bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dichotomous response to oral citrate in hypocitraturic stone formers
Authors: Lederer Eleanor , Gianella Fabiola , Maalouf Naim 
Published: May 2023

Background and Hypothesis: Hypocitraturia is a marker of metabolic acidosis and a risk factor for kidney stone formation. Oral citrate replacement is a mainstay therapy for hypocitraturic nephrolithiasis. We have observed that a subpopulation of hypocitraturic stone formers do not respond to oral potassium citrate (KCit) with the expected increase in urine citrate despite evidence of adherence to therapy as measured by increased urine K, citrate nonresponders (NR). We hypothesize that altered kidney handling of citrate accounts for the failure of oral citrate to result in increased urine citrate. Methods: To study this hypothesis, we compared changes in urine electrolyte excretion before and after citrate administration in citrate responder (R) and nonresponder (NR) stone formers with hypocitraturia and normal kidney function. Net gastrointestinal alkali absorption was calculated by the method of Oh (Urine Na + K + Ca + Mg) – (Urine Cl + P). Results: We identified 7 R and 8 NR with 24h urine assessments pre and post KCit. 7/8 R and 6/8 NR were female and all were White. There were no significant differences in age, weight, BMI, or dose of citrate. Baseline serum K and bicarbonate (24 +/- 3 meq/L) were similar in both groups and did not show significant changes after KCit administration. By design, 24h urine citrate increased significantly more in R (2.2 +/- 1.4 to 8.3 +/- 3.8 meq/d) than in NR (1.9 +/- 1.4 to 2.9 +/- 1.2 meq/d). Urine pH increased in both groups similarly (6.64 to 7.03 NR, 6.6 to 7.06 R) as did 24h urine K. Urine calcium did not change in either group. Ammonia excretion decreased significantly in R but not NR. However, 24h urine titratable acid excretion decreased in both groups. Net acid excretion was higher at baseline in NR and decreased in both groups but to negative levels in R. Interestingly, net gastrointestinal alkali absorption increased similarly in both groups. Conclusions: These findings suggest that R and NR have equivalent gastrointestinal absorption of KCit. NR may have a greater acid burden enhancing kidney citrate reabsorption as suggested by the higher baseline net acid excretion or altered bone utilization of citrate resulting in reduced excretion of a citrate load. 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.
The effect of weight gain on locust jumping kinematics and extensor muscle activity (Schistocerca americana)
Authors: Ringer Christopher , Feller Kate 
Published: May 2023

Female locusts (Schistocerca americana) reach sexual maturity between 46 and 52 days after hatching and experience up to three ovigerous cycles. During these cycles, the females undergo a weight gain of up to 40% of their total body mass. However, previous research has shown that gravid female locusts continue to achieve similar jump height and distance during their pre-gravid and inter-gravid conditions. This finding indicates that female locusts might have intrinsic means to detect increases in body mass during gravidity and the capacity to modulate the neuromechanics of their jumping legs to escape predators as successfully as when they were lighter. This prediction contradicts the current understanding of the degree to which locusts can control their escape jumping movements, which are understood to be a fixed all-or-nothing output. We hypothesized that female locusts modulate the contraction time in their femur extensor muscles to augment the power achieved by their jumping legs during conditions of artificial weight gain. We also hypothesized that this degree of control is not performed in male locusts since they do not naturally experience substantial changes in body mass throughout their adult reproductive stage. Fifteen female and nine male locusts were recorded using simultaneous high-speed video capture (1500 frames per second) and bilateral electromyogram (EMG) recordings during evoked escape jumps. Multiple jumps were recorded for each individual, corresponding to different weight gain conditions. The locusts were mounted with an apparatus to hold clay beads representing a range of masses that would increase body weight by 20-50% of their total body mass. 205 jumps were recorded from females, and 128 jumps were recorded from males. The peak angular velocity and acceleration of the jumping legs were calculated using position tracking software (DeepLabCut) and subsequent kinematic analysis of the leg rotation using custom scripts in R. From the femoral extensor muscle EMG recordings, contraction time was calculated from the start of extensor activity to the beginning of tibia rotation from the femur. In comparing male and female locusts, contraction time was plotted as a function of angular velocity and acceleration to demonstrate the relationship between body mass and jump performance. These results parallel ongoing work investigating the relationship between decreased tidal volumes and jumping performance in female locusts and compensation mechanisms related to overcoming these physiological limitations. Student Research Grant from Union College 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.
