bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Water Homeostasis in a Novel Non‐human Primate Model of Gestational Hypertension
Authors: Weaver Chelsea C , Rhoads Megan K , Grobe Justin L , Osborn Jeffrey L 
Published: November 2023

De novo maternal hypertension, or gestational hypertension (GH), is a common yet poorly understood complication of pregnancy that may precede pre‐eclampsia (PE). PE affects 5–10% of pregnancies worldwide and may contribute to 40–60% of maternal deaths in underdeveloped countries. The only known treatment of PE is delivery of the offspring and placenta. Understanding the pathogenesis of GH and/or PE, as well as impacts on the fetus and newborn, could provide more effective diagnostics and treatments. At present, no animal model of spontaneous GH or PE has been identified. In this study, we report characteristics of GH and possibly PE in the nonhuman primate Chlorocebus aethiops sabaeus or vervet. GH was defined as a systolic blood pressure (SBP) exceeding 140 mmHg in the second trimester of pregnancy. Systolic blood pressures (SBP) were obtained using forearm plethysmography under ketamine sedation (15 mg/kg i.m.). Animals were characterized as normotensive (NT; SBP < 120 mmHg), borderline hypertensive (BHT; SBP ≥ 120 mmHg and < 140 mmHg), hypertensive (HT; SBP ≥ 140 mmHg), or GH (SBP ≥ 140 mmHg during pregnancy and NT either pre‐ or post‐pregnancy). Non‐pregnant SBP for NT was 119 mmHg (n = 1) and for GH was 107.67 ± 11.46 mmHg (mean ± SEM, n = 3). Peri‐pregnancy SBP for NT was 112 mmHg (n = 1) and for GH was 154.67 ± 6.39 mmHg (mean ± SEM, n = 3). Mean birth weights of babies born to pre‐pregnancy NT mothers was 309.51 ± 10.15 g (n = 4), to pre‐pregnancy HT mothers was 289.52 ± 18.35g (n = 3), and to GH mothers was 179.23 ± 49.23 g (mean ± SEM, n = 2). The average slope of growth rates from birth to 7–16.5 weeks of age for babies born to NT mothers was 34.04 ± 2.00 g/wk (n = 4), to HT mothers was 26.95 ± 1.80 g/wk (n = 3), and to GH mothers was 43.59 ± 2.34 g/wk (mean ± SEM, n = 2). Average daily water consumption for non‐pregnant females was 77.92 ± 23.53 ml/day (n=6) and for pregnant females was 210 ± 18.36 ml/day (mean ± SEM, n=5, p<0.05). Urine flow rate for non‐pregnant females was 65.56 ± 10.40 ml/day (n=6) and for pregnant females was 97.33 ± 13.05 ml/day (n=5, p=0.06). These data suggest significant positive water balance during pregnancy of female vervets, similar to the response in human pregnancies. Future studies include examination of renal glomerular structure, urinary protein excretion, characterization of plasma and urine osmolarity, osmolar excretion, plasma levels of human PE biomarkers including copeptin, sFlt‐1 and PlGF, free water clearance and placental transcriptomics to establish these animals as a novel spontaneous model of PE. Due to the shared organ physiology (eg ‐ placental structure) and close genetic homology to humans, identification of GH and possibly PE in C. aethiops (vervet) provides a highly translational physiological and genomic animal model to study these severe known pathologies of pregnancy.Support or Funding InformationBiomedical Science Research Group, LLC and the Gertrude Flora Ribble Foundation
Dihydrotestosterone Mediates Neuroprotective Effects via Estrogen Receptor Beta Following Brain Ischemia‐Reperfusion Injury in Male Mice
Authors: Shi Samuel , Liu Qiang , Gonzales Rayna J 
Published: November 2023

