bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Three Bovine Plasma Protein Fractions on the Human Gut Microbiota
Authors: Okerlund Adam , Van den Abbeele Pieter , Detzel Christopher , Rose Alexis , Deyaert Stef , Baudot Aurélien , Warner Christopher 
Published: May 2023

The gut microbiome plays a crucial role in the health of its host by regulating metabolism and protecting against pathogens. One of the key functions of the gut microbiome is to produce short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. Though each SCFA has distinct health benefits, all SCFAs have anti-inflammatory effects and decrease the pH of the colonic lumen which increases mineral absorption and inhibits the growth of pathogens. Previous studies show that various fractions of bovine plasma positively impact the gut health, though their effect on the microbiome and SCFA levels is unknown. The objective of our study is to examine the effect of different bovine plasma fractions (whole plasma, crude bovine serum albumin [BSA], and immunoglobulins [SBI]) on the SCFA composition of the gut microbiome. We hypothesize that the bovine plasma fractions will alter the microbiome with an increase of SCFA abundance, with each of the three fractions performing uniquely.SIFR technology (Cryptobiotix) was used to investigate the effects of the three plasma products on the fermentation of fecal microbiota samples provided by six donors. Each protein fraction was subjected to oral, gastric, and small intestinal digestion, simulated small intestinal absorption, and colonic fermentation. Samples were analyzed by examining metabolic activity metrics, including the pH, gas levels, abundance of various SCFAs and branched-chain fatty acids (BCFAs), and microbial composition by quantitative 16S rRNA gene profiling. The addition of any of the three bovine plasma fractions (5 g) showed significant changes in microbial activity, including the increase in acetate, propionate, and butyrate (p < 0.001), with the addition of SBI having the largest effect, followed by whole plasma then BSA. The increase in the SCFAs was accompanied by an increase of bacteria known to produce SCFAs for all dosed protein fractions, with the SBI fraction giving significant increases in Firmicutes (p < 0.05) and Bacteroides (p < 0.01) compared to the blank. Overall, the addition of bovine plasma fractions into an in vitro gut model increases SCFAs, including acetate, propionate, and butyrate, with SBI showing the largest impact. Though SBI is known to bind and neutralize opportunistic pathogens by immune and steric exclusion mechanisms in the gut, this work suggests that SBI further promotes gut health by increasing SCFAs and the bacteria that produce them. Commercial - Proliant Health and Biologicals funded the research. 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.
PCAF regulates cardiac muscle function via non-epigenetic regulation of ACTA1 acetylation
Authors: Habibian Justine , Evans Levi , Ferguson Bradley 
Published: May 2023

Historically, lysine acetylation has been studied in the epigenetic regulation of gene expression, in which it is known to play key roles in cardiac remodeling and dysfunction. However, recent evidence suggests that non-histone protein acetylation of myofilament proteins is also important for the regulation of cardiac contractility and relaxation. Lysine acetyltransferase (KAT) enzymes serve as writer proteins to acetylate histone and non-histone proteins. PCAF (p300/CBP associated factor) belongs to the GNAT family of lysine acetyltransferases and has been implicated in left ventricular hypertrophy (LVH), in which pharmacological inhibition of PCAF attenuated stress-induced LVH that was linked to changes in gene expression. Consistent with these reports, we show that garcinol, a p300/PCAF inhibitor, attenuated 2-weeks of isoproterenol-induced LVH, cardiac output (CO) and stroke volume (SV) in C57BL6J mice. Of interest, isoproterenol increased skeletal muscle alpha actin (ACTA1) protein acetylation in the left ventricle (LV) of mice and this was attenuated by garcinol treatment. ACTA1 is a fetal gene that is re-expressed in the myocardium of diseased hearts. These data imply that KATs acetylate (i.e. post-translational modification) this re-expressed gene, yet how acetylation of ACTA1 impacts cardiac function remains unclear. To determine this, we performed tail-vein injections of an adeno-associated virus (AAV) expressing either LacZ or an ACTA1 acetyl-mimic and performed echocardiography and gross morphology measurements in C57BL6J mice two-weeks post injection. Here, we report that pseudo-acetylation of ACTA1 increased LVH, and reduced fractional shortening (FS) and ejection fraction (EF) in mice. Lastly, we show that PCAF acetylated ACTA1 but not cardiac myosin; p300 failed to acetylate ACTA1 in vitro. Combined, these data suggest that PCAF acetylates ACTA1 to regulate cardiac contractility in response to β-adrenergic over-activation. While PCAF can serve as an epigenetic regulator of gene expression, these data highlight a non-epigenetic role for PCAF in cardiac function. Funding: This research was funded by the USDA NIFA (Hatch-NEV00767), the Dennis Meiss & Janet Ralston Fund for Nutri-epigenetic Research, the National Institute for General Medical Sciences (NIGMS) of the NIH (P20 GM130459), the National Heart, Lung, and Blood Institute of the NIH (R15 HL143496), National Institute of Aging of the NIH (R21 AG077248) and NSF EPSCOR Track II (OIA-1826801) to B.S.F. 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.
