bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supraclavicular brown adipocytes arise from myogenic Tbx1-lineage progenitors
Authors: Ruan Hai-Bin , Huang Zan , Zhang Zengdi 
Published: May 2023

Brown adipose tissue (BAT) is a thermogenic organ that promotes metabolic fitness. In humans, there are two spatiotemporally distinct phases of BAT ontogeny: the prenatally developed dorsal-anterior-located interscapular BAT (iBAT); and the postnatally emerged supraclavicular BAT (sBAT). It has been established in rodents that the dorsal-anterior-located iBAT depots predominately arise from a Pax3 +/ Myf5 + lineage in the epaxial dermomyotome that also forms the trunk muscle. However, the developmental origins of the supraclavicular BAT that adult humans have remain unknown. In this study, using lineage tracing mouse models, we found that these supraclavicular BAT depots are not derived from the Pax3 + or Myf5 + precursor cells. Knock out of PPARγ, the master regulator of adipogenesis, in Myf5 + cells caused severe atrophy of iBAT, but did not affect the supraclavicular depots. Instead, we identified that most of the supraclavicular brown adipocytes are progeny cells of the developmental Tbx1 + lineage that also gives rise to neck muscle cells. PPARγ deficiency in this lineage did not perturb iBAT development, but caused paucity in the supraclavicular regions, thus sensitizing mice to cold-induced decrease in body temperature.In summary, our results suggest that there are region-specific myogenic precursors that contribute to BAT development at different anatomical locations. Future studies to understand the pathophysiological regulation of these developmentally distinct BAT depots could inspire new approaches to measure BAT mass and to activate BAT activity in humans for the treatment of obesity, diabetes and related metabolic disorders. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Effects of intermittent fasting on brain tissue in male Fisher-344 rats
Authors: Sudasinghe Keshari , White Zachary , Rogers Liza , Hall Stephanie 
Published: May 2023

Introduction: Intermittent fasting (IF), time-restricted food intake without any caloric restrictions, has been shown to improve cognition in animal models. Several pathways have been identified in IF-induced neuroprotection; here, we observed the effect of IF on neuroprotection targeting molecular markers of protein synthesis (mTOR), autophagy (ATG5/ LC3A), and antioxidant expression (SOD2). We hypothesized that IF would improve autophagy and antioxidant expression and reduce protein synthesis in male fisher-344 rats. Methods: Twenty-four, 10-week-old male Fisher-344 rats were randomly assigned into two groups (ad-libitum, or IF) and housed 4 per cage, on a 12:12 light: dark cycle. Ad-libitum group had 24/7 access to food and water while the IF group had 24/7 access to water and full access to food on an every-other-day basis (i.e. alternate day fasting) for ten weeks. At 20 weeks of age, animals were euthanized and brain tissues (hippocampus and cortex) were sectioned and snap-frozen in liquid nitrogen. Following homogenization, western blots were completed via Jess Protein Simple automated western blotting (Bio-Techne, Minneapolis, MN). Specific proteins of interested included, LC3 (Novas, NB100-2331), ATG5 (Novas, NB110-538185S), mTOR (Santa Cruz, sc-517464) and SOD2 (Abcam, ab68155). Compass software generated area under the curve values were used to determine protein expression. Group differences were analyzed with a two-tailed T-test per Prism Graph Pad software. Results: In cortex tissue, a significantly lower mTOR expression was observed in the IF group compared to the AL group (p<.001), however, mTOR expression was not significantly different in the hippocampus. Antioxidant enzyme, SOD2, was significantly higher in IF cortex tissues (p<.05) compared to AL controls. In contrast, SOD2 was significantly lower in IF hippocampal tissues (p<.01) compared to controls. No significant effect was documented in the LC3 and ATG5 autophagy markers. Conclusion: In the present study, IF significantly impaired protein synthesis (via mTOR expression) in the cortex only. Previous work has also concluded the downregulation of mTOR with both calorie restriction and fasting. However, the fact that no decline was present in the hippocampus is intriguing and will be the focus of follow-up investigations. As expected, IF increased antioxidant enzyme (SOD2) expression in the cortex and interestedly, IF decreased antioxidant expression in the hippocampus. While the hippocampus is noted for its high antioxidant content, this decreased expression induced with IF warrants more research. P20GM113109 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.
