bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cold-water foot immersion and physiological strain of adults with coronary artery disease during hot and humid heat exposure
Authors: Mornas Adèle , Bettremieux Léa , Sardar Soha , Iglesies-Grau Josep , Capon Tony , Crandall Craig G. , Fiataronesingh Maria 
Published: May 2024

Introduction: Heat extremes are associated with a greater risk of adverse cardiovascular outcomes, especially among adults with coronary artery disease. While air-conditioning provides exceptional protection during heat extremes, it is neither sustainable nor widely accessible. Cold-water foot immersion reduces physiological heat strain in healthy young adults but its effect in more vulnerable populations remains unknown. Objective and hypotheses: This study aims to identify the effect of cold-water foot immersion on markers of physiological heat strain in adults with coronary artery disease. We hypothesized that cold-water foot immersion would reduce physiological heat strain when used on its own and that this effect would be greater when combined with an electric fan. Methods: 17 adults living with stable coronary artery disease (2 females/15 males; 67±8 years) were exposed to a 38°C, 60% relative humidity environment for 3 hours on three separate, randomized occasions: i) no cooling (control; CON); ii) cold-water foot immersion (20 min of immersion each 30 min, ~30 cm in water kept at ~18°C; FI); iii) cold-water foot immersion and fan use (FI+FAN). Rectal and skin temperatures, heart rate (5-lead ECG), and whole-body sweat loss (change in nude weight) were measured. Results: The increase in rectal temperature did not differ between conditions (CON: 0.40±0.24°C, FI: 0.41±0.29°C, and FI+FAN: 0.36±0.22°C; p≥0.49). The increase in skin temperature was reduced with FI and FI+FAN compared to CON (CON: 4.9±0.8°C, FI: 4.1±1.2°C, and FI+FAN: 4.3±0.8°C; p≤0.01), with no difference between FI and FI+FAN (p=0.15). Similarly, the increase in heart rate was reduced with FI and FI+FAN compared to CON (CON: 8±6 bpm, FI: 4±6 bpm, and FI+FAN: 3±6 bpm; p≤0.01), with no difference between FI and FI+FAN (p=0.45). Sweat loss was also reduced by FI and FI+FAN compared with CON (CON: 823±114 g, FI: 544±174 g, and FI+FAN: 671±255 g; p≤0.03), with sweat loss during FI sweat loss being lower than during FI+FAN (p=0.03). Conclusion: The results show that cold-water foot immersion, used alone or in combination with an electric fan, reduces the increase in heart rate and whole-body sweat loss of adults living with coronary artery disease exposed to a hot and humid environment for 3 hours. This could be linked to the lower increase in skin temperature with foot immersion. National Health and Medical Research Council of Australia (APP1147789). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Depressing Ubiquitin-Dependent Proteolysis in a Hibernator Whose Body Temperature Is Normally Variable: The Common Tenrec
Authors: Aviles Hector , van Breukelen Frank 
Published: May 2024

In a canonical mammalian hibernator like a ground squirrel, the cold body temperatures (Tb) of the torpid squirrel depresses protein degradation at the level of the 26S proteasome. Ubiquitylation per se is less temperature sensitive as ubiquitylation rates of colder temperatures continue at 30% to 60% of the maximal rates of warmer temperatures. This leads to an accumulation of ubiquitin-conjugated proteins of 2-3 fold in torpid squirrels as compared to active squirrels. The common tenrec is a bizarre Afrotherian placental mammal with many plesiomorphic traits such as a cloaca, internal testes, indeterminate growth, and the smallest brain of all extant mammals with very little neocortex. Interestingly, these tenrecs may be fully active with a Tb of 12°C or hibernating at a Tb of 28°C. Moreover, oxygen consumption rates may vary 25 fold in active tenrecs. We found expected decreases of 26S proteolytic activity at low temperatures. Capacitance for proteolysis varied by state and there was no evidence that torpor per se would arrest protein degradation. Indeed, in sharp contrast to the squirrel, ubiquitylation rates were essentially unaffected by temperature and ranged at colder temperatures from 80% to 90% of the maximal ubiquitylation rates. In other words, the only in vitro evidence for the control of ubiquitin-dependent proteolysis that we found would only be available to very cold tenrecs independent of if they were active or torpid. However, ubiquitin-conjugate concentrations appear low but unaffected by state. All in all, we hypothesize a ‘Life in the Slow Lane’ model for tenrecs wherein an inability to effectively regulate proteolysis led to a modest rate of degradation that is not as affected by changes incurred by torpor state or changes in Tb. NSF and Department of Education (GAANN). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Distribution and Metabolism of Dietary Nitrate in Porcine Ocular Tissues
Authors: Park Ji Won , Piknova Barbora , Tunau-Spencer Khalid J , Cai Hongyi , Walter Peter J , Jenkins Audrey , Hellinga David G 
Published: May 2024

