bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of varying dietary potassium on the development of salt-sensitive hypertension and expression of basolateral Kir channels
Authors: Zietara Adrian , Levchenko Vladislav , Palygin Oleg , Staruschenko Alexander 
Published: May 2023

The inverse effects that dietary sodium and potassium have on blood pressure have been known for some time. High sodium consumption is detrimental, while potassium supplementation is known to be beneficial, and the ratio of sodium/potassium consumption is also very important to consider when determining how these electrolytes affect salt-induced hypertension; however, the mechanisms behind the beneficial effects of potassium are still not yet entirely established. Inwardly rectifying potassium (Kir) channels have been shown to play a major role in potassium transport and homeostasis in the kidney and might contribute to these effects. Here we aimed to examine how different variations in the sodium/potassium ratio affect the development of salt-sensitive hypertension and how channels and transporters in the kidney are altered to accommodate these changes. We hypothesize that these diets will affect the development of salt-sensitive hypertension, and that Kir channels will play a major role in the renal adaptations to varying intakes of potassium. At 9 weeks of age, male Dahl SS rats were given a high salt (4% NaCl) diet for 5 weeks either supplemented with high potassium (HK, 1.41% K+), normal potassium (NK, 0.36% K+), or a potassium depleted diet (DK). Telemetry blood pressure recordings revealed that potassium supplementation attenuated the development of salt-sensitive hypertension in rats fed HK diet compared to NK; surprisingly, the DK group did not develop hypertension. Diets had a similar effect on heart rates, we observed the largest heart rate in the NK group, which was reduced with HK, and even further reduced in DK. Comparing terminal body weights, there was no difference between the HK and NK groups, but rats fed DK diet were significantly smaller. The 2 kidney/total body weight ratios were not different in the HK and NK groups, but the potassium deficient rat kidneys were significantly larger, likely due to their smaller body weights. There was no difference in heart/body weight ratios in the HK, NK, or DK groups; however, there is a trend in increased heart weight the lower the dietary potassium. Female animals were also utilized for experiments and followed similar trends as seen in the male rats. Western blot analyses further revealed the expression of Kir channels in Dahl SS rats fed a high salt diet supplemented with varying amounts of potassium. Altogether we provided a comprehensive analysis of various potassium diets on the development of salt-sensitive hypertension and Kir channels. National Institute of Health R35 HL135749 and the Department of Veteran Affairs I01 BX004024 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.
Diversifying Anatomical Models
Authors: Carroll Jazmine , Bouslog Yosajandy , Brown Isabella , Jones April , Zunick Peter , Leal Anna 
Published: May 2023

To increase diversity in health and science, technology, engineering, and math (STEM) fields, it is imperative to create inclusive laboratory tools and environments for students. Unfortunately, most human anatomical models depict white males who are young and lean. This limited representation may discourage students who are considering careers in STEM fields and medicine. Therefore, we painted anatomical models to represent more diverse skin tones. First, the models (3B Deluxe Human Torso) were taped with painters' tape to cover areas that did not need to be painted. Then, the models were cleaned using alcohol prep pads to remove any excess dirt or dust. Commercial grade interior paint (Valspar Satin Interior Paint in colors Cordovan and Cowboy Hat) was applied to the anatomical models with paint brushes (Master’s Touch soft nylon). To create more realistic skin tones, we mixed red and blue acrylic paints (Master’s Touch in Permanent Red and Phthalocyanine Blue) into each paint shade to achieve unique colors. Three layers of paint were applied to each model and each layer dried within one hour. Details such as lip and eye color and hair texture were also added to the models. To maintain the longevity of the paint, clear varnish (Liquitex Finishing Varnish in Satin) was applied. The total process (preparation, paint, and dry time) for one model took a total of five hours. One of the primary goals of our work is that our painting process can be used as a blueprint for other educators and medical professionals to increase inclusivity in their learning spaces and labs and further diversify their anatomical education tools. Creating an inclusive education experience may encourage more students of color and underrepresented minorities to pursue health and STEM graduate degrees. This will increase healthcare quality for patient populations and move the field towards greater health equity. 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.
Evaluation of interactions between nesfatin-1 and B lymphocytes
Authors: Steffen Tara , Kolar Grant , Samson Willis , Yosten Gina 
Published: May 2023

