bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal colon exhibits enhanced post-ischemic repair relative to the neonatal jejunum
Authors: Rose Elizabeth , Ziegler Amanda , Blikslager Anthony 
Published: May 2023

Intestinal ischemia is the most common cause of gastrointestinal-related morbidity and mortality within the neonatal intensive care unit. Ischemia-induced loss of the intestinal epithelial barrier predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. Early barrier restoration relies on epithelial restitution to achieve wound closure, followed by rearrangement of tight junction proteins to re-establish barrier resistance. To inform putative therapeutics that promote rapid barrier repair in neonates, we have developed a highly-translational model of intestinal ischemia in the neonatal pig. Previous studies have demonstrated a significant defect in post-ischemic repair of the neonatal pig (2-weeks-old) jejunum relative to the juvenile (6-weeks-old) pig. Therefore, we hypothesized that the neonatal colon will demonstrate a similar defect in epithelial barrier repair. Segments of distal jejunum and spiral colon were subjected to surgically-induced ischemia followed by ex vivo recovery on Ussing chambers. Barrier repair was calculated by percent mucosal epithelialization, a measure of restitution, as well as transepithelial electrical resistance, a measure of barrier resistance. Unexpectedly, the ischemically-injured, ex vivo-recovered neonatal colon demonstrated significantly increased epithelial wound healing by restitution (p<0.005) as well as barrier resistance (p<0.05) relative to the neonatal jejunum. Furthermore, scanning electron microscopy revealed that colonocytes demonstrate a restitution phenotype defined by loss of their columnar morphology, marked flattening of their cellular profile and frequent formation of lamellipodia-like processes. Under identical experimental conditions, enterocytes do not demonstrate this phenotypic change. These findings suggest the presence of a colon-specific mechanism of intestinal epithelial barrier repair that is not present in the jejunum. Ongoing experiments aim to better elucidate the inter- and intracellular pathways that define this colon-specific mechanism of repair. Defining these pathways may inform the formulation of future pharmaceuticals that directly upregulate these pathways along the entire length of the intestine and therefore mitigate the effects of ischemic injury in neonates. NIH K01 OD 028207, NIH-NICHD R01 HD095876, U01 TR002953, T32OD011130 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.
Glutamine metabolism improves cardiac function after myocardial infarction independent of macrophage polarization
Authors: Mouton Alan , Aitken Nikaela , Stanford Joshua , Brown Jordan , Schrimpe-Rutledge Alexandra , Codreanu Simona , Sherrod Stacy , McLean John , da Silva Alexandre , Do Carmo Jussara , Omoto Ana , Wang Zhen , Hall John 
Published: May 2023

During myocardial infarction (MI), macrophages (MØ) infiltrate the ischemic left ventricle (LV) and mediate cardiac remodeling and healing. Metabolic shifts in the LV and infiltrating MØs is a hallmark of the response to injury. Glutamine is a major metabolic fuel for cardiac muscle and MØs. However, the role of GLN metabolism in the remodeling heart after MI is not well understood. We used a model of permanent coronary artery ligation in adult male C57BL/6J mice to assess GLN metabolism in extracted cardiac MØs at post-MI days (D) 1, 3, and 7. Using untargeted metabolomics, we found time-dependent changes in metabolites related to GLN and glutamate (GLU) metabolism in cardiac MØs (p=6E-4). GLN levels were significantly increased at day 3, while GLU was decreased at day 7, and the GLN/GLU ratio was higher at both D3 and 7 compared to D1 post-MI. Using Seahorse extracellular flux analysis, GLN consumption in MØs was increased on D1 and 3. In the remote area of the heart (RA), genes for GLN-metabolizing enzymes (Glud1, Got1, Gpt1) were decreased at D3 and 7, indicating a loss of GLN metabolism. We then administered GLN (1 g/kg body weight, i.p.) daily post-MI for up to D3 or 7. Compared to vehicle, GLN administration increased ejection fraction at D3 (1.2-fold increase) and 7 post-MI (1.6-fold increase), and attenuated anterior and posterior wall thinning at D7 by 1.6-fold and 1.3-fold, respectively. GLN also restored expression of genes associated with GLN metabolism (Gls1, Glul, Got1, Gpt1, Glud1) in the RA, as well as glucose oxidation (Pdha1). GLN also restored Myh6 expression and attenuated Myh7 expression, indicating favorable expression of myosin heavy chains. However, GLN did not affect cardiac MØ phenotype, as assessed by flow cytometry and cytokine mRNA levels (Il1b, Tnf, Il6, Ccl2, Il18, and Il10). We then blocked GLN metabolism by administering BPTES (12.5 mg/kg daily i.p. in corn oil) to mice for 3 days post-MI. BPTES exacerbated anterior wall thinning (1.4-fold decrease) and further decreased EF (1.4-fold) after MI, and also increased expression of Myh7 in the RA. However, BPTES did not affect MØ phenotypes. In conclusion, dysregulation of GLN metabolism is a hallmark of post-MI cardiac remodeling, and enhancing GLN metabolism may improve cardiac function, but may not be effective for reducing MØ-mediated inflammation post-MI. Funding: NIDDK 1R01121411, P20GM104357, U54GM115428, AHA856365 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.
Piezo1 activation stimulates Na, K-ATPase-mediated ion transport in mouse lens
Authors: Delamere Nicholas , Lopez Rosales Joaquin , Mathias Richard , Gao Junyuan , Shahidullah Mohammad 
Published: May 2023

