bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insight into the increased risk associated with CRISPR-generated African G6PD variant (N126D) in rat model of sugen-5416-induced pulmonary hypertension
Authors: Signoretti Christina , Matsumura Shun , Fatehi Samuel , Gupte Sachin 
Published: May 2023

Pulmonary Hypertension (PH) is a cardiopulmonary disease associated with sustained increase in pulmonary arterial and right ventricular pressures, resulting in smooth muscle cell remodeling and the thickening of vasculature. Glucose-6-phosphate dehydrogenase (G6PD) is the rate limiting enzyme in the pentose phosphate pathway and is often associated with oxidative stress and the pulmonary vascular remodeling mechanism seen in PH. CRISPR-mediated single nucleotide polymorphism modeling was used to generate the African G6PD variant (N126D; G6PDN126D), which is an X-linked gene mutation resulting in a 20% decrease in G6PD activity and subsequent hypothesized increased risk of cardiovascular diseases for sub-Saharan individuals. The goal of this study was to determine the effects of the G6PDN126D variant using the Sugen-5416 (20 mg/kg in DMSO)/Normoxia (SU/NX)-induced PH rat model. Cardiac catheterization determined that the G6PDN126D variant-SU/Nx group had higher (G6PDN126D: 29.3 ± 5.2 vs WT: 19.5 ± 2.2; mmHg; p<0.05) mean right ventricle pressure and pulmonary artery remodeling as compared to the WT-SU/Nx group. Further, G6PDN126D variant-SU/Nx had lower nitric oxide levels (G6PDN126D: 10.6 vs WT: 13.6; mM/mg protein; p<0.05) and higher second messenger IP3 levels (G6PDN126D: 4.00 vs WT: 0.52; ng/mg protein; p<0.05) as compared to the WT-SU/Nx group. The data suggests that the African G6PD (N126D) mutation results in increased PH in rats and may be associated with increased risks of severe PH in the sub-Saharan population. These results imply more studies are required to develop personalized medicine for the treatment of PH. RO1HL132574 (SAG), RO1HL166546 (SAG), AHA Grant-in-Aid 17GRNT33670454 (SAG) 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.
Using Limulus Amebocyte Lysate (LAL) to discover the presence of endotoxins in the tanks at the Pritzker Marine Biology Research Center
Authors: Haas Sydney 
Published: May 2023

Endotoxins are harmful for many organisms, including those that live in the water. Therefore, it is important to identify effective ways in identifying if they are present in water environments. Research has been conducted to show that Limulus amebocyte lysate (LAL) is an effective way to determine if endotoxins are present. In this study, LAL was used as the main reagent to detect if endotoxins were present in the tanks at the Pritzker Marine Biology Research Center. It is believed that LAL will be able to detect the presence of any endotoxins within the tanks at Pritzker. The first part of the procedure to do this was to collect 5mL of water from each tank at Pritzker. After the LAL reagent was dissolved in LAL Reagent Water, the gel-clot assay was then produced. 0.1mL of the reagent was added to each assay tube. 0.1mL of each product sample or control was transferred into each assay tube, beginning with the negative control and ending with the highest endotoxin concentration. The contents of the tubes were mixed and incubated undisturbed in a 37 C heating block for 60 minutes. After incubation, each tube was examined for gelation. A positive test is defined as the formation of a firm gel capable of maintaining its integrity when the assay tube is inverted 180 degrees. A negative test is characterized by the absence of gel or by the formation of a viscous mass which does not hold when the assay tube is inverted. Endotoxins were detected in an average of 13 tanks at the Pritzker. To expand upon these findings, quantifying how many endotoxins are present in the tanks and what types of endotoxins are present in the tanks will be tested. Biology department funds at the New College of Florida 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.
Effects of cholecalciferol and calcitriol on skeletal muscle proteolysis in angiotensin II-induced atrophy in differentiated C2C12 cells
Authors: Hirunsai Muthita , Srikuea Ratchakrit 
Published: May 2023

