bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy is inhibited in hypertrophied skeletal muscle in response to 8 weeks of progressive resistance exercise
Authors: kwon insu , Jang yong‐chul , Cho Joon‐Yong , Lee Youngil 
Published: November 2023

Although autophagy induced by endurance exercise is a catabolic adaptive process by which muscular biochemical and morphological alterations occur, the effects of resistance exercise used for enhancing anabolic processes on autophagy have not been clearly understood. Here, we showed that while 8 weeks of rigorous resistance exercise significantly increased muscle mass and strength, autophagy was repressed. Twenty male Wistar rats (age: 6 weeks) were randomly divided into two groups: sedentary control (SC, n=10) and resistance exercise (RE, n=10). After familiarized with ladder climbing, RE group performed the ladder climbing exercise as a resistance exercise (3 times/week for 8 weeks with progressively reinforced intensity). 48 hours after the last session of training, Flexor Digitorum Profundus (FDP) muscles were excised, weighed, and homogenized for western blot analysis. We found that the relative muscle mass in concordance with weight carrying capacity was significantly increased in RE group. Effective training stress was proved by increases in heat shock protein 72 (HSP72) and an antioxidant protein MnSOD levels, respectively. Intriguingly, we observed that RE antagonized an autophagic process evidenced by a decline in LC3 II/I ratio and an increase in p62 levels and that this phenomenon occurred without the alterations of Beclin‐1 and BNIP3 levels. To examine why RE dampened autophagic flux, we measured levels of LAMP2 and TFEB, a master regulator of lysosomal biogenesis and found that neither TFEB nor LAMP2 levels were changed. Interestingly, however, an active form of Cathepsin L level was markedly suppressed in RE group compared to SC. Taken together, our study suggests that muscular hypertrophy by RE is inversely related to autophagy possibly by inhibiting lysosomal degradation process.Support or Funding InformationThis project was supported by a grant from the University of west Florida through the Office of Research and Sponsored Programs.
Chronodisruption and Pregnancy
Authors: Gezahegn Beakal Meseret , Martin‐Fairey Carmel , England Sarah 
Published: November 2023

Circadian rhythms are endogenous entrainable oscillations of approximately 24 hours. The tissues of the female reproductive system, from preovulation to parturition, are regulated by circadian rhythms. Studies have shown that disruptions of circadian rhythms during pregnancy result in adverse maternal (preterm birth and miscarriage) and fetal outcomes (impaired cognition). We hypothesize that knockout of chief circadian clock genes Per1/Per2, Clock, vasoactive intestinal polypeptide (VIP), and vasoactive intestinal polypeptide receptor (VIPR2) will decrease gestation length and impair offspring cognition. To test our hypothesis, we used C57BL/6 mice (WT) and mice deficient Per1/Per2, VIP, and VIPR2. These mice were blindly monitored throughout their pregnancies in a 12 hour light/dark cycle, with lights turning on at 7:00 AM and off at 7:00 PM. Archival data on mouse birth records did not provide a refined temporal resolution, but research in our laboratory indicates shorter gestation lengths in Per1−/−/Per2−/−knockout mice when mating was more discretely timed, with 1‐minute resolution. Preliminary results also show a difference in the frequency of certain behaviors attributed with sleep between genotypes. Mice that are either advanced or delayed in their cycles showed an uncharacteristic onset of sleep, occurring well before lights turned on. Other mice showed significant differences in frequency of behavior associated with wakefulness. This and further monitoring could help us get closer to understanding the link between circadian rhythms and the timing of birth.Support or Funding InformationAcknowledgements: Thank you to the Herzog Lab and the England Lab at Washington University, as well as APS STRIDE Undergraduate Summer Research Fellowship, supported by the American Physiological Society and a grant from the National Heart, Lung and Blood Institute (NHLBI; 1 R25 HL115473‐01), and March of Dimes.
Placental pathology, corticotropin‐releasing hormone (CRH), and fetal growth in the Pregnancy Outcomes and Community Health (POUCH) cohort
Authors: Perng Wei , Talge Nicole M. , Senagore Patricia K. , Holzman Claudia 
Published: November 2023

