bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoid Resistance Increases PPARγ Activity and Drives Hepatic Lipid Accumulation via Increased Eicosanoid and Monoacylglyceride Synthesis
Authors: Martinez Genesee , Kipp Zachary , Stec David , Hinds Terry 
Published: May 2024

A diet high in fat induces adiposity and obesity, and chronic feeding can lead to multiple metabolic complications, including type II diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. The glucocorticoid receptor (GR) regulates genes that control metabolism. The GR has two isoforms (GRα and GRβ) that arise from the GR gene ( NR3C1) due to the alternative splicing of exon 9. The GRα isoform is the classical receptor that binds to glucocorticoids. However, the GRβ isoform has a truncated C-terminus. It cannot bind glucocorticoid steroids, and as a result, this isoform induces a glucocorticoid-resistant state when its expression is increased. We hypothesized that increasing levels of GRβ from long-term excess glucocorticoid exposure or a high-fat diet induces adiposity by affecting lipid metabolism and lipogenesis, causing fat to accumulate in the adipose and liver tissues. We first overexpressed GRβ (GRβ-Ad) or control (Vec-Ad) using adenovirus delivery and fed the mice a normal chow diet. The GRβ-Ad mice had significantly higher lipid accumulation within five days. Western blotting analysis revealed a significant increase (p-value <0.05) in the GRβ-Ad livers for fatty acid synthase (FAS) expression, and there was a remodeling of the hepatic lipid content as measured by mass spectrometry lipidomic analysis. The data indicate an increased level of monoacylglyceride lipid species and some species of long-chain triacylglycerides and diacylglycerides. mRNA analysis revealed a significant increase (p-value <0.05) in Carbohydrate-responsive element-binding protein (ChREBP), PPARγ, and Cyp2j6, indicating an increase in de novo lipogenesis and eicosanoid synthesis. We conclude that glucocorticoid resistance due to increased levels of GRβ drives de novo lipogenesis and increases eicosanoid synthesis, possibly via synergism with PPARγ. A better understanding of the GR isoforms and glucocorticoid resistance could benefit people with obesity and other metabolic disorders to improve obesity-associated comorbidities. R01DK121797 (T.D.H.J.), R01DA058933 (T.D.H.J.). 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.
Increasing confidence in mentoring strategies for predoctoral and postdoctoral scholars through implementation of a mentoring academy
Authors: Becker Rena , Shacka John , De Miguel Carmen , Mitchell Tanecia , Wyss J. Michael , Hopper Mari , Pollock Jennifer 
Published: May 2024

In support of the development of undergraduate researchers and the mentor development of predoctoral and postdoctoral scholars (Near Peers), a targeted near peer mentor training program was developed. Innovative and highly impactful early training experiences in research play a key role to inspire and motivate the next generation of scientists. Predoctoral and postdoctoral trainees are often asked to assist in the training and mentoring of short-term summer undergraduate researchers. Previous studies have shown that the efforts of these “near peers” to educate, train, and develop the summer undergraduate scholars have a positive impact on the undergraduate researchers. However, many near peer mentors have limited mentor training/experience and lack confidence in their ability to mentor undergraduate scholars. Thus, developing avenues and opportunities to train near peers on mentoring is vital to enhancing the experience of both the undergraduate researchers and near peers. The Kidney Undergraduate Research Experience (KURE) at the University of Alabama at Birmingham (UAB) engages undergraduate summer scholars with a wholistic research experience which includes an involved team of near peer mentors. A near peer mentor training program was developed with input from near peer focus groups, based on their interest in expanding their mentoring abilities and developing confidence in their role as a near peer mentor. The aim of this study was to determine whether this mentoring program was effective in increasing near peer mentoring abilities and confidence levels through quantitative and qualitative measures. Evaluations were given to near peers prior to, during, and at the end of the 6-month program (44 scholars started the program in Fall 2022 and 33 scholars completed all activities). We found that 83% of near peers expressed increased confidence in mentoring (n=24). Improvement in specific mentoring abilities were also assessed, such as “confidence in effectively communicating expectations” (pre- 4.02, ±0.82, n=44; post- 4.83 ±0.37, n=24; using a scale from 1 = not at all to 5 = very confident). We also identified the most impactful elements of the program including facilitation, topics, and platforms. Through assessing these aspects of the program, we determined essential and sustainable elements for future near peer mentor training programs. We conclude that a near peer mentor training program builds confidence and enhances the ability of predoctoral and postdoctoral scholars in their roles as near peer mentors. NIH R25DK115353 — 05S1. 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.
Acute Peripheral Irisin Administration Increases Hippocampal Mass in Young, Healthy Rat Cohort
Authors: White Zachary , Sudasinghe Keshari , Hall Stephanie 
Published: May 2024