Decreased arterial elastance following a novel RSK3/mAKAPß gene therapy is associated with improved bradykinin-dependent pial artery dilation in aortic-banded, Western diet-fed female Ossabaw swine
Authors: Tharp Darla , Amin Amira , Thorne Pamela , Mueller Christina , Li Jinliang , Olver T. Dylan , Kapiloff Michael , Emter Craig 
Published: May 2023

Cardiogenic dementia is associated with increased risk of mortality in heart failure. Cognitive decline is more prevalent in females, of which cardiac function is a strong predictor. We have demonstrated cerebrovascular insufficiency in female Ossabaw swine with cardiometabolic heart failure (CM-HF). The purpose of this study was to examine the effect of a novel gene therapy that displaces p90 ribosomal S6 kinase 3 (RSK3) from perinuclear muscle A-kinase anchoring protein β (mAKAPβ) signalosomes using a systemically delivered adeno-associated virus (AAV) to express a RSK3/mAKAPβ anchoring disruptor peptide (RBD) controlled by a cardiomyocyte-specific promoter (AAV9.RBD). We hypothesized that disruption of RSK3/mAKAPβ by AAV9.RBD would improve cardiac and cerebrovascular function in parallel, diminishing cardiogenic pathology. Female Ossabaw pigs were assigned to HF control (HF; n=4) and HF AAV9.RBD-treated (HF+RBD; n=5) groups. Animals were fed a Western diet (3 mo. old) and aortic banded (6 mo. old) prior to euthanasia (12 mo. old). Pressure-volume hemodynamics were used to measure arterial elastance (Ea), the ratio of end systolic pressure:stroke volume (SV). Pressure myography was used to assess in vitro cerebral vascular function (2a pial arterioles; inner diameter 267 ± 19 μm HF & 248 ± 9 μm HF+RBD). Group comparisons were made using student’s t-test and repeated measures ANOVA with significance reported at the P≤0.05 level. Ea was decreased in HF+RBD animals compared to HF (mmHg/mL; 2.3 ± 0.2 HF & 1.7 ± 0.2 HF+RBD) and driven by increased SV (mL; 40 ± 2 HF & 50 ± 2 HF+RBD). Decreased arterial load was associated with increased endothelial-dependent dilation to bradykinin (BK) in the HF+RBD group compared to HF (Group x Dose interaction) in isolated pial arteries. BK-induced dilation was decreased in the presence of L-NAME (nitric oxide synthase inhibitor) in HF, but not HF+RBD animals (Group x Dose interaction). In contrast, BK-induced dilation was decreased in the presence of indomethacin (prostaglandin synthesis inhibitor) only in the HF+RBD group (Group x Dose interaction). In conclusion, decreased cardiac arterial load (Ea) was coupled with improved endothelial-dependent cerebral vascular function that was mechanistically characterized by altered nitric oxide/prostaglandin balance in female Ossabaw swine with CM-HF. These findings suggest AAV9.RBD-mediated disruption of RSK3/mAKAPβ signalosomes in cardiomyocytes has a positive cardiogenic effect on cerebrovascular function. Department of Defense (DOD) W81XWH-18-1-0179 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.
