bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifespan Effects of Muscle-specific Androgen Receptor Overexpression on Body Composition of Male and Female Rats
Authors: Barsky Sabrina Tzivia , Monks Douglas Ashley 
Published: May 2024

Androgenic actions of gonadal testosterone are thought to be a major mechanism promoting sex differences in body composition across the lifespan. However, this inference is based largely on studies of androgen receptor (AR) function in late adolescent or emerging adult rodents. Here we assess body composition and quantify AR expression in skeletal muscle of rats at defined ages, comparing wild-type (WT) to transgenic HSAAR rats which overexpress AR in skeletal muscle. Male and female HSAAR and WT Sprague Dawley rats (N=288) underwent DEXA scanning and tissue collection at post-natal day (PND) 1, 10, 21, 42, 70, 183, 243, and 365. As expected, sex differences in body composition and muscle mass largely onset with puberty (PND-21), with no associated changes to skeletal muscle AR protein. In adulthood, HSAAR increased tibialis anterior (TA) and EDL mass in males, and reduced the expected gain in gonadal fat mass in both sexes. In WT rats, AR protein was reduced in soleus, but not TA, throughout life. Nonetheless, soleus AR protein expression was greater in males than females at all ages of sexual development, yet only at PND-70 in TA. Overall, despite muscle AR overexpression effects, results are inconsistent with major sex differences in body composition during sexual development being driven by changes in muscle AR, but rather suggest that changes in ligand promote sexual differentiation of body composition during pubertal timing. Nonetheless, increased skeletal muscle AR in adulthood can be suffcient to increase muscle mass in males, and reduce adipose in both sexes. This work was supported by an NSERC Grant awarded to D.A.M. (RGPIN 312458). 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.
Allometric scaling of the parameters characterizing venous return surface in the generalized framework of circulatory equilibrium
Authors: Sato Kei , Peterson Jon , Uemura Kazunori , Nishikawa Takuya , Yokota Shohei , Matsushita Hiroki , Morita Hidetaka 
Published: May 2024

Study objective: In the generalized framework of circulatory equilibrium (GCE), the integrated cardiac output (CO) curve characterizes the pumping abilities of the left and right hearts, whereas the venous return (VR) surface characterizes the preloading properties of the systemic and pulmonary circuits. Equilibrium CO (= VR), left (PLA) and right (PRA) atrial pressures are predicted from the intersection between the CO curve and VR surface. In VR surface, VR is theoretically related with stressed blood volume (V), PLA and PRA as: VR =V/W − Gs × PRA − Gp × PLA, where Gs and Gp is a ratio of systemic (Cs) and pulmonary (Cp) vascular compliance to W (time constant of the systemic and pulmonary circuits), respectively. However, there was a concern whether the standard parameters can be applicable to animals with different body size including human. The objective of this study is to experimentally investigate whether an allometric scaling of the parameters (Gs, Gp, W, Cs, Cp) of the VR surface is feasible. Hypothesis: Kleiber’s law indicates that an animal's metabolic rate scales to the 3⁄4 power of the animal's body weight (BW). Based on this, we hypothesize that Cs and Cp may be proportionate to BW, W may be proportionate to BW1/4. Hence, Gs and Gp may be proportionate to BW3/4. Methodology: Seven mongrel dogs (BW 26±2.8 kg) and 4 beagles (BW 9±0.5 kg) were anesthetized, and their left and right hearts were replaced by dual mechanical pumps. While V was kept constant, by controlling the speed of the fluid pumps, VR (ml/min), PLA and PRA (mmHg) were changed variably over a wide range to obtain six sets of VR, PLA and PRA. After the change of a known amount of V (4 mL/kg), six sets of VR, PLA and PRA were obtained in a similar manner. Using 12 sets of VR, PLA and PRA, we obtained Gs, Gp, W, Cs, and Cp using regression analysis in each animal. Finally, we analyzed relations between BW and all these parameters using regression analysis over the 11 animals. Data: Gs (r2=0.73, p value for independent variable piv<0.01; p value for intercept, pi=0.57) and Gp (r2=0.81, piv<0.01, pi=0.64) were proportionate to BW3/4. Cs (r2=0.37, piv=0.027, pi=0.40) and Cp (r2=0.61, piv<0.01, pi=0.48) were proportionate to BW. However, W (r2=-0.11, piv=0.90, pi=0.17) was not associated with BW1/4. Summary of results: All parameters characterizing VR surface except for W were significantly associated with BW. W did not show a significant association with BW, potentially due to the low variations of BW. Conclusions: Allometric scaling of VR surface may be feasible and effective in future clinical application of GCE. NTT Research, Inc. 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.
Enhanced DNA Damage Response in a Clade of Long-Lived Bats Resolved Using Chromosome-Length Genome Assemblies
Authors: Vazquez Juan , Lauterbur M Elise , Capel Samantha , Enard David , Buchalski Michael , Sudmant Peter 
Published: May 2024

