bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol, not fat, is critical in atherogenesis induced by intermittent hypoxia and hypercapnia
Authors: Xue Jin , Poulsen Orit , Meadows Jason , Zhou Dan , Haddad Gabriel 
Published: May 2023

Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by intermittent hypoxia and hypercapnia (IHC) and is known to increase risk for atherosclerosis. Most of OSA patients are obese. However, the particular role of high fat and high cholesterol in inducing or promoting atherosclerosis under IHC remains obscure. To dissect the mechanisms involved, we examined atherosclerotic formation in the Aorta, Aortic arch and Pulmonary artery (PA) in pro-atherogenesis mouse model, the apolipoprotein E ( ApoE) deficient mice, after IHC exposure on either high fat diet (HF, 60% fat by Kcal and 0.003% cholesterol by weight) or high fat high cholesterol diet (HFHC, 42% fat by Kcal and 1.3% cholesterol by weight), and compared them to room air (RA) control groups fed with HF, HFHC or regular chow (RC, 10% fat by Kcal and 0.003% cholesterol by weight). Our data revealed that HFHC-treated mice had significantly more atherosclerotic lesions than those fed with RC in room air (e.g. Aorta, RA-HFHC 8.1±0.76% vs RA-RC 1.0±0.27%, p<0.01). 10-week IHC treatment further accelerated atherogenesis in Aorta, Aortic arch and PA as compared to RA controls in the presence of HFHC (Aorta, IHC-HFHC 13.8±0.96% vs RA-HFHC 8.1±0.76%, p<0.01; Aortic arch, IHC-HFHC 28.5±1.88% vs RA-HFHC 16.6±2.00%, p<0.01; PA, IHC-HFHC 28.9±2.81% vs RA-HFHC 12.2±1.51%, p<0.01). Intriguingly, HF diet alone didn’t cause significant difference in terms of atherosclerotic lesions among RA-RC, Air-HF and IHC-HF groups (Aorta, IHC-HF 0.6±0.20% vs RA-HF 0.1±0.06% vs RA-RC 0.4±0.08%, p>0.01; Aortic arch, IHC-HF 2.0±0.73% vs RA-HF 0.4±0.20% vs RA-RC 1.0±0.26%, p>0.01; and PA, IHC-HF 1.4±0.33% vs RA-HF 0.2±0.20% vs RA-RC 0.0±0.04%, p>0.01), indicating that high fat alone is insufficient to induce atherosclerosis under both RA and IHC conditions. In conclusion, our data demonstrated that (1) high cholesterol, but not high fat, plays a critical role in the development of atherosclerosis; (2) impact of IHC on atherosclerosis depends on the presence of HFHC. This study is supported by the National Institutes of Health grant 1R01HL157445-01A1. 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.
Periodontitis accelerates the development of arterial hypertension in spontaneously hypertensive rats (SHR)
Authors: Buzinari Tereza , Castania Jaci , Salvador Sergio , Salgado Helio 
Published: May 2023

Objectives: Arterial hypertension and the inflammatory process are pathophysiologically associated. Of note, it is well understood that periodontitis is an inflammatory morbidity, epidemiologically related to cardiovascular mortality, particularly with the risk of developing arterial hypertension. Considering that in Spontaneously Hypertensive Rats (SHR) the elevation of arterial pressure starts from the 7th week of age, this study aimed to evaluate whether periodontitis accelerates the onset of arterial hypertension, for instance, in 5-week-old SHR. Methods: Induction of periodontitis was started in 3-week-old SHR and maintained for 2 weeks through the ligation of the left first molar with a silk suture, followed by the Porphyromonas gingivalis (strain W83) administration, p.o., 3 times a week. The femoral artery of 5-week-old SHR was cannulated, and 24 hours later, with the animals awakened, the systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressures were recorded. Results: 5-week-old control SHR (SHAM) did not have installed arterial hypertension, while SHR with periodontitis (PER) exhibited a higher arterial pressure when compared to the SHAM group (SAP PER: 150±4 vs. SAP SHAM: 124±3 mmHg, n=8, p≤0.001; DAP PER: 103±5 vs. DAP SHAM: 85±5 mmHg, n=8, p≤0.05; MAP PER: 119±4 vs. MAP SHAM 98±4 mmHg n=8, p ≤0.01). Conclusion: The differences observed in the pressure values between the groups studied demonstrate that periodontitis accelerates the development of hypertension in SHR. Funding Sources: Fundação de Amparo à Pesquisa do Estados de São Paulo - FAPESP, Process 2021/08622-7 and 2020/06043-7. Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq, Process 306994/2021-6 and 423999/2021-4. 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.
Sex based differences in muscle regeneration
Authors: Liu Siyu , Kostek Matthew , Omstead Kailey 
Published: May 2023