Introduction: Skeletal muscle-brain crosstalk is highlighted as an important contributor to the beneficial relationship between exercise and the brain. Irisin is a key crosstalk myokine due to the ability of irisin to cross the blood-brain barrier and mediate effects of exercise in the brain. Importantly, the influence of irisin in the brain is often demonstrated through chronic administration or supraphysiological dosing of irisin. The aim of the present study is to determine if an acute, non-supraphysiological dose of exogenous irisin is suffcient to induce previously established effects in the hippocampi of young, healthy rats. Methods: Twenty-four 2–3-month-old male and female F344 rats were divided into two groups of 12 (50% male/female) which either received an irisin (100 μg/kg) or vehicle intraperitoneal injection. Forty-eight hours following irisin injections, brains were sectioned and weighed. Levels of total and phosphorylated hippocampal cyclic-AMP Response Element Binding Protein (CREB), a downstream target of irisin signaling, were quantified with Jess Simple Western automated western blot analysis. Values are mean ± standard deviation. Results: Irisin administration resulted in greater hippocampi mass (relative to brain mass, %) compared to vehicle treated animals (3.65±0.24 vs 3.28±0.32%, p<0.01). Further, pCREB/CREB in the hippocampus of irisin animals (0.58±0.13) was 24.6% greater than vehicle (0.47±0.09, p<0.05). Irisin administration did not influence body mass or whole brain mass relative to body mass. Conclusions: The present study demonstrates that a non-supraphysiological dose of irisin is suffcient to increase hippocampal mass and CREB phosphorylation 48 hours post-injection. This work supports irisin as an important, physiologically relevant mediator of the beneficial relationship between exercise, skeletal muscle, and the brain. NIH P20GM113109. 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.
Aging Related Changes in Smooth Muscle Contractile and Regulatory Proteins
Authors: Bandi Rishiraj , Han Young , Sieck Gary , Brozovich Frank 
Published: May 2024

Aging is a significant risk factor for cardiovascular disease and is known to be associated with an increase in vascular stiffness and decrease in sensitivity to NO mediated vasodilatation. However, the underlying mechanism for these changes in vascular function is unknown. Smooth muscle tone is known to be regulated by the expression and phosphorylation of both nonmuscle (NM) and smooth muscle (SM) myosin. NM and SM phosphorylation is regulated by the activity of myosin light chain kinase (MLCK) and MLC phosphatase. MLC phosphatase is a trimeric enzyme consisting of enzymatic, myosin targeting (MYPT1) and a 20kDa subunit of unknown function. Two isoforms of MYPT1 are produced by alternative mRNA splicing, which differ by the presence or absence of a COOH-terminal leucine zipper (LZ+/-), and the relative expression of LZ+/LZ- MYPT1 determines the sensitivity to NO mediated vasodilatation. We defined NM myosin expression using two-dimensional SDS PAGE and LZ+/LZ- MYPT1 expression using immunoblotting in aortic and tertiary mesenteric smooth muscle from 6mo and 24mo old Fischer344 rats. The data demonstrate that aging is associated with a significant decrease in the expression of both LZ+ MYPT1 and NM myosin. The reduction in LZ+ MYPT1 expression would both decrease the sensitivity to NO mediated smooth muscle dilatation and increase vascular tone, which is a hallmark of the vasculature in aging. On the other hand, the reduction in NM myosin would result in a decrease in vascular tone and could represent a compensatory mechanism to normalize blood pressure during aging. These data demonstrate that there are changes in the expression of smooth muscle regulatory and contractile proteins during aging and these changes in protein expression contribute to molecular mechanism for the decrease in sensitivity to NO mediated vasodilatation as well as the increase in vascular tone or the vascular dysfunction that occurs with aging. Supported by a Mayo CV Prospective Grant (FVB). 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.
Investigation of social variables affecting the subjective experience of Boston University pre‐health students
Authors: Nessen Evan , Lyons Nicholas , Capuano John Paul , Roberts Lisa , Moreira Jesse 
Published: May 2024