Purpose: Lens ion homeostasis is dependent on Na, K-ATPase and NKCC1. TRPV4 and TRPV1 channels, which are mechanosensitive, are known to regulate the activity of both these transporters. Here, we examined another mechanosensitive channel, piezo1, which also is expressed in the lens. Methods: Rubidium (Rb) uptake rate was measured as an index of inward potassium transport. Cytoplasmic calcium was measured using Fura-2. Hydrostatic pressure in cells at the lens surface was determined using a manometer-coupled microelectrode approach. Results: Rb uptake was increased in intact lenses (CTRL 2.0±0.3 vs Yoda1 3.3±0.5 nmoles/Kg lens dry wt., n=5, p<0.05) and cultured lens epithelium (CTRL 0.23±0.006 vs Yoda1 0.44±0.01 μmoles/mg protein/10 min, n=6, p<0.001) exposed to Yoda1, a piezo1 agonist. While most Rb uptake is Na, K-ATPase-dependent, there also is an NKCC-dependent component. In the presence of the Na, K-ATPase inhibitor ouabain, Yoda1 did not increase Rb uptake. However, Yoda1 increased Rb uptake similarly in the presence or absence of the NKCC inhibitor bumetanide. The Rb uptake response to Yoda1 was inhibited by a piezo1 antagonist GsMTx4 (5 μM) and also by nonselective stretch-activated channel antagonists, ruthenium red (50 μM) and gadolinium (50 μM). In intact lenses Yoda1 was observed to cause a pronounced but transient decrease of surface intracellular hydrostatic pressure. Yoda1 increased cytoplasmic calcium in isolated cultured lens epithelium (peak concentration: CTRL 181±53 vs Yoda1 683±194 nM, n=10, p<0.001). The calcium and Rb uptake responses to Yoda1 were absent in calcium-free bathing solution, consistent with calcium entry when piezo1 is activated. Conclusion: The findings point to stimulation of Na, K-ATPase, but not NKCC, when piezo1 is activated. Na, K-ATPase is the principal mechanism responsible for ion and water homeostasis in the lens. The functional role of lens piezo1 is a topic of further study. NIH (NEI) grant, R01EY029171 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.
Are observed sex differences in forearm exercise vasodilation mediated through differences in cytochrome P450 2C9 signaling?
Authors: Song Jiwon , Buelow Alexander , Matney Jacob , Skillett Sarah , Ashley John , Mixon Chris , Bemben Debra , Larson Daniel , Kellawan J 
Published: May 2023