The function of nesfatin-1, corresponding to the nucleobindin2 (NUCB2) precursor, was first identified in the hypothalamic nuclei, and was reported to be potently anorexigenic (Oh-I et al. 2006). More recently it has been shown that expression of Nesfatin-1 is not restricted locally to the hypothalamus but is widely expressed in many peripheral tissues, including adipose tissue, and associated with a range of physiological effects. For example, when Nesfatin-1 is genetically knocked out ( Nucb2-/-) in mice fed a high fat diet there is a resultant increase in the gene expression of pro-inflammatory mediators and cytokines, including Tlr4, in the subcutaneous white adipose tissue compared to WT animals also fed a high fat diet. These data support that Nesfatin-1 has anti-inflammatory properties, but the mechanistic actions of this peptide in this setting have yet to be fully described (Gharane et al. 2022). To begin to evaluate the interactions of Nesfantin-1 and immune cells more in depth we began with B lymphocytes where Nubc2, the Nesfatin-1 precursor, was originally identified (Miura et al. 1993). Using an immortalized B lymphocyte cell line, Raji, and primary cells from human donors we determined the ability of Nesfatin-1 to bind to the cell surface and affect B lymphocyte proliferation. Furthermore, we determined if treatment with Nesfatin-1 is sufficient to protect against toll like receptor-4 (TLR4) and B cell receptor (BCR) induced cytokine and antibody release from B lymphocytes. This work is the beginning characterization of a novel interaction between Nesfatin-1 and B cells. Given the anti-inflammatory activity of Nesfatin-1 and its potential direct effects on immune cells, there is a broader impact for this work in protection during chronic inflammation caused by obesity and metabolic disorders. Saint Louis University 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.
The Anoctamin 4 Homolog Limits Bacterial Infection and Calcium Oxalate Crystallization in Drosophila Renal Tubules
Authors: Foresto-Neto Orestes , Turin Daniel R. , Holmes Heather L. , Reynolds Carmen J. , Arneson Mariah L. , Cabrero Pablo , Jayachandran Muthuvel , Dow Julian A.T. , Lieske John C. , Furrow Eva , Romero Michael F. 
Published: May 2023

Anoctamins (ANO) are activated by intracellular Ca2+ and function as phospholipid scramblases and/or Cl- channels. ANO4 is mutated in miniature schnauzers with calcium oxalate stones (CaOx), and ANO4 protein in urinary extracellular vesicles is decreased in human CaOx stone formers. In Drosophila Malpighian tubules (MT), subdued (ANO4-homolog) functions as Ca2+-activated Cl- channel, scramblase, and plays a role in host defense against gram-negative bacteria. Increasing evidence shows the participation of bacteria in urinary stone formation in humans. We used a Drosophila avatar to investigate whether subdued changes CaOx crystallization and if crystallization increases with bacterial infection.Uro:Gal4 flies were crossed with UAS:subdued-RNAi flies to knockdown (KD) subdued in MT principal cells (PC) or with w1118 flies to generate normal controls (WT). F1 generation underwent CaOx crystallization in association or not with uropathogenic E. coli (UPEC) infection. In vivo, flies were fed on diet supplemented with 20mM sodium Ox (NaOx) + UPEC:eGFP for 4 days. For ex vivo assays, dissected MTs were submerged in solution containing 10mM NaOx+ UPEC:eGFP for 90 minutes. subdued-KD in PC reduced subdued mRNA by 56% in MT. Neither crystal number nor size were changed by subdued-KD after prolonged NaOx feeding. However, when UPEC is introduced with the NaOx diet, subdued-KD flies exhibited a large bacterial presence in MT lumen and produced enlarged CaOx crystals compared to WT flies. Similar augmented presence of UPEC in subdued-KD MTs was observed during ex vivo assays. Short-term exposure to NaOx+UPEC resulted in increased number of crystals in subdued-KD MTs compared to WT MTs, but no difference was observed in crystal size.Fly cell atlas ( flycellatlas.org ) revealed that subdued is also found in MT stellate cells (SC; water and Cl- secretion). C724:Gal4>UAS:subdued-RNAi flies were used to assess the effect of subdued-KD in SC. This s ubdued-KD slightly increased bacterial infection but did change CaOx crystallization in MTs after 4 days of NaOx+UPEC feeding.The presence of subdued in PC limits CaOx crystals formation and aggregation through reducing bacterial invasion in the MT lumen. These Drosophila results suggest a role for ANO4 in bacterial-related human and dog kidney stone formation. Future experiments will determine whether other functional aspects of subdued affect CaOx crystallization. U54-DK100227, R01-DK092408, FAPESP (2022/01226-1), Mayo Foundation. 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.
Up-regulation of the kidney renin angiotensin system contributes to long-term renal dysfunction in severe food restricted-refed female rats
Authors: Patel Riddhi , Milicic Stanic Branka , Ji Hong , Ecelbarger Carolyn , de Souza Aline 
Published: May 2023

