bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal Injury and Cross Sex Steroid Therapy in Aging Male Rats
Authors: Mallette Jordan H. , Crudup Breland F. , Nabors Harley S. , Oudomrath Speyrer Adrian , Willis Alex T. , Rawls Adam Z. , Cockrell Kathy L. 
Published: May 2024

Significance: Transgender females (TGF) are individuals who were born male but identify as female. Gender affrming hormone therapy (GAHT) is used to align physical characteristics with gender identity. In the TGF, GAHT includes 17β-estradiol (E2) combined with surgical intervention (castration, CTX). The long-term effects of GAHT on cardiorenal health are unclear. Thus, using our model of cross sex steroid therapy whereby E2 is significantly elevated in association with a significant reduction in testosterone in E2+CTX male rats, we hypothesized that renal injury is elevated with GAHT, and that age-related increases in renal injury are enhanced in E2+CTX compared to age-matched control. Methods:Male Sprague-Dawley rats were randomly assigned to: Control or E2+CTX with E2 [5 mg/day, silastic capsule s.c., replaced every 3 weeks] started at 14 (young, Y) or 52-65 (middle-age, MA) weeks of age followed by CTX two weeks later (N=8-10/grp). Experimental protocol: lean and fat mass (EchoMRI), 24-hour metabolic collection for proteinuria, KIM-1, NGAL (ELISA); creatinine (Chemistry Analyzer) up to 14 wks in Y and 20 wks in MA rats post GAHT. Two-way ANOVA with Tukey’s post hoc analysis was performed with P<0.05 considered significant. Results: Body weight and lean mass were significantly decreased in Y and MA E2+CTX vs age-matched Control. Fat mass was significantly reduced in MA E2+CTX vs MA Control. 24-hour urinary protein did not differ in Control vs E2+CTX at either age but was increased with age vs Y groups ( p<0.05). Creatinine was significantly increased in MA groups vs Y but decreased in MA E2+CTX vs MA Control ( p<0.05). NGAL and KIM-1 were significantly increased in MA Control vs all other groups ( p<0.05); NGAL was increased in MA E2+CTX vs its Y counterpart ( p<0.05) but not Y Control. Conclusion: Collectively, these data indicate that markers of renal injury are not increased in Y GAHT males. However, in MA, age-related increases in KIM-1and NGAL are attenuated in GAHT. Future studies will determine if male GAHT are more sensitive to a second hit such as renal ischemia reperfusion and quantitate renal function via a direct method to account for loss of lean mass in E2+CTX males. [Formula: see text] HL143459, P20-GM-104357, P20-GM121334, AHA CDA 938320, T32-HL105324. 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.
Specific Microbiome Signature Dynamics Could Predict Aging Continuum and Cognitive Impairment in Older Adults
Authors: James Adewale S. , Chaudhari Diptaraj S. , Jain Shalini , Goltz Dayna , Tangudu Divyani , Yadav Hariom , Consortium MiaGB 
Published: May 2024

The global population is aging, facing a substantial burden of age-related disorders, including cognitive impairment (CI), Alzheimer's disease (AD), and related dementias (ADRD). The lack of effective strategies for preventing and treating these conditions can be attributed to our incomplete understanding of the biology of aging. Emerging evidence strongly suggests that the gut microbiome plays a pivotal role in aging and its association with cognitive decline and ADRD. Yet, the transformations occurring within the microbiome during the aging continuum remain insuffciently studied. We have addressed these significant knowledge gaps by analysing samples and data from 176 older adults participating in the multi-site Microbiome in Aging Gut and Brain (MiaGB) consortium. Whole-genome metagenomic analysis unveiled distinct microbiome profiles among three aging categories: (i) 60-69 (n=62), (ii) 70-79 (n=78), and (iii) 80+ (n=36), spanning from phyla to species-level phylogeny. Notably, in older adults, changes in the microbiome were observed with respect to the aging continuum and cognitive impairment (CI). The abundance of Lachnospiraceae, Eggerthellaceae, Dorea, Blautia, and Eggerthella decreased, while Veillonellaceae increased in the gut of older adults with CI but not within the aging continuum. Interestingly, only Proteobacteria, Firmicutes, Candidatus melainabacteria, Coriobactericeae, Ruminococcaceae, Anerostipe hadrus, and Collinsella aerofaciens decreased, while Bacteroidetes, Bacteroidiceae, and Bacteroides uniformis increased within the aging continuum but were not impacted in CI sub-groups. However, both Ruminococcus torques and Streptococcus thermophilus decreased with aging continuum and CI. These results indicate unique microbiome changes specific to the aging continuum, as well as distinct changes with CI, independent of age. Thus, they not only hold promise as prognostic markers for assessing the risk of cognitive decline and dementia in older adults but also pave the way for designing precision microbiome interventions to mitigate the risks posed by these debilitating public health issues. We thank the Ed and Ethel Moore Alzheimer’s Disease Research Program, Florida Department of Health (22A17), National Institutes of Health, National Institute of Aging (R56AG069676, R56AG064075, RF1AG071762, R21AG072379, U01AG076928), and Department of Defense (W81XWH-18-PRARP AZ180098) for funding support. 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.
Isotope-guided metabolomics dissects kidney arginine metabolism
Authors: Chrysopoulou Maria , Jägers Johannes , Bleich Markus , Himmerkus Nina , Rinschen Markus 
Published: May 2024