Introduction: Students who are pre-health experience higher levels of stress and adopt maladaptive coping behaviors including alcohol and drug use. Additionally, students belonging to sexual and gender minority (SGM) groups are more likely to drop out from science, technology, engineering, and math (STEM) majors. Studies have yet to determine how SGM identities influence self-perceived ability and desire to pursue careers in healthcare. Hypothesis: Pre-health students belonging to SGM groups have lower self confidence in their career trajectory as a function of identity compared to their cisgender, heterosexual peers. Methods: Pre-health students at Boston University were surveyed using quantitative Likert-like items and open response questions. Survey content explored the degree to which students agreed with statements regarding how their sexual orientation and gender has affected their career trajectory as a pre-health student. Responses were grouped by gender and sexual orientation and unpaired Mann-Whitney rank tests were used to assess differences at an alpha of 0.05. Results: Of the 71 respondents, 44 (61.97%) identified as heterosexual women, 14 (19.71%) identified as queer women, 10 (14.08%) identified as heterosexual men and 3 (4.22%) identified as queer men. Queer women, compared to heterosexual women, reported higher perceived effects of sexual orientation (p=0.0228, median 2.0, IQR 1-2 vs. 1.0, IQR 1-2) and gender identity (p=0.0079, median 2.0, IQR 1-3.5, vs. median 1.0, IQR 1-2) on career trajectory. There were no significant differences between responses from queer men and heterosexual men regarding perceived effect of sexual orientation and gender identity on their career trajectories. Conclusion: Queer women in pre-health tracks may benefit most from targeted supportive intervention. This study was unfunded. 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.
Psoralen mediates BMSCs osteogenic differentiation via cross-talk between Wnt/β-catenin and BMP/smad signaling pathways
Authors: Li Wenxiong , Chen Feifei , Chen Menghan , Zhong Yuan , Yang Feng 
Published: May 2024