Dependence of cardiomyocyte force, velocity, and power generation on ATP concentration
Authors: Beard Daniel , Baker Anthony , Jezek Filip 
Published: May 2023

Theoretical analysis and computer modeling of myocardial energy metabolism under physiological and heart failure conditions predicts that cytoplasmic ATP and ADP levels both fall roughly in proportion to reductions in total adenine nucleotide pool observed in heart failure. Assessing sub-maximal force and velocity in loaded myocardial muscle at MgATP levels in the range of 2 to 8 mM, Beard et al. ( Biophys. J. 2022. 121: 3213–3223) observed effects of MgATP on myocardial power generation that suggest that although maximal force and velocity are not substantially sensitive to differences in [MgATP] that occur in the normal versus failing myocardium, maximal power generation, which occurs at submaximal force and velocity, is sensitive to [MgATP]. Previously developed computational models are not able to reproduce the observed dependence on MgATP. The goals of the present study are to construct and analyze a computational model of muscle dynamics to analyze data on the dependence of maximal force, velocity, and power generation on [MgATP] in order to determine a potential mechanism to explain the MgATP-dependent phenomena. Model development and identification was guided by dynamic measurements on permeabilized mouse trabecular fibers. The data include force-velocity relation and time constant of tension development. The mathematical model used to simulate cardiomyocyte crossbridge mechanics was based on the previous crossbridge and calcium models from Tewari et al. (J Mol Cell Cardiol, 2016. 96: 11-25) and Campbell et al. (Biophys J, 2018. 115: 543-553). The developed model includes strain- and metabolite-dependent transition between attachment states, and ATP-dependent destabilization of the super-relaxed (SRX) myosin state. Model-based analysis of force and velocity dyanmics is consistent with the hypothesis that ATP assocition with the myosin protein influence the kinetics and thermodynamics of transitions between the SRX and disorded (DRX) states. Funding: Department of Veterans Affairs Merit Review Award I01BX000740 (A.J.B.) and National Heart, Lung, and Blood Institute grant R01 HL154624 (A.J.B., D.A.B.) 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.
