bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving hydration in underhydrated, free-living young adults results in better running performance
Authors: Kooima Parker , Colburn Abigail , Vento Kaila , Chan Yat , Doyle Amanda , Hoel Tyler , Boro Tanner 
Published: May 2024

Dehydration impairs endurance exercise performance, especially in the heat. However, it is unclear how exercise performance is affected by improved hydration status in underhydrated individuals. Therefore, this study examined the impact of a one-week hydration intervention on endurance running performance. We hypothesized better hydration would lead to a faster 2-mile running time. Eighty-nine healthy and moderately fit individuals completed a 2-mile run as fast as possible before (PRE) and after (POST) a 1-week hydration intervention. Performance was incentivized by providing prize money based on ranked average times. First-morning urine samples were collected on the day of each run. If PRE urine specific gravity was >1.020, the subjects were instructed to increase their water intake for one week before the second run. The remaining subjects were instructed to maintain their water intake. All subjects were provided with a filter water bottle. Of the 89 subjects that completed both runs, 44 (18% female, age: 21±2 y, weight: 73.3±12.5 kg, height: 1.76±0.10 m, body mass index: 23.6±3.2 kg/m2) were included in the analysis. Subjects were classified as improved hydration (IMP) if UOsm decreased between PRE and POST by ≥100 mmol/kg and POST was <800 mmol/kg. Subjects were classified as diminished hydration (DIM) if UOsm increased between PRE and POST by ≥100 mmol/kg and POST was >500 mmol/kg. The subjects were removed from the analysis if they met any of the following three conditions: a) had a small UOsm change (<100 mmol/kg) between PRE and POST, b) lowered UOSM but it was still >800 mmol/kg, and c) increased UOsm but it was still <500 mmol/kg. The 2-mile runs took place in Phoenix, Arizona, during the morning (0700 hours) with a maximum ambient temperature of 22±2℃, relative humidity of 37±10%, and WBGT of 16±2℃. UOsm significantly decreased for IMP from PRE: 791±197 to POST: 419±136 mmol/kg (p<0.05) and increased for DIM from PRE: 532±283 to POST: 799±235 mmol/kg (p<0.05). The 2-mile run time significantly improved in IMP from PRE: 13.5±1.8 to POST: 13.3±1.8 min (-11.4±25.8 sec, P=0.03), but did not change in DIM from PRE: 14.2±2.7 to POST: 14.3±2.6 min (+4.8±19.9 sec, P>0.05). The results suggest that improving hydration in underhydrated subjects via one week of increased water intake may improve 2-mile running performance in moderately fit individuals. This study was funded by a grant from the Arizona State University’s Global Sport Institute. Brita donated the filter water bottles. 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.
Endothelial PPARD regulates nutrient transport and exercise endurance in mice
Authors: Tian Xiao-Yu , Wu Yalan , Wong Wing Tak Jack 
Published: May 2024

Vascular endothelial cell function is important for regulating vascular perfusion, which is increased in the skeletal muscle during exercise. Our previous research identified endothelial selective PPARD, a transcription factor, which is critical for endothelial cell function and homeostasis. Loss of PPARD in endothelium enhances vascular inflammation and disrupts endothelial integrity. In the present study, we aims to investigate whether endothelial PPARD is involved in nutrient transport in the muscle endothelial cells and whether it is involved in exercise endurance and training effcacy. The Cdh5-Cre driven deletion of the floxed Ppard allele was used for making the endothelium selective Ppard knockout (PpardEC-KO) mice and wild type littermates (PpardEC-WT). Human endothelial cells were used to examine glucose and fatty acid uptake and its transport to myocytes. Treadmill exercise with incremental speed and inclination was used. Both PpardEC-WT and PpardEC-KO mice were viable and did not show abnormalities at baseline. Both PpardEC-WT and PpardEC-KO mice were put on treadmill to test their running endurance. Deletion of Ppard in endothelium resulted in early exhaustion, shortened distance, and less speed. Running exercise for 4 weeks partially improved endurance in the PpardEC-KO mice. PpardEC-KO mice had less oxidative muscle fibers both at baseline and after training. Higher blood lactate level and less glucose preservation were found in PpardEC-KO mice after running the same distance as PpardEC-WT mice. In human endothelial cells, PPARD knockdown resulted in less glucose and fatty acid uptake. Glucose transport to myocyte from endothelial cells was also attenuated with PPARD knockdown. PPARD may act through SGK1 responsible for GLUT1 expression and glucose uptake. Our study showed an important role of endothelial cell in regulating nutrient transport into skeletal muscle during physical exercise. Impaired endothelial transport of glucose and fatty acid reduces exercise endurance. This study is funded by the General Research Funds 14107822 and 14105321 from the Hong Kong University Grant Council. 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.
Insights into Disease Progression with spatial transcriptomics
Authors: Jin Yufang , Paniagua Karla , Flores Mario 
Published: May 2024

