courses for the two neurotransmitters. Intriguingly, in HFD-fed mice we found that the amplitude of light evoked IPSCs was significantly decreased. These data suggest that liver-related neurons in the VLM/VMM are co-inhibited by GABA and glycine and in HFD-fed mice inhibition of liver-related neurons is reduced. This reduced inhibition of ventral brainstem neurons may contribute to increased sympathetic activity in diet-induced obesity. Supported by: NIDDK122842 and Tulane Brain Institute Marko Spark Innovation Research Fund. 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.
Student Self-Reported Metacognition and Self-Effcacy in an Upper-Division Human Anatomy and Physiology Course Increased Post-COVID Pandemic Compared to Fall 2019
Authors: Schaefer Jennifer 
Published: May 2024

Metacognition and self-effcacy are important components of self-regulated learning. Given the academic and personal upheaval that students experienced, and given faculty-observed declines in certain academic skills and student mental health throughout the COVID-19 pandemic, this study hypothesized that students would report lower self-effcacy and metacognitive self-regulation upon entering an upper-division Human Anatomy and Physiology course in fall 2022 compared to fall 2019. Students reported self-effcacy and metacognition at the beginning and end of both semesters using the MSLQ metacognitive self-regulation (revised) and MSLQ self-effcacy for learning and performance subscales, respectively. Data indicate that students not only reported higher self-effcacy and metacognitive self-regulation at the beginning of the course, but also continued to report higher self-effcacy and metacognitive self-regulation throughout the course. It may be that the unique academic and personal challenges presented between March 2020 and September 2022 required students to develop improved metacognitive practices and strengthened students’ academic self-effcacy. Alternatively, it may be that some combination of high academic and personal turmoil, isolation from other students and faculty, and/or lowered faculty expectations throughout the COVID-19 pandemic skewed students’ frames of reference for self-reported measures. No support or funding was received for this project. 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.
Cardiomyocyte Derived Extracellular Mitochondria in Inflammatory Response During Oxidative Stress
Authors: Shrestha Lenee , Gu Haiwei , Chen Qin M. 
Published: May 2024

Increased production of reactive oxygen species (ROS) occurs in a variety of disease states. Elevated oxidative stress often co-exists with inflammatory response. A burst of ROS production due to myocardial ischemia or infarction causes damage to the mitochondria, tissue injury and inflammation. The mitochondria have evolved with quality control mechanisms to maintain the homeostasis for energy metabolism, and to control cell death. We have found secretion of mitochondria as a novel mechanism of mitochondrial quality control and for cell-cell communication. Sublethal doses of H2O2 cause an increased release of mitochondria from cardiomyocytes to the extracellular space. Extracellular mitochondria (EM) appear to be smaller with an average diameter of 524.67±54.69nm (control) and 563.27±41.82nm (H2O2 treated cells), compared to the corresponding intracellular mitochondria (IM) having an average diameter of 1192±256.50nm and 818.37±62.74 nm. LC-MS/MS based proteomics showed an increased levels of peroxiredoxins and several respiratory chain proteins in the EM from stressed cells. However, metabolomics did not reveal significant changes in the EM metabolites collected from control or stressed cells. Both have reduced NAD, ATP, ADP, or AMP but increased nicotinamide, lactate, and a number of amino acids compared to the IM. Inhibiting ceramide synthesis, a sphingolipid derivative, reduced the number of EM released from oxidatively stressed cardiomyocytes, indicating a role of lipids in regulating mitochondrial release. Functionally, EM from oxidatively stressed cardiomyocytes caused activation of M1 and M2 macrophages, as measured by cytokine markers TNFα and CD163. Our data have unveiled a novel mechanism of oxidative stress response and secretion of the extracellular mitochondria as a vehicle for initiation of inflammatory response. NIH R01 GM125212, R01 GM126165, Holsclaw Endowment and the University of Arizona College of Pharmacy start-up fund. 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.
Oleanolic acid administered during neonatal stage preserves granule cell layer volume, cell density and neurogenesis in the dentate gyrus of Sprague-Dawley rats fed a high fructose diet
Authors: Nyakudya Trevor , Nkomozepi Pilani , Ngcakaza Nokwanda , Erlwanger Kennedy 
Published: May 2024

