bluuebunny/crossref_metadata_2025 huggingface dataset:
Epac1 Regulates Intestinal Epithelial Barrier Function by Recruiting JAM‐A via RAP2C‐TNIK Signaling Pathway
Authors: Sheikh Irshad , Kazi Mirajul
Published: June 2021

cAMP is one of the most potent signaling molecule to stabilize epithelial barrier function. However, the regulatory mechanism by novel cAMP effector, Exchange Protein directly Activated by cAMP (Epac1) is unknown. Incubating T84 cells with Epac1 agonist 8‐pCPT‐2′‐O‐Me‐cAMP or cAMP elevating agent forskolin (FSK) in presence of PKA inhibitor H89, caused transient reduction of Transepithelial Electrical Resistance (TER) that restored to normal value after short period of time while FSK alone drastically lower TER and disrupt TJ integrity. T84 cells with silenced Epac1 protein (Epac1KDT84) had reduced TER, increased paracellular flux of 4kDa FITC‐dextran and decreased paracellular permeability of Na+. Confocal study revealed mislocalization of major TJ protein, Junctional Adhesion Molecule‐A (JAM‐A) in Epac1KDT84 cells while no such change was observed in other TJ protein such as occludin. Surface biotinylation assay showed reduced band intensity of JAM‐A in Epac1KDT84 cells than in T84 cells. Silencing downstream Epac1 effector Rap2C and TNIK had similar changes in TER and flux as observed in Epac1KDT84 cells. Preincubating T84 cells with recycling endosome inhibitor, primaquine caused reduced surface expression of JAM‐A which was not observed in Epac1KDT84 cells. Shigella flexneri 2a infected T84 cells showed high expression of Epac1 protein while invasion rate of Shigella significantly increased in Epac1KDT84 cells. We conclude that Epac1 regulates intestinal barrier function by recruiting JAM‐A at the level of tight junction by a novel Rap2C‐TNIK signaling pathway which may have therapeutic value in treating inflammatory diarrhea.
Pyruvate‐Enhanced Cardiocerebral Resuscitation Via Nrf2/ARE Pathway
Authors: Scott Gary
Published: June 2021

Background

Cardiac arrest‐cardiocerebral resuscitation (CA‐CCR) inflicts ischemia‐reperfusion (I/R) brain injury and glutamate excitotoxicity‐related cognitive deficits. Plasma pyruvate lowers blood glutamate to enhance brain glutamate efflux and neurocognition. Purpose: To test pyruvate reduction of plasma glutamate via Nrf2/antioxidant response element (ARE) regulated pathways. Methods: Swine subjected to CA received iv pyruvate or NaCl infusion to 4 mM during CCR. Carotid artery and frontal cortex lysates were assessed for Nrf2/ARE binding activity and glyoxalase1 (GLO1) activity, and pre‐ and post‐CA glutamate concentrations were measured in plasma. Results: In carotid artery and cortical lysates, Nrf2/ARE activity and Nrf2‐regulated GLO1 reductions were rescued by pyruvate. Plasma glutamate increased after CA‐CCR, but was sharply reduced by pyruvate.

Conclusions

Nrf2/ARE binding and GLO1 activity in cortex and carotid arteries were suppressed after CA‐CCR but partly restored by pyruvate. Similarly, post‐CA plasma glutamate surges were reversed by pyruvate in a manner supporting Nrf2‐regulated mechanisms of brain glutamate clearance, reduced excitotoxicity and brain protection.

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Effects of Exercise Intensity on Cortisol, Antioxidant, and DNA damage in Smokers and Non‐Smokers
Authors: Ponte Luis , Valdez Ruben , Medina Erika , Martinez Diego , Park Kyung‐Shin
Published: June 2021

The purpose of the study was to examine blood level changes of cortisol, total antioxidant status, and 8‐oxo deoxyguanisine (8‐OXO) before and after exercise at different intensities in smokers and non‐smokers.

Methods

Fourteen physically inactive smokers and non‐smokers were recruited. Each subject completed three treadmill runs at different intensities in a random order (60%, 70%, and 80% of VO2max). Running distance for all three runs was equivalent to a 30‐min run at 70% VO2max. Blood samples were collected at rest (PRE), immediately after (POST), and 1 hour following (1H) each run.

Results

Smokers (SM) showed higher levels of Cortisol (P=.043) and 8‐OXO (p=.024) and lower level of antioxidant (P=.001) as compared to non‐smokers (NS) (group effect). Cortisol levels were elevated in both SM and NS following the 80% VO2max run [SM (PRE:611.9±13.6nmol/L→POST:761.6±16.2, Mean±SE, P=.0001); NS(498.2±13.9→624.2±16.2, P=.0001)]. Total antioxidant increased only in SM following runs (60%:1.58±.04mM→1.76±.06, P=.0001; 70%:1.57±.04→1.72±.08, P=.001; 80%:1.59±.04→1.71±.09, P=.012). 8‐OXO elevated at POST following 70% (SM:3188±242pg/mL→4667±199, P=.001; NS:2432±181→3586± 199, P=.011 ) and 80% (SM: 3268±234→5832±488, P=.0001; NS:2473±200→3813±255, P=.003) VO2max runs.