In this work we present a pipeline (DeepTME) that integrates single cells transcription, spatial location of cells, cell type composition, and tissue morphology, using deep learning. DeepTME classifies the tissue microenvironments (TME) at single cell resolution by learning low-dimensional features from all transcription profiles, images similarity, neighboring information, and cell type composition, The proposed approach is able to capture important TME features than can used to quantify disease progression and severity and ultimately identify the molecular components of disease progression and obtain insight into their mechanisms. National Institutes of Health. 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.
MAL-based, Cost-Effective Digital Complementary Alternative to the Traditional/Classic R&D Mindset
Authors: Chou Ting-Chao 
Published: May 2024

In the search for the fundamental unified, integrated principle of science in biology, Chemistry, Physics, Mathematics, and Philosophy, the Mass-action Law (MAL) is the common denominator. This unique system study leads to the MAL dynamics/algorithm of biodynamics, pharmacodynamics, combination index, and bioinformatics (MAL-BD/PD/CI/BI). The theme is that one problem may be solved in multiple ways. Three basic revelations are i. The median-effect equation (MEE) for Action (Chou, 1976). It is also called the Doctrine of the Median (DOM); ii. The combination index equation (CIE) for Interaction (Chou-Talalay, 1984), where CI=1, <1, and >1 indicate additive effect, synergism, and antagonism, respectively, for all systems; iii. The dose-reduction index equation (DRIE) was introduced in 1988 (Chou et al.) for the consequence of interaction. All mathematical terms of MEE, CIE, and DRIE are dimensionless relativity ratios; thus, they have unlimited applicability independent of the unit, physical state, structure, size, and mechanism. This unified theory-based concept of the “top-down” approach is a departure from the observation/statistics-based traditional, classical R&D mindset. These two approaches are opposite yet complementary alternatives to one another. The MEE, CIE, and DRIE of MAL are all based on “One,” thus leading to the Unity of One Theory (UOT) as reported at AACR-NCI-EORTC (DOI: 10.1158/1535-7163.TARG-23-LB_B20, Boston, October 2023). The above MAL-based theory/algorithm has been largely neglected or encountered resistance for over two decades, but now, it achieves broad enthusiasm internationally, as indicated by citations in over 1,540 scientific journals and 1,328 patents or patent applications. The related MAL theory and algorithm have been discussed at ASBMB Dicovery-2023 (DOI: 10.1016/j.jbc.2023.103419), Meetings of ASPET -2023 (DOI: 10.1124/jpet.122.185320), and AACR -2023 (DOI: 10.1158/1535-7163.TARG-23-A017). More details will be given in an 11-chapter book, “Mass-Action Law Dynamics Theory and Algorithm for Translational and Precision Medicine Informatics.” (Academic Press 2024, in press). The same mathematical approach of MAL led to the discovery of the Second Degree Pascal Triangle, where all element numbers are squared, and introduced the algorithm for the weighted h-index for n-authored papers ( wh-index) for a fair attribution. This author will present an overview of this MAL-fundamental approach and further updates on new advancements in this research field at the APS Physiology Summit 2024. No. Retired Director at MSKCC, since June 1, 2013.Founder, PD Science3, LLC (USA). 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.
Cardiorespiratory Disturbances in Alzheimer's Disease: A Focus on the Contribution of Sympathetic Premotor Neurons
Authors: Toledo Camilo , Del Rio Rodrigo 
Published: May 2024