Background: Normal skeletal muscle healing can be affected by various factors including biological sex. Males and females differ in the healing process such as the time course of the inflammation, recovery of muscle force, and period of regeneration. How exactly these processes differ is not well understood. Glycerol injections are a novel chemical model of skeletal muscle injury that mimic aspects of muscular dystrophy but currently there are no sex comparisons for this model. Therefore, the purpose of this study is to compare the difference in skeletal muscle healing between males and females, in a time course study, using this new method. Method: Male and female mice were split into two groups. Mouse gastrocnemius muscle was injected with glycerol (experimental) or saline (control) on day 0. Muscle physiology testing was performed 3 days (n=14) and 12 days (n=14) after injection, followed by hind-limb muscle collection and preservation for H&E, F480, necrosis, and eMyHC histological analysis. Result: Male groups had significantly higher muscle force production than the female groups (p<0.001). The improvement of muscle force production in the female group from 3 days to 12 days is significant (p<0.05), but the recovery of males did not reach statistical significance during this time period (p=0.659). There was greater pathology in the female group than the male group at 12 days after glycerol injection. Muscle regeneration occurred more at 12 days in females based on eMyHC analysis (p<0.05). Histological analysis is ongoing, but preliminary observations concur with the muscle physiology testing. Conclusion: The timeline of the muscle repair is different between the male and female groups. Muscle repair and regeneration are still ongoing at 12 days, which means interventions can be applied and studied during this time period. The difference in muscle regeneration between male and female groups is possibly due to hormone effects such as estrogen. Our laboratory is currently planning therapeutic trials based on levels of estrogen and exercise. 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 statin therapy on vascular reactivity in patients with Heart Failure with Preserved Ejection Fraction
Authors: Iacovelli Jarred , Alpenglow Jeremy , Bunsawat Kanokwan , Ma Christy , Ryan John , Wray D 
Published: May 2023

Background: HFpEF is characterized by peripheral vascular dysfunction, which likely underlies clinical presentations such as dyspnea on exertion and severe exercise intolerance in this population. HMG-CoA reductase inhibitors, also known as “statins,” can exert beneficial pleiotropic effects on the vasculature that may be related to improvements in nitric oxide (NO) signalling. However, it has yet to be investigated whether statin therapy can improve vascular function in patients with HFpEF. We hypothesized that 30-day statin therapy would improve upper limb conduit vessel and microvascular function, as determined by brachial artery flow-mediated dilation (FMD) and reactive hyperemia (RH), respectively, and improve locomotor muscle microvascular responsiveness, as determined by passive limb movement (PLM). Methods: Using a double-blind, parallel design, patients with HFpEF were studied before and after randomization to 30 days of statin therapy (atorvastatin, 10 mg; QD, n = 4) or placebo ( n = 3). FMD, RH, and PLM testing was performed via ultrasonography according to published guidelines. Results: Compared to baseline values, FMD tended to improve following statin therapy (2.8 ± 2.4% to 4.7 ± 1.5%, day 0 to day 30, P=0.06), with no change following placebo (P=0.87). FMD adjusted for shear also tended to improve following statin therapy (0.09 ± 0.08AU to 0.15 ± 0.03AU, day 0 to day 30, P=0.07), with no change following placebo (P=0.79). RH was unchanged following both statin (P=0.24) and placebo (P=0.31) interventions. PLM AUC appeared to improve following statin therapy (98 ± 62ml to 184 ± 111ml, day 0 to day 30, P=0.22), with no change following placebo (P=0.64). The peak blood flow response to PLM was unchanged in both statin (P=0.31) and placebo (P=0.28) groups. Conclusions: While no statistically significant differences were observed, qualitative analyses suggest that statin therapy may improve upper limb conduit vessel function and locomotor muscle microvascular responsiveness in patients with HFpEF, supporting the potential efficacy of this drug class to improve vascular function. These improvements in vascular reactivity provide preliminary evidence for improved NO bioavailability that may translate to improvements in functional capacity and exercise tolerance in this patient group. Funded in part by grants from the U.S. Department of Veteran’s Affairs (1I01CX002152, D.W.W., 1IK2RX003670, K.B.) and the National Institutes of Health (5T32HL139451, K.B.). 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.
TRPV4 and mechanosensitive regulation of hemichannel function in ocular nonpigmented ciliary epithelium
Authors: Shahidullah Mohammad , Delamere Nicholas 
Published: May 2023