Lifespan is one of the most variable traits across the entire tree of life, and especially in mammals. Differences in lifespans between closely-related species provides a promising avenue for discovering novel pro-longevity pathways using evolutionary techniques. Previous studies focused on the evolution of longevity-associated traits, such as DNA damage response, have been hampered by a combination of low-quality genomes, low-phylogenetic coverage, or long evolutionary times, all of which can negatively affect their power to detect genes associated with longevity. In order to comprehensively study the evolution of aging and aging-associated traits in bats, we generated chromosome-level reference genomes and primary cell line libraries from a 10-million-year-old clade of 9 California Myotis species spanning a 3-fold range of lifespans. Increases and decreases in longevity independent of body size have evolved multiple times in this clade, providing a dynamic range which can be studied through functional genomics. Leveraging both genomes and cell lines, we identify several pathways specifically associated with longevity, in addition to other longevity-associated traits such as DNA repair and immunity; and show that these changes are associated with cellular resistance to various forms of chemically-induced DNA damage. These pathways represent new targets for exploration using primary cell cultures, and contribute to our understanding of how both agonistic and antagonistic pleiotropy play a role in the evolution of longevity. NSF PRFB 2109915 NIH 5R35GM142916-03. 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 Breathing Room Air Through a Two-Way Non-Rebreathing Valve on HRV in BI and NBI College-Aged Students
Authors: Poff Hannah , Talens Kate , Ehlert Luke , Wiseman Connor , Martino Paul , Miller Daniel P. , Miller Justin 
Published: May 2024

Behavioral inhibition (BI) is a temperament associated with increased vulnerability to stress compared to non-behaviorally inhibited (NBI) individuals. Heart-rate variability (HRV) analysis to assess physiological stress has been growing in popularity due to its association with crucial physiological functions, including cardiac activity, autonomic nervous system activity, and physiologic stress. Previous studies in our lab have demonstrated that HRV in female college-age students expressing a BI temperament is significantly lower than in NBI individuals while breathing room air through a two-way non-rebreathing valve. These findings suggested that the parasympathetic nervous system is partially inhibited at rest in BI females; however, it is unknown if the parasympathetic nervous system in these individuals is inhibited prior to or after breathing through a breathing valve. Our current study will address this question by measuring HRV in BI and NBI individuals while breathing room air for 15 minutes without a breathing valve and for 10 minutes with a two-way breathing valve. Raw electrocardiogram signals will be collected throughout the study protocol and will be used to calculate HRV, which will be measured using a BIOPAC data acquisition system during the experiment. BI individuals will be identified through a series of self-reported questionnaires. Our preliminary results indicate that BI individuals have a lower HRV and are stressed throughout the duration of the study. Thank you to Carthage College's Biology and Neuroscience Department for allowing this research project to be conducted. 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.
Phenotypic Sexual Dimorphism in Response to High Fat Diet in C57BL/6J Mice Lacking Liver Androgen Receptor
Authors: Rahman Md , Andrisse Stanley 
Published: May 2024