Background: Severe food restriction (sFR) due to various psychological, environmental, and economical reasons can have adverse consequences to cardiovascular functioning and health. Less understood are the long-term risks for developing cardiovascular disease after the sFR period has ended. The renin-angiotensin system (RAS) is responsible for regulating blood pressure and we have found that the RAS is chronically upregulated months after the sFR is over and body weight (BW) recovered due to refeeding (sFR-Refed). AIM: Determine the role of the kidney in the chronic up-regulation of the RAS in sFR-Refed rats. Methods: We investigated the long-term consequences of sFR after refeeding on kidney structure and function in sFR-Refed rats. Female Fischer rats (3-months-old) were maintained on normal chow (Ctrl) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received regular chow ad libitum for 3 months. Kidney function was analyzed by precision ultrasound. ACE expression (qPCR) and activity (fluorescent assay) were measured and renal pathology was assessed by H&E staining. Results: After 2 weeks of sFR, rats lost 15% of their initial BW [DFinal/Initial): Ctrl, 1.50±0.80 vs sFR, -15.4±1.1; p<0.001; n=8]. After 3 months of refeeding, there was no detectable difference in BW, blood pressure and heart rate between Ctrl and sFR-Refed groups. However, the renal artery blood flow was reduced by 13% [(mm/s): Ctrl, 255 ± 12 vs sFR-Refed, 199 ± 7.8; p<0.02; n=4-8 Glomeruli size was reduced [(mm): Ctrl, 399 ± 6.2 vs sFR-Refed, 383 ± 3.8; p<0.05; n=9] and renal AT1R mRNA expression was increased by 1.3-fold [(fold of Ctrl): Ctrl, 1.00 ± 0.060 vs sFR-Refed, 1.29 ± 0.040; p<0.005; n=8]. Conclusion: In summary, AT1Rs in the renal cortex are up-regulated under conditions in which kidney structure and function are impaired months after the sFR period has ended and BW is restored to normal levels. These findings suggest increased renal AT1R activity contributes to the long-term renal dysfunction observed in sFR-Refed rats. Further research is needed to understand how women who are subjected either voluntarily (e.g., crash diets) or involuntarily (e.g., very low food security) to periods of inadequate caloric intake could be at increased risk for developing renal disease later in life. AHA: 940246 (AS); IH 1R01HL119380 (KS) 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.
Adenylate Cyclase 3 and Cyclic Nucleotide-Gated Channel Alpha 2 Are Downstream Signaling to H2S/Olfr78 to Carotid Body Responses to Hypoxia
Authors: Peng Ying-Jie , Wang Ning , Nanduri Jayasri , Chen Xuanmao , Storm Daniel , Prabhakar Nanduri 
Published: May 2023