Extensive recent studies have provided evidence of the important role of dietary nitrates in improving cardiovascular health and enhancing exercise performance. This is generally attributed to the conversion of these nitrate ions (NO3−) obtained from dietary sources into nitrite (NO2−) and subsequently into nitric oxide (NO) within the body. In a prior study, we demonstrated that porcine ocular tissues contain significant amounts of nitrate and nitrite, comparable to those found in the blood. Notably, cornea and sclera exhibited the capability to reduce nitrate to nitrite. In our current study, we sought to gain a deeper understanding of ocular nitrate metabolism. To achieve this, we administered two groups of pigs either NaCl or Na15NO3 orally and evaluated the levels of both total and 15N-labeled nitrate and nitrite in various ocular tissues three hours after Na15NO3 ingestion. We observed a substantial increase in both 15NO3− and 15NO2− in all parts of the eye measured by LC-MS/MS. Particularly, the aqueous and vitreous humor displayed a remarkably high 15NO3− enrichment similar to that of plasma and even higher 15NO2− enrichment than that of plasma. Cornea, sclera, retina and lens also showed notable increases in 15NO3−. The 15NO2− analysis revealed that most eye parts, except aqueous and vitreous humor, had levels similar to those observed in plasma. Furthermore, the total amounts of NO3− and NO2− measured by chemiluminescence in these tissues exhibited patterns consistent with those observed in the 15N analysis. These findings provide valuable insights into the distribution and metabolism of dietary nitrates within ocular tissues, shedding light on their potential roles in ocular health and function. This work was supported by intramural NIDDK/NIH grant ZIA DK 025104-15 to Alan N. Schechter. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Single-Nuclei RNA-Sequencing Uncovers Alterations in the Transcriptional Profile of Skeletal Muscle in Peripheral Artery Disease
Authors: Pass Caroline , Palzkill Victoria , Tan Jianna , Kim Kyoungrae , Thome Trace , Yang Qingping , Fazzone Brian 
Published: May 2024

BACKGROUND: Lower extremity peripheral artery disease (PAD) is caused by atherosclerotic occlusion of lower limb blood vessels, impacting >200 million people worldwide. PAD causes life-altering symptomatology such as claudication, ischemic rest pain, and gangrene, with limited effective treatment options. Herein, we performed single-nuclei RNA-sequencing (snRNAseq) to facilitate a better understanding of the complex pathobiological environment within the PAD limb and intercellular communication. METHODS: Gastrocnemius muscle specimens were collected from 20 patients with PAD and 12 non-PAD controls. Patients with PAD were classified as Rutherford category 3 (severe claudication). Non-PAD participants were of similar age, body mass index and medication usage as patients with PAD. Nuclei were isolated and snRNAseq was performed. Bioinformatic analysis was conducted to determine differences in gene expression between PAD and non-PAD nuclei, as well as analysis of intercellular signaling networks. Histological analysis of muscle specimens assessed the following: myosin heavy chain fiber distributions, myofiber cross-sectional area and myofiber denervation. RESULTS: 57,364 high-quality nuclei were captured (21,417 PAD; 35,947 non-PAD) and unsupervised clustering revealed 12 distinct nuclei populations based on their transcriptional profile. Quantification of the relative abundance of nuclei populations identified several differences, including PAD muscles having a lower percentage of type I myonuclei, muscle stem cells, and endothelial cells but a higher proportion of type II and regenerating myonuclei. Differentially expressed gene analysis of myonuclei populations uncovered upregulation of genes involved in stress response, autophagy, and atrophy in patients with PAD. Ligand-receptor interactions were used to determine how PAD alters the communication between identified nuclei populations. The inferred strength of interactions was greater in non-PAD compared to PAD patients. Further, intercellular communication network analysis revealed fibro-adipogenic progenitors as a primary signaling hub in PAD muscle. CONCLUSION: snRNAseq uncovered novel transcriptional differences and intercellular communication pathways unique to PAD muscle. This study was supported by National Institutes of Health (NIH) grant R01-HL149704 (T. Ryan). K. Kim supported by the American Heart Association grant POST903198. T. Thome supported by NIH grant F31-DK128920. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Sex-dependent benefit of B vitamins on cardiac function and lipid metabolism in a murine model of heart failure with reduced ejection fraction
Authors: David Chloé , Deschênes Sonia , Daneault Caroline , Robillard Frayne Isabelle , Shi Yan Fen , Higgins Marie-Ève , Tardif Jean-Claude 
Published: May 2024