BRCA1-mediated DNA repair protects tubular epithelial cells during Acute Kidney Injury
Authors: Silvaroli Josie , Pabla Navjot 
Published: May 2023

Acute kidney injury (AKI) is a common clinical syndrome that is associated with adverse short and long- term sequelae. AKI usually occurs in the setting of other disorders, such as sepsis, rhabdomyolysis, and cardiovascular and oncological diseases, where the underlying disease and or associated therapy cause an abrupt loss of renal function. While the underlying pathophysiological mechanisms are incompletely understood, renal tubular epithelial cell (RTEC) dysfunction and cell-death are the hallmarks and the underlying cause of AKI. Recent studies have shown that DNA damage contributes to RTEC dysfunction during AKI. However, due to the technical challenges in studying DNA repair in vivo, it remains unknown if RTECs can repair their DNA during or after AKI. Here we have used a novel DNA repair reporter mouse to demonstrate that functional homologous recombination (HR) mediated DNA repair occurs in RTECs early during the development of Ischemia-reperfusion associated AKI. Importantly, RTEC-specific deletion of HR-linked DNA repair protein, BRCA1 exacerbates RTEC dysfunction and AKI in both male and female mice. Overall, our studies suggest that DNA repair pathways play a protective role during acute kidney injury and are a promising target for therapeutic interventions. The current study was supported by an American Heart Association Predoctoral Fellowship (AHA-900765) to J.A.S and NIDDK 1R01DK132230 to N.P. 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.
Neuraminidase causes endothelial phosphatidylserine externalization and ADAM17 activation: implications for shedding of insulin receptor and endothelial insulin resistance
Authors: Ferreira-Santos Larissa , Foote Christopher , Gonzalez Juan , Augenreich Marc , Manrique-Acevedo Camila , Martinez-Lemus Luis , Padilla Jaume 
Published: May 2023

Endothelial insulin resistance represents a causal factor in the pathogenesis of type 2 diabetes (T2D) and vascular disease, thus underscoring the need to identify molecular mechanisms underlying defects in endothelial insulin signaling. We previously showed that a disintegrin and metalloproteinase-17 (ADAM17) is increased while insulin receptor α-subunit (IRα) is decreased in the vasculature of patients with T2D, leading to impaired insulin-induced vasodilation. We also showed that ADAM17 is a sheddase that targets IRα. Externalization of phosphatidylserine (PS) from the inner to the outer leaflet of cell membranes has been proposed as a pivotal step in the activation of ADAM17. However, whether PS externalization increases ADAM17 sheddase activity and, consequently, shedding of endothelial IRα in T2D is not known. Herein, we hypothesized that neuraminidase (Neu), an enzyme we showed is upregulated in diabetes, leads to PS externalization via activation of Ca2+ influx and subsequent induction of ADAM17 sheddase activity. All reported differences are significant at P<0.05. In support of this hypothesis, we report that Neu and ADAM17 activities are increased in plasma of individuals with T2D, relative to non-T2D subjects. In experiments using cultured endothelial cells, we show that exposure to Neu increases Ca2+ influx and ADAM17 activity. We also find that augmenting endothelial Ca2+ influx using a calcium ionophore (A23187) increases adhesion of lactadherin (a peptide that binds externalized PS) to the surface of endothelial cells, as does treatment with the ADAM17 activator, PMA, which also reduces IRα on the cells. Importantly, overexpression of ADAM17 in endothelial cells reduces IRα in cell lysates and this coincides with a tendency towards increased IRα in the cell culture supernatant, indicative of protein shedding. Collectively, these findings suggest that Neu causes Ca2+ influx in endothelial cells, favoring PS externalization and, consequently, increased ADAM17 activity and shedding of IRα. Hence, inhibition of Neu and ADAM17 sheddase activities should be considered as novel potential strategies to improve endothelial insulin signaling in T2D. R01HL151384 (to LAML and JP), R01HL153264 (to LAML and JP), and R01HL137769 (to JP). 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.