We previously showed that activation of Olfr78 by H2S as an important component of carotid body(CB) O2 sensing. Present study delineated signaling associated with H2S/Olfr78 interaction. Odorant receptor activation is linked to olfactory G protein GOlf, which increases cAMP through type III adenylyl cyclase (AC3), and subsequent activation of cyclic nucleotide-gated channel alpha 2 (Cnga2). Immunohistochemistry showed that carotid body glomus cells were positive for GαOlf, AC3, and Cnga2. Hypoxia (medium Po2~40 mmHg) or H2S(50 μM) increased cAMP in the carotid body and these responses were absent in tyrosine hydroxylase-specific AC3 mutants. AC activators forskolin and 8-Bromo-cAMP enhanced ex vivo CB sensory response to hypoxia and H2S. The effects of 8-Bromo-cAMP were absent in Cnga2 mutants. Hypoxia and H2S stimulated ex vivo CB sensory activity and elevated intracellular calcium of glomus cells in wild type but not AC3 or Cnga2 mutants. Whole body plethysmography showed impaired ventilatory response to acute hypoxia (12%O2, 5 min) but not to hypercapnia in AC3 or Cnga2 mutants. The data suggest that AC3-cAMP-Cnga2 signaling contributes to H2S/Olfr78-dependent O2 sensing by the CB to regulate breathing. Supported by NIH-HLBI P01-HL-44454 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.
ApoE4 undermines phrenic motor plasticity elicited by acute intermittent hypoxia with or without hypercapnia during the active phase
Authors: Marciante Alexandria , Nair Jayakrishnan , Welch Joseph , Mitchell Gordon 
Published: May 2023

Acute intermittent hypoxia (AIH) elicits respiratory motor plasticity and is emerging as a promising strategy to improve breathing and other (non-respiratory) movements in clinical disorders that end life due to respiratory insufficiency ( e.g., spinal cord injury & ALS). AIH-induced phrenic long-term facilitation (pLTF) is the most commonly studied form of respiratory motor plasticity and presents as a persistent increase in phrenic nerve activity after AIH. Specific factors ( e.g. aging, inflammation, hypoxia severity/duration) undermine AIH-induced pLTF; however, little information is available concerning the role of specific genes that regulate AIH-induced phrenic motor plasticity. Apolipoproteins (ApoE) are highly expressed in the central nervous system and function as lipid carriers. The ApoE gene is tri-allelic ( E2, E3 and E4); ApoE2 and E3 proteins are associated with neuroprotective and neuro-neutral phenotypes, respectively. ApoE4 impairs cortical and synaptic plasticity and is implicated in neurodegeneration, particularly Alzheimer’s Disease. Indeed, humans heterozygous for ApoE4 ( e.g., ApoE3/4) have reduced plasticity in diaphragm motor-evoked potentials versus non- ApoE4 carriers using an optimized protocol combining AIH with hypercapnia (AIHH; 15, 1 min O2=9.5%, CO2=5% episodes). To demonstrate causality, we tested the hypothesis that ApoE4 undermines AIH-induced pLTF vs ApoE3 in knock-in rats. Anesthetized, vagotomized, paralyzed and ventilated adult (3-4 months) male Sprague-Dawley rats with knock-in humanized (h) ApoE3 and (h) ApoE4 were presented with AIH (15,1 min hypoxic episodes; O2=9%; arterial PO2 = 40-50mmHg) or AIHH (inspired CO2=4%; arterial PCO2=50-55 mmHg). During the mid-active phase, AIH-induced pLTF was significantly greater in h ApoE3 (33±11%) vs h ApoE4 rats (-22±7%; p<0.001; both n=5). AIHH enhanced pLTF in h ApoE3 rats (60±11%; n=4) vs AIH, alone (p=0.046), but not h ApoE4 rats (-3±7%; n=3; p=0.970). These experiments demonstrate a causal relationship whereby ApoE4 undermines both AIH- and AIHH-induced pLTF during the active phase in rats. Since AIH has emerged as a promising neurotherapeutic to preserve/restore breathing in clinical disorders such as spinal cord injury and neuromuscular disease, understanding how genetic factors impact phrenic motor plasticity will help identify individuals most/least likely to respond to treatment. Such biomarkers are essential for success/failure in the translation of AIH/AIHH as a therapeutic modality. NIH (HL148030, HL149800 & T32HL134621), Craig H. Neilsen Foundation (JW) and UF Brain and Spinal Cord Injury Trust Fund (BSCIRTF). 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.
Extracellular histone proteins are novel activators of P2XR7 channel current
Authors: Al-Aqtash Rua'a , Collier Daniel 
Published: May 2023