Background: Heart failure (HF) is a global health problem requiring more effective therapeutic alternatives. While HF involves disturbances in cardiac metabolism associated with lipidomic remodeling, there is a lack of approaches to specifically target cardiac metabolism. Recently, it has been shown in murine models of HF, that the use of nicotinamide riboside (vitamin B3) alone or the combination of B9 and B12 vitamins, before the development of HF, improved cardiac metabolism and function. Our hypothesis is that the combination of B3, B9 and B12 vitamins, used when HF is declared, will improve lipid metabolism, cardiac function and survival. The aim of this study is to evaluate the curative benefit of a synthetic diet enriched with the combination of these three vitamins (VitB) in a murine model of HF with reduced ejection fraction (EF). Method: Pressure overload was induced by constriction of the transverse aorta (TAC) in male and female mice. After 4 weeks, TAC mice reaching a pressure gradient of 60 mmHg, an increased left ventricle mass >30% and a reduced EF >10%, were randomized to a VitB-enriched diet or not. Results: In females, VitB improved survival and cardiac hypertrophy (-24%, p<0.05) as well as EF (+22%, p<0.01). We also observed a reduction of cardiac fibrosis emphasized by a significant decrease expression of collagen 1a and 3 (-30% and -19% respectively) and hydroxyproline concentration (-32%, p<0.01). No benefit was observed in males in terms of survival, cardiac function and fibrosis. Untargeted mass spectrometry (MS)-based lipidomics on plasmas at 8 weeks of treatment showed a decrease in several individual triglycerides (TG from 43 to 48 %; p<0.05) in TAC females that were normalized by VitB. In contrast, in TAC males, most of the annotated TGs were increased (from ̴35 to 210%; p<0.05), a profile exacerbated upon VitB treatment. MSMS identification of TG side chains revealed a differential profile in terms of fatty acid composition according to sex and treatment. In VitB females, longer and polyunsaturated TGs (53 to 60C; 5 to 12 double bonds) were significantly increased (1.6- to 2.1-fold) while, in VitB males, the increased TGs (1.2- to 5.2-fold) were shorter (24C to 48C) and saturated (no double bonds). Conclusion: Our study pointed out a sexual dimorphism in the response to VitB treatment in HF in favor of females and implying a lipidomic remodeling promoting cardioprotective polyunsaturated TGs. European Research Area Network on Cardiovascular Diseases, Canadian Institutes of Health Research, Fonds de recherche du Québec - Santé. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effect of dosage duration on oropharyngeal and locomotor in a toxicological rat model of Parkinson’s disease
Authors: Patel Shivam , Wojtas Ireneusz , Gould Francois 
Published: May 2024

