bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of endurance training under calorie restriction on the metabolic enzyme activity and transporter levels in mouse skeletal muscle and liver
Authors: Takahashi Kenya , Kitaoka Yu , Hatta Hideo 
Published: May 2024

Although endurance training (ET) and calorie restriction (CR) induce metabolic adaptations in skeletal muscle, the interaction of them have yet to be clarified. This study investigated the effects of endurance training with calorie restriction on the metabolic enzyme activity and transporter levels in mouse skeletal muscle and liver. Ten-week-old male ICR mice were fed ad libitum or subjected to 30% CR. The animals were subdivided into sedentary and ET groups. The animals in the ET group performed treadmill running (20 m/min, 30 min) five days a week for five weeks. Respiratory gas analysis during 24 h of rest showed that CR, but not ET, reduced carbohydrate consumption. While ET enhanced hexokinase (HK) activity in the plantaris and soleus muscles, CR decreased HK, phosphofructokinase, and lactate dehydrogenase activities and monocarboxylate transporter (MCT) 4 protein content. Although ET and CR alone increased citrate synthase (CS) activity and MCT1 protein content in the plantaris muscle, no additive or synergistic effects were observed. In the soleus muscle, ET increased CS, β-hydroxyacyl-CoA dehydrogenase (β-HAD), and total carnitine palmitoyltransferase (CPT) activities; however, CR significantly decreased CS and β-HAD activities but enhanced total CPT activity. Additionally, CR enhanced the glucose transporter 4 protein content in the plantaris and soleus muscles. In the liver, CR enhanced the protein levels of glucose 6-phosphatase, fructose 1,6-bisphosphatase, and mitochondrial phosphoenolpyruvate carboxykinase. Moreover, ET partially normalized the CR-induced increase in fatty acid synthase and acetyl-CoA carboxylase. These observations suggest that CR enhances the capacity for glucose and fatty acid synthesis in the liver as well as the glucose and lactate uptake capacity in skeletal muscle while reducing carbohydrate consumption in skeletal muscle. It is suggested that CR partially interferes with skeletal muscle adaptations to ET. This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant numbers 20H04071, 21K21249, and 23K16718). 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.
Exogenous Thyroxine Increases Cardiac AS160 Phosphorylation in Insulin Resistant OLETF Rats
Authors: Yang Xue , Mendez Dora A. , Vazquez-Anaya Guillermo , Nishiyama Akira , Ortiz Rudy M. 
Published: May 2024

Thyroxine (T4) is the most abundant thyroid hormone secreted by thyroid gland and contributes to glucose metabolism via both insulin and non-insulin dependent pathways. Akt substrate 160 (AS160) is a Rab-GDP activating protein and a downstream effector of protein kinase B (Akt) required for glucose transport and upregulation of GLUT4 activating vesicle (GSV). The phosphorylation of AS160 (p-AS160) is required for the regulation of GLUT4 translocation to the membrane. It is also involved in insulin-mediated traffcking of GLUT4 in skeletal muscle and adipose tissues. The accumulation of AS160 has also been implicated in promoting cardiac hypertrophy, which is commonly associated with the metabolic syndrome (MetS). This study explores how thyroid hormones can affect the phosphorylation status of cardiac AS160 during insulin resistance. Under normal conditions, AS160 is phosphorylated by Akt to upregulate GSV, allowing glucose to cross the cell membrane through GLUT4. We hypothesize that exogenous T4 increases cardiac phosphorylation of AS160 expression during insulin resistance. Insulin resistant, Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the effects of exogenous thyroxine (T4) on cardiac p-AS160. Rats were assigned to four groups: (1) lean, Long Evans Tokushima Otsuka (LETO; n=6), (2) LETO + T4 (8 μg/100g BM/d × 5 wks; n=7), (3) untreated OLETF (n=6), and (4) OLETF + T4 (n=7). Exogenous T4 did not significantly alter native AS160 protein expression among all four groups. However, p-AS160 was reduced in the non-treated OLETF group by 61% (p<0.01) compared to healthy LETO control group. Exogenous T4 increased p-AS160 by 16% (p<0.05) compared to non-treated OLETF group and by 36% (p<0.05) in treated LETO compared to control LETO group. We have previously demonstrated that exogenous T4 increased the translocation of cardiac GLUT4 and the present findings suggest that this increased translocation is mediated by activation of AS160, resulting in improved glucose metabolism in the heart during insulin resistance. American Heart Association. 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.
Transcutaneous evaluation of hemoconcentration response to hypoxia simulated and hypobaric hypoxia of 5050 m
Authors: Moraga Fernando , Riquelme Sylvia , Lopez Ivan , Calderon-Jofré Rodrigo , Pedreros Andres , Langer Vania , Sanzana Francisco 
Published: May 2024