Macrophage to Myofibroblast Transition in Diastolic Dysfunction Development
Authors: Mora Christoph , Liu Yunmeng , Benson Lance , Deck Katherine , Guo Yunping , Mu Shengyu 
Published: May 2023

Heart failure is the top killer in the U.S and worldwide, often caused by hypertension, aging, or cardiac toxicity. Diastolic Dysfunction (DD), the often the first step of heart failure, occurs when the chambers of the heart are not able to expand during the filling phase. In addition, hypertension is the leading cause of DD. Though this is known, the progression of hypertension into DD remains poorly understood. Of note is the ability of M2 macrophages to differentiate into a myofibroblast-like phenotype, known as macrophage to myofibroblast transition (MMT). This transition has been observed in interstitial fibrosis in chronic renal allograft injury. The researchers noted that MMT account for 50% of the myofibroblast population. To our knowledge, the extent of fibrotic remodeling due to MMT in the heart has not been ardently investigated. Therefore, we aim to answer whether MMT plays a causal role in the progression of hypertension to DD and the pathogenesis of heart failure.Utilizing the uninephrectomized, DOCA-salt model, mice were subjected to this treatment and hypertension was induced. As a negative control, another group of mice received a uninephrectomy and the same salt in their drinking water, however, DOCA was not administered (Sham group). MMT prevalence, identified as CD68+ α-SMA+ expressions, was observed inside the hearts of DOCA and Sham mice. The hearts were isolated and homogenized via gentleMACS tissue Dissociator, the monocytes were purified via Percoll isolation, and flow cytometry was used to identify the population of CD68+ α-SMA+ expressing cells.As soon as 10 days post DOCA implantation, the DOCA group exhibited worsening diastolic function as it took longer for the pressure to change in the hearts of DOCA mice than in Sham (-dp/dt). These data were gathered via left ventricular (LV) catheter insertion. At a later time, utilizing a different cohort of mice preliminary data show an increase of monocyte (CD68+) and fibroblast (α-SMA+) double-positive expressing cells in the hearts of hypertensive mice.MMT has been observed in the hearts of hypertensive mice. This transition may exacerbate Diastolic Dysfunction. More research must be performed to investigate the wide variety of functions of macrophages (i.e., M1 to M2 ratio and transition, macrophage residence or infiltration, and macrophage stimulation of myofibroblasts), as well as the specific interactions between macrophages and cardiomyocytes, or other immune cells, that might mediate this transition. These data provide a preliminary, but interesting glimpse, into the role of macrophages in exacerbating Diastolic Dysfunction and mediating Heart Failure. NIH RO1-HL146713 and AHA 15BGIA25730047 (Shengyu Mu) 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.
Dietary-induced changes in the hindgut microbiome and metabolism of a marine herbivorous fish
Authors: Herrera Michelle , Heras Joseph , Catabay Caitlyn , Connor Kwasi , German Donovan 
Published: May 2023

To advance our understanding of the factors that influence gut physiology and function, we are examining how the gut microbiome changes under varying environments and diets. We integrated the gut transcriptome and microbiome to understand how dietary changes impact Cebidichthys violaceus, an herbivorous fish native to the California coast that is known to have an active microbial community in its hindgut. Wild-caught fish from San Simeon, California were fed either herbivore, omnivore, or carnivore diets in the laboratory for six months. We expected the microbiome, as well as the hindgut and liver transcriptome, to change with dietary perturbations, with wild herbivorous fish being most similar to lab-herbivore fish. Wild fish microbial communities were indeed different from laboratory-fed fish (P<0.001, Bray-Curtis distances), but the laboratory-omnivore diet fish were the most similar to wild fish, sharing a high abundance of taxa in the Bacteroidota and Bacillota (Families Ruminococcaceae and Rikenellaceae), whereas the laboratory-herbivore and laboratory-carnivore fish shared a high abundance of taxa from the Pseudomonodota (Families Burkholderiaceae and Oxalobacteraceae). The microbial diversity patterns in multivariate space among the fish on the different diets directly resembled that of host distal intestine gene expression in multivariate space (i.e., wild and lab-omnivore diet fish were the most similar). The hindgut had 519 differentially expressed genes, and wild fish highly express genes involved in ion transport and lipid and glucose metabolism. The liver, on the other hand, presented 4650 differentially expressed genes, and wild fish highly express genes for fatty acid synthesis and proteolysis. These data show how the gut microbiome and transcriptome varies as a function of different diets in an herbivorous marine fish. Our project provides insight into what it takes for fish to deal with shifting resources, which is important for marine resource management and new potential aquaculture species development. NSF Grant IOS-1355224 and William Townsend Porter Pre-doctoral Fellowship from the American Physiological Society. 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.