Hydration status mediates racial differences in circulating copeptin among young adults
Authors: Linder Braxton , Hutchison Zach , Barnett Alex , Tharpe McKenna , Culver Meral , Jeong Soolim , Nichols Olivia , Watso Joseph , Fuller-Rowell Thomas , Robinson Austin 
Published: May 2023

Background: Arginine vasopressin production is directly associated with increased cardiometabolic disease risk. Hydration influences the release of arginine vasopressin which can be measured using the surrogate marker copeptin. Furthermore, there are well documented race differences in both hydration status and copeptin. However, it remains unclear whether race differences in hydration status contribute to racial differences in copeptin. Therefore, the purpose of this analysis was to determine whether hydration status mediates observed racial disparities in plasma copeptin concentration. Methods: 54 young adults (24 Black: 15 female/9 male, 21.6 ± 0.7 years; 30 White: 12 female/18 male, 21.3 ± 0.8 years) were included in this analysis. Participants were instructed to follow their normal food and fluid intake practices and collect a 24-hour urine sample. We assessed hydration status via urine osmolarity (OSM) and specific gravity (USG). We also assessed plasma copeptin concentration as a surrogate measure of arginine vasopressin. Independent sample T-tests (normally distributed data) and Mann-Whitney U tests (non-normally distributed data) were used for racial comparisons for descriptive data and hydration biomarkers. We used Cohen’s d as a measure of effect size. Mediation analysis was used to determine whether hydration status (OSM and USG) mediated potential racial differences in plasma copeptin concentration. Significance was set a priori as p ≤ 0.05. Results: Black adults exhibited higher urine OSM (Black 640 ± 534, White 439 ± 303; p = 0.007, d = 0.435), USG (Black 1.020 ± 0.001, White 1.015 ± 0.001; p = 0.043, d = 0.569), and plasma copeptin concentrations (Black 6.22 ± 3.1, White 4.62 ± 2.4; p = 0.046, d = 0.329). Regarding mediation, OSM mediated 66% of the racial difference in plasma copeptin concentrations (β = 1.022 [standard error: 0.46], p = 0.027) and USG mediated 47% of the racial difference in plasma copeptin concentrations (β = 0.745 [standard error: 0.40], p = 0.064). Conclusions: Young Black adults exhibited higher urine OSM, USG, and circulating copeptin than young White adults; and differences in USG, and particularly OSM, mediate the race difference in copeptin. Although additional data are needed, the significance of our findings are that racial differences in hydration status appear to be a major driver of racial disparities in arginine vasopressin, as opposed to an inherent physiological difference. Auburn University Presidential Graduate Research Fellowship (BAL); UAB CCTS TL-1 Program (UL1TR003096) (BAL); NIH Grant K01 HL147998 (ATR) 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.
Investigating the role of the Locus Coeruleus in context-dependent respiratory tolerance to opioids
Authors: Szujewski Caroline , Sullere Shivang , Warden Matthew , Garcia Alfredo 
Published: May 2023

Pairing an environmental context with repeat opioid use (ROU) can result in increased tolerance to the effects of the opioid. This context-dependent tolerance has been extensively studied with respect to the analgesic effects of opioids, yet a knowledge gap exists in understanding whether there is context-dependent tolerance that develops in opioid induced respiratory depression (OIRD). While activity in the Locus Coeruleus (LC), the primary noradrenergic center of the brain, is involved in cue-reward related behaviors, it also enhances breathing in response to changes in blood gas homeostasis. The objective of this study is to investigate the role of the LC in context-dependent respiratory tolerance. Adult mice expressing GCaMP in the noradrenergic cells of the LC underwent a ROU protocol consisting of an initial five-day period of context pairing where each mouse was administered fentanyl (0.7mg·kg-1·day-1; i.p.) in a distinctive fentanyl-paired context (FP), and saline was administered in different distinctive saline-paired (SP) context. Following context pairing, each mouse was administered fentanyl in both the FP and SP, while LC activity and breathing were simultaneously assessed using fiber photometry and unrestrained whole body plethysmography, respectively. Independent of context, fentanyl administration caused LC activity to increase and become rhythmic during OIRD (n=6). In the FP, however, the OIRD nadir occurred 10 min after fentanyl in all subjects (n=6/6); whereas the OIRD nadir in the SP occurred 5 min after fentanyl administration in the majority of subjects (n=5/6). The difference in time to OIRD nadir corresponded to a greater amount of LC activity in the FP prior to fentanyl (n=5 of 6, p=0.03) and during OIRD (n=5 of 6, p=0.021). These results implicate the potential involvement of LC activity and increased central noradrenergic status in producing context-dependent tolerance delaying the OIRD nadir. Our findings may be leveraged to better predict and/or mitigate overdose-related deaths associated with ROU. NIH: R01NS107421; R01HL163965; R01DA057767 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.