Objective: To evaluate the effect of normobaric and hypobaric hypoxia of 5050 m on hemoconcentration response in population without experience to hypoxia and acclimatized population to chronic intermittent hypobaric hypoxia (CIHH). Materials and Methods: 16 subjects without experience to altitudes over 1500 m (9 women/7 men) and 39 subjects acclimatized workers to CIHH at high altitude (5050 m, 9 women/32 men) were recruited. Normobaric hypoxia were performed in 3 steps: 5 min breathing ambient air, 20 min breathing hypoxic air (11,5% O2, equivalent to 5050 m) and 5 min of recovery breathing ambient air. CIHH condition represents a normal exposure characterized by 8 days working at high altitude and 6 days resting at low altitude (<1500 m). Subjects were evaluated at sea level and 5-6th day of exposure to CIHH at 5050 m. In each condition, Hemoglobin concentration (Hb), Carboxyhemoglobin (COHb), Methemoglobin (MetHb), Pulse oximetry (SPO2), heart rate (HR) were measured using a transcutaneous sensor (Rad 67 pulse Co-Oximeter, Masimo). Results: In evaluations performed at sea level, both groups of hypoxia (normobaric and CIHH) exhibited a lower hemoglobin concentration in women in comparison with men. During exposure to simulated hypoxia, a significative increase in hemoglobin concentration was showed, associated to decrease in SpO2 and increase in HR. However, an increased level of MetHb in women and men and only increased level of COHb in women were observed. During hypobaric exposure, Hb concentration increased, with reduced SpO2, and increased HR in comparison to sea level. Lower HR was observed in men respect of women. Lower level of COHb was observed in men respect of women. In addition, in women was observed an increase of level COHb related with time of exposure, in contrast, a tendency to reduction in level of COHb and MetHb in men was observed. Conclusion: The use of transcutaneous sensor to measure SpO2 and Hb showed an increase in hemoglobin concentration in normobaric and hypobaric hypoxia, in agreement with previous results from our laboratory. In addition, we reported new information about level of COHb and MetHb in two different model of exposure simulated hypoxia and hypobaric hypoxia at extreme altitude. SUSESO ACHS 279-2022. 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.
During exposure to 3%, 5%, and 7% CO2, both Behaviorally Inhibited and Non-Behaviorally Inhibited individuals increased minute ventilation through different mechanisms
Authors: Ehlert Luke , Wiseman Connor , Poff Hannah , Talens Kate , Martino Paul , Miller Daniel P. , Miller Justin R. 
Published: May 2024