Conclusion

Higher levels of cortisol and lower antioxidant status induced greater DNA damage in smokers, especially following runs at 70% and 80% VO2max, indicating that DNA damage in blood immune cells following moderate‐high and high intensity aerobic exercises is greater in Smokers than Non‐Smokers. Therefore, smokers may need to avoid high intensity aerobic exercise since combined stress from exercise and chronic smoking may aggravate immune function.
Effects of single‐dose dietary nitrate on oxygen consumption during and after prolonged submaximal exercise in healthy humans
Authors: Kocoloski Genevieve , Crecelius Anne
Published: June 2021

Dietary nitrate (NO3‐) has been shown to impact oxygen consumption (VO2) as well as exercise performance in a number of prior studies. To date, previous investigations have observed NO3‐ effects at moderate to high‐intensity (e.g. time to fatigue, time trials) exercise and often in trained athletes. However, less is known in regards to prolonged exercise and the potential impact of NO3‐ on post‐exercise excess oxygen consumption (EPOC), particularly in untrained individuals. Here, we tested the hypothesis that acute dietary nitrate supplementation would attenuate VO2 during and following prolonged cycle ergometry. Six young, moderately active, healthy males (age: 26±2 years, body mass index: 23.5±0.5 kg/m2; VO2max: 37.7±5.1 ml/kg/min) performed step‐wise maximal cycle exercise and prolonged submaximal cycle exercise (45 min; 38±2% of max work rate) in control (anti‐bacterial mouthwash) and acute NO3‐ supplemented conditions [70ml concentrated beet root juice (0.4g NO3‐), 2 hrs prior to exercise] on separate occasions. Measurements of VO2 (indirect calorimetry), arterial blood pressure (MAP; sphygmomanometry), and heart rate (HR; ECG) were made for 45 min prior, during, and 60 min following exercise bouts. NO3‐ reduced MAP at rest ~1‐3mmHg and this was accompanied by reflex‐mediated HR increases (2‐4 bpm). However, NO3‐ had no impact on VO2 during exercise (average of min 25‐45, Ctrl: 24.6±2.4 ml/kg/min vs NO3‐: 26.8±3.3 ml/kg/min) or EPOC (area under the curve, Ctrl: 0.86±0.3 L vs NO3‐: 0.95±.2 L). Thus, while NO3‐ supplementation may have performance benefits, especially in elite athletes exercising at high intensities, in recreationally active males, there appears to be little impact on changes in VO2 due to submaximal prolonged exercise.
Quantifying Children's Self‐Paced Physical Activity: Rethinking Accelerometer Calibration
Authors: Moghaddaszadeh Asal , Jamnik Veronica , Belcastro Angelo
Published: June 2021

The purpose was to examine the ability of accelerometry (ACC) to estimate oxygen consumption (VO2) for self‐paced physical activity (PA). Children's (n=15; 9.3±1.2 yrs.) VO2 responses to paced treadmill (TM) activity and self‐paced PA using six games were determined using FITMATE. The vertical axis (V) and vector magnitude (VM) were used to quantify both paced and self‐paced PA with ACC (ActiGraph GT3X+ and expressed in counts/10sec). Linear regression and Bland‐Altman plots were used to compare VO2 for continuous paced (TM) and intermittent self‐paced (games) PA by assessing ACC vertical axis (ACC‐V), ACC vector magnitude (ACC‐VM) and the relative contribution of each axes (using ANOVA; p=0.05). Paced (TM) PA showed positive relationships (r) for VO2 plus ACC‐V and for VO2 plus ACC‐VM of 0.90±0.03 and 0.89±0.05, respectively (p>0.05). Results for measured VO2 showed higher VO2 for self‐paced vs. paced (TM) PA between 100‐1000 cnts/10sec (ACC‐VM) (i.e., VO2 at 300 cnts/10sec were 22 vs. 12 mLO2•kg‐1•min‐1, respectively (p<0.05). Thus, VO2 estimates from TM‐derived equations (both ACC‐VM and ACC‐V) for self‐paced PA were under‐estimated compared to measured VO2 for self‐paced PA (p<0.05); with low agreement (a dynamic bias especially as the intensity (>6METs) increased) as observed on Bland‐Altman plots. Comparing paced vs. self‐paced PA it was observed that the contribution of axis dominance to ACC‐VM for the two types of PA existed ‐ larger differences for paced (41±14%) and smaller differences for self‐paced (7±5%) (p<0.05). This study reveals that the poor estimates of VO2 for intermittent self‐paced PA using equations from continuous paced TM PA is attributed to the presence of a dominant axis.
Response of CAPN2 to Exercise Intensity and Total Energy Expenditure
Authors: Belcastro Angelo
Published: June 2021

The purpose was to investigate whether the response of skeletal muscle calpain (SM‐CAPN2) activity to exercise varies by intensity, energy expenditure (EE) and/or muscle type. Rats were assigned to a control group (CG) and either a lower or higher energy expenditure exercise (LEE and HEE) group, which included three intensity groups (15m/min, 25m/min and 35m/min). Soleus (SOL), plantaris (PL) and vastus lateralis (VL) muscles were assessed for CAPN2 activities. Blood CK and SM‐CAPN2 activity increased in a dose‐dependent manner in response to exercise (r=0.66). Exercise increased SM‐CAPN2 activities from control (13.07 ± 3.51 U/G wet wt), to LEE (15.36 ± 3.40 U/G wet wt) and HEE (24.65 ± 4.21 U/G wet wt) (p<0.05). The greater SM‐CAPN2 activities observed when going from LEE (70 kcal/session) to HEE (140 kcal/session) were similar across all muscles (i.e., SOL = 67.7%, PL = 57.9% and VL 62.2%). For both LEE and HEE SM‐CAPN2 activities increased with exercise intensity in an observable dose‐dependent manner. At 15m/min (50% VO2max) PL CAPN2 activities for the LEE and HEE groups were 14.1 ± 4.2 and 22.5 ± 5.5 U/g wet wt, respectively (p<0.05); at 25m/min (70% VO2max) CAPN2 activities were 17.6 ± 4.4 and 33.8 ± 7.2 U/g wet wt, respectively, for LEE and HEE (p<0.05). Comparable effects of intensity were observed with the VL muscles, but not so for SOL; which had mixed responses to exercise intensity with larger inter‐animal variability. The greater response of SM‐CAPN2 activity with increasing EE and at higher exercise intensities may contribute to the increased protein release and/or protein turnover with physical activity. Supported by NSERC to ANB
Effects of Chemotherapy and Radiation Exposure on Brachial Artery Blood Flow during Dynamic Handgrip Exercise
Authors: Didier Kaylin , Reiter Landon , Ederer Austin , Caldwell Jacob , Ade Carl
Published: June 2021