Parkinson’s Disease (PD) is a prevalent and devastating neurodegenerative disorder that causes progressively worsening motor symptoms affecting locomotor and oropharyngeal function. There is limited research in animal models on swallowing dysfunction in PD. To examine how neurodegeneration in PD produces progressive impairment in the oropharyngeal and locomotor processes, rotenone, a type II mitochondrial inhibitor, was injected into Lewis rat models to reproduce a parkinsonian phenotype. We hypothesized that the animal models injected with the rotenone will exhibit both oropharyngeal dysfunction and locomotor deficiency with an increased deficit that correlates with prolonged treatment. We utilized 18 rats receiving either 2.75 mg/kg of rotenone or vehicle intraperitoneal injections. Animals received daily injections for 17 or 8 days. At the end of the injections in each group brains were perfused and immunostained for striatal tyrosine hydroxylase (TH). High speed (200 fps) videofluoroscopic recording was taken of these rats and average chew cycle length, chewing rate, and total chewing time data were collected from days 0, 1, 4, 7 and 16 of those recordings. The number of rears by a rat in a glass cylinder over 4 minutes was counted on the same days to assess locomotor behavior. We used mixed model ANOVA, controlling for the effect of individual variation, to test the impact of rotenone treatment on feeding and locomotor variables. We used a Kruskall-Wallis non parametric test to test the effect of rotenone treatment on striatal TH levels. Total chewing time, and average chew cycle duration increased in rotenone treated rats from day 0 to day 4, but the difference disappeared from day 7 onwards. However, rearing behavior was consistently reduced in rotenone treated rats for all 16 days. TH staining intensity in the striatum decreased consistently over the course of the injections. These results suggest that rotenone treated rats have temporary/short term deficiency in chewing function, despite sustained reduction in spontaneous locomotor activity. The restoration of function after day 4 may indicate a learned behavior to compensate for this dysfunction in chewing, or point to a different neurological impairment than that seen in locomotor behavior. Further research needs to be undertaken to understand this phenomenon. Internal Rowan funding to F. Gould supported this work. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Sex differences in a novel transgenic mouse model of Alzheimer’s Disease
Authors: Smith Cassandra N. , Shahab Nusaira Beenta , Weiss Robert M. , Zimmerman Kathy , Yang Liping , Sabharwal Rasna 
Published: May 2024

Alzheimer’s disease (AD) is the most common form of dementia characterized by memory deficits, cognitive impairment, and presence of amyloid plaques and tau tangles in the brain. In the United States, six million people over the age of 65 live with AD, four million of whom are women. The apolipoprotein ( APOE) gene is the strongest genetic risk factor for late-onset AD, with the ε4 allele increasing AD risk relative to the ε3 allele. Mechanisms driving sex-based prevalence in the APOE4 genotype remain unknown. Previously, we have reported that female APOE4 mice develop hypertension and increased levels of vasoconstrictor angiotensin II (Ang II) in CSF with aging [FASEB J 2022: 36S1]. To better recapitulate human AD pathology and phenotype, we have recently generated unique mouse strains - 3XE4 and 3XE3 mice, by breeding human APOE4/APOE3-knockin with APPsw, PS1dE9, and tauP301S transgenes. Our goal is to study sex differences in the 3XE4 mice with AD. Blood pressure (BP, tail cuff), cognition (novel object recognition test), and cardiac function (echocardiography) were measured in both control 3XE3 (n=6) mice and 3XE4 (n=6) mice before and after Ang II (osmotic minipump, 1000 ng/kg/min). As expected, female mice weighed less than the male mice (Table). Basal BP and ejection fraction were higher in male 3XE4 mice compared to female 3XE4 mice (p<0.05). Total exploration time of novel object was significantly delayed in 3XE4 mice (p<0.05); the impairment was greater in the female 3XE4 mice. Notably, Ang II increased BP in male 3XE4 mice (151±5 mmHg) but not in female 3XE4 mice (125±2 mmHg). Unlike the 3XE3 mice, total exploration time of novel object was delayed (impaired) in both male and female 3XE4 mice at baseline and during Ang II. Although additional studies are needed to explore the underlying mechanisms, our results implicate potential sexual dimorphism in blood pressure regulation and cognition in Alzheimer’s Disease. [Formula: see text] Funding: NIH R01HL149677 and R21AG070188. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Motor function is not impaired in all components of the oral phase of feeding in a rat rotenone model of Parkinson’s disease
Authors: Gould Francois , Wojtas Ireneusz , Charles Nicole 
Published: May 2024