Purpose: Previously we reported a mechanosensitive ion channel, TRPV4, along with functional connexin hemichannels on the NPE basolateral surface. In the lens, we have evidence of TRPV4-mediated hemichannel opening as part of a feedback mechanism that enables the lens to sense and respond to swelling. The present study was undertaken to test the hypothesis that TRPV4 and hemichannels might function as a mechanosensor in ocular nonpigmented ciliary epithelium (NPE). Methods: Porcine NPE cells were cultured on either plastic culture plates to study effects of osmotic swelling stretch, or on flexible membranes (Flexcell) to study effects of axial cyclic stretch. ATP release and the uptake of the large molecule propidium iodide (PI) from the bathing medium were taken as indicators of hemichannel opening and determined by luminescence and fluorescence. Results: NPE cells subjected to cyclic stretch for 1-10 min (10%, 0.5 Hz) significantly increased ATP release (CTRL 0.3±0.002 vs Stretch 0.7±0.004, nmoles/mg protein, n=6, p<.0001) into the bathing medium. The same stretch stimulus also increased uptake of large molecule propidium iodide (PI) from the bathing medium (CTRL 1.5±0.09 vs stretch 2.49±0.09, Fl unit/mg protein, n=6, p<0.001). The ATP release and PI uptake responses both were prevented by a TRPV4 antagonist, HC067047 (10 μM) and a connexin blocking peptide, GAP27 (200μm). Cells subjected to a hypoosmotic stimulus (200 mOsm) also displayed a significant increase in PI uptake (CTRL 4.65±0.24 vs Hypo 8.26±0.43 nmoles/mg protein, n=5, p<0.001) and the response was abolished by HC067047. The TRPV4 agonist GSK1016790A (10 nM) markedly increased ATP release (CTRL 0.56±0.03 vs GSK 1.24±0.06 nmoles/mg protein, n=12, p<0.001) and PI uptake (CTRL 1.83±0.05 vs GSK 3.69±0.09 Fl unit/mg protein) in the absence of any swelling or stretch stimulus and both responses were abolished by GAP27. Conclusion: The findings are consistent with TRPV4-dependent connexin hemichannel opening in response to mechanical stretch. The TRPV4-hemichannel mechanism may act as mechanosensor that facilitates release of ATP and other autocrine or paracrine signaling molecules that influence fluid (aqueous humor) secretion by the NPE. This research was funded by an NIH (NEI) grant, R01EY029171. 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.
Student Performance in Cardiovascular and Respiratory Physiology is Unaffected by the Number of Courses Tested at Once
Authors: Johnson Fruzsina , Johnson Robert 
Published: May 2023

Physiology has been a foundational course in medical curriculums for several decades. At William Carey University College of Osteopathic Medicine (WCUCOM), Medical Physiology is taught in both semesters of the first-year curriculum. Cardiovascular and respiratory physiology are the first two major organ systems we teach after the foundational lectures and take up most of the Fall semester. An ongoing debate at our school is whether to test foundational courses by themselves or rather via combined (“integrated”) exams that more closely resemble the board exams. The students prefer the smaller exams, but often end up setting up cycle studying patterns only focusing on one course at a time that ends up hurting them in the second year where combined integrated exams are standard in our curriculum. Going from the 2020-2021 to the 2021-2022 academic year we moved from combined integrated exams where four courses were tested at once to smaller exams where one to two courses were tested at one time. We were also undergoing the second stage of a planned class size increase from 150 students to 175 students, but we previously reported that the first stage of the class size increase did not adversely affect physiology outcomes. In this study, we compared overall student performance on the traditionally challenging cardiovascular and respiratory physiology sections between the Fall 2020 and Fall 2021 student cohorts. In 2020, 156 students completed the Fall semester at WCUCOM. Their average exam score on the cardiovascular questions was 83.11±9.51%, and the average exam score on the respiratory questions was 82.63±11.12%. In 2021, 182 students completed the Fall semester at WCUCOM. Their average exam score on the cardiovascular questions was 84.73±8.06%, and the average exam score on the respiratory questions was 84.42±10.12%. The increase in the mean exam score between cohorts was not statistically different between the two groups (P=0.354, Mann-Whitney rank sum test for cardiovascular questions, and P=0.177, Mann-Whitney rank sum test for respiratory questions). These findings show that student performance on the cardiovascular and respiratory sections of the Medical Physiology course at WCUCOM were similar between the Fall 2020 and Fall 2021 semesters. Our results suggest that the number of courses tested at once may not significantly affect student performance. 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 IBD-candidate gene, PTPN2, Regulates Goblet Cell Number and Expression of Intestinal Epithelial Cell Markers in a Regional-specific Manner in Mice
Authors: Canale Vinicius , McCole Declan 
Published: May 2023