Chemotherapy and radiation cancer treatments have been shown to alter peripheral cardiovascular function. Therefore, the purpose of this study was to investigate if the vascular responses to dynamic handgrip exercise are blunted in individuals who have undergone chemotherapy and/or radiation treatment. To date, 1 cancer survivor (CS) and 1 healthy control (HC) have completed two dynamic handgrip exercise protocols at relative (10 and 20% maximal voluntary contraction (MVC)) and absolute (3 and 9 kg) workloads. Simultaneous measurements of forearm blood flow (FBF; Doppler Ultrasound), and mean arterial pressure (MAP) were taken during each of the workloads. Forearm vascular conductance (FVC) was calculated from MAP and FBF. Plasma concentrations of endothelial microparticles (EMPs) which are suggestive of apoptotic and activated endothelial cells (CD31+/CD42b‐ and CD62E+ EMPs, respectively) were isolated from venous blood samples. Preliminary results: FBF was decreased in CS compared to HC at: 10% MVC (111.72 vs. 228.17 ml min‐1) and 20% MVC (148.60 vs. 362.53 ml min‐1). FVC was reduced in CS when compared to HC at: 10% MVC (107.65 vs. 205.32 ml min‐1 100 mmHg‐1) and 20% MVC (135.35 vs. 287.64 ml min‐1 100 mmHg‐1). During absolute workloads FBF and FVC of the CS compared to HC was similar at 3 kg (143.91 vs. 135.26 ml min‐1 and 162.33 vs. 124.42 ml min‐1 100 mmHg‐1, respectively), but less at 9 kg (156.11 vs. 307.42 ml min‐1 and 155.24 vs. 263.54 ml min‐1 100 mmHg‐1, respectively). Due to time constraints plasma EMP concentrations are unavailable at this time. In conclusion, chemotherapy and radiation treatment in cancer survivors results in alterations to exercise blood flow regulation during dynamic exercise.
Alterations in endothelial function and fractional O2 extraction in long‐term cancer survivors treated with chemotherapy and radiation
Authors: Ade Carl , Brown Michael , Caldwell Jacob , Didier Kaylin , Reiter Landon , Ederer Austin
Published: June 2021

Chemotherapy and radiation cancer therapeutics increase arterial stiffness and decrease aerobic exercise capacity. During exercise, the profile of microvascular fractional O2 extraction measured via near‐infrared spectroscopy (NIRS) derived muscle deoxygenation (Δdeoxy‐[Hb+Mb]) provides information on the dynamic matching of O2 delivery‐to‐O2 utilization. We tested the hypothesis that cancer survivors would have an altered profile of Δdeoxy‐[Hb+Mb] during exercise that would be related to decreases in endothelial function. To date, 2 cancer survivors (CS) and 1 healthy control (HC) completed a brachial artery flow‐mediated dilation test (FMD) and ramp exercise test on a cycle ergometer. During exercise Δdeoxy‐[Hb+Mb] of the vastus lateralis and rectus femoris was measured, normalized from baseline (0%) to the gas exchange threshold (GET) (100%). The power output at GET (POGET) was lower in CS compared to HC. CS had a smaller shear rate normalized FMD compared to HC (1.07 × 10‐5 vs. 3.54 × 10‐5 %Δ/s‐1 s, respectively). Both groups displayed a linear increase in %Δdeoxy‐[Hb+Mb]. The %Δdeoxy‐[Hb+Mb] slope of the vastus lateralis was greater in CS compared to HC when plotted as a function of POGET (2.04 vs. 0.80 % W‐1, respectively) and %POGET (1.84 vs. 1.17 % %W‐1, respectively). A greater %Δdeoxy‐[Hb+Mb] slope of the rectus femoris was also observed in CS compared to HC (1.29 vs. 0.74 % W‐1 and 1.17 vs. 1.09 % %W‐1, respectively). In conclusion, the greater reliance on fractional O2 extraction in CS during exercise suggests an impaired matching of O2 delivery‐to‐O2 utilization relationship during exercise compared to HC, which may be the result of decreased endothelial function.
Relationship of VO2 with Cardiac Hemodynamics Improves During Exercise in Cystic Fibrosis Patients
Authors: Van Iterson Erik , Wheatley Courtney , Baker Sarah , Snyder Eric
Published: June 2021

Background

Although lower vs. healthy individuals, diffusion capacity of lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) (may influence oxygen uptake, VO2) are higher during exercise vs. rest in cystic fibrosis patients (CF). Thus, because the Fick equation suggests cardiac output (Q) increases linearly with VO2, we sought to study relationships between VO2 with cardiac function from rest to peak exercise as increases in Q, DLCO and DLNO occur during exercise in CF.

Methods

50 individuals participated (ages 22 ± 2 vs. 27 ± 2, BSA = 1.7 ± 0.1 vs. 1.8 ± 0.0 m2, VO2peak = 24 ± 2 vs. 35 ± 2 ml/kg/min, CF (n = 19) vs. controls (CTL, n = 31), mean ± SEM, p<0.05 for all). Acetylene rebreathe was used to assess Q and calculate stroke volume (SV), and standard gas‐exchange was used to assess VO2 (mL/kg/min). Cardiac power (CP, Qi × MAP) and stroke work (SW, SVi × MAP) were calculated. Q and SV were indexed to BSA (Qi and SVi).