Background: L-arginine is a key amino acid for detoxification, protein metabolism, and kidney and cardiovascular health. In the urea cycle, ammonia is incorporated into urea through the transformation of arginine to ornithine and urea, a reaction that occurs mostly in the liver but also in the kidneys. Hypothesis: An imbalance of kidney arginine metabolism can be associated with kidney injury. Aim: To detect the arginine uptake and its metabolic fate in kidney in vivo and ex vivo models by metabolic flux analysis. Method: Healthy C57BL/6 mice (n=22) were fed with normal and 13C6-15N4-arginine diet for 1, 2 and 8 weeks. Extracted metabolites from kidney cortex and medulla were analyzed with UHPLC/QQQ-based mass spectrometry targeting arginine-related metabolic pathways: the urea cycle, polyamines, the nitric oxide pathway, arginine/proline/glutamate interconversion, as well as modified forms of arginine. Additionally, micro-dissected nephron segments (glomeruli, proximal convoluted tubules (PCT), proximal straight tubules (PST), thin ascending limb of the loop of Henle (TAL), distal convoluted tubules (DCT), collecting ducts (CD)) from 4 healthy C57BL/6 mice, were incubated with 13C6-arginine and analyzed accordingly. Results: Isotope tracing allowed us to follow the fate of arginine in the kidney cortex and medulla of the 13C6-15N4-arginine-fed animals. The ex vivo experiments confirmed that all nephron segments take up and metabolize arginine, except for the TAL. More specifically, ornithine was found in all segments apart from the CD. Agmatine was formed in the PST and the CD, whereas arginine contributed to the proline and glutamine formation in the glomeruli, the PCT and the CD. Methylated forms of arginine were observed in the PST and the DCT. Conclusion: This study enabled the detection of arginine-related metabolites inside the kidney and showed that the metabolic fate of arginine differs along the nephron. The detailed isotope-based arginine metabolic flux and its role in kidney disease models will be determined next. This work is supported by the Young Investigator Award from the Novo Nordisk Foundation (grant number NNF19OC0056043), awarded to Markus Rinschen. 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.
Dysfunction of M channels in the insular cortex is involved in pathogenesis of primary hypertension
Authors: Li De-Pei , Sheng Zhao-Fu , Zhang Hua , Zheng Peiru 
Published: May 2024

Heightened sympathetic nerve activity is critically involved in the pathogenesis of primary hypertension. However, the sources driving increased sympathetic vasomotor tone remain unclear. The posterior insular cortex (PIC) is a brain region involved in regulating blood pressure and sympathetic tone. Neurons in the PIC project to the rostral ventrolateral medulla (RVLM), a key brain stem region in regulating sympathetic nerve activity and blood pressure. The non-inactivating voltage-dependent K+ channels, M channels (Kv7/KCNQ channel family) encoded by KCNQ2/3 genes, play a unique role in stabilizing the neuronal membrane potential and regulating neuronal excitability. Here, we determined if the M channel activity of neurons in the PIC is altered in a primary hypertension. Compared with Wistar-Kyoto (WKY) rats, the mRNA and protein expression levels of Kv7.2/Kv7.3 in the PIC tissue were significantly reduced in spontaneously hypertensive rats (SHRs). Microinjection of M channel blocker 10, 10-bis (4-pyridinylmethyl)-9(10H)-anthracnose (XE-991) into the PIC increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in anesthetized WKY rats, while induced minimal changes of ABP and RSNA in SHRs. M currents recorded from PIC neurons in brain slices labeled by retrograde tracer, Fluospheres, injected into the RVLM were significantly smaller in SHRs than in WKY rats. Furthermore, bath application of specific M channel blocker XE-991 increased the firing rate of PIC-RVLM output neurons in WKY rats while caused a minimal increase in firing rate of PIC-RVLM output neurons in SHRs. In addition, M currents recorded from PIC-RVLM output neurons in SHRs were significantly smaller than those recorded from WKY rats. These data suggest that M channel activity is diminished in PIC-RVLM output neurons in SHRs, and the diminished Kv7 channel activity contributes to elevated sympathetic outflow in primary hypertension. This novel information provides new a mechanistic insight into the pathogenesis of neurogenic hypertension. Supported by grants from National Institutes of Health (HL139523, HL142133, and HL159157 to DPL). 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 bacteria contribute to rodent hypertension via modulation of colonic serotonin and gut vagal 5ht3aRs
Authors: de Araujo Alan , deLartigue Guillaume , Zubcevic Jasenka 
Published: May 2024