Behavioral inhibition (BI) is a temperament associated with increased vulnerability to stress compared to their non-behaviorally inhibited (NBI) counterparts. Previous studies have demonstrated that BI individuals have a higher stress response than NBI individuals, suggesting that BI individuals have significantly less parasympathetic nervous system output at rest. However, this study only compared room air to 7% carbon dioxide (CO2) concentrations. The difference in the sympathetic nervous system activation between BI and NBI individuals under constant increasing stress is still unknown. Our current study tested the hypothesis that BI individuals will have an increased stress response as the inhaled CO2 concentration increases. In humans, we tested the effect of increasing CO2 concentrations on tidal volume, breathing rate, heart rate, and blood pressure. BI individuals were identified through self-reported questionnaires, such as The Adult Measure of Behavioral Inhibition (AMBI). A 15-minute control period of room air breathing was completed followed by 5 minutes each of 3% and 5% inspired CO2, and 3 minutes of 7% inspired CO2. Preliminary results indicate that BI individuals breathe differently at a physiological level and differ in their stress response. Thank you to Carthage College's Student Travel Grant as well as the Neuroscience and Biology department for supporting this research. 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.
Mapping the Vagus Nerve with Anatomical Scaffolds
Authors: Christie Richard , Lin Mabelle , Chopovda Valerie , Nickerson David , Hunter Peter 
Published: May 2024

Phase 2 of the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program ( https://commonfund.nih.gov/sparc ) aims to build a comprehensive map of the anatomy and functional connectivity of the human vagus nerve, allowing comparisons of inter-subject variability, and helping guide experiments on vagus nerve stimulation and the development of neuromodulation devices. Following approaches used in Phase 1 of the SPARC program, segmented nerve and fascicle data (using various imaging modalities) of vagus nerves from a large number of human subjects will be registered into an Anatomical Scaffold. This is a geometric model of the vagus nerve providing a common coordinate system across subjects. Registration is achieved by fitting a subject-specific vagus scaffold to digitized subject data, using standardized annotations for trunks, branches, fixed landmarks and orientation marks in the data and for the corresponding features of the Scaffold. We report here on progress and issues in the early stages of the study. A particular complication of the vagus is inter-subject variability. While the left and right vagus trunk are quite consistent across subjects, the number and locations of branches innervating a particular organ or target is quite different from one subject to another. This dictates generating a scaffold for each subject with its own unique branching structure. Once data is available for a reasonable number of subjects these will be remapped to a common or representative vagus scaffold. At the conclusion of this study all vagus imaging, plus derived data including the scaffold and embedded fascicles, their groupings and distributions will be freely available on the SPARC Portal ( https://sparc.science/ ). Mapping to a common scaffold allows these data to be compared and visualized at equivalent locations across all subjects in the study. This work is supported by the NIH SPARC program under award number OT3OD025347. 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.
Transposable element-derived double-stranded RNAs stimulate pro-inflammatory activation in human astrocytes
Authors: McEntee Cali , Cavalier Alyssa , LaRocca Thomas 
Published: May 2024

Astrocyte-related inflammation contributes to neuroinflammation with brain aging and Alzheimer’s disease (AD), but the causes of pro-inflammatory astrocyte activation in this context are incompletely understood. One driver of pro-inflammatory signaling in astrocytes may be endogenous double-stranded RNA (dsRNA) derived from transposable elements (TEs). TEs make up more than 50% of the human genome, and recent evidence suggests a role for TEs in pro-inflammatory signaling with aging and neurodegenerative diseases. However, the role of TEs and/or TE-derived dsRNA in astrocyte-related inflammation, and the specific TEs involved, have yet to be investigated. Here, we increased the expression of TE transcripts in human astrocytes by suppressing ADAR1 (an enzyme involved in the suppression/regulation of endogenous dsRNA) and performed RNA-seq to broadly characterize resulting biological changes. Using a computational pipeline (SPRINT) to detect potential dsRNA transcripts through adenosine-to-inosine (A-to-I; a marker of ADAR1 activity) edits, we found that dsRNA transcripts were more likely to come from TEs compared to coding genes. Of these TEs, highly edited and increased transcripts consisted of the TE families Alu and LINE-1 (L1) elements. We confirmed the increase in L1 transcripts in vitro by characterizing colocalization of J2 (antibody for dsRNA) and an L1 element via fluorescence in situ hybridization. Increases in these TEs were associated with increases in pro-inflammatory signaling and decreases in expression of genes relating to astrocyte identity/function (e.g., synapse modifying and cholesterol-related genes). Lastly, we found similar increases in Alu and L1 transcripts in brain tissue of AD patients and older subjects. Together, these data suggest a role for TE-derived dsRNA in pro-inflammatory activation in astrocytes, and possibly in aging and AD. To expand on these findings, we have performed RNA immunoprecipitation sequencing to identify the specific TEs that form dsRNA with ADAR1 suppression in astrocytes, and we are developing an approach to mitigate their effects by increasing ADAR1 expression in the brains of old mice. NIA: F31AG084330, R01AG078859. 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.
Different subsets of V2a propriospinal neurons respond differently to spinal cord injury
Authors: Crone Steven 
Published: May 2024