Results

Linear regression (R2) between VO2 with SVi, Qi, CP, and SW at rest were similarly negligible for CF vs. CTL (p=ns). At 50 % VO2peak, R2 between VO2 with SVi (0.25 and 0.43, p<0.05), Qi (0.37 and 0.41, p<0.05), CP (0.18, p=ns and 0.25, p<0.05), and SW (0.12 and 0.30, p=ns) improved for CF and CTL, respectively. At VO2peak, stronger R2 between VO2 with SVi (0.41, p<0.05), Qi (0.47, p<0.05), CP (0.24, p<0.05), and SW (0.19, p=ns) occurred in CF; but, R2 weakened in CTL (0.28, p<0.05; 0.33, p<0.05; 0.07, p=ns; 0.02, p=ns, respectively).

Conclusions

From rest to VO2peak the relationship between VO2 with cardiac function improves in CF patients. Participation in exercise may benefit relationships between gas‐transfer with cardiac hemodynamics in CF patients.
Novel protective role of HSP72‐mediated exercise preconditioning against spinal cord injury in rats
Authors: Lin Mao‐Tsun , Chang Ching‐Ping
Published: June 2021

The heat shock protein 72 (HSP72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercise rats (given pre‐SCI exercise) had significantly higher levels of neuronal and astroglial HSP72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non‐exercise rats. pSUPER plasmid expressing hsp72 small interfering RNA (siRNA‐hsp72) was injected into the injured spinal cord. In addition to reducing neuronal and astroglial HSP72, the (siRNA‐hsp72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP72 on protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP72‐mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI.
Aerobic Exercise Increases Parasympathetic Activity on BDNF Genetic Variant Val66Met Carriers
Authors: LEMOS JUNIOR JOSE , de SOUZA SILVIA , RIBEIRO JUNIOR ROBERTO , DIAS RODRIGO , SILVA MICHELLE , ALVES CLEBER , TROMBETTA IVANI
Published: June 2021

Aerobic exercise training (ET) can improve autonomic control, we aimed to investigate the influence of BDNF variant polymorphisms over the sympatho‐vagal balance, pre and post ET in police officers of São Paulo's State Military Police. We hypothesized: 1) presence of the allele Met is associated with a higher rest heart rate (restHR) and lower heart rate variability (HRV), 2) ET will reverse this impairment on the carriers of the Val66Met polymorphism. 80 healthy male (25±4 yrs) underwent to ET on a running track for 5 months. Autonomic control was assessed by the HRV (ECG) at rest. BDNF genotyping resulted in 27.5% (n=22) of Val66Met and 72.5% (n=58) of Val66Val individuals. In the pre ET period, Val66Met presented higher restHR compared with Val66Val (86±13vs.68±6 bpm; p<0.05). HRV was similar between groups. ET similarly improved functional capacity in Val66Met and Val66Val. The pre ET difference on restHR disappeared (67±4 vs. 68±11 bpm; p>0.05). Further analyses showed negative association between restHR changes and oxygen consumption increases (r=‐0.52 e p<0.05). The presence of Met allele could impair parasympathetic modulation of restHR, which is abolished by ET.
The Study of Cardio‐Pulmonary Function, Anaerobic Power, and Body Composition According to Sports Type in Highschool Athletes
Authors: Jin Haeng Mi , Kim Young Jun , Kang Hye‐Ryun , Moon Hwasil
Published: June 2021

The aim of this study was to examine cardio‐pulmonary capacity for gymnasium, anaerobic power, and body composition according to the motion load examination in highschool athletes. A total of 33 highschool athletes who are playing 4 different types of sports including basketball, soccer, tennis, weight lifting were participated in this study and their cardio‐pulmonary function, anaerobic power and body composition were investigated. Collected data were analyzed by one way ANOVA using windows SPSS Ver.12.0 and Duncan technique was used for post‐hoc test. P‐value less than .05 was considered as statistical significance. Basketball, soccer, and tennis players presented significantly higher maximum oxygen consumption than weight lifting players, while there was no difference in maximal heart rate according to different sports type in highschool athletes. There were no statistical differences in peak power and average power in highschool athletes. Weight lifting athlete presented significantly higher BMI and % body fat than basketball, soccer, and tennis players and statistical difference was observed in their fat free mass as well. In conclusion, cardio‐pulmonary function and body composition were different according to types of sports in highschool athletes while there was no difference in anaerobic power. These results may provide basic scientific data to improve the performance of highschool athletes by comparing cardio‐pulmonary function, anaerobic power, and body composition according to types of sports.
Safety Of Resistance Training with Elevated Arterial Stiffness
Authors: DeVallance Evan , Fournier Sara , LeMaster kent , Lee Kyuwan , Bonner Daniel , Donley David , Chantler Paul
Published: June 2021

Arterial stiffness, a strong independent risk factor for cardiovascular (CV) disease, is elevated in patients with metabolic syndrome. Central arterial stiffening can be non‐invasively measured by pulse wave velocity (PWV), were 1 standard deviation change is associated with a 15% increase in CV risk. Therapeutic interventions aimed at decreasing PWV and other CV risk factors are clinically important to reduce the risk of CV disease and events in metabolic syndrome. Resistance training (RT) is under investigation, but to date results have been controversial with some showing increases in PWV. This increase could be detrimental to someone with preexisting arterial stiffness, but none of these studies included subjects with metabolic syndrome. We hypothesize that 8 weeks of progressive RT would not increase PWV in subjects with metabolic syndrome. Following RT there was a non‐significant reduction in triglycerides (12%) and body fat (11%) in the RT MetS group. We found 8 weeks of progressive RT did not cause a rise in PWV in metabolic syndrome patients (Pre 7.7 ± 0.4 Post 7.6 ± 0.3 m/s). Further, we found correlations between high baseline PWV (r=‐0.7, p<0.01), carotid intima media thickness (r=‐0.5, p<0.05), and systolic blood pressure (r=‐0.5, p<0.01) with improvement in PWV pre to post. Backward elimination models showed baseline PWV (β=‐0.7, p<0.01) as the best predictor of a decrease in PWV following RT. In summary progressive RT is a safe exercise modality for individuals with metabolic syndrome to reduce CV risk factors and improve arterial function.
Effects of normoxic and hypoxic exercise regimens on monocyte‐promoted thrombin generation in sedentary men
Authors: Wang Jong‐Shyan
Published: June 2021