Previous research has identified that women have greater vasodilation during exercise at the same relative intensity when compared to men and these differences are not due to nitric oxide or cyclooxygenase mechanisms. Therefore, we tested the hypothesis that sex differences in exercising vasodilation were due to differences in cytochrome P450 2C9 signaling. Methods: 18 healthy young adults (11 females, F, 10 males, M, 22.0±3yrs, 23.9±4yrs, respectively) completed two 5 minute of bouts dynamic forearm exercise at 20% effort, supine with arms at heart level, separated by ≥ 72hrs. 120 min prior exercise participants ingested 150mg of fluconazole (FLZ) to inhibit cytochrome P450 2C9 or a placebo (microcrystalline cellulose, PLA) in randomized, single-blind, counter balanced fashion. All female participants were regularly menstruating and examined during days 1-5 of their cycle (early follicular phase). Forearm blood flow (FBF; Echo and Doppler ultrasound; ml/min), forearm lean mass (FLM; DXA, g), mean arterial pressure (MAP, finger photoplethysmography, mmHg) were measured to calculate relative forearm vascular conductance (rFVC) = FBF/100mmHg/100g FLM. Results: Expressed as mean ± SD. There were no differences or interaction observed in rFVC at rest (PLA, M: 3.5±2 vs F: 3.4±2, FLZ, M: 3.9±2 vs F:4.3±1, p=0.51, η2=0.02). Interestingly, while no significant interaction between sexes and treatments were found, a large effect size (η2) was observed (PLA, M: 23.9±10 vs F:26.2±7, FLZ, M:22.8±7 vs F:32.5±9, p=0.07, η2 =0.16). Expressing the data as the change in rFVC from rest to exercise yields the same interpretations. Conclusion: In contrast to our hypothesis, both sexes showed similar rFVC responses to dynamic forearm handgrip exercise with no effect of cytochrome P450 2C9 inhibition. However, the large observed effect size indicates this investigation is likely underpowered to observe an effect of sex and cytochrome P450 2C9 inhibition. Therefore, these data advocate for further data collection in this investigation and provide justification for additional research into mechanistic differences of skeletal muscle vascular control between men and women. 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 animal physiology Pressbook (OER) creation process, a synergistic collaboration with undergraduates and faculty
Authors: Joo Eddie , Hannah Rachael 
Published: May 2023

OERs or Open Educational Resources have shown to reduce financial barriers in undergraduates by providing low cost or no cost textbooks. However, the potential OER textbooks available for a three-hundred level Biological Sciences and Natural Sciences majors Animal Physiology course (BIOLA310) at UAA do not align with the foundation of this course’s structure of homeostasis and core concepts in physiology. Thus an OER Pressbook was created by a former BIOLA310 undergraduate student for future students that mapped the course outline, utilizing the essential core concepts of Homeostasis, Systems Integration, and Scientific reasoning. This study explores current attitudes regarding OER usage of undergraduates enrolled in BIOLA310 as compared to undergraduates that were enrolled in Fall 2021 BIOLA310, when there was not an official OER textbook. Anonymous demographic data, including first generation student and pell grant status will be collected for all participants to explore any potential differences in OER impression based on student resources. Data will also be collected regarding the informational component of the OER pressbook that students engage with the most. Hypothesis: Students connected more directly with the material of the undergraduate created Pressbook OER’s, as compared to a previous version of instructor curated OER materials in Fall 2021, due to low cost, the information presented from a near peer, and how the textbook was designed for the course. Data will be collected by an anonymous qualtrics survey to protect the identity of the volunteers. Pressbooks, the web host of the Animal Physiology OER gathers Key Performance Indicators (KPIs) and tracks relevant metrics, to compare student perception of use to actual use of the materials. Data will be analyzed to assess usage evaluated by financial barriers and perceived inclination due to the OER being designed by a fellow student. Supporting student learning from diverse perspectives, OER’s created with content expert faculty and undergraduate student interpretation might increase OER availability. By lowering the barrier of OER creation, then potentially more curated resources are created that resonate with near peer learning that will increase the diversity of learning viewpoints to support undergraduate students. Research reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103395. 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.
Effect of bodyweight support and incline running on electromyographic activity of triceps surae
Authors: Paizis Christos , Timbert Tom , Amiez Nicolas , Cometti Carole , Babault Nicolas 
Published: May 2023