Stroke accounts for almost 6.7 million deaths each year and is the foremost cause of disability worldwide. So far therapeutic options are limited clinically. Experimentally, gonadal sex steroids have been shown to be effective neuroprotectants and part of their neuroprotective actions has been attributed to their anti‐inflammatory properties. We have previously shown that androgens, particularly dihydrotestosterone (DHT), an endogenous and nonaromatizable androgen receptor (AR) agonist, and its endogenous downstream metabolite, 5α‐androstane‐3β,17β‐diol (3β‐diol) elicit anti‐inflammatory effects in human cerebrovascular cells during conditions of hypoxia plus glucose deprivation, an in vitro model of ischemia. Effects of DHT and 3β‐diol were AR independent and estrogen receptor beta (ERβ) dependent. Since inflammation is a critical component in the pathogenesis of stroke and our previous data show that these endogenous androgens elicit anti‐inflammatory actions, we investigated whether DHT or 3β‐diol elicits beneficial effects following cerebral ischemic injury. Adult male mice were subjected to transient focal middle cerebral artery ischemia for 60 min followed reperfusion. A bolus amount of DHT (5 mg/kg), 3β‐diol (5 mg/kg), or vehicle (0.01% etoh) was subcutaneously injected immediately following establishment of reperfusion. Neurodeficits and lesion volume were assessed at 24 and 72 h post reperfusion using 2,3,5‐triphenyltetrazolium chloride histology and magnetic resonance imaging. At both time points post reperfusion, DHT and 3β‐diol reduced lesion volume suggesting protection from ischemic injury in both the striatum and cortex. In addition, we also demonstrated that DHT and 3β‐diol significantly improved neurodeficits with the treated population scoring an average of 4 scores less in the modified neurological severity score at 24 and 72 h time points when compared to vehicle controls. Treatment of DHT in combination with the selective ERβ antagonist, PHTPP, reversed DHTs effect and resulted in a comparable lesion size to the vehicle control group at both 24 and 72 h post injury and during reperfusion. This suggests that the neuroprotection observed in the DHT group is ERβ dependent. In conclusion, our data suggest that endogenous androgens are an important mediators of ischemic damage and promote neuroprotection post cerebral ischemia and reperfusion. Our ongoing studies will determine the specific mechanisms associated with DHT and 3β‐diol and their involvement in selective ERβ activation in attenuating ischemic brain injury.Support or Funding InformationValley Research Partnership Program Grant (RG) and American Heart Association Grant 16SDG27250236 (QL)
25 (OH) D3 treatment improves inflammatory pathway on monocytes lineage (U937) in uremic environment
Authors: de Oliveira Brito Rodrigo Barbosa , Rebello Jacqueline Ferritto , dos Santos Oliveira Willian Rubens , Grabulosa Caren Cristina , Matos Yves Siva Teles , Malta Camila Soares , Dellê Humberto , Dalboni Maria Aparecida 
Published: November 2023

The chronic kidney disease (CKD) is characterized by an inflammatory state caused by the presence of uremic toxins in plasma of patients. This inflammatory condition is associated with a higher risk for cardiovascular diseases and infections. In CKD there is a deficiency of vitamin 25 (OH) D, which has immunomodulatory properties, and that supplementation of the same can decrease inflammation present in uremia.The aim of this study was to evaluate the effect of 25 (OH) D of inflammatory pathways such as toll like receptor 4 (TRL4), oxidative stress (ROS) and expression of vitamin D receptor (VDR), 1‐α hydroxylase, 24‐hydroxylase and inflammatory mediators in monocytes in uremic environment.The monocyte U937 cell line were treated with or without 25 (OH) D 50ng/ml for 24 hours and then they were incubated with 50% serum of healthy patients or uremic patient sera Durantes 24 hours at 37 °C and 5 CO2. The monocytes were characterized by expression of CD14 + cells. The TRL4, VDR, CYP24, Cyp27 and ROS was evaluated by flow cytometry. It was performed in the cell culture supernatant ELISA for IL‐6, TNF‐α, IL‐10, MCP‐1 and cathelicidin.We observed a high expression of TRL‐4, IL‐6, TNF‐α, IL‐10 cathelicidin and MCP‐1 in monocytes incubated with uremic serum, when compared incubated with healthy serum. Pretreatment with 25 (OH) D were able to reduce the expression TRL4, cathelicidin‐1 and MCP opposite uremic environment. There was no difference in the expression of VDR and CYP27 and CYP24 enzymes.We conclude that the uremic environment induces inflammation by increasing TRL4 and inflammatory mediators and the vitamin D treatment indicates an improvement in the inflammatory parameters and may result in reduced inflammation in uremic environment.Support or Funding InformationFAPESP 2014/14192‐1
Decrease in Inflammation (CRP) and Heart Rate Through Mirthful Laughter
Authors: Bains Gurinder , Berk Lee , Lohman Everett , Daher Noha , Miranda Belinda 
Published: November 2023