Hypertension is associated with gut dysbiosis and autonomic dysfunction in humans and rodent models. While hypertension-associated gut dysbiosis elevates blood pressure in rodents, the precise mechanisms are unknown. In our model gut dysbiosis-induced hypertension, fecal matter transplant from hypertensive SHR reduced colonic serotonin and relative expression of serotonergic 5ht3a receptors (5ht3aRs) on vagal afferents in the control WKY rats. To investigate the role of serotonergic gut vagal axis in regulation of blood pressure, in a cre-dependent manner we first overexpressed channelrhodopsin 2 in the 5ht3aR-expressing gut-projecting vagal afferents (NG5ht3Ar) in 5ht3aR Cre rats. Acute bilateral optic stimulation of NG5ht3Ar produced an immediate decrease in blood pressure and heart rate. Conversely, chronic ablation of NG5ht3Ar by cre-dependent expression of caspase elevated blood pressure in 5ht3aR Cre rats. This effect was potentiated both by the infusion of low dose of angiotensin II and exposure to acute restraint stress separately. On the other hand, overexpression of 5ht3aRs in NG5ht3Ar reduced blood pressure in the SHR, the effect that was further potentiated by dietary tryptophan supplementation. Altogether, these data propose that hypertension-associated microbiota contribute to rodent hypertension via modulation of colonic serotonin and gut vagal 5ht3aRs. NIHR01HL152162. 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.
Bmal1 Knockout in Rats Results in Hydrocephalus and Behavioral Defects
Authors: Grady Caroline , Andrade Cavalcante Moraes Yaslle , Holland Marshall , Becker Bryan 
Published: May 2024

Circadian rhythms drive many aspects of physiology including brain water homeostasis with increased cerebral spinal fluid flow and brain parenchyma clearance during periods of sleep. Our group has previously reported maintained diurnal rhythms in blood pressure and renal function in rats lacking the core clock gene, ARNTL, or Bmal1. However, we have also observed a robust increase in brain water content and blood brain barrier permeability in knockout rats compared to wildtype (WT) controls. Patients with normal pressure hydrocephaly (NPH) display a triad of symptoms including memory dysfunction, gait disturbances, and urinary incontinence. We hypothesized that the Bmal1 knockout (Bmal1 KO) rat has behavioral symptoms similar to those seen in NPH patients. In an initial series of behavioral tests, we utilized open field and rotarod testing to measure exploratory behavior and locomotion. Following a training trial, male and female rats were tested over 4 different trials performed on sequential days. In 10 minute open field tests, Bmal1 KO rats had a trend toward decreased total movement compared to WT (1980 ± 185 vs 2369 ± 144 cm; p = 0.1430; n = 5 and 6 respectively). Anxiety-like behavior was pronounced in the Bmal1 KO rats compared to WT as evidenced by lower frequency of entries (3.6 ± 0.7 vs 11.0 ± 2.0 entries; p = 0.0098) and decreased time spent (8.0 ± 2.4 vs 25.4 ± 5.6 seconds; p = 0.0261) in the center zone of the open field. Rotarod testing of ramps from 0 to 16.5 cm/s over 5 minutes uncovered a strong trend towards decreased average distance ran (937 ± 256 vs 1540.0 ± 176 cm; p = 0.0775) and max velocity achieved (11.1 ± 1.5 vs 14.5 ± 0.8 cm/s; p = 0.0666) in Bmal1 KO compared to WT. Bmal1 KO rats also had more falling events on the rotarod compared to WT (0.95 ± 0.04 vs 0.73 ± 0.6 falls/trial; p = 0.0098). These findings indicate that in addition to the overt hydrocephalus phenotype of Bmal1KO rats and increased blood brain barrier permeability, lack of Bmal1 induces behavioral and locomotor symptoms similar to those seen in human patients with NPH. We propose that the Bmal1 KO rat can serve as a pre-clinical model for NPH and other forms of hydrocephalus and will shed light on mechanisms of altered central fluid flow that are present in many neurodegenerative diseases associated with aging. 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.
CD4+ T Cells from Women with Preeclampsia During Pregnancy Contribute to Hypertension, AT1-AA, and Neurovascular Dysfunction in a Pregnant Rat Model of PE
Authors: Campbell Nathan , Simmons Kimberly , Herrock Owen , Deer Evangeline , Morris Rachael , Turner Ty , Amaral Lorena 
Published: May 2024