ObjectiveTo examine the associations of five histopathology‐based placental pathology constructs (maternal vascular – obstructive [MVO]; fetal vascular – obstructive [FVO]; maternal vascular – disturbance of integrity [MVI]; fetal vascular – disturbance of integrity [FVI]; maternal vascular – developmental [MVD]) and second trimester corticotropin‐releasing hormone (CRH) levels with birthweight‐for‐gestational age z‐score (BW/GA).MethodsWe studied 1,154 women in the Pregnancy Outcomes and Community Health (POUCH) study, a community‐based pregnancy cohort in Michigan. Using survey weights to account for the POUCH sampling scheme, we conducted multivariable linear regression to quantify differences and 95% confidence intervals (CI) in BW/GA with respect to evidence of placental pathology (yes vs. no), while also accounting for pre‐pregnancy BMI, race, gestational diabetes, and smoking habits.ResultsMedian age at enrollment was 26.7 ± 0.2 years. The majority (67.3%) of women were White, and 22% were African American. Mean ± SD BW/GA was 0.13 ± 0.04. In the overall sample, only MVO was associated with BW/GA (−0.53 [95% CI: −0.76, −0.31]). Stratification by preterm delivery status (n = 286 vs. 868) revealed that MVO corresponded with lower BW/GA in both term (−0.52 [95% CI: −0.77, −0.28] z‐scores lower BW/GA) and preterm births (−0.59 [95% CI: −0.99, −0.19] z‐score lower BW/GA), while FVO was related to lower BW/GA among preterm births only (−0.42 [95% CI: −0.72, −0.13] z‐scores). We observed evidence for effect modification by CRH for MVO, FVO, and FVI among preterm births, thus we further explored relations of CRH (Q1 as lowest, Q2+3 as referent, Q4 as highest) with BW/GA by placental pathology status, only among preterm deliveries. Among mother‐infant dyads with MVO and FVO, higher CRH was associated with 0.80 (95% CI: 0.07, 1.53) and 1.05 (95% CI: 0.51, 1.59) z‐scores lower BW/GA as compared to their counterparts with CRH in the middle quartiles. Among participants with FVI, lower CRH was associated with 0.53 (95% CI: 0.12, 0.95) z‐scores higher BW/GA.ConclusionsOur findings suggest that (1) maternal vascular obstructive complications are related to poor intrauterine growth regardless of preterm birth status, and (2) high CRH may be a biomarker of poor intrauterine growth in pregnancies that culminate in preterm delivery and exhibit placental pathology related to obstruction of the maternal and fetal circulations.
Association between Hormonal Contraceptive Use and Prevalence of Premenstrual Symptoms
Authors: Jarosz Alicia Caroline , Jamnik Joseph , El‐Sohemy Ahmed 
Published: November 2023

BackgroundHormonal contraceptive (HC) use may be associated with a reduction in some premenstrual symptoms, however, the evidence remains equivocal.ObjectiveTo determine the prevalence of premenstrual symptoms in a multiethnic population of women and to investigate the association between hormonal contraceptive use and premenstrual symptoms.Methods1048 women aged 20–29 years participating in the Toronto Nutrigenomics and Health Study provided data on their premenstrual symptoms and HC use. Severity of symptoms was classified as none, mild, moderate, or severe. Frequencies of premenstrual symptoms were determined as a total and by ethnicity. Logistic regressions were used to calculate the odds ratio (OR) and 95% confidence interval (CI) to analyze the associations between symptoms and use of HCs, adjusting for ethnicity.ResultsThe prevalence of individual symptoms differed as follows: cramps (75%), bloating (74%), mood swings (72%), increased appetite (64%), acne (61%), fatigue (55%), sexual desire (50%), anxiety (35%), desire to be alone (33%), depression (28%), headache (26%), confusion (21%), clumsiness (15%), nausea (15%), and insomnia (11%). Prevalence of cramps, bloating, acne, sexual desire, headache, confusion, and nausea differed between ethnicities (P<0.05). For example, cramps were reported by 79% of Caucasians and 84% of South Asians, but only 67% of East Asians. The OR (95% CIs) for experiencing the following moderate/severe symptoms in women using HCs compared with those not using HCs were: cramps 0.48 (0.33–0.70), fatigue 0.64 (0.44–0.95), depression 0.35 (0.19–0.65), desire to be alone 0.32 (0.18–0.58), clumsiness 0.22 (0.06–0.74), confusion 0.21 (0.08–0.54), and anxiety 0.41 (0.24–0.70). Premenstrual symptoms of acne, mood swings, bloating, increased appetite, headache, insomnia, nausea, and sexual desire were not associated with HC use.ConclusionThis study demonstrates that the prevalence of premenstrual symptoms varies widely between symptoms and ethnicities. Our findings also indicate that HC use is associated with a lower risk of experiencing many, but not all premenstrual symptoms.Support or Funding InformationResearch support: A.C.J. is a recipient of a Natural Sciences and Engineering Research Council Graduate Scholarship
Characterization of Basal and Stimulated Gnrhr Expression in Pituitary Cells
Authors: Janjic Marija M , Bjelobaba Ivana , Tavcar Jovana , Kucka Marek , Tomic Melanija , Stojilkovic Stanko 
Published: November 2023