IntroductionWith the growth in life expectancy, there is a need for whole‐person care that enhances Quality of Life. Humor associated mirthful laughter has proven to yield numerous whole person health related benefits such as lowering the stress hormone cortisol and improving vascular function. High sensitivity C Reactive Protein (hs‐CRP) is an inflammatory bio‐marker. There are no known studies that compared humor/laughter and a distress state in acute hs‐CRP blood levels.PurposeTo evaluate the effect of humor associated mirthful laughter and distress on acute CRP and heart rate (HR) modulation in a humor group vs. a distress group.MethodsThirty‐two healthy adults were enrolled (humor group, n = 16; distress group, n = 16). The humor group consisted of 8 males and 8 females with a mean age of 26.4 ± 4.4 years. The distress group consisted of 8 males and 8 females with a mean age of 27.1 ± 3.0 years. The hs‐CRP levels were obtained through a finger stick blood test. The hs‐CRP levels were collected at three time points; immediately after signing the informed consent, immediately after watching a 20‐minute humorous video or distressing video, and 30 minutes after the second hs‐CRP test. HR was taken immediately before the first hs‐CRP sample and then five minutes after the first, second, and third hs‐CRP measurement. The humor group self‐selected a humor video of either 20 minutes of Russell Peters stand‐up comedy or a montage of America's Funniest Home Videos. The distress group watched the first 20 minutes of the movie Saving Private Ryan.ResultsThere were no significant differences in mean CRP levels and HR over time (p=.24 and p=.06 respectively). For the humor group, CRP levels decreased from 1.65 ± 1.25 mg/L (baseline) to 1.42 ± 1.03 mg/L (post humor); p=.025. For the distress group, there was no significant change in CRP levels for the same time period. For the humor group, HR decreased from 79.5 ± 14.1 bpm (baseline) to 73.4 ± 10.2 (5 minutes post humor) and to 71.2 ± 10.6 bpm (35 minutes post humor); p=.01 and .001 respectively. For the distress group, however, there was no significant change in HR for the same time period.ConclusionThe health benefits of humor associated mirthful laughter showed a decrease in inflammation (hs‐CRP) and HR and thus, is more beneficial than being in a state of distress. Our pilot study shows potential rehabilitative benefits that can be integrated to whole person wellness platforms. Results indicate that humor and laughter can provide essential components in improving Quality of Life. Further research is needed to expand these positive findings.Support or Funding InformationLoma Linda University School of Allied Health
Hypoxia/re‐oxygenation increases the response of afferent arterioles to angiotensin II ‐ Investigation in mouse kidney slices
Authors: Pahlitzsch Tamara , Braun Diana , Ludwig Marion , Persson Pontus B. , Patzak Andreas 
Published: November 2023

Hypoxia/re‐oxygenation (H/R) plays an important role in the pathogenesis of acute kidney injury (AKI). However, the influence of H/R on cortical microvessel function, especially that of afferent arterioles, is sparsely investigated. We hypothesize that H/R increases the vasoreactivity to angiotensin II (Ang II), which may promote the development of kidney injury. To test the hypothesis, we applied an innovative in situ model of live kidney slices.Experiments were performed in acute kidney slices (200 μm) of C57BL/6 mice. The TUNEL assay was used to estimate viability of slices by determining the percentage of apoptotic cells. For functional experiments, kidney slices were situated in a chamber at 37°C. Bath solution was equilibrated with carbogen. The afferent arterioles were visualized by differential interference contrast applied to an inverted microscope. To characterize arteriolar reactivity in this model of kidney slices, Ang II, norepinephrine, endothelin‐1 and ATP were administered. For H/R experiments, the slices were transferred into a hypoxia chamber (1% O2) for 30, 60 or 90 minutes and re‐oxygenated for 10 or 20 minutes.H/R did not significantly influence the apoptotic cell portion in the slice compared to control conditions. Afferent arterioles responded to the bolus application of Ang II (10−7 mol/l) with a maximum constriction, to 44.5 ± 2.8 % of the initial diameter. Norepinephrine (10−5 mol/l), endothelin‐1 (10−5 mol/l) and ATP (10−5 mol/l) reduced the diameter under control conditions to 50.0 ± 2.2%, 45.3 ± 2.6% and 74.1 ± 1.8, respectively. Inhibition of the NO‐synthesis by L‐NAME (10−4 mol/l) significantly enhanced the vasoconstriction to Ang II (32.3 ± 2.3 %). H/R increased the Ang II response of afferent arterioles compared to control conditions. Longer periods of hypoxia were associated with greater arteriolar vasoconstriction to Ang II (30/20 vs. 90/20: 39.7 ± 4.1% vs. 25.9 ± 2.0 %.). Also, increasing the duration of re‐oxygenation resulted in increased vasoconstriction (90/10 vs. 90/20: 34.7 ± 3.5% vs. 25.9 ± 2.00%).TUNEL staining and functional testing with vasoactive substances indicates the usefulness of the in situ model for the investigation of afferent arteriolar function. The increased response to Ang II in H/R suggests this effect as one component in the multifactorial genesis of AKI.Support or Funding InformationGerman Research Foundation (DFG PA 479/10‐2)
Surviving low oxygen: exploring the role of AMP‐activated Kinase in anoxia‐tolerance
Authors: Van Carter Amen‐Geb 
Published: November 2023