While propriospinal neurons play a crucial role in recovering function post-spinal cord injury, it remains unclear whether these neurons exhibit largely similar responses to injury or if their diversity requires distinct alterations in gene expression. Here, we focused on one population of spinal neurons, the V2a class, previously shown to be important for recovery of locomotor and respiratory function after spinal cord injury. Using single nuclei gene expression analyses, we delineate substantial molecular and cellular heterogeneity of V2a propriospinal neurons subtypes in adult mice and examine how individual subtypes are altered by injury. Remarkably, a subset of V2a neurons expressing Rbms3+/Nav3+ and enriched for synaptic transmission and axon guidance molecules were found to be nearly absent following injury. The remaining V2a populations exhibited distinctive transcriptional alterations, indicating a potential rewiring of cellular interactions within the spinal cord microenvironment. Thus, our study reveals the diverse responses of propriospinal neurons to injury. These analyses provide a foundation for understanding changes in propriospinal neurons that may lead to adaptive (or maladaptive) changes in circuit function following injury. NIH R01 NS112255 (PI:Crone) Spinal Circuitry for Ventilatory Control and Compensation Craig H. Neilsen Foundation- Spinal Cord Injury Research on the Translational Spectrum (PI: Crone) Targeting propriospinal neurons to improve breathing following injury. 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.
Interactive maps of nerve-organ anatomy and function on the SPARC Portal
Authors: Wu Man Chung , Brooks David , Yu Jianwei , Balachandran Keeran , Khorasanee Jesse , Sorby Hugh , Garny Alan 
Published: May 2024

The integrated maps viewer of the SPARC Portal ( https://sparc.science ) provides interactive, modular, and continually-updated visualizations of nerve-organ anatomy and function. SPARC data and knowledge is registered onto two-dimensional flatmaps, and three-dimensional anatomical organ and whole-body scaffolds. Flatmaps are zoomable maps built from a range of sources and portray anatomy and nerve knowledge of a given species, and scaffold maps are geometric models able to represent the spatial distribution of connectivity knowledge, observed data, and computational models. These maps, and their annotations, are published as SPARC datasets and they are available for public viewing using the map viewers on the SPARC Portal ( https://sparc.science/maps ).The map viewers provide visual interfaces for exploring data and tools in the context of knowledge about neural connectivity. Visualization on the viewer can be customized using different settings. Search can be conducted on both the flatmap and scaffold maps to find and highlight specific features. Data and literature sources and other relevant information of a network and connectivity can be explored comprehensively based on standardized annotations. Multiple maps can be visualized simultaneously using a split-pane display system. Users are able to dynamically create permalinks to specific views, allowing knowledge and corresponding visualization to be shared and cited. Development of the map viewers are on-going and new features continue to be deployed to the SPARC Portal. Subject-specific vagus nerve exploration on the flatmaps and whole-body scaffolds is a key feature planned to be available later this year. This work is supported by the NIH SPARC program under award number OT3OD025347. 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.
Gut Microbiome Response to the Reduction of Diet Induced Obesity by Vitamin B1 Supplementation
Authors: Dutta Disha , Ortañez Jericho , Leano John , Curras-Collazo Margarita , Deol Poonamjot , Sladek Frances , Degnan Patrick 
Published: May 2024