This study investigates how normoxic and hypoxic exercise training affect procoagulant monocyte‐derived microparticle (MDMP) formation and monocyte‐promoted thrombin generation (TG) under severe hypoxic stress. A total of 40 sedentary males were randomized to perform either normoxic (NET; 21%O2, n=20) or hypoxic (HET; 15%O2, n=20) exercise training (60%VO2max) for 30 min/day, 5 days/week for 5 weeks. At rest and immediately after hypoxic exercise test (HE, 100W under 12%O2 for 30 min), the MDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography, respectively. Before the intervention, acute HE increased coagulant factor V (FV)/FVIII‐rich, phosphatidylserine (PS)‐exposed, and tissue factor (TF)‐expressed MDMP levels and enhanced the peak height and rate of TG under treatment of monocyte with oxidative‐low density lipoprotein, which were accompanied by elevated concentrations of norepinephrine/epinephrine, myeloperoxidase, and lnterleukin‐6 in plasma. However, both NET and HET decreased the FV/FVIII‐rich, PS‐exposed, and TF‐expressed MDMP levels and the peak height and rate of TG in monocyte‐rich plasma (MRP) following HE. However, HET significantly attenuated the extents of HE‐enhanced procoagulant MDMP formation, dynamic TG in MPR, and plasma catecholamine, peroxide, and proinflammatory cytokine levels, compared to NET did. Hence, HET effectively suppresses monocyte‐mediated TG by decreasing procoagulant MDMP formation under severe hypoxic stress.
Long‐Time Saturation Exposure Changes Gut Microbiota Composition And Intestinal Antimicrobial Defense In Mice
Authors: Xiang Dao , Luo Beibei , Fang Yiqun , Xu Ji , He Jia , Chen Xin , Chen Peijie
Published: June 2021

PURPOSE

Long‐time saturation exposure may induce anxiety, loss of appetite, and digestive disorders, which relate to impairment of intestinal mucosal immune system and gut microbiota homeostasis. Our study examined the effects of 4‐day of saturation exposure on gut microbiota and intestinal antimicrobial peptides (AMPs) in mice.

METHOD

20 male C57 Mice, 8‐week old, were randomly divided into saturation exposure group (SE, n=10) and control group (CON, n=10). SE exposed to N2/O2 mixed gas at 500kPa for 4 days in pressure chamber. Intestines were excised and stained with HE and AB‐PAS. Feces and Intestines were collected and extract gDNA and RNA respectively. We used qPCR to assay bacterial population (Bacteroides, Clostridia, Lactobacilli, Enterobacteria, and Akkermansia muciniphila) of the feces, and the AMPs (Defα5/β1, Retnlβ, Reg3β/γ) of small intestine and colon.

RESULTS

Within 4 days, SE mice did not exhibit nitrogen narcosis behavior. By comparing with the 16S rRNA genes, results revealed a significant increase in the relative abundances of A. muciniphila (9.28±5.67) and Clostridia (3.45±0.63) in SE. The relative abundance of Lactobacilli was lower (0.40±0.24) in SE. Moreover, a distinct increase of Enterobacteria (23.34±8.88) was observed in SE compared with CON. Gene expressions for Defα5/β1 in SE were decreased in small intestine, while Defβ1 and Reg3γ in SE were significantly decreased, and Defα5 and Reg3β increased in colon.

CONCLUSION

In sum, the data showed that a four‐day saturation exposure induced changes in the mRNA level of AMPs, and the gut microbiota composition in mice.

Found: NSFC 31471135
Sex‐Specific Heart Rate Responses to Apneic Manipulations in Young Healthy Subjects
Authors: Vela Jeffrey , Usselman Charlotte , Bruce Christina , Skow Rachel , Abrosimova Maria , Pfoh Jamie , Day Trevor , Davenport Margie , Steinback Craig
Published: June 2021

Contributions of lung stretch and chemoreflex stimulation to heart rate (HR) responses to apnea have not been elucidated independently in men and women. We tested the hypothesis that HR responses to apnea would be exaggerated in men relative to women. Relative changes in HR (ECG) were analyzed during 4 maximal apneic maneuvers: 1) end‐inspiratory (INSP), 2) end‐tidal expiratory (ETE), 3) INSP following hyperoxic breathing (HX), and 4) INSP following hyperventilation (HV). HR data from all apneas were analyzed in 10s bins. The first 5 bins (50s) of each apnea were compared between sexes in these analyses. INSP caused similar changes in HR between sexes (‐8 ± 11 and ‐7 ± 6 bpm, P=0.8), and the time courses of the changes in HR were also similar. Although the nadir bradycardic response to ETE (designed to unload lung stretch receptors) was similar between men and women (‐9 ± 7 and ‐9 ± 8 bpm, P=0.9) onset of bradycardia was delayed in women (30s bin) compared with men, in whom the bradycardia was immediate (10s bin). During HX (eliminating the influence of O2) and HV (eliminating the influence of CO2) both the time courses of the HR responses and the HR nadirs (HX: ‐17 ± 13 and ‐14 ± 11 bpm, P=0.6; HV: ‐33 ± 12 and ‐35 ± 17 bpm, P=0.9) were similar between men and women, respectively. These data suggest that sex differences in HR responses to apnea are not dependent on changes in O2 or CO2 but, rather, are unveiled during the unloading of lung stretch receptors. Supported by NSERC, AIHS, Mount Royal University Innovation Grant, and the University of Alberta Human Performance Scholarship Fund.
Enhanced Neurotrophin Signaling Following Chronic Hypoxia Potentiates Catecholamine Release from Adrenal Chromaffin Cells
Authors: Scott Angela , Zhang Min , Nurse Colin
Published: June 2021

