bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using synaptic connections to dissect neural microcircuitry
Authors: Clark John , Horn Madison , Farrell Evan , Dang Alice , Quiroga Liliana , Williams Cole , Valadez Jullian , Beaudoin Gerard 
Published: May 2023

There are a number of methods used to study synapses through selective labeling and control. However, these techniques are often cytotoxic, difficult to implement, or lack the selectivity required to most effectively study microcircuits. We aim to create two novel techniques for studying how the brain is wired – a method for transsynaptic genetic labeling and a method for selectively destroying synapses. For synaptic labeling we are using the C. elegans orthologs for the Notch-Delta signaling system, Glp-1 and Lag-2. Glp-1 was modified by replacing the intracellular portion of the protein with cre recombinase, a site directed DNA recombination enzyme. It is hypothesized that when a cell expressing the chimeric Glp1-Cre protein comes in close contact with a cell expressing Lag-2, cre recombinase will be released allowing for the selective expression of a fluorescent molecule based on cell proximity. In vitro testing via confocal microscopy indicates that the labeling mechanism performs as expected, labeling cells based on contact in HEK 293T cells.To selectively destroy synapses, we have developed a chimeric protein, CadPlexin, that will activate repulsion signals through homophilic binding between two cells connected by a synapse. CadPlexin is composed of the extracellular domain of fruit fly DE-Cadherin and the transmembrane and intracellular domains of mouse plexin-B2. Cadherins bind to one another homophillically, acting to bind cells with one another. Plexins, when dimerized and activated by their usual ligand, Semaphorin, will cause a downstream signaling cascade that induces cell-cell repulsion. We hypothesize that, when two cells expressing CadPlexin are in close contact (i.e. at a synapse), CadPlexin will selectively destroy the synapse, as the extracellular domains from DE-Cadherin will bind together and mimic semaphorin binding and clustering required to activate plexin signaling. Preliminary results from in vitro experiments suggest that CadPlexin performs as expected, seen through stress fibers in the actin cytoskeleton of Cos7 cells transfected with CadPlexin – a characteristic cytoskeletal change induced through Plexin signaling. Together, these techniques will allow us to label synaptically connected neurons and destroy synapses with surgical precision. Funding Sources: Murchison Summer Research Fellowship, Trinity University Start-Up Funds, McNair Scholars Program, the Brain and Behavior Research Foundation NARSAD Young Investigator Award, Mary E. Groff Foundation, Women in STEM Program. 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.
Electronic cigarettes exposures modulate Heart Rate and Heart Rate Variability
Authors: Castellanos Jocelyn , Cornett Carson , Luna Karla , Li Liqiao , Gonzalez David , Middlekauff Holly , Gupta Rajat , Jordan Maria , Ruenger Dennis , Zhu Yifang , Shao Xuesi , Roos Kenneth , Araujo Jesus 
Published: May 2023

Background: Despite a lack of empirical data, an unprecedented rise in electronic cigarettes (ECs) has been widely perceived as safe. Multiple studies support a causal link between tobacco cigarette (TC) use and cardiovascular (CV) diseases; however, there is a lack of data with EC use. We have previously shown that chronic and acute EC use decreases heart rate variability (HRV) in humans, likely via increased sympathetic nervous system activation. Objective: We aimed to evaluate HRV effects induced by brief EC exposures utilizing an in-vivo model for freely moving C57BL/6 mice. Methods and Results: Telemetry devices were implanted in the abdomen of six 10-week-old C57BL/6 male mice to monitor electrocardiographic activity continuously. Mice underwent an exposure protocol designed to reflect human vaping topography with two EC exposures, each lasting 15-minutes (4-sec puff/ 26-sec Air) followed by 45-min post-exposure periods. Air (primary control) and PBS (secondary control) were also included, each with their own post-exposure events. During EC exposures, we observed bradycardic effects in heart rate (HR) with the standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and the proportion of adjacent normalized RR intervals that differed by more than 6 ms (pNN6) significantly (p< 0.05) altered as compared to Air exposures. After EC exposures, SDNN, RMSSD and pNN6 parameters significantly decreased compared to Air. No significant differences between Air and PBS were observed in these parameters. Frequency domain parameters also indicated significant changes in HRV; the low frequency (LF) and high frequency (HF) bands showed marked increases during and after the EC exposures, while the log (LF/HF) ratio remained relatively unchanged, suggesting a possible coactivation of both parasympathetic and sympathetic branches of the autonomic nervous system. Conclusion: Short-term EC exposures lower heart rate and altered HRV in mice in an acute manner, suggesting that ECs may not be safe as previously assumed. This work was funded by the Tobacco-Related Disease Research Program (TRDRP) which included the High Impact Pilot Research Award [28IP-0036], the Cornelius Hopper Diversity Award Supplement and the Student Research Award Supplement, the UCLA Center for Occupational and Environmental Health (COEH) Student Project Award, and in part by the National Institute of Environmental Health Sciences (NIEHS) via the Student-to-Scientist Bridge program at California State University, Northridge [5R25ES025507]. 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.
Expression of human sPRR in renal collecting duct cells increases blood pressure in female mice independently of its circulating levels
Authors: Arthur Gertrude , Poupeau Audrey , Nichols Kellea , Osborn Jeffrey , Hinds Terry , Loria Analia 
Published: May 2023