Dietary deficiencies in vitamins such as thiamine (Vitamin B1) produce a range of deleterious health effects and can occur even in developed countries. We’ve hypothesized that a physiological deficiency in thiamine can exacerbate conditions like obesity, diabetes, and fatty liver that are associated with consumption of high fat diets rich in soybean oil (SO) and that one or more of these conditions might be associated with changes in the composition of the gut microbiota. We first evaluated the short-term effect of thiamine deficiency on the gut microbial composition in fecal pellets from C57BL/6N male mice. Mice provided a thiamine regime of 1 mg/kg of low-fat diet for 4 weeks showed marked decreases in fecal community diversity and are characterized by “missing”’ microbes compared to animals provided a standard low-fat thiamine diet (5 mg/kg). Combined with a LC/MS metabolomic analysis these data confirmed changes in the microbiome are coincident with changes of physiological levels of thiamine in the mice. To test the effect of thiamine availability directly on obesity, a separate cohort of C57BL/6N male mice were fed either a low-fat chow (OSD) or an obesogenic soybean oil high fat diet (SO-HFD), with or without supplementation with a thiamine analog (640 mg/kg of diet). Over an 18-week period we found that animals on the SO-HFD with the added thiamine analog gained ~40% less weight compared to animals on the SO-HFD only. Longitudinal sampling of fecal pellets at week 0, 10, 16 and 18 demonstrate major shifts in the microbial composition and diversity over time for animals in all four diet groups. A nested PERMANOVA of Bray-Curtis dissimilarities confirmed the microbiome differences between the SO-HFD and OSD diet (adonis, p = 0.001) and with and without the thiamine analog supplementation (adonis, p = 0.009) at week 16. Measures of microbial diversity show significant increases in diversity for animals consuming the thiamine analog (Kruskall-Wallis, q < 0.05), consistent with the trend observed in the short-term diet trial. Taxonomic classifications for species (ASVs) that significantly increased in these animals are primarily in the Lachnospiraceae family from the Bacillota (Firmicutes) phylum. Together, these data identify major compositional and inferred functional changes to the microbiome in response to the SO-HFD diet as well as thiamine supplementation that may contribute to the observed differences in body weight gain. Funding: The Thiamine Advocacy Foundation. Acknowledgements: UCR Genomics Core. 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.
Induced Ablation of Prmt1 in Endothelial Cells Causes Endothelial Dysfunction Associated with Pulmonary Thromboembolic Hypertension
Authors: Tran Thi Thuy Vy , Jeong Yideul , Kang Jong-Sun 
Published: May 2024

Endothelial cells (ECs) play vital roles in regulation of vascular homeostasis, vascular tone, leukocyte traffcking, and barrier function to ensure pulmonary function. Endothelial dysfunction is a key factor for the progression of pulmonary pathogenesis. Protein arginine methyltransferase 1 (Prmt1) catalyzes asymmetric di-methylation of substrates on arginine residues and is implicated in a variety of cellular processes, including cardiovascular function. In the current study, we examined the role of Prmt1 in endothelial function by using tamoxifen-inducible EC-specific Prmt1 ablation (KO) mice. EC-specific Prmt1 ablation in adult mice (KO) for 8 weeks led to lethality, concurrent with pulmonary hypertension and thromboembolism. The lung bulk RNA sequencing and single EC RNA sequencing analyses revealed that Prmt1 ablation increased inflammation, endothelial junction disruption, apoptosis, and fibrosis. Comprehensive analysis through bulk RNA and single cell RNA sequencing revealed that Prmt1 ablation in ECs triggers homeostatic disturbance accompanied by inflammation and endothelial dysfunction, associated with hyperactivation of NFkB and Stat signaling. In conclusion, the current study suggests that Prmt1 plays a key role in pulmonary endothelial function and vascular homeostasis via the suppression of NFkB-induced endothelial dysfunction. The National Research Foundation Grant funded by the Korean Government (MIST) (NRF-2022R1A2B5B02001482). 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.