TRPM8 channel activation induces relaxation in pudendal artery and corpus cavernosum: Can TRPM8 channel be a target to improve diabetic erectile dysfunction?
Authors: Priviero Fernanda , Moraes Raiana , Araujo Fenix , Jesus Rafael , Silva Liliane , Arishe Olufunke , Pernomian Laena , Wenceslau Camilla , Webb Clinton , Silva Darizy 
Published: May 2023

Erectile dysfunction (ED) is one of the most common and underestimated complications of diabetes. Previous studies have shown that TRPM8 activation triggers relaxation of internal pudendal arteries (IPA) with increased sensitivity in hypertensive rats. Despite the correlation between ED and diabetes, research on the role of TRPM8 channels in the IPA and corpus cavernosum (CC) in diabetes still needs to be elucidated. We hypothesized that preserved TRPM8 channel function in diabetic mice could be a therapeutic target for the treatment of ED. Male lean and db/db mice were euthanized, and the IPA were mounted on DMT wire myographs and CC were mounted on AVS organ bath for the measurement of isometric force. Concentration-response curves to icilin or menthol (TRPM8 agonists) were obtained. The CC TRPM8 channels expression was evaluated by western blot. Second harmonic generation was used to evaluate collagen deposition in IPA. Data are expressed as mean ± S.E.M of 3-5 mice. Non-linear regression curve was performed, and the maximum response (Emax) was analyzed using Student’s t test (p<0.05). Similar TRPM8 channel expression was observed in the CC from lean and db/db mice. Menthol-induced relaxation of the CC was reduced in diabetic mice (Emax: 105.00 ± 5.00%) compared to lean mice (Emax: 139.44 ± 15.91%) . Relaxant effect induced by icilin and menthol was similar between IPA from db/db (Emax icilin: 95.56 ± 0.86% and Emax menthol: 93.88 ± 2.33%) and lean (Emax icilin: 97.05 ± 0.87% and Emax menthol: 101.10 ± 1.75%) mice. Interestingly, pre-incubation with icilin (10-4M) for 30 minutes decreased the potency of phenylephrine-induced contraction compared to untreated IPA rings in both db/db and lean mice. In the IPA, diabetes decreased the sensitivity to acetylcholine compared to lean. However, the relaxation induced by acetylcholine was not changed by pre-incubation with icilin. Diabetic mice (db/db) IPA tended to have a decrease in arterial collagen content compared to lean mice. Although menthol-induced relaxation of the CC was reduced in diabetic mice, icilin and menthol were able to promote similar relaxation in IPA from diabetic and lean mice. In this way, TRPM8 function was preserved in IPA from diabetic mice. Icilin reduced sensitivity to phenylephrine in IPA from both mice. These data suggest that activation of TRPM8 could be a therapeutic target for the treatment of ED. SMSNA, NIH (RO1DK132948) and FAPESB 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.