While therapeutic approaches targeting neurodegenerative mechanisms associated with cognitive impairment in Alzheimer's disease (AD) have been intensively explored, other comorbidities closely linked to AD progression, such as sleep-disordered breathing and autonomic dysfunction, have not been thoroughly investigated. In preliminary studies, we showed an increase in neural activity of catecholaminergic premotor neurons located in the rostral ventrolateral medulla region (RVLM-C1), a main region involved in cardiorespiratory regulation, in experimental AD. Therefore, in the present study, we aimed first to characterize cardiorespiratory function in AD patients and then to determine the role of RVLM-C1 neurons in autonomic and sleep-disordered breathing in APP/PS1 double transgenic mice, an experimental model showing AD-like pathology. Sixteen subjects (8 AD and 8 age-matched controls) were enrolled to assess sleep breathing disorders and to record cardiac autonomic function. Whole-body plethysmography and blood pressure monitoring in freely moving mice were used to study sleep-associated cardiorespiratory disorders. Bilateral stereotaxic injections of anti-dopamine β-hydroxylase-saporin (DβH-SAP) into the RVLM were used to selectively destroy C1 neurons. Compared to age-matched healthy subjects, patients with AD showed larger increases in neural sympathetic discharges during autonomic testing. In addition, heart rate variability analysis in AD patients showed a shift in spectral components towards a more sympathetic influence. Remarkably, we found that autonomic function impairment in the APP/PS1 mice resembles what we found in AD patients. Compared to wild type (WT), APP/PS1 mice displayed sympatho-excitation (ΔHR: -80±5 vs -125±10, WT vs APP/PS1, respectively), a higher incidence of cardiac arrhythmias (events/h 6.0±1.0 vs 12±1.5, WT vs APP/PS1, respectively), and sleep-disordered breathing (AHI: 8.5±2.0 vs 18.0±3.0, WT vs APP/PS1, respectively). Partial ablation of RVLM-C1 neurons (~70%) in APP/PS1 mice resulted in a two-fold and three-fold reduction in cardiac sympathetic drive and arrhythmogenesis, respectively. Furthermore, APP/PS1 mice treated with DβH-SAP showed marked improvements in breathing regularity (IS: 7.9±1.1 vs 16.9±2.2, APP/PS1DβH-SAP vs APP/PS1, respectively) and a restoration of normal sleep effciency (SE: 75.5±4.3 vs 58.1±6.4, APP/PS1DβH-SAP vs APP/PS1, respectively) compared to untreated APP/PS1 mice. Our results show that RVLM-C1 neurons play a main role in the development/maintenance of cardiorespiratory disorders in experimental AD. FONDECYT 11220962, 1220950. 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.
Neuropeptide Y affects B-cell activation functions
Authors: Millet Antoine , Zhu Fengli , Jendzjowsky Nicholas 
Published: May 2024