Vitamin D3 has been proposed as a potential treatment to improve muscle atrophy in sarcopenic patients. Several lines of evidence suggested a possible crosslink between vitamin D and renin-angiotensin system contributing to skeletal muscle atrophy in response to chronic diseases in aging population. Nevertheless, effects of vitamin D and its metabolite on skeletal muscle cells challenged with angiotensin II remain unclear. Therefore, the effects of cholecalciferol (VD3) and calcitriol (1,25VD3) on the ubiquitin-proteasome pathway in angiotensin II-induced skeletal muscle cell atrophy were investigated. Differentiated C2C12 skeletal muscle cells (myotubes) were used as in vitro study model. Myotubes were assigned into vehicle (veh), 1 μM angiotensin II (AII), 1 μM angiotensin II+100 nM cholecalciferol (AII+VD3), 1 μM angiotensin II+1 nM calcitriol (AII+1,25VD3) and 1 μM angiotensin II+10 μM losartan (AII+Lo) groups. Myotubes were applied with angiotensin II on day 4-6, while VD3 and 1,25VD3 were treated on day 5-6 of the differentiation phase. For AII+Lo group, losartan was administered at 2 h before angiotensin II at day 4 of the differentiation period. Cells were harvested at day 7 of differentiation phase for morphological and biochemical analyses. Angiotensin II resulted in significantly decreased myotube diameter and tended to increase protein expression of the transcription factor; FoxO3a and ubiquitin ligases; MURF-1 and atrogin-1, the major muscle protein catabolism pathway when compared with veh-treated group. Treatment of VD3 and losartan could protect angiotensin II-induced myotube atrophy. In contrast, 1,25VD3 accelerated muscle protein breakdown in myotube-challenged with angiotensin II. Protein expression of FoxO3a, MuRF1 and atrogin-1 was significantly up-regulated in AII+1,25VD3 group compared to veh, AII+VD3 and AII+Lo-treated groups. By which these occurs were accompanied with the overexpression of vitamin D receptor in myotube co-treated with angiotensin II and 1,25VD3. Herein, differential effects of VD3 and 1,25VD3 in angiotensin II-induced myotube atrophy were demonstrated. Administration of VD3 resulted in attenuated degree of muscle loss-induced by angiotensin II, while 1,25VD3 possessed the negative impact to skeletal muscle protein metabolism. Collectively, vitamin D3 supplement may be considered as an alternative adjuvant to alleviate muscle atrophy in the patients related to high level of angiotensin II. This work was financially supported by Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation (Grant No. RGNS 63-216 to M.H.) and Srinakharinwirot University (to M.H.). 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.
Erythropoiesis-related RNAs biomarkers are sensitive and specific to low-dose erythropoietin treatment at sea level and altitude
Authors: Loria Francesco , Breenfeldt Andersen Andreas , Bejder Jacob , Bonne Thomas , Grabherr Silke , Kuuranne Tiia , Leuenberger Nicolas , Baastrup Nordsborg Nikolai 
Published: May 2023