Objective: Preeclampsia (PE) is characterized by new onset hypertension (HTN) during pregnancy and is associated with activated CD4+ T cells and agonistic antibodies against the angiotensin II type 1 receptor (AT1-AA). Interestingly, having had COVID-19 during pregnancy is associated with increased incidence of a PE-like phenotype. Both PE and CV have long lasting neurological implications. We sought examine a role for CD4+ T cells from PE with or without a CV Hx to contribute to a PE phenotype and neurovascular dysfunction postpartum (PP). Methods: We utilized adoptive transfer of one million placental CD4+ T cells from PE and normotensive (NT) patients with or without a CV (Hx) during pregnancy injected i.p. into gestational day (GD) 12 nude athymic rats athymic and determined neurological consequences at 12 weeks PP. At GD19, blood pressure (MAP) and AT1-AA were measured. At 3 months PP, memory and error in navigation were assessed by Barnes maze consecutively for 5 days. CBF was measured by laser Doppler flowmetry. A two-way ANOVA was used for statistical analysis. Results: In pregnant recipient rats, MAP increased in CV Hx PE (113±2, n=8) and PE (115±2 mmHg, n=10) compared to CV Hx NT (104±4, n=7) and NT (98±2 mmHg, n=7 p<0.05). AT1-AA increased in PE (8±2 ΔBPM, n=4) and CV Hx PE (4±2 ΔBPM, n=4) compared to NT (-3±2 ΔBPM, n=4, p<0.05) and CV Hx NT (2±2 ΔBPM, n=2) respectively. At 3 months PP, PE and CV Hx PE had impaired CBF autoregulation compared to CV Hx NT and NT rats, and both PE groups exhibited greater mistakes and latency in maze navigation, however, the scores were worse in those receiving T cells from PE patients without a Hx of CV compared to all other groups. Conclusion: Our findings indicate that pregnant recipients of CD4+ T cells from PE with or without a CV Hx during pregnancy cause HTN and increased AT1-AA compared to recipients of NT or NT Hx CV-19 CD4 + T cells. Interestingly, recipients of T cells from PE patients without a Hx of CV had worse CBF and cognitive function at 3 months PP, demonstrating the importance of CD4+ T cells in HTN and impaired neurological function during pregnancy PP in patients with previous PE. This study was supported by NIH grants RO1HD067541 (BL), F31HD110230 (NC), P20GM121334 (BL, LMA), and American heart association (AHA) early career award 19CDA34670055 (LMA). 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.
Identifying and Responding to Gaps in Services for International Graduate Students and Postdoctoral Fellows to Enhance the Graduate Community and Promote Quality Research Outcomes
Authors: Crider Emily A , Dent Elena , Sullivan Jennifer C 
Published: May 2024

The growing enrollment of international students in doctoral science, technology, engineering, and mathematics (STEM) programs in the U.S. has contributed to the need for an increase in specifically-designed programs, resources, and services that address the unique challenges of the international student population. When transitioning to the U.S. to pursue higher education, international students often experience obstacles, including language barriers, sociocultural challenges, and academic alienation, which significantly impacts the ability to successfully adapt to the new learning and living environment, oftentimes continuing throughout the duration of the program. Furthermore, international postdoctoral fellows engaged in STEM research fields may lack a sense of belonging due to similar barriers. The recruitment and retention of competitive international students and postdoctoral fellows directly impacts the quality and magnitude of research outcomes, while also enhancing and enriching the cultural diversity and experience of the graduate community. We use data collected from an international student and postdoctoral survey distributed to more than 65 students and 90 postdoctoral fellows as well as listening sessions to identify gap areas where additional resources are required and where modifications are needed to more productively serve the international population at Augusta University. Our findings indicate that international students and postdoctoral fellows experience more anxiety and isolation when they are not supported, personally, socially and academically, by their administrative leaders, faculty, peers, and surrounding community. Incoming students who were connected with current graduate students prior to their arrival to the U.S. experienced a greater level of support and were more confident and comfortable in their adjustment to society in the U.S. The implementation of additional events and experiences led by the responses of the international population, including research shadowing opportunities in on-campus laboratories, social gatherings connecting students and postdoctoral fellows of different cultures, writing circles and professional development workshops, and one-on-one sessions enhances community belonging and prioritizes personal and professional growth among this vulnerable student population. 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.