High altitude, stroke and cardiorespiratory disorders are damaging to mammalian tissues in that they cause oxygen (O2) deprivation in organs that are energy‐demanding. The zebrafish model provides unique insight into mechanisms of adaptation to O2 deprivation, as zebrafish embryos can adapt to low O2 by entering a state of developmental arrest that conserves cellular energy (ATP). The zebrafish model may therefore reveal targets for therapeutic treatment of hypoxia‐related injury. The Brewster lab aims to identify the signaling pathways that induce the arrested state in response to anoxia (zero O2).We hypothesize that AMPK (AMP‐activated kinase) is a key mediator of developmental arrest. AMPK is activated by anoxia and conserves ATP by inhibiting cell cycle progression and protein translation in various contexts. We predict that activation of AMPK under anoxia is necessary for the zebrafish embryo to enter developmental arrest. If our hypothesis is correct, we predict that loss of AMPK function under anoxia will lead to premature death. In our ongoing study, we are testing this prediction by comparing arrest and survival rates of Wt (wild‐type) zebrafish embryos to that of mutant zebrafish embryos that are unable to activate AMPK due to a mutation in LKB1, an upstream activator of AMPK.In order to test this prediction, we are comparing the survival of Wt and LKB1 mutant zebrafish embryos under anoxia. We report here on preliminary studies assessing the LD‐50, the duration of sustained anoxia at which 50% of embryos survive after reintroduction to normal O2‐levels for 24 hours, on Wt embryos at dome stage. We have found that the LD‐50 for Wt zebrafish embryos at dome stage is between 18 and 24 hours under our environmental conditions. Similar studies using LKB‐1 embryos at the dome stage are underway. We anticipate that these studies may reveal a novel role for AMPK in anoxia‐induced arrest and survival.Support or Funding InformationFunding: American Physiological Society STRIDE program. Acknowledgments: Ikenna Okafor (Graduate Mentor), Sharlene Brown (Graduate Mentor), Dr. Rachel Brewster (PI)
Hypoxia activates BK and Kv channels in rat carotid body glomus cells
Authors: Kim Donghee , Wang Jiaju 
Published: November 2023

Inhibition of BK and/or Kv has been proposed to be involved in hypoxia‐induced depolarization and subsequent elevation of intracellular [Ca2+] in carotid body glomus cells. However, depolarization and/or elevation of [Ca2+] are well known to activate BK and Kv, which would oppose glomus cell excitation. First we studied the effect of hypoxia on BK in cell‐attached patches, where the cell Em and intracellular [Ca2+] were allowed to change naturally in response to hypoxia. In cell‐attached patches (140 mM KCl in the pipette and 5 mM in the bath), hypoxia reversibly activated BK while causing inhibition of TASK. In cells partially depolarized by elevating extracellular [KCl] from 5 mM to 12–15 mM KCl, hypoxia also activated BK reversibly. In inside‐out patches showing different levels of BK activity, hypoxia produced no significant effect on BK. Kv could not be detected clearly in cell‐attached patches. Therefore, the role of Kv was tested indirectly by studying the effect of guangxitoxin (GxTX: Kv2 blocker) on hypoxia‐induced rise in intracellular [Ca2+]. GxTX inhibited the outward K+ current by ~50%, and enhanced the hypoxia‐induced elevation of intracellular [Ca2+] 2.3 fold, indicating that hypoxia activated Kv2. These results show that hypoxia activates BK and Kv in rat glomus cells, which helps to limit the hypoxia‐induced excitation of glomus cells.Support or Funding InformationSupported by NIH
Macula Densa Cell Gene Profiling
Authors: Riquier‐Brison Anne , Desposito Dorinne , Moon Ju‐Young , Peti‐Peterdi Janos 
Published: November 2023