Investigating Krtcap3 as a novel stress gene
Authors: Szalanczy Alexandria , Fitzpatrick Mackenzie , Bui Trangdai , Dyson Christina , Eller Seth , Giorgio Gina , Goff Emily , Landry Julia , Scott Christina , Seshie Osborne , Grzybowski Michael , Klotz Jason , Geurts Aron , Redei Eva , Weiner Jeff , Solberg Woods Leah 
Published: May 2023

While obesity is an increasingly prevalent disease, genetic susceptibility is poorly understood and more research is sorely needed. Our lab has sought to confirm Keratinocyte-associated protein 3 ( Krtcap3) as a novel adiposity gene and characterize its role using an in vivo whole-body knock-out (KO) model on the Wistar-Kyoto (WKY) rat strain.We obtained conflicting adiposity and food intake results between two in vivo studies conducted before and after the COVID-19 pandemic, which brought along drastic environmental changes in the animal facility. Compared to pre-pandemic, in the quieter post-COVID-19 environment wild-type (WT) rats were eating more and gaining more weight, without corresponding changes in KO rats. We hypothesized that the prior environment had affected the stress levels of the rats, and that Krtcap3 may be a novel stress-related gene whose effects on adiposity are tangential.A significant environmental change was supported by altered expression of genes associated with glucocorticoid metabolism. Most interestingly, KO rats consistently have lower basal corticosterone (CORT) compared to WT rats and have a much stronger increase in CORT when their cage mate is removed for euthanasia.We have since sought to characterize the role Krtcap3 may play in the stress response. Despite the genotype differences in CORT response seen at euthanasia, there were no differences in the CORT response during a restraint test, indicating that both WT and KO are capable of responding to acute stressors. In WKY rats, there is high Krtcap3 expression in the pituitary gland and along the gastrointestinal tract, suggesting potential tissues of action for further investigation. Surprisingly, when we exposed WT and KO rats long-term to white noise and unpredictable mild stress, there was a stronger increase in the anxiety response of KO rats as compared to WT. This supports that Krtcap3 expression affects the response to stress, but suggests that the type of stress may also play a role. Taken together, these data demonstrate that Krtcap3 participates in the stress response. Though more work is needed to elucidate the finer mechanisms of the role of Krtcap3, these findings have important implications for human health, where stress is a known co-morbidity for many diseases, including obesity. R01 DK106386, T32 DA041349 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.
Oxygen-offloading rate from mouse Red Blood Cells of genetically diverse strains
Authors: Zhao Pan , Boron Walter 
Published: May 2023

O2 diffusion across red blood cell (RBC) membranes is a critically important physiological process for the maintenance of life. Our previous work on murine RBCs ( bioRxiv. doi: 10.1101/2020.08.28.265066 ) showed that (a) the genetic deletion of aquaporin-1 (AQP1) and the Rh complex (mainly RhAG) together reduce O2 permeability of RBC membranes ( P M, O2) by ~55%, and (b) the double knockout (dKO) of AQP1 and RhAG plus pCMBS (sulfhydryl reagent and nonspecific inhibitor of membrane proteins that is nonetheless excluded from the RBC interior) reduces P M, O2 by ~91%. In order to identify the unknown membrane protein(s) that may function as O2 channels and contribute to the missing 91% – 55% = ~36% of P M, O2, we use comparative physiology. Using stopped-flow absorbance spectroscopy to monitor the hemoglobin (Hb) absorbance spectrum, we studied the oxygen-offloading rate from hemoglobin ( k HbO2) of RBCs from genetically diverse mouse strains. We compared two different mouse strains purchased from Jackson Labs—C57BL/6J and BALB/cJ with our standard mouse strain that ultimately derives from mice received from UCSF—C57BL/6Case. We found that, compared with C57BL/6Case, C57BL/6J mice have a k HbO2 for intact RBCs that is ~22% higher (N=18, 9 male plus 9 female, p<0.01), and a k HbO2 for pure hemolysate that is ~7% lower (N=12, 6 male plus 