Excessive fructose consumption induces metabolic syndrome (MetS) characterised by hyperglycaemia, dyslipidaemia, obesity and a decline in cognitive capacity, partly due to derangements in the hippocampus. We evaluated the potential protective effects of neonatally administering oleanolic acid (OA) against high fructose-induced reduction in granule cell layer volume, cell density and neurogenesis in the rat dentate gyrus (DG). Sprague Dawley rat pups (seven days old) were randomly assigned to three groups and administered orally: distilled water (DW), high fructose diet (20%w/v) and oleanolic acid (OA; 60 mg/kg) for 7 days. The rats were weaned (21 days old) onto normal rat chow diets up to post-natal day 55. From post-natal day 56-110, half of the rats in each experimental group were continued on plain water while the other half on a high fructose solution to drink. The rats were euthanized on day 112, before blood, visceral fat and brain tissue samples were collected. Body adiposity and impact on lipid metabolism was determined by measuring plasma triglycerides and visceral fat accumulation while brain tissue was used for histology. High fructose (HF) consumption led to the development of body adiposity (increased visceral fat accumulation), dyslipidaemia (increased triglyceride levels) and apoptosis in the DG. In addition, HF led to significant (p<0.05) reductions in volume, cell density and neurogenic activity in the dentate gyrus of the hippocampus. However, administration of OA during the neonatal period attenuated these deleterious effects of high fructose. We conclude that orally administered OA in the neonatal period may potentially be used to prevent the development of fructose-induced deleterious effects on the brain and most likely cognitive function. National Research Foundation of South Africa (grant number IRF 2010041900009). 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.
MyoTRIM, an engineered tripartite motif (TRIM) protein, recapitulates canonical phosphatidylserine binding and enhances cell membrane resealing capacity
Authors: Lopez Perez Miguel A. , Banford Kassidy K. , Bulgart Hannah R. , Giarrano Gianni , Weisleder Noah 
Published: May 2024

Duchenne Muscular Dystrophy (DMD) is the most prevalent hereditary neuromuscular disease and involves progressive muscle degeneration that contributes to early death. DMD is caused by mutations in the dystrophin gene, which eliminates its expression and leads to compromised structural integrity of the muscle cell plasma membrane. Although there is no cure for DMD, a recently approved gene therapy has shown desirable primary endpoints, including dystrophin expression, but limited secondary functional endpoints. Moreover, this genetic approach is limited to patients within a narrow age range. Therefore, novel therapies addressing the underlying structural cause of the disease remain necessary. The tripartite motif protein 72/mitsugumin 53 (TRIM72/MG53) is integral for an effective membrane repair response after injury. We have reported that overexpression of MG53 or exogenous delivery of recombinant human MG53 protein (rhMG53) can increase membrane repair capacity in many different cell types and improve pathology in multiple muscular dystrophy animal models. MG53 is thought to mediate this effect by binding phosphatidylserine (PS) at membrane injury sites. Yet, the structural basis of this therapeutic interaction is poorly understood. Here, we test the hypothesis that we can recapitulate the therapeutic effects of rhMG53 by engineering a novel TRIM protein, MyoTRIM, that retains PS binding capabilities while eliminating its canonical enzymatic activity. Using molecular, cellular, and physiological methodologies, we tested an engineered catalytic inactive MG53 variant, MyoTRIM. We found that enzymatic activity is dispensable for canonical subcellular localization and improved membrane resealing kinetics when endogenously overexpressed or made available exogenously as a recombinant protein. We report MG53’s propensity to aggregate in the presence or absence of specific canonical protein domains. Additionally, we demonstrate that MyoTRIM can bind PS and establish that carboxy-terminal domains are required for effcient PS binding. Lastly, we show preliminary data highlighting MyoTRIM’s therapeutic potential in dystrophic mouse models, suggesting improved functional outcomes, i.e. increased membrane repair and muscle force production. Taken together, these data suggest that the engineered protein MyoTRIM can recapitulate MG53’s therapeutic effect on membrane resealing while eliminating the canonical E3 ligase catalytic activity, thereby eliminating undesirable metabolic side effects during treatment. 5F31AR080555. 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.