During rehabilitation, body weight support (BWS) system is often used. It can be useful for optimizing time to return to practice by unloading joints and muscles. The present study aimed to explore the effects of Body Weight Support (BWS) and Incline Running (IR) on electromyographic activity (EMG) of triceps surae. We hypothesized that running with a slope of 7% and 30% of BWS could result in EMG comparable to level running. Eighteen healthy individuals participated in four randomized experimental sessions of ten minutes run at 10 km/h: 1) level running and 0% of BWS (LR), 2) incline running at 7% and 0% of BWS, 3) incline running at 7% and 15% of BWS, 4) incline running at 7% and 30% of BWS. EMG activity of Vastus Lateralis (VL), Gastrocnemius Lateralis (GL), Gastrocnemius Medialis (GM), and Soleus (SOL) was recorded during each 10 minutes running conditions and before two times during 30 seconds level running to normalize EMG activity (baseline). In addition, gait spatiotemporal parameters were taken at 1’, 5’ and 9 minutes and Rating of Perceived Exertion RPE was asked at 5’, 7’, and 10 minutes. Tests were conducted before and two minutes after running conditions. They included Counter Movement Jump (CMJ), and quadriceps low-frequency fatigue test.The results of the present study revealed a significant decrease in electromyographic activity of SOL at IR at 30% of BWS condition compared to IR without BWS (P < 0.002). Moreover, a significant decrease in electromyographic activity was observed of VL at IR at 30% of BWS condition compared to level running and IR conditions without BWS (P < 0.002 and P < 0.001). No changes were found in jump test (P = 0.246) and gait spatiotemporal parameters (P > 0.05) except in flight time (decrease with IR, increase with BWS, P < 0.006). Rate of Perceived Exertion was decreased with 30% of BWS (P < 0.002) and was no different to level running (P = 0.079). 15% of BWS (vs. uphill without BWS) did not significantly decrease the difficulty perception (P = 0.570). Also, low-frequency fatigue of the quadriceps was induced without BWS (P = 0.011) but not with 15% and 30% BWS (P > 0.05)Our results show that EMG activity of the triceps surae can be similar between running on a flat surface and running on a slope and 30% BWS. Furthermore, muscle fatigue, perceived exertion rate and spatio-temporal running parameters were similar between running on a flat surface and 30% BWS at 7% IR. Therefore, it can be useful to optimize the return time to practice and it is recommending for monitoring loads in Achilles Tendon and triceps surae. 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.
Perinatal ethanol exposure alters respiratory chemoreflex responses in anesthetized rats
Authors: Wollman Lila , Fregosi Ralph 
Published: May 2023

In the USA 10-15% of pregnant women drink alcohol (ethanol) leading to a variable compilation of developmental abnormalities, including deficits in critical homeostatic functions such as poor coordination of suckling, breathing, and swallowing. Here, we test the hypothesis that perinatal ethanol exposure alters respiratory chemoreflex responses in neonatal rats. Pregnant rats were exposed to 5% ethanol through their drinking water starting on embryonic day 5, which exposes the fetuses to ethanol during gestation and then after birth through the breast milk. Pups of both sexes were studied in the first week of life (postnatal days (P) 1-5). First, in awake pups, we used head-out plethysmography to assess the effects of ethanol exposure on the respiratory response to a brief, 5- minute episode of hypoxic hypercapnia (12% O2/5% CO2, balance N2, delivered through a nose cone). We found no significant differences in the frequency (P = 0.6667), tidal volume (P = 0.3627), or minute ventilation (P = 0.1582) responses to the challenge between control and ethanol exposed pups (2-way ANOVA, n = 6 control and 6 ethanol pups). In a second experiment, we used electromyography in anesthetized pups to study the diaphragm and tongue muscle responses to nasal occlusion, which results in strong muscle efforts but an absence of lung inflation, as well as hypoxia, hypercapnia, and acidosis. Here, we found that both diaphragm and tongue muscle EMG responses were significantly blunted in ethanol exposed animals compared to control. This included a decrease in the peak amplitude responses of both muscles (2-way ANOVA: diaphragm, P = 0.0175; tongue, P= 0.0317, n = 8 control and 8 ethanol pups), as well as a delay in the onset of the tongue muscle activation (Student’s unpaired T-test, P = 0.0219, n = 8 control and 8 ethanol pups). Together, these data indicate that perinatal ethanol exposure causes impairments in respiratory chemoreflex control, which appear to be highly dependent on level of arousal. NIH 5R01HD071302-08 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.
Endothelial-endothelial signaling as a mechanism for neurovascular coupling
Authors: Krolak Trevor , Kaplan Luke , Chen Lujing , Navas Kathleen , Birmingham Austin , Ryvkin Daniel , Izsa Victoria , Gu Chenghua 
Published: May 2023