Introduction: Sympathetic nerves secrete neurotransmitters in response to pathogenic organisms in various immunological contexts. Most studies have focused on norepinephrine (NE) which has shown numerous immunomodulatory effects involving pro- and anti-inflammatory responses. However, sympathetic neurons contain also varicosities where neuropeptides, mainly neuropeptide Y (NPY), are stored. NPY play roles in various physiological processes, including regulating metabolism, vascular function, and immune function but little is known on its action during bacterial respiratory infection. The regulation of its secretion and its impact on the immune system during infection remains unclear. We investigated the role of NPY in B-cell responses during bacterial infection. Methods: Naïve B-cells isolated from mice splenocytes (2M/2F) were stimulated with IL-4 and LPS, along with NE or NPY. After 96 hours, cells were stained and analyzed by flow cytometry and transcripts were isolated for quantitative real-time PCR. Media was collected until immunoglobulin analysis. To investigate NPY role during infection, we used a mice model of bacterial lung infection. Mice were intranasally exposed twice with streptococcus pneumoniae (serotype 19F on day 0: 104 CFU and on day 9: 108 CFU); experiments took place 16 hours later. Control animals were infused with vehicle only. Results: Apart from beta2-adrenergic receptor, isolated B-cells were found to express alpha2- and beta1-adrenergic receptor transcripts. In vitro stimulation of B-cell with IL-4 and LPS (T-cell independent activation) downregulated beta-adrenergic and upregulated alpha2-adrenergic, as well as NPY receptors (Npy1r, Npy2r, Npy4r, Npy5r). Unlike NE, NPY has shown to affect B-cell proliferation and drastically increases IgG positive-cells during stimulation. However, neither NE nor NPY seem to regulate IgG release in this condition. In vivo experiments indicate that NPY level increased in the lung in response to streptococcal challenge, contrasting with the unchanged levels of NE. Conclusion: Our findings contribute to our understanding of how sympathetic neurotransmitters regulates B-cell expansion, memory, and antibody production during infection. Furthermore, our research gives new insights into the function(s) and antimicrobial capacity of neuropeptide Y. These findings allow for the development of new and more effective therapeutic strategies for invasive bacterial infections. 1R21AI159221, UCOP TRDRP T32KT4708. 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.
Role of Opioid Mu1-Recptors (μ1Rs) in The Inhalation of Carfentanil (CRF) Aerosol-Induced Respiratory Disorder in Awake Rats
Authors: Gao Xiuping , Zhuang Jianguo , Chen Zikuan , Shi Shan , Xu Fadi 
Published: May 2024

Our previous study has shown that inhalation of fentanyl (100 mg/m3) for 10 min initially induces apnea, hypotension and bradycardia, leading to ventilatory and then cardiac arrest within 15 min in anesthetized rats (Zhuang J., et al, 2024). CRF acts on opioid mu-receptors (MORs) with a potency 100 times that of fentanyl. Inhalation of aerosolized CRF as a chemical weapon has been reported to cause sudden death in humans (Wax PM et al, 2003), but the cause of the death is not fully understood. Moreover, though the opioid-induced respiratory disorder is known to mainly result from the action of μ1Rs, the contribution of μ1Rs to the CRF-induced cardiorespiratory disorder remains unknown. Therefore, we asked whether acute inhalation of overdose CRF would induce cardiorespiratory disorder and sudden death via acting on μ1R in awake rats. The rats were exposed to aerosolized vehicle and CRF at 12.86 (low dose) or 20 mg/m3 (high dose) for 15 min with cardiorespiratory (VE, VT, fR, and HR) responses recorded for 60 min. The low and high doses of CRF induced sudden death in 1/6 and 2/2 rats respectively. Compared to aerosolized vehicle, the low dose of CRF initially decreased VE and HR by ~50% within 3 min exposure, which were maintained to the end of experiment, and all responses disappeared on the next day in the survived rats. Interestingly, the responses of breathing pattern to the CRF exposure were sequentially characterized by the rapid shallow breathing (within several seconds of the exposure), slow and deep breathing and then only slow breathing. In comparison, the dVE and bradycardia became much more aggravated after 15 min CRF aerosol-delivery in the dead rats than the survived ones, resulting in ventilatory and cardiac arrest within ~25 min post exposure. The cardiorespiratory responses to the low dose of CRF aerosol exposure were also performed after pretreatment with naloxone hydrochloride (NLX to systemically antagonize opioid receptors) or naloxonazine (NALZ to selectively antagonize μ1Rs). The CRF-induced dVE and bradycardia were fully blocked by NLX and largely alleviated by NALZ. In conclusion, our experiments not only establish a rat model of acute inhalation of CRF-induced cardiorespiratory disorder and sudden death, but also demonstrate a key role of opioid receptors, especially μ1Rs, in the CRF-induced cardiorespiratory disorder. Supported by NIH R01 grants HL163512 and DA059063. 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.
The effect of the lateral hypothalamic leptin circuit on cardiorespiratory control
Authors: Jiang Jingwei , Singh Uday , Cui Huxing 
Published: May 2024