Background: To explore the mechanism of psoralen mediated Wnt/β-catenin and bone morphogenetic protein (BMP) signaling pathway to induce osteogenesis of BMSC. Methods: Bone marrow mesenchymal stem cells (BMSCs) were treated with psoralen to detect its osteogenic differentiation. In addition, lentivirus and siRNA were used to construct cell models of β-catenin or BMP2 overexpression and knockdown, separately. They may help to clarify the role of β-catenin and BMP2 crosstalk in osteogenic differentiation of BMSCs. What’s more, C57BL/6 mice were selected to be treated psoralen with psoralen to further verify the osteogenic effect. Results: Various in vitro studies on BMSCs showed that psoralen could promote the osteogenic differentiation of BMSCs. Overexpression of β-catenin could promote the expression of BMP2 in BMSCs, and psoralen can enhance the effect of bone differentiation. Knockdown β-catenin decreased the expression of BMP2 and inhibited psoralen in promoting bone differentiation. In addition, it was found that the effect of psoralen on β-catenin level did not change significantly after overexpression or knockdown of BMP2, but the effect of psoralen on promoting bone differentiation was inhibited by knockdown of BMP2. In mice, psoralen intervention regulated the crosstalk of Wnt/β-catenin and BMP signaling pathway to reached to promote osteogenic differentiation of bone tissue. Conclusions: Psoralen can activate β-catenin signaling pathway and up-regulate the expression of BMP signaling pathway to increase the cross talk between β-catenin and BMP, to eventually reach to promote osteogenic differentiation of BMSCs. This trial was funded by the Program of National Natural Science Foundation of China (81973889 to FY), the Program of Shaanxi Province Natural Science Foundation (2023-YBSF-210 to FY & 2023-JC-QN-0978 to WL), the Program of Shaanxi Education Department (19JC013 to FY & 22JK0346 to WL), the Program of Shaanxi Administration Bureau of Traditional Chinese Medicine (2021-01-22-009 to FY &2022-QCYZH-029 to WL), Youth Innovation Team in Shaanxi universities, and the Program of Health Commission of Shaanxi Province (2022B002 to WL). 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.
Does ungrading promote student engagement and learning in Course-based Undergraduate Research Experiences (CUREs)?
Authors: Beason-Abmayr Beth 
Published: May 2024

The goal of assessment should be to encourage learning to drive student engagement and success. However, grades make students focus on the evaluation of their work, often limiting the learning process. In forcing me to rank students, grades promote extrinsic rather than intrinsic motivation and direct attention to how well students are doing rather than engaging them with what they are doing. Ungrading is an alternative approach to grading that increases the focus on feedback and growth and decreases the emphasis on "points." In the Fall 2023 semester, I piloted ungrading in one introductory and in two advanced Course-Based Undergraduate Research Experiences (CUREs). Although students will earn a grade for the course at the end of the semester, they did not get letter or number grades for individual assignments. Student learning was assessed using qualitative, not quantitative, approaches with an emphasis on quality feedback from me, reflections/self-assessments/surveys where students think critically about their own learning, and peer review for certain assignments and activities. In addition to the course learning goals, each student set individual goals for the course at the beginning of the semester, discussed their progress with me, and shared evidence of their learning throughout the semester. At mid-semester and also at the end, students suggested a course grade and explained how they arrived at that grade. Initial analysis of mid-term reflections/self-assessments shows evidence of students making progress towards personal goals as well as course learning goals: they are asking me more questions about the assignments both before submitting them and after receiving feedback, and they are actually reading my feedback; and the grades they suggested for themselves are mostly in agreement with my evaluation of their progress. Overall, students are engaged during class and seem more relaxed and less stressed because they are not worried about earning as many points as possible for each assignment. Further analysis of reflections and self-assessments will highlight student expectations and attitudes towards ungrading and showcase evidence of learning. Student feedback on an end-of-course survey about ungrading will help me refine the approach to improve student learning in future courses. I predict implementation of this ungrading policy in my courses will foster a collaborative and equitable environment where students are encouraged to learn and grow, and I plan to adapt this alternative grading practice in my animal physiology course as well as an additional advanced CURE in the Spring 2024 semester. All protocols were approved by Rice University IRB (Protocol IRB-FY-2023-239). Rice University Department of Biosciences. 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.
Time-restricted Eating to Improve Metabolic Health: Investigating the Mechanisms Underlying Glycolytic and Lipolytic actions
Authors: Abo Stéphanie , Layton Anita 
Published: May 2024