Gonadotropin‐releasing hormone (GnRH) is a potent stimulus for expression of multiple genes in pituitary gonadotrophs, including the gene encoding GnRH receptor (Gnrhr). Here we examined the signaling pathways accounting for Gnrhr expression in vitro, using primary cultures of rat and mice anterior pituitary cells and mouse immortalized LβT2 gonadotrophs. After removal of anterior pituitary glands and cell dispersion, there was decay in Gnrhr expression, which progressed in cultured cells, with the rates not affected by substitution of horse or fetal calf serum with BSA and by application of a GnRHR antagonist. The decay in gene expression reached a steady state level during 40–50 h incubation to about 20% of that observed in vivo and the residual expression was termed basal. Pulsatile as well as continuous application of GnRH restored, at least partially, Gnrhr expression in a time‐dependent manner, with a peak in expression after about 6 h of application. In pituitaries from neonatal and infantile animals, the profiles of GnRH‐induced responses were similar in females and males and the amplitudes of responses were low. During juvenile to postpubertal period, the profiles of GnRH‐induced gene expression were also comparable in cells from both sexes, but the amplitudes of responses were several‐fold higher in female cells. GnRH‐stimulated Gnrhr expression was independent of cAMP‐PKA signaling pathway and was mediated by calcium and protein kinase C signaling pathways; downstream elements of protein kinase C pathways included ERK1/2 but not JNK, p38, or big MAPK. In naïve LβT2 cells (never previously stimulated with GnRH), there was also a substantial basal Gnrhr expression not affected by removal of fetal calf serum for 24 h and by application of a GnRHR antagonist; these cells also expressed functional GnRHR, as indicated by GnRH‐induced calcium signaling. However, application of GnRH was unable to elevate gene expression in LβT2 cells. Pharmacological activation of cAMP‐protein kinase A, calcium, and protein kinase C signaling pathways were also ineffective. On the other hand, basal Gnrhr expression was reduced by inhibition or depletion of classic protein kinase C isozymes in both normal and immortalized pituitary cells. These results indicate that Gnrhr expression is operative in the absence of any hormonal stimulation, probably reflecting intrinsic protein kinase C activity. Physiologically, such activity secures the presence of sufficient number of functional GnRHR needed to up‐regulate Gnrhr expression and initiate the expression of signature and other genes once GnRH is available.Support or Funding InformationThis work was supported by the Intramural Research Program of the National Institute of Child Health and Human Development (ZIA DH000195‐22).
Replacing pork and chicken with herring (Clupea harengus) increases plasma glucosamine and decreases carbon flux through the citric acid cycle in overweight men and women
Authors: Ross Alastair , Vincent Andrew , Savolainen Otto , Lindqvist Helen , Lind Mads V , Sandberg Ann‐Sofie 
Published: November 2023