Background: Indirect detection of recombinant human erythropoietin (rhEPO) abuse in Anti-Doping world is done by hematological module of athlete biological passport (ABP). However, actual markers (reticulocytes (%RET) and hemoglobin (HGB)) of this module are not enough specific and have difficulties to distinguish recombinant human erythropoietin (rhEPO) administration from altitude sojourn especially if both condition are merged. Previous study have demonstrated that erythropoiesis-related RNAs, genes 5’-aminolevulinate synthase 2 ( ALAS2) and carbonic anhydrase 1 ( CA1) in capillary dried blood spots (DBS) could be potential biomarkers to increased specificity and sensitivity of the ABP in case of hypoxic conditions. Study design and methods: In the present study, we monitored ALAS2 and CA1 expression in DBS after injection of 20 IU kg bw-1 epoetin alpha at sea level and the effect merged with altitude exposure. For this purpose, DBSs samples collected from 39 volunteers’ males and females were analyzed. Participants were divided in two groups (EPO and placebo) and subjects from both groups sojourned at sea level and at altitude. The purpose was to evaluate the performance of RNAs biomarkers for the detection of rHEPO injection in a longitudinal blinded setting. Results: Our results illustrated a clear significant increase of ALAS2 until to 300% when treated at sea level and at altitude. Regarding CA1 the increase is up to 200% in both conditions. Interestingly, our results suggested no combined effect of altitude and rhEPO injection on ALAS2 and CA1 biomarkers as previously demonstrated with %RET values. In placebo group. Moreover, no effect of altitude on ALAS2 and CA1 was observed in contrast to %RET parameter. Results from blind setting test demonstrated a performance of interpretation of 92% regarding ALAS2 and CA1 monitoring. Conclusion: Erythropoiesis-related RNAs in capillary DBS such as ALAS2 and CA1 were sensitive and specific biomarkers for low-dose rhEPO misuse at sea level and altitude. Interestingly, altitude seemed not to be a confounding factors for ALAS2 and CA1 biomarkers in contrast to %RET. Furthermore, this investigation provide evidence that low-dose of rhEPO injections can be detected in a longitudinal blinded setting with RNA biomarkers in DBS. World Anti-Doping Agency (WADA) 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.
Conniving of prophetic variables of diagnostic importance and their impending role to develop fibromyalgia
Authors: Tariq Nusrat , Malik Arif 
Published: May 2023

OBJECTIVE: Fibromyalgia (FM) is a widespread syndrome that lacks any evident reason and is characterized by the existence of chronic pain of unknown etiology. Various variables of medical importance were previously studied among the patients to determine their specificity and sensitivity involved in the pathogenesis of the disease but still, the well-defined etiology and theranostic approach are deficient. The current study aimed to determine the specificity and sensitivity of serum biomarkers to establish blood-based tests for the diagnosis of fibromyalgia. HYPOTHESIS: As fibromyalgia disease has an undefined etiology so its diagnosis and treatment are a challenge for medical professionals. The hypothesis of the current research work was to assess that the assayed biomarkers may have sensitivity and specificity regarding fibromyalgia which may become valuable theranostic variables to diagnose fibromyalgia. MATERIALS AND METHODS: The study population comprised of hundred fibromyalgia female subjects, diagnosed according to the ACR criteria of fibromyalgia. Hundred healthy female subjects served as control. Serum levels of interleukins (IL-1,2,6,7,8,9,10,17,18,1B,1RA), matrix metalloproteases (MMP-2,7,9), tumor necrosis factor (TNF-α and β) were assayed by their respective commercially available ELISA kits. A contingency table was drawn upon the recorded data to rule out sensitivity, specificity, accuracy, and odds ratio at 95% CI. RESULTS: Analysed data helped state the potential markers involved in the pathogenesis of fibromyalgia. It showed that IL-1, IL-1RA, MMP-2, and TNF-α stand to be the most sensitive (SN) and specific (SP) markers with SN-SP of (73%-95%, 67%-93%, 67%-88%and, 53%-76%) respectively. Moreover, it showed the odds ratio of IL-1,1RA and MMP-2 remained (49, 26.8, and 14) among the patients. CONCLUSION: Findings of the current study entitles the importance of IL-1, IL-1RA, TNF-a, and MMP-2 as they show maximum accuracy along with high sensitivity and specific range in fibromyalgia. Higher values of the odds ratio determine that IL-1, IL-1RA, TNF-a, and MMP-2 are more specific and sensitive for fibromyalgia. Thus, their early detection could have significant importance in ruling out the disease condition. Maximum accuracy and a higher sensitivity range of the said variables may have medical and theranostic importance in treating fibromyalgia. This research did not receive any special grant from funding agencies in the public, commercial or not-for-profit sectors. 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 Physiology of Migraine and its Prevention by Nutrition
Authors: Stanton Angela 
Published: May 2023