Extracellular histone proteins have been identified as important damage associated molecules that contribute to vascular dysfunction. Histones are elevated in circulation after traumatic injury and activation of the innate immune response. In prior work, we demonstrated that extracellular histone proteins induced endothelial cell (EC) Ca2+ influx, increased EC propidium iodide labeling, and decreased vasodilatory responses. These paradoxical observations could be explained by activation of a non-selective cation channel. The ionotropic purinergic receptor 7 (P2XR7) stands out as a candidate as it has been shown to form a high-conductance, poorly selective, cation channel capable of conducting large cationic dyes. Herein, we test the hypothesis that P2XR7 channels are activated by histone proteins. We expressed mouse P2XR7 (C57BL/6J variant 451L) in heterologous cells ( Xenopus oocytes) and measured inward cation current using two-electrode voltage clamp (TEVC). Cells expressing mouse P2XR7 had robust ATP- and histone-evoked inward cation currents. ATP- and histone-evoked currents reversed approximately at the same potential. Current decay with agonist removal was much slower for histone-evoked than ATP- or BzATP-evoked currents. As with ATP-evoked P2XR7 currents, histone-evoked currents were inhibited by non-selective P2XR7 antagonists (Suramin, PPADS, and TNP-ATP). GW791343, a selective P2XR7 antagonist with a known binding site distinct from the ATP binding site, inhibited ATP-evoked currents but did not inhibit histone-evoked currents. As with ATP-evoked currents, histone-evoked P2XR7 currents were also increased in conditions of low extracellular Ca2+. These data demonstrate that P2XR7 is necessary and sufficient for histone-evoked inward cation currents. These results suggest a new allosteric mechanism of P2XR7 activation by histone proteins that may guide the development of more effective P2XR7 pharmacology and therapeutic strategies for a wide array of pathologies that involve P2XR7 function. DMC is supported by NIH R00HL133451 and R01HL155180 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.
Emotional responsiveness to daily stress is related to exaggerated cardiovascular stress reactivity in adults with major depressive disorder
Authors: Darling Ashley , Dominguez Cynthia , Mogle Jacqueline , Saunders Erika , Almeida David , Greaney Jody 
Published: May 2023

Increased frequency of exposure and affective responsivity to daily stressors are predictive of future cardiovascular disease (CVD)-related health outcomes and mortality. Profound stress system dysfunction is a hallmark characteristic of major depressive disorder (MDD), likely contributing to MDD-CVD comorbidity. Although a greater increase in negative affective responsivity (NA-R) to daily stress is evident in adults with MDD, whether this is linked to heightened cardiovascular stress reactivity remains unclear. We hypothesized that the slope of the positive relation between daily stress (quantified as both exposure frequency and NA-R) and the magnitude of acute stress-induced increases in heart rate (HR) and blood pressure would be steeper in adults with MDD compared to healthy non-depressed adults (HA). For 8 consecutive days, stressful events encountered in everyday life and while in naturalistic environments (e.g., argument with a partner) were assessed via an ambulatory daily diary in 40 HA (22±4 yrs; 24 female) and 40 adults with MDD (23±6 yrs; 32 female). On the last day of the daily dairy, HR (electrocardiogram) and mean arterial pressure (MAP; finger photoplethysmography) were measured during the cold pressor test (CPT). Daily stress exposure frequency was calculated as the percentage of days with at least one stressor reported across the 8-day protocol, and NA-R was calculated as the intra-individual slope of the change in negative affect on stressor days (at least 1 stressor) compared to negative affect on stressor-free days (no stressors). There were no group differences in the frequency of daily stressor exposure [36±26 (range: 0-100) HA v 41±23% (range: 0-100) MDD; p=0.32]; however, as expected, NA-R was greater in adults with MDD [0.23±0.10 (range: 0.09-0.52) HA vs 0.34±0.16 a.u. (range:0.09-0.71) MDD; p<0.01]. Daily stressor exposure frequency was not related to CPT-induced increases in HR or MAP in either group (all p>0.05). However, NA-R was positively related to both the CPT-induced increase in HR (β=35.18, SE=9.04, p<0.01) and MAP (β=20.20, SE=9.16, p=0.03) in adults with MDD but not in HA (HR: β=2.89, SE=21.23, p=0.89; MAP: β=1.70, SE=17.78, p=0.92). These data suggest that increased emotional vulnerability to common stressors that occur in naturalistic environments and as a part of day-to-day living is linked to potentiated cardiovascular stress reactivity in young adults with MDD, likely contributing to increased CVD risk. NIH R21MH123928 and R00 HL133414 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.