Environmental stressors, including chronic hypoxia, stimulate catecholamine secretion from adrenomedullary chromaffin cells (AMCs); however, the underlying molecular mechanisms remain unclear. Here, we investigated the role of brain‐derived neurotrophic factor (BDNF) signaling in rat AMCs exposed to chronic hypoxia. In rat adrenal glands, BDNF and its tropomyosin‐related kinase B (TrkB) receptor were highly expressed in the cortex and medulla, respectively. Exposure of AMCs to chronic hypoxia (2% O2; 48 hr) in vitro caused a significant increase in TrkB mRNA expression. A similar increase was observed in an immortalized chromaffin cell line (MAH cells); however, it was absent in MAH cells deficient in the transcription factor HIF‐2a. Activation of TrkB with a specific agonist, 7,8 dihydroxyflavone (7,8 DHF), or BDNF on chronically hypoxic (Chox) AMCs increased intracellular Ca2+ ([Ca2+]i) and quantal catecholamine release to a greater extent than normoxic (Nox; 21% O2) controls. The TrkB‐induced [Ca2+]i rise was sensitive to the tyrosine kinase inhibitor K252a and nickel, but not the Ca2+ store‐depleting agent, cyclopiazonic acid. TrkB activation also induced membrane depolarization and action potential firing that occurred with a higher frequency in CHox cells. This was accompanied by a conductance increase, and the spike discharge was inhibited by pyrazole‐3, a selective TRPC3 channel blocker. These data demonstrate that, during chronic hypoxia, enhancement of BDNF‐TrkB signaling increases membrane excitability and extracellular Ca2+ influx in chromaffin cells, which leads to a marked potentiation in catecholamine secretion. This work was funded by the Natural Sciences and Engineering Research Council. A.S. is a NSERC Post‐doctoral Fellow.
Hydrogen Sulfide and Hypoxia‐Induced Changes in K2P3/9 (TASK) current and [Ca2+]i in Rat Carotid Body Glomus Cells
Authors: Kim Donghee , Wang Jiaju , Kim Insook , Carroll John
Published: June 2021

Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca2+ concentration ([Ca2+]i). Recent studies suggest that hydrogen sulfide (H2S) may serve as an oxygen sensor/signal in the carotid body during acute hypoxia. To further test such a role for H2S, we studied the effects of NaHS (a H2S donor) on the activity of TASK channel and intracellular [Ca2+]i, which are considered crucial for mediating the hypoxic response. Like hypoxia, NaHS inhibited TASK activity and elevated [Ca2+]i. To block the production of H2S, glomus cells were incubated (3 hr) with DL‐propargylglycine, aminooxyacetic acid, beta‐cyano‐L‐alanine (0.3 mM) that inhibit cystathionine‐beta‐synthase and cystathionine‐gamma‐lyase. Cell H2S production induced by L‐cysteine and hypoxia was strongly reduced by the inhibitors, as assessed using SF‐7 fluorescence. In cells treated with inhibitors, the hypoxia‐induced reduction of TASK activity and elevation of [Ca2+]i were similar in magnitude to those observed in untreated cells. In control or inhibitor‐treated cells, BK channel was not open at rest. These findings suggest that H2S does not mediate the hypoxia‐induced changes in TASK activity and [Ca2+]i in rat glomus cells.
ZnT2‐mediated Zn Transport Modulates Prolactin Stability and Secretion to Maintain Lactation
Authors: Lee Sooyeon , Kelleher Shannon
Published: June 2021

Prolactin (PRL), secreted from lactotrophs into circulation and from mammary epithelial cells (MECs) into milk, regulates mammary gland (MG) differentiation, milk production and secretion during lactation. Zinc (Zn) is implicated in PRL oligimerization (stability) and storage in secretory vesicles. We previously found that in MECs, the Zn transporter ZnT2 imports Zn into vesicles for secretion into milk and ZnT2 mutations in women result in substantial reduction in milk Zn levels. To test the hypothesis that ZnT2 provides Zn for PRL stability and thus modulates MG function during lactation, we used ZnT2‐null mice and studies of MECs in vitro. Lactating ZnT2‐null mice had substantial defects in MG architecture and MEC sub‐structure, reduced Stat5 activation, impaired milk secretion and 60% less milk PRL. MECs in vitro showed that ZnT2 and PRL were co‐localized in vesicles. ZnT2‐attenuated MECs had significantly greater intracellular PRL but reduced PRL oligimerization and secretion compared to ZnT2‐expressing cells, suggesting that ZnT2‐mediated Zn transport regulates PRL stability and secretion. Moreover, ZnT2‐attenuation eliminated the ability to activate Stat5 and increase expression and secretion of β‐casein. Finally, breastfeeding women with a common loss‐of‐function variant in ZnT2 (D103E) had significantly less milk PRL concurrent with significantly greater milk sodium, a hallmark of MG dysfunction. Taken together, these results establish that ZnT2 is critical for regulating PRL stability, storage and secretion in the MG to maintain the differentiated epithelium and milk secretion during lactation.
Effects of Coconut Water on Reproductive Functions in Danazol Treated Wistar Rats
Authors: Kunle‐Alabi Olufadekemi , Akindele Opeyemi , Oyovwi Mega , Duro‐Ladipo Marian , Raji Yinusa
Published: June 2021