Many national nutrition recommendations recommend reducing meat intake and increasing fish intake, due to the association between higher fish intake and reduced risk of cardiovascular disease. Although many studies have looked at the health benefits of the n‐3 fatty acids abundant in fatty fish, few intervention studies have investigated the short‐term effects of replacing meat with fish. As part of a wider series of studies revisiting the comparative effects of meat and herring on human metabolism, we used GC‐MS/MS metabolomics to investigate the effects of replacing lean chicken and pork with herring in overweight and obese adults. In a researcher blinded randomised crossover study, eleven subjects ate five frozen meals/wk over 4 wk, with the frozen meals containing 150 g each of either pork or chicken fillets, or herring fillets. The diets were similar in macronutrient content except for a higher amount of fat in the herring meals. Major metabolic changes observed in plasma were that glucosamine, glutamine and ornithine concentrations increased after the herring diet (all p<0.05 after four wk), while chicken and pork led to increases of agmatine, citric acid, isocitric acid and oxalic acid (all p<0.05 after four wk). Glucosamine is commonly associated with better joint health, though we are unaware of any association between increasing plasma concentrations of glucosamine and lower incidence of joint‐related diseases or complaints. Chicken and pork increased concentrations of citric and isocitric acid, while herring increased glutamine, suggesting that these two different diets had an effect on central carbon metabolism, with a differential regulatory effect at α‐ketoglutaric acid. A further effect was evident on arginine metabolism, possibly related to flux through the urea cycle, based on higher concentrations of arginine/ornithine after the herring diet, while chicken and pork increased agmatine, an arginine metabolite via arginine decarboxylase. An additional finding was that methyl histidine, previously suggested to be biomarker of meat intake in urine, was found to be higher after two weeks of the chicken and pork diet (p=0.003), though this was no longer significant after four wk (p=0.05). These findings add to our understanding of the wider effects of both fish and meat on human metabolism beyond effects on lipids and underline the importance of protein choice on health.Support or Funding InformationThis work was supported by a Chalmers Life Sciences Area of Advance Grant to A Ross and by grants from Region Västra Götaland, the Swedish National Board of Fisheries (Dr 223‐2451‐01), The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) (Grant No 2001‐1246).
The Role of Tight Junction Membrane Dynamics in the Serine Protease‐Induced Increase in Epithelial Barrier Function
Authors: Ronaghan Natalie Jane , Colarusso Pina , Shen Le , Turner Jerrold R. , MacNaughton Wallace K. 
Published: November 2023

One of the main contributors to intestinal epithelial barrier function is the composition of the tight junction (TJ) between epithelial cells. In IBD, inflammatory mediators induce disruption of the TJ and may contribute to pathogenesis. We have found that the apical addition of the serine proteases trypsin and matriptase to colonic epithelial cell lines induces a rapid and sustained increase in barrier function. However, the mechanism is incompletely understood. Tight junction proteins are continuously trafficked in and out of the junction to maintain and modulate barrier properties. We aimed to determine if serine proteases alter tight junction dynamics in the membrane using fluorescence recovery after photobleaching (FRAP). Previous studies using siRNA suggest that occludin is an important TJ protein in the serine protease‐mediated increase in TER. EGFP‐occludin was stably expressed in SCBN intestinal epithelial cells, plated on transwells and mounted on a Live Cell Instruments flow chamber, placed on a closed Olympus FV1000 confocal microscope at 37°C, and the chamber perfused continuously on the apical side with heated Krebs that was equilibrated with 5% CO2. Triplicate baseline FRAP runs were conducted along the junction between two epithelial cells strongly expressing EGFP‐occludin. Cells were then perfused apically with trypsin for 15 minutes, and then follow‐up triplicate FRAP experiments were conducted. The mobile fraction, half time of recovery, and direction of recovery were then determined. FRAP recovery curve analysis shows SCBN cells treated with trypsin exhibit significantly increased EGFP‐occludin in the photobleached area after 90 seconds of recovery compared to untreated cells. The mobile fraction is increased but not significantly different (before treatment 58.08 ± 6.99% and after trypsin treatment 73.35 ± 4.59% (SEM) p=0.1164 n=6). Half time of recovery is also not changed (before trypsin 100.8 ± 8.6s and after trypsin 82.42 ± 10.4s p=0.279). From observation and kymograph analysis, there was also no change in direction of occludin recovery, which was from the lateral membrane, after serine protease treatment. Our results suggest that serine proteases may induce an increased trafficking of occludin into the membrane, or change how occludin binds to other tight junction proteins. Future experiments will investigate phosphorylation and binding of occludin with other TJ proteins and the change in membrane dynamics of other TJ proteins such as ZO‐1, tricellulin, and claudin‐1.Support or Funding InformationCIHR, NSERC
The Coordination of Cough and Swallow Behaviors in Humans
Authors: Brown Edward H. , Aslan Sevda C. , Ovechkin Alexander V. , Pitts Teresa 
Published: November 2023