Parkinson’s disease results in pathological swallowing, or dysphagia, in up to 90% of cases. Severity and extent of functional impairment of feeding is highly variable in this disease. Feeding is a multi step neuromuscular process of tightly coordinated orofacial behaviors -transport, food reduction, pharyngeal swallowing- involving multiple musculoskeletal systems — tongue, jaw muscles, hyolaryngeal muscles — innervated by multiple cranial and cervical spinal nerves. The type of food being ingested further affects this sequence. The pesticide rotenone, a type II mitochondrial inhibitor, has been epidemiologically linked to Parkinson’s disease. The goal of this project is to identify how parkinsonian neurodegeneration affects this sequence in an animal model. We hypothesize that not all elements of the sequence will be equally affected. Twelve young adult male Lewis rats received daily intraperitoneal injections of either 2.75 mg/kg of rotenone or vehicle control for 8 days. The rats were trained to eat breakfast cereal and drink water mixed with barium in front of a high speed (200 fps) videofluoroscope. From the high speed video recording duration of intraoral transport and chewing of solid food as well as lick duration for liquid drinking were measured for multiple swallows per individual on day 0 (before injection), day 1, day 4, and day 7. On day 8 animals were perfused and brains harvested, sliced, stained with immunofluorescent markers for striatal tyrosine hydroxylase to confirm effectiveness of the model. Mixed model ANOVA was used to test the hypothesis that duration of the phases varied over the course of treatment. Duration of intra oral transport changed in neither control nor rotenone treated animals (p=0.1136), but duration of chewing increased in rotenone treated rats only by day 4 (p<0.001). Duration of licks increased in liquid drinking rats from day 0. Different components of the oral feeding process vary in degree and timing of impairment in the rat rotenone model of Parkinson’s disease, with coordinated rhythmic tongue and jaw movements (licking and chewing) being most sensitive. The neurological basis for this differential sensitivity remains unclear. Internal Rowan funds to Dr. Gould supported this work. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Impact of Aging and High-Fat Diet on Adipose Tissue-Derived Extracellular Vesicle miRNA Profiles in Mice
Authors: Cho Young-Eun , Shaoshuai Chen , Crouch Keith , Yun Joseph , Klingelhutz Aloysius 
Published: May 2024

Background: Middle-aged adults show the highest obesity rates, leading to significant health complications in later years. Obesity triggers the release of altered molecules including extracellular vesicles (EVs) from excess adipose tissue (AT), contributing to various health complications. In this study, we assessed the effects of age and high-fat diet (HFD) on white AT-derived EV miRNA profiles to understand their potential roles in aging and obesity. Hypothesis: Our hypothesis is that the white AT-derived EV miRNA profiles of middle-aged mice fed HFD will demonstrate deleterious features due to the potential synergistic effects of aging and long-term HFD consumption. Method: C57BL/6 male mice were subjected to a normal chow diet (NCD) or a HFD for either 10-12 weeks (young mice, n=10) or 50-61 weeks (middle-aged mice, n=12). After evaluating metabolic characteristics, white AT-derived EV miRNAs were profiled using a NanoString miRNA panel (n=599). Results: Middle-aged mice exhibited obesity regardless of diet. Young mice fed HFD showed similar metabolic traits to middle-aged mice. In NCD group, 131 differentially expressed miRNAs (DE-miRNAs) emerged in middle-aged mice compared to young mice, including miR-21, miR-148a, and miR-29a associated with cancer, neuro/psychological disorders and reproductive diseases. In HFD group, 55 DE-miRNAs were revealed in middle-aged mice compared to young mice. These miRNAs were associated with significantly suppressed IGF1R activity. Conclusion: This study has demonstrated the altered characteristics of WAT EV miRNAs by aging and diet. Aging and diet induce significant changes in EV miRNA profiles of AT. We suggest that there might be a selective sorting mechanism of miRNAs in AT EVs, contributing to the disease progress or pathogenesis related to aging and obesity. We also suggest that AT EVs in middle-aged mice fed HFD might play a protective role in aging and obesity by inhibiting IGF1R activity. University of Iowa College of Nursing. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.