Higher levels of vigorous physical activity are associated with enhanced nocturnal blood pressure dipping
Authors: Ernst Jackson , Gimblet Colin , Nuckols Virginia , Holwerda Seth , Stroud Amy , DuBose Lyndsey , Wooldridge Nealy , Ajibewa Tiwaloluwa , Fiedorowicz Jess , Pierce Gary 
Published: May 2023

Introduction: Nocturnal blood pressure (BP) dipping determined from 24-hour ambulatory blood pressure monitoring (ABPM) is associated with reduced cardiovascular disease (CVD) risk. Physical activity lowers the risk of CVD related, in part, to preserved endothelial function and lower aortic stiffness, however the relation between physical activity and nocturnal dipping remains unclear. The objective of our cross-sectional retrospective analysis was to assess the relation between physical activity and nocturnal BP dipping, and whether this relation was confounded by measures of vascular function. We hypothesized that higher levels of physical activity would be associated with greater nocturnal BP dipping. Methods: Healthy adults (n=172, age 19 to 65 years, 55% female) had 24-hour ABPM measured. BP recordings were taken every 30 min during the daytime and every 60 min during the nighttime. Nocturnal “dippers” had a 10-20% difference between their mean daytime and nighttime systolic BP and “non-dippers/inverse dippers” had <10% difference. The modifiable activity questionnaire was used to assess physical activity levels via self-reported days/week with greater than 30 min of moderate activity (3.0-6.0 METs) and vigorous activity (>6.0 METs). Endothelial function (brachial artery flow-mediated dilation, FMD), and aortic stiffness (carotid-femoral pulse wave velocity, cfPWV) were also assessed. Results: Nocturnal BP dippers performed more days/week of moderate and vigorous physical activity compared to non-dippers (P=0.007 and P=0.008, respectively). Both moderate (B=0.386, P=0.042) and vigorous physical activity (B=0.604, P=0.002) were associated with nocturnal BP dipping in univariate linear regression analyses. However, only vigorous activity (B=0.926, P=0.001) remained associated with nocturnal BP dipping after adjustment for age, BMI, 24-hr systolic BP and diastolic BP, brachial FMD and cfPWV. Conclusion: Vigorous physical activity may attenuate CVD risk in part from enhanced nocturnal BP dipping. Future studies should investigate additional mechanisms by which vigorous physical activity may enhance nocturnal BP dipping. This study was supported by grants from the National Institutes of Health (AG063790; HL014388, HL07121; AG043722). Dr. Pierce is supported by the Russell B. Day and Florence D. Day Endowed Chair in Liberal Arts and Sciences, University of Iowa. 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.
Effects of exercise prior to a night of partial sleep deprivation on ambulatory blood pressure
Authors: Bommarito Julian , Millar Philip 
Published: May 2023

Introduction: Blood pressure (BP) follows a circadian rhythm intertwined with the sleep-wake cycle, dipping during sleep and surging in the morning. Prior work has found that sleeping ≤4.5 hours for one night (i.e., acute partial sleep deprivation [PSD]), can increase ambulatory BP during the night and subsequent day, resulting in increased 24-hour BP - a risk factor for increased mortality. In contrast, a bout of aerobic exercise can reduce ambulatory BP for up to 24 hours, termed post-exercise hypotension. The primary aim of this study is to examine if exercise can attenuate the rises in 24-hour ambulatory BP caused by acute PSD. We hypothesized that exercise would attenuate the elevated 24-hour BP response caused by acute PSD. Methods: Twenty young, healthy adults (22 ± 4 years; 7 males and 13 females; Sleep chronotypes: 4 early, 10 intermediate, and 6 late) completed a randomized crossover trial where they slept normally (sleep: 2300 to 0700 hours), sleep was partially deprived (sleep: 0330 to 0700 hours), or exercise (50-minutes continuous cycling at 70-80% age predicted heart rate maximum) was performed before a night of PSD (sleep: 0330 to 0700 hours). Sleep duration was assessed using self-report and an accelerometer worn on the wrist (wGT3X-BT, ActiGraph). Ambulatory BP (Oscar2, SunTech Medical) was measured in 30-minute intervals over the course of a 27-hour epoch. Results: Acute PSD