6 female, p<0.01). Comparing with C57BL/6Case, BALB/cJ mice have a k HbO2 for intact RBCs that is ~9% lower (N=18, 9 male plus 9 female, p<0.01), and a k HbO2 of pure hemolysate that is ~10% higher (N=12, 6 male plus 6 female, p<0.01). Because changes in k HbO2 of pure hemolysate are opposite in direction to changes in k HbO2 of intact RBCs, differences in Hb cannot contribute to the observed differences in O2-offloading rates in the two Jackson strains. Likewise, changes of mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), together, would only produce minor percent changes of k HbO2 in either C57BL/6J or BALB/cJ mice. Thus, it is likely that the differences in k HbO2 for intact RBCs among the three mouse strains reflect major differences in the O2 permeabilities of the RBC membranes. Planned comparative analyses of morphology (e.g., major diameter of biconcave discs), proteomics, lipidomics, and genomics (for deduced amino-acid sequences of proteins) will provide valuable insight into the contribution of specific membrane proteins and lipids to the relatively large differences in k HbO2 of intact RBCs between C57BL/6J and BALB/cJ mice. Office of Naval Research (N00014-16-1-2535 and N00014-21-1-2366), and NIH research grant (1RO1HL 160857-01) 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.
Effect of carbohydrate source in a higher protein diet on body weight, body composition, and metabolic health outcomes in adults at risk for type 2 diabetes
Authors: Thomas Ada-Miette , Hayat Mariya , Boudrey Sydney , Hawley Aubrey , Baum Jamie 
Published: May 2023

Objective: The objective of this study was to determine the impact of carbohydrate source in higher protein diets on body composition and markers of metabolic health in adults at risk for type 2 diabetes. We hypothesized that carbohydrate source would not impact body composition or markers of metabolic health. Methods: Male and female participants between the ages of 25 and 50 years old were recruited to participate in this 16 week, randomized, controlled, parallel design study (n=21; 14 females and 7 males; age 35.5 ± 10.5). To qualify participants had meet the following criteria: two or more characteristics of metabolic syndrome (body mass index (BMI) > 25, abdominal obesity, triglyceride level over 150 mg/dl, HDL cholesterol < 40 mg/dl in men and 50 mg/dl in women, systolic blood pressure of 130 mm Hg or diastolic blood pressure of 85 mm Hg, and/or fasting glucose > 100 mg/dL) and were consented to participate in this study. Participants were randomized to one of two treatments groups: 1) higher protein diet containing white potatoes (WP; n=11) or 2) higher protein diet with starch carbohydrate (SC; n=10). All diets were isoenergetic within individual participants. Energy content for weight maintenance per individual was calculated using the Harris Benedict equation x 1.35. Each participant was instructed to follow a macronutrient ratio of 30% protein, 30% fat, and 40% carbohydrates. Body composition was measured via DXA at baseline and 16 weeks. Biomarkers of metabolic health were measured at baseline, 4, 8, 12, and 16 weeks. Ethical approval for this study was obtained from the Office of Research Compliance Institutional Review Board of the University of Arkansas (Fayetteville, AR). This study was registered at clinicaltrials.gov (NCT03935048). Written consent was obtained from all participants prior to beginning the study. Results: There was no effect of carbohydrate source on fasting total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, or blood pressure after 16 weeks of dietary intervention. There was a significant effect of time and diet (p<0.05) on body weight (WP:-2.06±4.62; SC: +2.90±6.20 lbs) and an effect of diet on (p<0.05) on BMI (WP: -0.39±0.74; SC: 0.42±1.06). Participants following SC had increased loss of fat mass and an increase in fat-free mass compared to WP, but this change was not significantly different. Conclusion: Preliminary data suggests that carbohydrate source in a higher protein diet may influence body composition with no effect on biomarkers of metabolic health. Alliance for Potato Research and Education 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.