Macula densa (MD) cells are chief but still mysterious cells localized at a strategically important anatomical location at the glomerular entrance, and play key regulatory roles in renal and glomerular hemodynamics, body fluid and electrolyte homeostasis, and blood pressure maintenance. The present study aimed to establish the true nature of MD cells by performing unbiased MD gene profiling using two separate and independent approaches. A new mouse model (MD‐GFP mice) was generated with inducible and conditional MD‐specific expression of the fluorescence reporter EGFP by crossing nNOS‐CreERT2 and mTmG‐floxed mice. MD cells were freshly isolated from digested kidneys of MD‐GFP mice using FACS sorting, followed by MD RNA isolation and sequencing. Alternatively, MD RNA isolation and sequencing was performed in another new mouse model by crossing floxed L10a‐EGFP and nNOS‐CreERT2 mice and using the Translating Ribosome Affinity Purification (TRAP) strategy. Compared to whole kidney and adjacent non‐MD tubular epithelial cells, MD‐specific enriched genes included members of secreted angiogenic (Ccn1, Pappa‐2, Gdf15), extracellular matrix remodeling (Mmp14, Ca12), growth factor (Fgf2), developmental and differentiation transcription factor (Bmp3/7, Wnt10a, Hoxa1, Fos), cell cycle and DNA damage regulating (Gmnn, Wee1, Gadd45b) gene families. Our results paint a new picture of MD cells and suggest their new non‐traditional roles in renal interstitial, vascular, and glomerular tissue remodeling.Support or Funding InformationNIH R01 64324, AHA, ADA
Renal Response to Acidosis: RNA‐Seq and Role of NaDC1
Authors: Yadav Santosh , Huang Weitao , Coleman‐Barnett Joycelynn , Hamm Lee , Hering‐Smith Kathleen S 
Published: November 2023

Metabolic acidosis is a common pathophysiologic condition that can occur either acutely or chronically in a variety of settings and diseases. Acidosis has a number of adverse effects including progression of chronic kidney disease, bone loss, and muscle wasting. The kidneys are the main organs which respond to acid loads to protect against systemic acidosis. To enhance our understanding of the renal response to acidosis, we performed RNA‐Seq on kidneys from acid loaded animals. Additionally, since NaDC1 (sodium dicarboxylate transporter 1 in the proximal tubule) is known to respond to acidosis, we addressed the role of NaDC1 in the response to acidosis. NaDC1 reabsorbs citrate and various dicarboxylate Krebs cycle intermediates, some of which have downstream G protein coupled receptors.NaDC1 Knockout (KO) and wild type (WT) mice (C57BL/6 background) were studied on normal or acid diet (0.4M HCl added to chow, X 3 days). Kidney RNA was extracted & integrity validated. RNA‐seq was performed at the Tulane Center for Aging Genomics and Biostats Core using an Ion Proton platform with 20M reads/sample. Bioinformatics completed at Tulane Cancer Crusaders NGS Analysis Core. For qRT‐PCR, RNA was isolated from same kidneys & mRNA relative expression was calculated by ΔΔCt.In WT with acidosis, 1173 transcripts were differentially expressed >1.5 fold (each statistically significant), 525 transcripts upregulated and 648 down regulated. Results were similar to prior microarray data (Nowik et al Physiol Genomics 2008). Among those upregulated many have been previously reported to be involved in the response to acidosis: e.g., PCK1, GLUD1, Car2, SNAT1, NaDC1. Also 36 genes from SLC family were identified and differentially expressed under acidosis. By qPCR, SLC genes 13a2, 13a3, 16a9, 26a6 & 38a3 were upregulated & consistent with RNA‐seq. But we also identified many additional genes that indicate a broader cellular metabolic response to acidosis. In contrast, in KO with acidosis many more transcripts (945) were upregulated >1.5 fold and downregulated (1270) >1.5 fold.In sum, metabolic acidosis significantly alters the expression of hundreds of genes, some directly linked to homeostatic responses, but others involving a variety of metabolic and signaling pathways. The response to acidosis in NaDC1 KO mice is even more profound and may indicate that in the absence of NaDC1, additional response pathways are necessary. This implies that NaDC1 plays a more important role in the response to metabolic acidosis than previously recognized..Support or Funding InformationNIH/NIDDK RO1 DK095879