The brain is an energetically expensive organ, consuming 20% of the body’s cardiac output at rest while only accounting for 2% of its mass. Unable to store long-term energy reserves, the brain rapidly redistributes blood flow to active regions in order to meet moment-to-moment changes in metabolic demand. This dynamic process, known as neurovascular coupling, is the basis of most non-invasive human imaging and plays a crucial role in maintaining brain health. However, despite its broad-ranging importance, the cellular mechanisms that underlie neurovascular coupling remain elusive. During neurovascular coupling, activity-evoked signals drive smooth muscle relaxation, resulting in arterial dilation and a robust increase in downstream capillary blood flow. These dilation events occur quickly – on the order of milliseconds – and spread rapidly through the arterial network to effectively recruit perfusion. Electrical signals propagated along the cerebrovascular endothelium are increasingly speculated to underpin this phenomenon, but this idea remains fundamentally untested. Here, we leverage a combination of mouse genetics, molecular biology techniques, and in vivo imaging in awake mice to evaluate the role of propagated electrical signals in the neurovascular coupling response. Our preliminary results indicate that brain endothelial cells are capable of electrical communication and establish a foundation to test the physiological significance of the signals they relay. R01 HL153261/HL/NHLBI NIH HHS/United States; HHMI/Howard Hughes Medical Institute/United States 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.
Bone marrow macrophage migration is dependent on ASIC2 and betaENaC
Authors: Drummond Heather , Pittman Katarina , Wasson Robert , Fleming Adam , Granger Joey 
Published: May 2023

Monocyte-macrophages play an important role in phagocytosis of pathogens and cellular debris following infection or tissue injury in several pathophysiological conditions. Naïve macrophages (Mf), can be polarized into proinflammatory (M1), and/or anti-inflammatory (M2) phenotypes. M1 cells are more phagocytic and adhesive/less motile than anti-inflammatory M2 macrophages. A previous study from our laboratory in the RAW monocyte-macrophage cell line suggests that polarization to M1 macrophages involves inhibition of Epithelial Na+ Channel (ENaC) expression, leading to loss of motility. To determine if a similar relationship between ENaC and migration exists in bone marrow macrophages (BMM), we examined chemotactic migration in BMMs from mice lacking βENaC and ASIC2a (KO). BMMs were harvested from the femurs of male and female WT and KO mice (6-12 weeks of age), expanded in culture with colony stimulating factor 1 (CSF1, 20 ng/ml) and cryopreserved for later use. Chemotactic migration responses were inhibited in BMM from KO male (94±4 vs 60±2 cells/FOV, n=35-42 FOVs) and female (142±5 vs 74±3 cells/FOV, n=42) mice. ENaC blockade using 1 μM amiloride inhibited migration in WT BMMs equivalent to migration in untreated KO BMMs and had no further inhibitory effect on KO BMM migration. These findings suggest βENaC and/or ASIC2 account for up to 50% of chemotactic migration in BMM and 100% of amiloride-dependent migration. BMM migration responses were rescued in stable transfected male KO BMMs with βENaC (88±4) or ASIC2a (77±5) compared to the EGFP_control KO (60±2 cells/FOV), providing further evidence of the importance of βENaC and/or ASIC2 in BMM migration. Polarization of male BMMs with IFNg (10 ng/mL, 18 hr) inhibited migration in BMM from WT (64±3 vs 22±1 cells/FOV) and KO (48±2 vs 16±1) animals, suggesting KO BMMs do not behave like fully polarized M1 macrophages. Taken together, our findings indicate that βENaC and ASIC2a play an important role in BMM migration response. Loss of βENaC/ASIC2a leads to a low migratory phenotype like M1 macrophages. Restoration of βENaC or ASIC2 rescues BMM migration. Targeting ENaC activity/expression in BMMs may limit their ability to migrate to sites of injury. Whether this is benefical or detrimental to non-infectious tissue injury is unclear. NIH R01HL136684, P20GM104357, and P20GM121334. 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.