Alpha-7 Nicotinic Acetylcholine Receptors Contribute to the Combined Electroacupuncture Modulation of Hypertension in Salt-Sensitive Rats
Authors: Gong Yiwei , Fu Liang-Wu , Nguyen Anh , Guo Zhi-Ling , Malik Shaista , Tjen-A-Looi Stephanie 
Published: May 2023

Elevated sympathetic activities and low-grade chronic inflammation are observed in hypertensive (HTNive) patients and animals including dahl salt-sensitive hypertensive (DSSH) rats. We have shown that stimulation of the deep peroneal nerve and the tibial nerve by combined electroacupuncture (cEA) at the combination of two sets of acupoints ST36-37 and SP6-7 decreased blood pressure (BP) and proinflammatory cytokines in HTNive subjects through sympathoinhibition and anti-inflammation. Acetylcholine (ACh), the primary neurotransmitter of parasympathetic nerves, is known to participate in modulation of inflammation. We hypothesized that α-7 nicotinic acetylcholine receptors (α7nAChR) play an important role in the BP lowering effects of cEA in DSSH rats. DSS rats were fed with 4% salt diet and randomly allocated into three groups (4 rats/group). Once they developed moderate hypertension (SBP 160±5 mmHg), one group was treated with Sham-EA (no electrical stimulations), and two groups were treated with cEA. Both cEA and Sham-EA groups were given twice weekly for eight weeks. Methyllycaconitine (MLA) is a α7nAChR antagonist. MLA (2.4 mg/kg) was injected intraperitoneally (ip) daily into one group of cEA treated rats (n=4) during the last three weeks with cEA treatments. In a similar manner, the other cEA group and the Sham-EA group received daily saline ip injection for three weeks. Another four DSS rats were fed with standard rat chow and treated as the normotensive (NTN) controls. Systolic/diastolic BP (SBP/DBP) of rats were measured with Tail-cuff via CODA system once a week. At the end of the experiment, compared to Sham-EA rats (207.8±2.5 mmHg, DBP 144.6±3.2 mmHg), cEA decreased SBP (138.8±0.8 mmHg) by 33.2% and DBP (98.6±1.7 mmHg) by 24.25%. Blockade of α7nAChR with MLA partially reversed the cEA BP lowering effects (SBP 193.4±2.6 mmHg and DBP 136.5±2.4 mmHg), and BPs in cEA+MLA treated rats were still significantly lower than Sham-EA-treated rats after the reveral. BPs of NTNive rats remained in the normal BP ranges throughout the 13 weeks of the experiment (from 135.9±2.8 to 134.2±1.1 mmHg). In conclusion, systemic antagonism of α7nAChR with MLA partially reversed the BP lowering effects of cEA in DSSH rats. National Institute of Health National Center for Complementary & Integrative Health Grant (1RO1AT011306). 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.