It is not currently known if the coordinated motor control of cough and swallow behaviors described in animal models is preserved in humans. We hypothesized that similar relationships exist, namely the increased muscle activation and decreased swallow duration during combined cough and swallow behaviors. Young healthy individuals were recruited, and during the experiments voluntary cough was elicited by asking subjects to cough “like there was something stuck in their throat” and continue until instructed to stop. Swallow was initiated by infusing 3 ml of water into the subject's mouth and instructing them to “swallow whenever you need to.” Cough and swallow were elicited individually as well as together to mimic an “aspiration” response. Cough excitability was measured by recording the airflow taken from the mouth and surface electromyographic (sEMG) activity from the 6th intercostal, rectus abdominus, abdominal obliques, and submental muscles. Swallow excitability was measured by submental sEMG. All subjects produced multiple cough epochs and swallows to the stimuli. In the combined condition swallows occurred during the inter‐bout interval, with increased intercostal and abdominal drive during cough; and an increased submental drive during swallow. These results confirm the theory of a highly cooperative airway protection system in the human. Furthermore, this model could be used as a novel diagnostic tool for dysphagia/dystussia, eliminating the ceiling effect of a single cough trial. Supported by HL 111215, HL 103750, and P30‐GM103507.Support or Funding InformationSupported by HL 111215, HL 103750, and P30‐GM103507.
Does maternal omega‐3 supplementation have beneficial effect on control of breathing in rat pups?
Authors: Baldy Cécile , Tenorio‐Lopes Luana , Mercier Océane , Pothier‐Piccinin Olivier , Seaborn Tommy , Marc Isabelle , Kinkead Richard 
Published: November 2023

AIMPreterm infants present respiratory instabilities and apneas owing to immaturity of the neural circuits that control breathing. Immaturity of respiratory reflexes such as the hypoxic ventilator response (HVR) and laryngeal chemoreflex (LCR) contribute to respiratory disorders in newborn. Fatty acids omega‐3 (Ω‐3) benefits brain development in several ways, including a reduction of neural inflammation. Thus, we tested the hypothesis that Ω‐3 supplementation (via maternal diet) improves respiratory control in rat pups.METHODSExperiments were performed on male and female pups (10–11 days old). Pups received Ω‐3 supplementation from an enriched maternal diet (13g/kg of Ω‐3) from birth to day 10–11. Mothers of control pups received a standard diet (3g/kg of Ω‐3) Whole body plethysmography was performed on intact, unanesthetized pups to measure breathing and metabolic responses at rest and during hypoxia (12% O2; 20min). To evaluate performance of chemoreflexes without the confounding effect of a metabolic response, we also compared the duration of LCR‐induced apneas in anesthetized pups. Immunolabeling (Iba‐1) of microglial cells was used to evaluate the effect of Ω‐3 supplementation on capacity for neuroinflammation in the brainstem.RESULTSBy comparison with controls, maternal Ω‐3 supplementation effectively raised Ω‐3 levels in the blood and brainstem. In awake pups, Ω‐3 increases the apnea index and metabolic rate, especially in females. Both males and females increase the HVR compared to their controls and decrease the drop in body temperature during hypoxia. In anestethized pups, Ω‐3 reduced 32% the apnea duration elicited by LCR stimulation. Finally, the number of microglia cells in caudal NTS was lower in Ω‐3‐supplemented pups.CONCLUSIONΩ‐3 supplementation generally improves reflexives ventilatory and metabolic responses. However, the higher apnea frequency observed at rest suggests that the effects of Ω‐3 are not homogeneous. The reduced capacity for neuroinflammation (as indicated by the reduced number of microglial cells) may contribute to the beneficial effect of Ω‐3.Support or Funding InformationThis research was supported by CIHR (RK and IM).