Previous research has indicated that liver androgen receptors may play a role in modulating disease. This study aims to investigate the pathophysiology of high fat diet (HFD) induced dysglycemia in male and female liver androgen receptor knockout (LivARKO) mice. We performed metabolic tests on LivARKO female and male mice fed a high fat diet (HFD) or a control diet (CD) (from Research Diets Inc) during months 1 or 2 after starting the diet. Additionally, we performed western blot and qRT-PCR analysis on the livers of the mice to examine intermediates in the insulin signaling pathway. LivARKO-HFD female mice displayed no difference in glucose tolerance compared to female LivARKO-Control mice. Whereas in WT female mice, HFD impaired glucose tolerance (IGT). Our data suggests that starting at one-month LivARKO may be protecting female mice from HFD-induced metabolic dysfunction. LivARKO-HFD female mice displayed significantly worse insulin sensitivity at 15 minutes compared to LivARKO-Control (Con) female mice; but, strangely, LivARKO-HFD female mice had significantly better insulin sensitivity at 60 and 90 minutes compared to LivARKO-Con female mice. Despite protecting against IGT, LivARKO did not protect against HFD-induced hyperinsulinemia (HI) in female mice. In contrast to females, male LivARKO-HFD mice displayed impaired glucose tolerance (IGT) compared to male LivARKO-Con mice. Thus, LivARKO is not protective against HFD-induced glucose metabolic dysfunction in male mice. Lastly, LivARKO-HFD female mice maintained hepatic insulin sensitivity whereas LivARKO-HFD male mice displayed hepatic insulin resistance. These findings suggest that LivARKO delayed the onset of HFD-Induced dysglycemia in female mice. Funding: S.A. grant support from the National Science Foundation (NSF) Inclusion across the Nation of Communities of Learners of Underrepresented Discoverers in Engineering and Science (INCLUDES, HRD-1931045). S.A. grant from the National Institutes of Health (NIH) 1R01DK126892-01A1. 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.
LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension
Authors: Steppan Jochen , wang Huilei , Nandakumar Kavitha , Poe Alan , Pak Lydia , Brady Travis , Gadkari Mahin 
Published: May 2024

Background: Conduit pulmonary arterial stiffening and the resultant increase in pulmonary vascular impedance has emerged as an important underlying driver of pulmonary arterial hypertension (PAH). Given that matrix deposition is central to vascular remodeling, we evaluated the role of the collagen crosslinking enzyme lysyl oxidase like 2 (LOXL2) in this study. Methods and Results: Human pulmonary artery smooth muscle cells (PASMCs) subjected to hypoxia showed increased LOXL2 secretion. LOXL2 activity and expression were markedly higher in primary PASMCs isolated from pulmonary arteries of the rat Sugen 5416 + hypoxia (SuHx) model of severe PH. Similarly, LOXL2 protein and mRNA levels were increased in pulmonary arteries (PA) and lungs of rats with PH (SuHx and monocrotaline (MCT) models). Pulmonary arteries (PAs) isolated from rats with PH exhibited hypercontractility to phenylephrine and attenuated vasorelaxation elicited by acetylcholine, indicating severe endothelial dysfunction. Tensile testing revealed a a significant increase in PA stiffness in PH. Treatment with PAT-1251, a novel small-molecule LOXL2 inhibitor, improved active and passive properties of the PA ex vivo. There was an improvement in right heart function as measured by right ventricular pressure volume loops in-vivo with PAT-1251. Importantly PAT-1251 treatment ameliorated PH, resulting in improved pulmonary artery pressures, right ventricular remodeling, and survival. Conclusion: Hypoxia induced LOXL2 activation is a causal mechanism in pulmonary artery stiffening in PH, as well as pulmonary artery mechanical and functional decline. LOXL2 inhibition with PAT-1251 is a promising approach to improve pulmonary artery pressures, right ventricular elastance, cardiac relaxation, and survival in PAH. This work was supported by a NHLBI grant R01HL105296 (to D.E.B.), a NHLBI grant R01HL148112 01 (to L.S.), two Stimulating and Advancing ACCM Research (StAAR) grants from the Department of Anesthesiology and Critical Care Medicine, JHU (to L.S. and J.S.), NHLBI grants R01HL073859 and R01HL126514 (to L.A.S) and a NHLBI K08 grant K08HL145132 (to J.S.). 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.
Physiopathological Mechanisms of Type 1 Cardiorenal Syndrome Induced by Acute Myocardial Infarction
Authors: Cavalheiro Rollssman , Brognara Fernanda , Aguiar da Silva Carlos Alberto , Castania Jaci , Salgado Helio 
Published: May 2024