increased 24-hour systolic (control: 118 ± 9 mmHg vs. PSD: 122 ± 9 mmHg. P<0.001) and diastolic (control: 67 ± 5 mmHg vs. PSD: 70 ± 7 mmHg, P<0.001) BP, but exercise did not blunt these responses (systolic BP: 122 ± 11 mmHg, P=1.0 vs. PSD; diastolic BP: 70 ± 6 mmHg; P=1.0 vs. PSD). Elevations in 24-hour BP were due to elevations in systolic (control: 104 ± 9 mmHg, PSD: 123 ± 12 mmHg, exercise + PSD: 121 ± 13 mmHg, P<0.001) and diastolic (control: 53 ± 7 mmHg, PSD: 71 ± 9 mmHg, exercise + PSD: 71 ± 9 mmHg, P<0.001) BP during the nighttime wakeful period (0000 to 0300 hours). Acute PSD blunted the magnitude of the morning BP surge (control: 24 ± 11 mmHg vs. PSD: 17 ± 8 mmHg , P=0.02) due to elevations in lowest sleep BP (control: 98 ± 7 mmHg vs. PSD: 104 ± 10 mmHg, P=0.007), but exercise did not reverse these responses (morning BP surge: 16 ± 8, P=1.0 vs. PSD; lowest sleep BP: 106 ± 13, P=1.0 vs. PSD). No sex or chronotype differences were observed. Conclusion: These findings suggest that acute PSD has minimal effects on the circadian BP profile in young, healthy adults irrespective of sex and chronotype, and continuous cycling exercise at a moderate intensity is not a sufficient stimulus to attenuate such effects. This research was supported by a Natural Science and Engineering Research Council (NSERC) of Canada Discovery Grant (P.J.M) 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.
Shear rate patterns during flow-mediated dilation in women with endometriosis: preliminary findings
Authors: Kirby Nathalie , Williams Auni , Content Virginia , Wolf S Tony , Dillon Gabrielle , Stachenfeld Nina , Alexander Lacy 
Published: May 2023

Purpose: Endometriosis is an estrogen-dependent gynecological disorder associated with systemic inflammation and arterial stiffness, which may negatively modulate shear stress patterns to promote a pro-atherogenic state, and thus contribute to the elevated cardiovascular disease risk observed in women with the disease. However, shear stress patterns have not previously been examined in this population. Therefore, the purpose of this study was to investigate whether arterial blood flow patterns are altered in women with endometriosis. We hypothesized that women with endometriosis would exhibit disturbed blood flow patterns, characterized by high retrograde shear rates and oscillatory flow as well as reduced anterograde shear rates, as compared with women without the disease. Methods: We examined anterograde and retrograde shear rates, and oscillatory shear index (OSI; |retrograde shear rate|÷[|antegrade shear rate|+|retrograde shear rate|]) in four women with surgically confirmed endometriosis and eight without (mean (SD), 28 (5) years, BMI 24.7 (4.2) kg·m-2) at rest, during hyperemia (60 s post-forearm occlusion at 220 mmHg) and recovery (120-180 s post-occlusion) from flow-mediated dilation using duplex Doppler ultrasound. Shear rates were compared using two-factor (group x phase) linear mixed-effects models with post-hoc corrections for multiple comparisons of three time-points. Results: Endometriosis patients exhibited greater OSI (interaction: p=0.001) at rest (mean difference [95%CI]; 0.095 [0.001, 0.188], p=0.033) and recovery (0.126 [0.034, 0.226], p=0.005), though not during hyperemia ( p>0.999) compared to controls. This was driven by greater retrograde shear (interaction: p=0.013) during recovery (15 sec-1 [2, 28], p=0.002), though retrograde shear did not differ between groups at rest ( p=0.155) or during hyperemia ( p>0.999). Anterograde shear (interaction: p=0.049) was greater in controls than in endometriosis patients during hyperemia (276 sec-1 [61, 613], p=0.026), but not during rest or recovery (both p>0.999). Conclusions: Women with endometriosis exhibited greater oscillatory shear at rest and greater oscillatory and retrograde shear during recovery from flow-mediated dilation, as compared to controls. However, anterograde shear was diminished in endometriosis patients during hyperemia. These data indicate that shear stress patterns are negatively altered in women with endometriosis, which provides novel mechanistic insight into the pathophysiology underlying the associated elevated cardiovascular disease risk. National Institutes of Health Grant R01 HL161000 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.