Attractor dynamics that govern breathing are differentially perturbed by inhibitory and excitatory populations of the Ventral Respiratory Column
Authors: Bush Nicholas , Ramirez Jan-Marino 
Published: May 2023

Distributed and diverse populations of neurons throughout the Ventral Respiratory Column (VRC) are involved in the generation and maintenance of breathing. We have recently shown that the network-wide dynamics of these populations evolve through rotational trajectories in a low-dimensional latent neural space. These rotations evolve continuously through both inspiration and expiration, and they target a low-dimensional inspiratory-off attractor. It remains unknown how these rotational dynamics respond to perturbations of specific subsets of VRC populations. Here we record from the rostrocaudal extent of the VRC using high-density Neuropixel probes in-vivo in anesthetized mice while optogenetically stimulating subsets of neurons by Cre-driven expression of channel rhodopsin. These stimulations cause both widespread activation and deactivation of recorded populations. We find that brainstem wide stimulation of inhibitory neurons perturbs low-dimensional population trajectories towards the inspiration-off attractor, regardless of trajectory location at the time of stimulation. After cessation of stimulation, all trajectories proceed inexorably toward the inspiration-off point, and the cycle resets. When inhibitory populations are stimulated during the expiratory period, the population dynamics are clamped close to the inspiration-off attractor. Stimulation of glutamatergic populations, in contrast, directs the trajectories to a different region near the center of the rotation. However, upon cessation of excitatory stimulation, the trajectories immediately relax to the closest point along the rotational manifold, and the cycle resumes. Stimulation of either GABA-ergic or glutamatergic populations perturbs the dynamics perpendicular to the ongoing rotations; however stimulation of either Dbx1+ or cholinergic populations perturbs the populations along the current heading of the trajectories. Together, these data highlight a critical role of inhibition in the procession of VRC population dynamics, and suggest that the inspiration-off attractor is targeted by inhibitory mechanisms. R01 HL151389; R01 HL126523; R01 HL144801; F32HL159904 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.
Student performance and satisfaction in the first iteration of an integrated renal and respiratory systems course in a redesigned one-pass preclinical curriculum
Authors: Villalobos Alice , Kruczek Cassandra , Bobulescu I. Alexandru 
Published: May 2023

Texas Tech University Health Sciences Center School of Medicine converted its legacy two-pass preclinical curriculum to a one-pass organ system-based format and changed the grading system from categorical to pass/fail (>70%). Our objective was to assess first-year medical student (MS1) performance and satisfaction in the first iteration of Organ Systems-2:Renal and Respiratory ( RNR), an 8-week block taught at the end of Year I. RNR integrates the physiology, pathophysiology, infectious diseases, and pharmacology of the renal system (Weeks 1-4) and respiratory system (Weeks 5-8), using reorganized and updated material from legacy Year-I blocks ( General Principles & Infectious Diseases and Structure & Function of Major Organ Systems) and Year-II blocks ( Immunity & Multisystem Disorders and Systems Disorders). Instruction was delivered via didactic lectures, team-based activities, case-based reviews, dry labs, cognitive integration of clinical reasoning (CICR) sessions, and simulations. Formative weekly quizzes and practice exams were assigned before each exam. Learning in the renal physiology, renal pathophysiology, and respiratory physiology units was assessed by instructor-generated exams at the end of Weeks 2, 4 and 6, respectively, and a final customized, comprehensive NBME exam at the end of Week 8. Aggregate performance on instructor-generated renal and respiratory exam questions was compared to that on similar questions from legacy curriculum exams. Aggregate performance on the NBME exam was compared to USMLE Step 1 exam difficulty, as the legacy curriculum did not include a dedicated renal/respiratory NBME exam. Aggregate performance on instructor-generated renal physiology and pathophysiology and respiratory physiology questions was comparable to that in the legacy curriculum. Average performance on the renal portion of the NBME exam was 0.76 vs. Step 1 exam difficulty of 0.78; average performance on the respiratory portion of the exam was 0.77 vs. Step 1 exam difficulty of 0.78. Per end of block survey and student focus group feedback, overall student satisfaction with RNR was 73%. Thus, the first iteration of the integrated organ systems-based renal and respiratory systems course in Year I yielded a MS1 performance on the NBME that was comparable to USMLE Step 1 source difficulty, and student satisfaction was positive overall. More detailed analysis of exam performance is needed. Further modifications of RNR will include additional simulations and flipped-classroom sessions. 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.