Objectives: Cardiovascular diseases are the leading global cause of mortality. Approximately 20 to 31% of acute myocardial infarction (AMI) cases progress to renal dysfunction, indicating concurrent cardiac and renal alterations, characterizing Cardiorenal Syndrome Type 1 (CS1). Therefore, this study evaluates the CS1 onset and progression three days after AMI by examining renal and cardiac function and their inflammatory responses. The study hypothesizes that inflammatory mediators are a key component contributing significantly to the onset and progression of CS1 pathophysiology. Methods: Male Sprague-Dawley rats (250-300g) were divided into AMI-SHAM (undergoing sham surgery for AMI) and AMI (left coronary artery ligation) groups. Samples were collected three days post-AMI from blood, urine, heart, and renal tissues. Assessments included osmolality (plasma and urine), creatinine (plasma and urine), glomerular filtration rate (GFR), and tissue cytokine levels. Left ventricular end-diastolic pressure (LVEDP) represented cardiac function. Results are presented as mean ± standard error. Results: LVEDP measurements (mmHg) demonstrated similar results from SHAM (5.89 ± 0.61, n=14) and AMI groups (6.38 ± 0.43, n=6). Tumor Necrosis Factor-Alpha (TNF-α) levels (pg/mg of tissue) from the heart [SHAM (2.74 ± 0.50, n=10) vs AMI (5.05 ± 0.83, n=8)] and renal tissue [SHAM (2.37 ± 0.69, n=7) vs AMI (5.53 ± 0.41, n=5)] were significantly different (p<0.05) concerning their respective groups. Of note, molecular biochemical analyses revealed similar results. Plasma Osmolality (kgH2O): SHAM (310.8 ± 5, n=13) vs AMI (310.4 ± 2.57, n=10); Urinary Osmolality: SHAM (1653 ± 140, n=14) vs AMI (2054 ± 166.9, n=9); Plasma Creatinine (mg/dL): SHAM (0.35 ± 0.21, n=14) vs AMI (0.39 ± 0.25, n=10); Urinary Creatinine: SHAM (118.9 ± 12.35, n=14) vs AMI (126.5 ± 18.90, n=10). GFR (mL/min/100g) was also similar: SHAM (1.22 ± 0.18, n=14) vs AMI (1.22 ± 0.12, n=9). Conclusions: The study shows that the increase of TNF-α is contributing to the onset and progression of the pathophysiology of CS1, in line with the original hypothesis. On the other hand, because the three-day post-surgery timeframe addressed the primary mechanisms triggering the CS1, it seems that the functional impairment of the heart and kidneys was not manifest yet. Support or Funding Information: FAPESP Process 2020/06043-7. CNPq Processes 306994/21-6 and 423999/21-4; FAEPA; CAPES/PROEX. 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.
Maternal Exercise Improves Infant Mesenchymal Stem Cell Lipid Storage and Oxidation, and Decreases Infant Adiposity
Authors: Claiborne Alex , Jevtovic Filip , Zheng Donghai , Biagioni Ericka , Wisseman Breanna , Krassovskaia Polina , Collier David 
Published: May 2024