Coconut water (CW) has been reported to improve semen quality and testosterone levels in male rats and to possess estrogen‐like substances which can impact positively on female fertility. The mechanisms through which CW may perform these actions are yet to be fully elucidated. This study explored the effects of CW on the hypothalamo‐pituitary‐gonadal axis (HPG) using Danazol (a GnRH antagonist). Wistar rats were randomly assigned into 7 male and 7 female groups (n = 6); Group 1: control (distilled water), group 2: 20ml/kg corn oil (vehicle for danazol), group 3: 20ml/kg CW, group 4: 40ml/kg CW, group 5: 200mg/kg danazol, group 6: 200mg/kg danazol + 20ml/kg CW and group 7: 200mg/kg danazol + 40ml/kg CW. Oral administration was done daily for 6 weeks after which the rats were sacrificed to obtain their sex organs and serum. Serum levels of LH, FSH, estrogen and testosterone were determined using ELISA. Sperm indices were assessed using cauda epididymal fluid. Histological and weight evaluation of all sex organs were carried out. The males showed a significant (p<0.05) increase in sperm count, sperm motility and serum estrogen concentration in groups 3, 4, 6 and 7, while a significant reduction in these variables was observed in group 5. The females showed a significant increase in serum estrogen levels in groups 3, 4, 6 and 7, with significant increases in serum LH, FSH and Testosterone concentrations in groups 6 and 7 when compared with group 5. There was a significant increase in uterine weight in group 4 and ovary weight in groups 6 and 7 when compared with group 5. Testicular and ovarian tissue appeared healthier in all CW groups. The results suggest that coconut water acts on the HPG to positively influence reproductive function in both males and females.
Assessment of Aphrodisiac Effects of Methanol Extract of Carpolobia lutea Root in Male Rabbits
Authors: Raji Yinusa , Dare Ayobami , Kunle‐Alabi Olufadekemi , Akindele Opeyemi
Published: June 2021

In spite of the folkloric use of the root of Carpolobia lutea as sexual stimulant in man, there is no scientific prove of its efficacy. This study was designed to evaluate the effects of methanol extract of Carpolobia lutea root (MECL) on sexual activity of male rabbits. Twenty adult male rabbits (1.5‐2.0kg) divided into four equal groups were treated daily (orally) for 28days as follows; group1‐control (2 ml/kg 1% tween‐20), group2 (40 mg/kg MECL), group3 (80 mg/kg MECL) and group4 (0.5 mg/kg sildenafil citrate). The male rabbits were then cohabited with sexually receptive female at estrus and sexual activities of the male were recorded on days 0, 1, 3 and 5 using a digital camera mounted on the mating arena. Indices of sexual activities were determined. The male rabbits were sacrificed on day 29 and serum testosterone concentration was measured by ELISA technique. Homogenates of the corpora cavernosa were also obtained for determination of nitric oxide concentration. The Carpolobia lutea extract significantly increased mount frequency, intromission frequency and ejaculatory latency, while it reduced mount latency, intromission latency and post ejaculatory latency (similar to sildenafil citrate) when compared with the control. The extract also caused a significant increase in nitric oxide concentration in corpora cavernosa but no change in serum testosterone concentration. The results suggest that the methanol extract of Carpolobia lutea root improves male sexual activity via an increase in nitric oxide concentration which may be useful in certain forms of sexual inadequacies such as premature ejaculation and impaired libido. The study thus provides scientific rationale for the traditional use of Carpolobia lutea in the management of penile erectile dysfunction.
Pulmonary mechanics of high‐altitude waterfowl
Authors: York Julia , Chua Bev , Milsom William
Published: June 2021

Previous work in this lab found that while both low and high‐altitude adapted species increase ventilation in response to hypoxia, high‐altitude species primarily increase tidal volume whereas low‐altitude species increase breathing frequency. Thus, we hypothesized that high‐altitude species should have higher respiratory compliance when compared to low‐altitude species to reduce the cost of breathing deeper. We measured dynamic and static compliance of the total system in five Andean species of ducks resident at Lake Titicaca, Peru and compared them to the low‐altitude migratory barnacle goose (n蠅6 for all groups). Static compliance was significantly higher in the high‐altitude ducks than the barnacle geese (1.8 ± 0.18 compared to 1.3 ± 0.06). Among the high‐altitude ducks the compliance was highest in the species that has spent the most evolutionary time at high‐altitude (2.98 ± 0.36), while the lowest compliance was found in the one species of diving duck studied (1.63 ± 0.23). The high‐altitude species also had a higher inspiratory capacity (215 ± 17 mL/kg) than the low‐altitude geese (154 ± 21 mL/kg). Thus high‐altitude species breathe with a more effective breathing pattern, reducing pulmonary dead space, without incurring an increased cost of overcoming elastic recoil forces, by increasing compliance of their respiratory system.
Temperature Enhanced Extremity Lengthening is Growth Rate Dependent
Authors: Kerby Jenna , Gray Miles , Tamski Holly , Heaberlin Aaron , Crow Nathaniel , Ion Gabriela , Serrat Maria
Published: June 2021

Limb length inequality is a potentially disabling condition with few noninvasive treatment options. Our lab has previously shown that unilateral heat increases bone elongation rate, suggesting that temperature therapy could be a non‐surgical way to promote limb length equalization. Treatment age is important because we have shown that temperature effects occur primarily when growth is most rapid. We compared heat effects on limb lengthening during early (3‐5 weeks age) and late (5‐7 weeks age) phases of post‐weaning growth in mice (N=24). We tested the hypothesis that heat‐induced limb elongation varies with postnatal growth rate. Female mice (N=6 per age) were treated with 40C unilateral heat for 40 minutes per day for 14 days. Controls (N=6 per age) were not treated. Tibial elongation rate, measured by fluorochrome labeling, was over two‐fold greater during the early phase. Bone elongation rate reflected overall body growth rate, with lower absolute heat‐induced differences during the later phase. Relative increases in extremity length on the heat‐treated side were similar during early and late phases, suggesting that a heat‐induced growth response is still possible during later postnatal growth. These results are important for designing therapies to treat children with linear growth disorders at different stages of development by demonstrating that treatments may not be restricted to early growth phases. Supported by ASBMR GAP, WV‐NASA, UK‐CCTS (NIH UL1TR000117), and NIH/NIAMS R15AR067451‐01.
Recruitment of Ankle Flexor and Extensor Muscles during Leg Movements in Chick Embryos
Authors: Sun SooYeon , Bradley Nina
Published: June 2021

Days prior to hatching, chick embryos produce repetitive leg movements (RLMs) in ovo featuring flexor and extensor muscle alternation at locomotor frequencies. Occasionally only repetitive ankle flexor activity accompanies RLMs. Thus, the objective of this study was to determine if recruitment differs between ankle flexor and extensor muscles during RLMs.