Time-restricted eating (TRE) is a behavioral intervention approach motivated by the emerging role of circadian rhythms in physiology and metabolism. In this approach, all caloric intake is restricted within a regular interval of less than 12 hours, with no overt attempt to reduce calories. We present a whole-body computational model of TRE that incorporates enzyme and substrate reactions as well as hormonal actions during fasting and postprandial states. The model is divided into seven compartments: brain, heart, skeletal muscle, gastrointestinal tract, liver, adipose tissue, and other tissues. We conducted simulations to test the hypothesis that TRE modulates whole-body glucose balance by improving postprandial hyperglycemia and hypertriglyceridemia, keeping these excursions to a minimum. We simulated different TRE schedules with meals varying in fat and carbohydrate content. Our results highlight the importance of chrono-pharmacological considerations in glycemic control: TRE modulates the interplay between glycogenolysis in the liver, lipolysis in adipose tissue and fatty acid oxidation in other organs to improve glucose control. The alternation of eating and fasting, in particular, could be manipulated to balance blood sugar levels. TRE simulations have also shown beneficial effects on the lipid front, such as lower triglyceride levels and improved lipolytic effciency, meaning the body is better able to use fat stores for fuel. This work was supported by the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery award. 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.
Electroacupuncture Rebalances Autonomic Nervous Activities Decreasing Blood Pressure in Salt-Sensitive Hypertensive Rats
Authors: Gong Yiwei , Fu Liang-Wu , Tjen-A-Looi Stephanie , Nguyen Anh , Guo Zhi-Ling , Malik Shaista 
Published: May 2024

High blood pressure (BP) associated with sympathetic overactivity is observed in hypertensive animals and patients. We have recently reported that electroacupuncture (EA) at two sets of acupoints ST36-37 and SP6-7 attenuates BP in Dahl salt-sensitive hypertensive (DSSH) rats through a positive interaction between sympathetic nerve activity inhibition (sympathoinhibition, SI-EA) and anti-inflammation (AI-EA). Chronic inflammation is not only influenced by sympathetic (SNA) but also by parasympathetic nerve activity (PNA). However, it remains unclear if combined SI-EA + AI-EA (cEA) rebalances autonomic nerve activity by both inhibiting SNA and exciting PNA that alleviate hypertension (HTN). We hypothesized that cEA decreased SNA and increased PNA in DSSH rats. Dahl salt-sensitive (DSS) rats were fed 4% salt diet and randomly allocated into two groups: cEA or Sham-EA (no electrical stimulation). Another group of DSS rats studied as normotensive (NTNive) controls were fed a standard rat chow throughout the experiment. Systolic/diastolic BP (SBP/DBP) were measured with Tail-cuff via CODA system once a week. Once DSSH rats developed moderate HTN (SBP 160±5 mmHg), cEA or Sham-EA was applied twice weekly for five weeks, while the NTNive control groups received five weeks of similar study procedures (restraining) without the intervention. After five weeks of treatments, rats were anesthetized for the neuronal recording of SNA and PNA. Cervical vagal nerve (CVN) or splanchnic sympathetic nerve (SSN) was isolated from surrounding connective tissue under a dissecting microscope. Multiple-unit nerve activities were recorded and analyzed with Spike2 software. We observed that SBP (189.2±3.5 mmHg) and DBP (138.6±2.2 mmHg) in Sham-EA treated DSSH rats were higher than SBP (140.8±1.8 mmHg) by 25.6% and DBP (105.5±1.4 mmHg) by 23.9% in rats treated with repetitive cEA. Throughout the study, SBP (132.7±1.8 to 135.2±2.1 mmHg) and DBP (74.1±1.7 to 82.9±2.6 mmHg) in NTNive rats remained within normal range. Furthermore, activity of SSN was significantly greater in Sham-EA treated DSSH rats (23.1±1.6 imp/s) compared to cEA treated rats (15.2±2.0 imp/s, P=0.043) and NTNive rats (11.5 ±0.8 imp/s, P=0.004). Activity of CVN was higher in DSSH rats treated with cEA (27.8±2.9 imp/s) than Sham-EA (12.5±2.3 imp/s, P=0.016). Relative to Sham-EA, activity of CVN was higher (42.5±2.9 imp/s, P=0.001) in normal rats. In conclusion, cEA treatment effectively alleviates hypertension by restoring the balance of autonomic nervous functions through sympathoinhibition and parasympathoexcitation. Funding: NIH 1RO1AT011306-01A1. 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.