Loss-of-function variants in the Protein Tyrosine Phosphatase non-receptor Type 2 ( PTPN2) gene are associated with increased risk of Inflammatory Bowel Disease (IBD). PTPN2 encodes T Cell Protein Tyrosine Phosphatase (TCPTP), a negative regulator of intracellular signaling pathways including JAK-STAT. PTPN2 is critical for intestinal epithelial cell (IEC) barrier maintenance, IEC-macrophage crosstalk, and modulating the gut microbiota in mice and IBD patients. Aim: To determine if Ptpn2 loss compromises IEC subtypes that restrict gut dysbiosis. Methods: Ileal and colonic IEC subtypes and their function were assessed by PAS staining of goblet cells and immunostaining. RNA isolated from colonic IECs of whole-body Ptpn2-wild-type (WT), heterozygous (Het) and KO mice was assayed by two separate Nanostring® panels: PanCancer and AutoImmune totaling >1500 targets. Flow cytometry was performed to evaluate abundance of mucosal-associated immune cells. Results: Goblet cells were reduced in the ileal and cecal crypts compared with WT mice (p<0.05; n=5) while numbers in the proximal and distal colon were variable. Ki-67 immunostaining revealed increased proliferating cells in the proximal and distal colon (p<0.01; n=3). Nanostring analysis had 1399 targets with detectable expression. Notably, expression of growth factors Egf and Fgfr3, differentiation factors Atoh1 and Mycn, tuft cell marker Dclk1, and intestinal stem cell marker Lgr5, were all downregulated in colonic IECs from Ptpn2-KO mice compared with WT (p<0.05; FDR<0.1; n=4). Moreover, abundance of mucosal neutrophils, macrophages, CD4+ expressing IFN-γ, CD8+ expressing TNF/IFN-γ, and CD4+ expressing IL-22 T-cells were higher in colon and cecum of Ptpn2-KO mice compared with WT and HET mice (p<0.01; n=5), whereas abundance of IL-4 expressing CD4+ cells, and Tregs expressing IL-10 were decreased in all intestinal segments of Ptpn2-KO mice (p<0.01; n=5). Conclusion: Ptpn2 loss negatively impacts abundance of IEC subtypes in a region-specific manner, affecting epithelial proliferation and expression of critical differentiation/cell markers. The elevated abundance of immune cells expressing pro-inflammatory signals accompanied by decreased levels of cells expressing IL-4 and IL-10, could contribute to a skewed abundance of IEC subtypes and their function. The observed effects may contribute to the increased susceptibility to infection and the dysbiotic microbiota in Ptpn2-deficient mice, and partly explain association of PTPN2 variants with dysbiosis in clinical IBD. Supported by NIH 2R01DK091281, 1R01AI153314-01, R21AI152017 and R01AI165490 (DFM). 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 Simplex (an online writing tool) to assist students when simplifying complex ideas towards various audiences: a pilot project
Authors: Zubek John , Murali Gokul , Chinoy Natasha , Joseph Jackson , Shaltry Christopher , Krishnan Arjun 
Published: May 2023

Professional skills development is an increasingly emphasized part of the undergraduate curriculum. Both physiology instructors and students of STEM place a high importance on effective communication of scientific information to a variety of audiences. However, it can be difficult for students to simplify technical jargon and ensure a clear message. Simplexalpha is an online writing tool to identify scientific jargon and assist the writing simplification process. The goal of this pilot project was to evaluate whether Simplexalpha assisted students when reducing scientific writing, improving knowledge retention, and increasing the effectiveness of communication. Participants in this study included 129 undergraduate science majors from Michigan State University. Each participant was given the same scientific abstract to rewrite and assigned to one of three groups. Group A utilized the Simplexalpha online tool, Group B was provided minimal feedback, and Group C was given no feedback. A knowledge assessment was completed, and participants were later asked to rate five random rewritten de-identified abstracts as to their perceived “effectiveness” based on the writing prompt. Group A performed slightly better on the knowledge assessment than groups B and C (89.3% vs. 88.3% vs. 86.9%). More participants in Group B simplified the abstract to the lowest grade levels vs. Groups A and C. There was a statistically significant difference in the effectiveness scores between the groups as Group B slightly outperformed Group C, while Groups B and C significantly outperformed Group A (P=0.004). Students using the Simplexalpha tool were highly complementary to its ease of use and the benefits of identifying technical jargon for simplification. However, Group A did not achieve as favorable “effectiveness” outcomes as those participants in Group B and Group C (minimal and no feedback respectively). It is not known whether the tool itself or the time spent attempting to simplify writing can be of greatest benefit. Further attenuation of the methods may need to be evaluated. Department of Physiology, Michigan State 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.