Embryonic day 20, ankle muscles were implanted bilaterally for electromyographic (EMG) and kinematic recording of spontaneous muscle activity. Criteria for RLM sequence selection were 蠅 4 rhythmic EMG bursts (1‐12 Hz) in 1 or more muscles accompanied by leg movements.

Flexor and extensor recruitment during RLMs was compared within‐subject (N=17). Left and right ankle muscle bursts were analyzed separately to account for effects of asymmetric posture. The number of flexor and extensor bursts (burst count) and recruitment failures (burst deletions) were determined. RLM burst amplitude and integrated amplitude were normalized to maximum value per muscle for statistical analyses.

Preliminary results indicated flexor muscles were more frequently recruited than extensors. Flexor bursts outnumbered extensor bursts in 16 of 16 embryos (left ankle) and 15 of 17 (right ankle). In 2 embryos, right ankle extensor bursts outnumbered flexor bursts, and flexor burst deletions were more prevalent. However, flexor and extensor burst amplitude parameters were similar.

Our data suggest locomotor drive for RLMs was greater to flexor motor pools than extensor motor pools. However, when active, flexor and extensor motor pools produced similar muscle recruitment amplitudes. Findings may indicate that there is selective locomotor drive to flexor and/or inhibitory drive to extensor motor pools during spatially constrained movement in ovo.
The Advantages of Self‐Testing Vary with Familiar Versus Unfamiliar Kinesiology Information
Authors: Dobson John , Yarbrough Mary Beth
Published: June 2021

Numerous studies have found learning strategies based on the “testing effect” promote greater recall compared to those that rely solely on reading; however, the advantages of testing are often not evident immediately after learning and they tend to emerge only after a delay of 2‐7 days. By contrast, our research, which has focused on kinesiology students studying kinesiology information (i.e., information with which they were familiar), has consistently demonstrated testing‐based strategies produce superior recall both immediately and following a one week delay. The purpose of this investigation was to determine if the advantages associated with a testing‐based learning strategy vary with one's familiarity with the to‐be learned information. Participants used both reading (only) and testing‐based strategies to repeatedly learn 3 different sets of material that consisted of: 1. previously studied human muscle information (Familiar), 2. a mix of previously studied and previously unstudied human muscle information (Mixed), and 3. previously unstudied muscle information that is unique to sharks (Unfamiliar). Learning was evaluated via free recall assessments administered both immediately and after a one week delay. The reading strategy resulted in immediate recall scores of 45.16 ± 2.86, 28.15 ± 2.92 and 11.65 ± 1.99 for the Familiar, Mixed and Unfamiliar information, respectively; whereas the testing‐based strategy produced scores of 54.35 ± 2.92, 29.03 ± 3.16 and 18.64 ± 2.33, respectively. In summary, the testing‐based strategy produced superior immediate recall with both familiar and unfamiliar muscle information, and the advantages of testing persisted for at least one week with the more familiar muscle information.
Teaching Plasma Osmolarity vs. Colloid‐Osmotic Pressure in Medical Physiology
Authors: Johnson Fruzsina , Babos Mary Beth , Seaman Michael
Published: June 2021

Body fluid distribution is a clinically highly relevant concept in human physiology. It is generally covered early in medical physiology courses by discussing osmosis, defining fluid compartments and walking through scenarios of hyper‐, iso‐, and hyposmotic volume contraction and expansion with discussion on volume and osmolarity changes of the intra‐ and extracellular fluid compartments. Yet, many students still struggle with clinical application of these concepts. Even after traditional calculation of Starling forces in a typical systemic capillary, they often have trouble with the concept of plasma colloid‐osmotic (oncotic) pressure and its relevance to edema formation. In the renal section, where hypoalbuminemia and electrolyte disturbances are both discussed confusion between plasma osmolarity and oncotic pressure often arises. Over the past four years, teaching medical physiology to physician assistant students we developed an alternate approach. During the initial fluid compartment lecture we emphasize the concept of “osmotically active substance” and compare permeability of the cell vs. capillary membrane. We also introduce plasma osmolarity and oncotic pressure and discuss their primary determinants. These concepts are then revisited during the cardiovascular and renal section of the course. We found this approach to be highly successful in preventing the confusion described above, and feel this to be a major step in reforming classic medical physiology education.
The Flipped Classroom Model Improves Undergraduate Test Performance in Human Physiology
Authors: Goodwill Adam
Published: June 2021

The intent of this study was to assess whether a flipped classroom based curriculum affects student performance in a comprehensive human physiology course intended for sophomore level undergraduate students. In year one, students (n = 32) received a traditional lecture based instruction lasting 2 hours and 40 minutes each Saturday for one semester. In year two, a separate group of students (n = 50) were required to watch the previous year's recorded lecture prior to class and then attend class where they received a weekly quiz (worth ~12.5% of their grade; cumulatively) followed by an interactive group‐based question and answer period designed to require integration of the information in the lecture. Students in the traditional lecture did not receive quizzes and there was no interactive or group‐based portion of the class. Identical homework assignments and access to tutoring was provided to both sections. Student performance in both sections was assessed based on performance on identical exams. At time of abstract submission, the students in the flipped section have completed two examinations over an identical span of time as the traditional class covering the first 13 chapters of Dee Unglaub Silverthorn's Human Physiology an Integrated Approach (6th Edition). To date, overall examination averages were higher in the flipped classroom (77 ± 1.7 vs. 83 ± 1.5; P = 0.02). Taken together, these data provide evidence that flipped classroom styles can be equally effective or improve performance in the instruction of physiology at the undergraduate level.