Migraine is a genetic condition associated with hypersensitive sensory neurons, more sensory neuronal connections, and different electrical properties than a non-migraine brain[1, 2]. Migraineurs waste 50% more sodium in their urine than typical subjects[3]. The most prominent migraine related genetic variants are associated with critical ionic channels that operate the brain’s electrical functions: action potential, resting potential, the delivery of neurotransmitters, and the resetting of membrane potential[4, 5]. Migraineurs’ brains are very sensitive to electrolyte imbalance as a result of channelopathy[6-8] and because of carbohydrate sensitivity. Migraineurs tend to end up with metabolic syndrome. In this paper I present case studies based on findings in a Facebook migraine group with over thirteen thousand migraine members, who have been able to abort and prevent all of their migraines while also tapering off of all of their migraine medications, by applying only nutritional and hydration changes.1. Ambrosini, A. and J. Schoenen, The electrophysiology of migraine. Curr Opin Neurol, 2003. 16(3): p. 327-31. 2. Tso, A.R., et al., The anterior insula shows heightened interictal intrinsic connectivity in migraine without aura. Neurology, 2015: p. 1043-50. 3. Campbell, D.A., E.M. Tonks, and K.M. Hay, An Investigation of the Salt and Water Balance in Migraine. British Medical Journal, 1951: p. 1424-1429. 4. Science, W.I.o. The Human Gene Database. GeneCards: The Human Gene Database 2017 [cited 2017 1/28/2017]; The Human Genome Database]. Available from: http://www.genecards.org . 5. Liu, H., et al., Resting state brain activity in patients with migraine: a magnetoencephalography study. The Journal of Headache and Pain, 2015. 16(1): p. 42. 6. Lee, J.-Y. and M. Kim, Current Issues in Migraine Genetics. J Clin Neurol, 2005. 1(1): p. 8-13. 7. Catterall, W.A., et al., Inherited Neuronal Ion Channelopathies: New Windows on Complex Neurological Diseases. The Journal of Neuroscience, 2008. 28(46): p. 11768-11777. 8. Longo, D.L., et al., Harrison's Manual of Medicine 18th Edition. 2013, New York: McGraw Hill Medical. Not funded 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 impact of skipping a meal on perceived stress and mental distress
Authors: Welch Megan , Rosenberg Lexis , Nagorny Katerina , Chowdhury Ushima , Bubis Sabrina , Begdache Lina 
Published: May 2023

The prevalence of food insecurity is exceptionally widespread, largely affecting those who do not have access to healthy and consistent food. Skipping a meal due to a lack of money or other resources is one prominent aspect of food insecurity that many must practice to survive. The aim of the study is to assess the impact of skipping a meal on participants’ perceived stress and mental distress. It is hypothesized that skipping a meal is directly related to an increase in perceived stress and mental distress. An anonymous questionnaire was administered through social media outlets, such as GroupMe, Facebook, and Instagram, to individuals over 18. The questionnaire included demographic questions and seven validated scales, including the Brief Resilience Scale, Stress Mindset Measure, Perceived Stress Scale, Food Mood Questionnaire, Food Insecurity Experience Scale, Academic Motivation Scale, Kessler-6, and the Psychological Distress Scale. These scales measured dietary and physical activity, the prevalence of food insecurity, stress, mental distress, resilience, academic motivation, and perceived stress. Data from 1005 individuals were analyzed using Spearman’s Rho correlation in IBM SPSS Version 25.0. Our results indicate that skipping a meal has a positive correlation with symptoms of mental distress, such as lack of confidence, nervousness, lack of energy, and irritability (p<0.01). This could be detrimental to students and older individuals alike, as food insecurities are a rising global issue and can negatively impact day-to-day life. Our study suggests that one aspect of food insecurity, such as skipping meals, may increase feelings of mental distress and negatively impact the quality of life. Currently applying to Binghamton University Undergraduate Research Center and Harpur Edge 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.
StomachSim: An in-silico simulator of gastric biomechanics with application to pyloroplasty
Authors: Kuhar Sharun , Seo Jung-Hee , Pasricha Pankaj , Mittal Rajat 
Published: May 2023