Rates of pediatric obesity are continuously rising and are likely to translate into high incidence of metabolic disease later in life. Maternal exercise during pregnancy has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to a multitude of infant peripheral tissue (e.g., skeletal muscle) and remain involved in mature tissue repair and maintenance. Importantly, these cells preserve the phenotype of an offspring donor and represent a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC collected during a randomized controlled trial to investigate if maternal exercise, regardless of exercise mode, affects infant adiposity and fatty acid oxidation. Compared to control, we observed >160% higher neutral lipid content in Ex-MSCs (p<0.01). However, this finding was coupled with significantly higher complete fatty acid oxidation to CO2 and lower incomplete fat oxidation (ASM production) in Ex-MSCs (p≤0.05). Infants in the exercise group had significantly lower body fat percentage compared to same age infants of controls at one month of age (p≤0.05). There was no difference in lean body mass volume (p>0.05) or infant one-month BMI (p=0.069). Together, these data indicate that maternal exercise exposure in utero is still associated with decreased infant adiposity one month after birth. MSC lipid content was positively associated with maternal fitness and exercise volume (p<0.01) during pregnancy. Finally, an increase in average maternal exercise volume (MET*min/wk; r=-0.4, p≤0.05) and total gestational MET*min (r=-0.36, p≤0.05), but not VO2max (p=0.07) was associated with infant 1-month body fat percentage. Together, these data showcase the influence of maternal exercise exposure on improvements in cellular metabolism and at 1 month of age. Collectively, our data suggests that exposure to maternal exercise could contribute to lower adiposity in early infancy. This project was supported by the American Heart Association (18IPA34150006 to L.E.M.). 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.
Canine Cognitive Dysfunction Is Associated with Alzheimer’s Disease-Related Changes in the Brain Transcriptome and RNA Changes in Plasma Extracellular Vesicles
Authors: Osburn Shelby , McEntee Cali , McGrath Stephanie , Moreno Julie , LaRocca Thomas 
Published: May 2024

Chronic, age-related diseases, such as Alzheimer’s disease (AD), can be diffcult to study longitudinally because humans have long lifespans and are highly heterogeneous. Recently, companion dogs have emerged as a promising model of AD because dogs: a) have a shorter lifespan than humans; b) are heterogeneous like humans; c) exposed to diverse human environments; and d) naturally develop canine cognitive dysfunction (CCD), similar to AD. However, the transcriptomic similarities between AD and CCD have not been evaluated, and emerging mechanisms of AD have not been explored in dogs. One such mechanism involves extracellular vesicles (EVs), ~100nm lipid bilayer particles that can package neurodegeneration-relevant cargo (e.g., RNAs, cytokines), export it to other cells, and contribute to aging/AD-relevant processes like inflammation. To better understand CCD and determine if EVs may play a role in it, we generated total transcriptome (RNA-seq) on cortex tissue and EVs isolated from plasma of young, old, and CCD dogs, and we evaluated cytokine expression in corresponding plasma samples via ELISAs. In the animals we studied, we observed functional differences between old healthy and CCD animals, reflected by Canine Dementia Scale scores (CADES; 6 and 57, respectively). In our RNA-seq analyses, we found marked age- and CCD-related transcriptome differences in the cortex (328 and 2673 differentially expressed genes, respectively), which mostly reflected changes in immune activation and neuronal health (similar to what has been observed in AD). Moreover, when we overlapped transcriptome data on the cortex and plasma EVs, we found a significant overlap in genes that were either up- or down-regulated in both samples (344 and 515, respectively). The processes related to these genes reflected changes in regulation of immune responses, as well as synaptic signaling. We also found evidence of CCL5 (RANTES, increased in AD) RNA in plasma EVs only in CCD samples, which corresponded with increased CCL5 expression in the brains of the same animals, although no differences were observed in plasma concentrations. While preliminary in nature, these results suggest that CCD is associated with AD-like transcriptomic changes in the brain, and with AD-relevant changes in EV cargo. Future studies are needed to determine the functional relevance of these data, but our results suggest the possibility of finding specific EV/RNA markers that could predict disease severity in CCD, and perhaps eventually in AD. NIA R01AG078859; CSU Catalyst for Innovative Partnership Award. 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.