In addition to its well-known roles in regulating metabolic homeostasis, leptin signaling in the brain has also been critically involved in cardiovascular and respiration functions. Although the central mechanisms mediating leptin’s effect on metabolic control have been extensively studied and elucidated, the neural substrates by which leptin exert its effect on cardiovascular and respiratory functions remain incompletely understood. Leptin receptors (LepRs) are expressed distinct hypothalamic nuclei, including the lateral hypothalamic area (LHA), a brain region historically known as the “feeding center”. We recently performed anterograde tract-tracing of LHA LepR-positive neurons and observed a broad but regionally enriched pattern of projections throughout the brain, including, but not limited to the brain regions involved in sympathetic control of cardiovascular function and breathing, such as the periaqueductal gray and ventrolateral medullar. Based on these preliminary neuroanatomical observations, we hypothesized that the LHA leptin circuit is critically involved in cardiorespiratory control. To test this hypothesis, we generated mice expressing hM3Dq-mCherry or mCherry (control) specifically in LHA LepR+ neurons by performing stereotaxic microinjection of Cre-dependent AAV-DIO-hM3Dq-mCherry or AAV-DIO-mCherry into the LHA of LepR-Cre+ mice. These mice were then subjected to radiotelemetry recording of blood pressure and whole-body plethysmography to evaluate the respiratory function. We found that chemogenetic activation of LHA LepR+ neurons by intraperitoneal injection of deschloroclozapine (DCZ, 0.5 mg/Kg) significantly elevated blood pressure (p<0.01) and heart rate (p<0.01) independently of locomotor activity. Whole-body plethysmography further revealed that activation of LHA LepR+ neurons also drastically increased the respiratory rate (p<0.0001) and minute ventilation (p<0.001) without a significant change in the tidal volume. Increased respiratory rate was associated with shortening both inspiratory and expiratory durations. These results identify the LHA as a novel hypothalamic node through which the circulating metabolic hormone leptin might influence cardiorespiratory control. This work is supported by the grants from the National Institute of Health (HL127673 and HL153274 to HC). 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.
Evolution of the peroxiredoxin gene family: an antioxidant enzyme in the context of hypoxia-induced by aquatic mammals dives
Authors: Selleghin-Veiga Giovanna , Nery Mariana 
Published: May 2024

Peroxiredoxins are a group of antioxidant enzymes that play a crucial role in eliminating hydrogen peroxide (H2O2) produced during cellular metabolism. In conditions such as tissue ischemia/reperfusion, H2O2 production is heightened. This scenario is recurrent in aquatic mammals, such as cetaceans and pinnipeds, when they perform breath-hold dives that lead to depletion of oxygen stores and cell hypoxia due to prolonged submersion. In such circumstances, peroxiredoxins are essential for regulating metabolism and preventing oxidative damage. Thus, our objective was to investigate evolutionary patterns of the peroxiredoxin gene family among aquatic mammalian species. Accordingly, we identified the number of ortholog and paralog genes among mammals, examining events of gene duplication, patterns of chromosomal distribution, and adaptive selection. We found that most subtypes of peroxiredoxins are characterized by single-copy genes with minimal missing data, with PRDX1, the most highly expressed subtype found in both the nucleus and cytoplasm, exhibiting an increase in gene copies in aquatic mammals, particularly in pinnipeds. The distribution of the copies was dispersed along the genome and the majority were retrocopies of the main coding sequence with little divergence among them. We also found evidence of positive selection in the PRDX3 gene, especially in a convergent mutation among two deepest-diving species, cuvier’s beaked whale and southern elephant seal in which the amino acid had radical physical-chemical property change, possibly affecting the protein function. These results suggest that the peroxiredoxin gene family has a role in the evolution of aquatic mammals by reducing oxidative damage intrinsic to diving behavior in these species. FAPESP - São Paulo Research Foundation. 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.