Aim: We have developed StomachSim, an in-silico simulator that is designed to simulate the biomechanics and fluid mechanics of a wide range of gastric conditions as well as gastric surgical procedures. Here we demonstrate its use in quantifying the effects of motility disorders and pyloroplasty on the hydrolysis and emptying of a liquid meal inside the stomach. Methods: A physiologically realistic model of the stomach, including the antral motility, is synthesized based on in-vivo imaging, and the mixing and gastric emptying are simulated using computational fluid dynamics (CFD). The enzymatic biochemistry for protein hydrolysis is also implemented by incorporating the secretion of a proteolytic enzyme from the proximal stomach walls and the subsequent enzymatic reaction with the protein dissolved in the liquid meal. Using this model, we measured the effect of stomach motility and the diameter of the pyloric orifice on the retropulsive and pyloric jets, the rate of hydrolysis in different regions, and the emptying of gastric contents. Results: This study presents a proof-of-concept for the application of StomachSim in gastric disorders and surgeries. The emptying rate of our model for the healthy case agreed with the in-vivo measurements of similar caloric density liquid meals. A stomach with a 50% lower motility amplitude had a 35% lower net emptying rate and a 41% lower emptying rate of the hydrolyzed protein. Furthermore, the emptying rate showed a non-linear variation with respect to the motility of the stomach. For a simulated pyloroplasty procedure where the pyloric orifice diameter is doubled and the orifice stays open permanently, the emptying rate of the lower motility case doubled over its original value. Conclusion: StomachSim offers a novel and potentially effective modality for examining the effect of gastric conditions and gastric surgical procedures on gastric function. Our simulations show that gastroparesis and pyloroplasty not only affect the emptying rate but also alter the mixing of contents thereby changing the rate of hydrolysis. The model helped quantify the changes in the flow of contents in the antro-duodenal region for varying degrees of gastroparesis and pyloroplasty. The authors acknowledge support from NSF award CBET 2019405 and NIH award 1R21GM139073-01. 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.
Epoxyeicosatrienoic Acid administration or Soluble Epoxide Hydrolase inhibition attenuates renal fibrogenesis in obstructive nephropathy
Authors: Padanilam Babu 
Published: May 2023

Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites with biological effects, including anti-apoptotic, anti-inflammatory, and anti-fibrotic functions. Soluble epoxide hydrolase (sEH)-mediated hydrolysis of EETs to dihydroxyeicosatrienoic acids (DHET) attenuates these effects. Recent studies have demonstrated inhibition of sEH prevents renal tubulointerstitial fibrosis and inflammation in chronic kidney disease (CKD) model. Given the pathophysiological role of the EET pathway in CKD, we investigated if administration of EETs regioisomers and/or sEH inhibition will promote anti-fibrotic and reno-protective effects in renal fibrosis following UUO. EETs administration abolished tubulointerstitial fibrogenesis, as demonstrated by reduced fibroblast activation and collagen deposition after UUO. Inflammatory response was prevented as demonstrated by decreased neutrophil and macrophage infiltration and expression of cytokines in EETs-administered UUO kidneys. EETs administration and/or sEH inhibition significantly reduced M1 macrophage markers while M2 macrophage markers were highly upregulated. Furthermore, UUO-induced oxidative stress, tubular injury, and apoptosis were all downregulated following EETs administration. Combined EETs administration and sEH inhibition however, had no additive effect in attenuating inflammation and renal interstitial fibrogenesis after UUO. Taken together, our findings provide a mechanistic understanding of how EETs prevent kidney fibrogenesis during obstructive nephropathy, and suggest EETs treatment as a potential therapeutic strategy to treat fibrotic diseases. NIH DK 116987 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.