Elevated circulating sPRR has been associated with essential hypertension, obesity-related hypertension, heart failure and chronic kidney disease in humans. However, the exact contribution of tissue-specific human sPRR in blood pressure control remains to be investigated. Therefore, we evaluated the effect of human sPRR on circulating sPRR and blood pressure control when expressed in mouse kidney, adipose tissue or liver from both male and female mice.Human sPRR-Myc-tag transgenic mice were bred with mice expressing either Hoxb7/Cre, Adiponectin/Cre or Albumin/Cre to selectively express human sPRR (HsPRR) in the collecting duct of the kidney (Kid-HsPRR), adipose tissue (Adi-HsPRR) or liver (Liv-HsPRR), respectively. The presence of human sPRR-Myc-tag (28 KDa) was validated in each mouse model by detecting the presence of C-myc. HsPRR and control (WT) male and female mice were fed a control diet throughout the study (n=8-12/group). At 6 months, baseline and acute blood pressure responses were assessed by radio-telemetry.Tissue expression of sPRR increased in kidney-derived HsPRR (M: 1.0±0.2 vs. 1.6±0.3 AU, F: 1.0±0.1 vs. 1.7±0.2 AU p<0.05), adipose-derived HsPRR (M: 1.0±0.3 vs. 4.7±1.5 AU, F: 1.0±0.2 vs. 3.2±1.4 AU p<0.05) and liver-derived HsPRR mice (M: 1.0±0.2 vs. 9.7±0.8 AU, F: 1.0±0.1 vs. 8.7±0.9 AU p<0.05) but only liver-derived HsPRR mice elevated circulating sPRR (M: 7.0±2.4 vs. 125.0±7.9 ng/ml, F: 2.2±0.4 vs. 93.9±13.4 ng/ml p<0.05). Human sPRR increased blood pressure only in female mice expressing HsPRR in kidney (F: 111±2 vs. 121±4 mmHg p<0.05). Also, only female mice expressing HsPRR in kidney displayed a blunted acute response to losartan injection (M: -30.1±3.3 vs. -22.1±3.7, F: -16.3±2.4 vs. 14.1±5.8 Δ mmHg p<0.05) and Ang II-induced pressor response in acute (M: 28.9±5.1 vs. 47.6±4.4 mmHg p<0.05, F: 35.2±7.2 vs. 26.9±7.5 mmHg) and chronic fashion (M: 33.9±3.6 vs. 30.7±5.0, F: 35.1±6.8 vs.17.6±3.2 Δ mmHg, p<0.05).Overall, our data show that increased intrarenal human sPRR expression contributes to increase blood pressure in a sex-specific manner. Taken together, increased HsPRR in kidney is associated with hypertension and impaired response to AT1R blockade and AngII-induced pressor response suggesting a dysfunctional AT1R-mediated signaling that could be due to ligand competition. These studies were supported by grants from the American Heart Association (13SDG17230008), the National Institute of General Medical Sciences (P30 GM127211), the Center for Clinical and Translational Sciences (UL1TR000117) and the National Heart Lung and Blood Institute (R01HL142969-01) 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.
Potential role of UCP-1 for mediating beneficial effects of exercise in an endometriosis rat model
Authors: Torres James , Cruz Myrella , Appleyard Caroline , Chompré Gladys 
Published: May 2023

Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue in areas outside the uterus. Previous studies in our laboratory demonstrated that endometriosis animals have increased mesenteric adipose tissue (MAT), inflammation, and implanted endometrial vesicles, which are all decreased by voluntary exercise. Interestingly, the levels of Uncoupling Protein 1 (UCP-1), a mitochondrial protein, are known to be increased by exercise promoting thermogenesis, and decreasing inflammation in rodents. However, the possible role of UCP-1 in endometriosis is still unclear. Our aim was to study the effects of exercise on UCP-1 in MAT near the endometrial implants in an endometriosis rat model. Hypothesis: UCP-1 increases due to exercise decreasing the MAT and thus beneficially impacts the endometrial vesicles. Methods: Endometriosis was induced by implanting uterine tissue on the intestinal mesentery in young adult female Sprague Dawley rats where the control group only received sutures. Exercise rats had access to a running wheel after induction: ENDO-EX or SHAM-EX, while non-exercised animals didn’t (ENDO and SHAM; n=10=11/group). After sixty days of intervention, animals were sacrificed and UCP-1 immunofluorescent staining was performed on collected MAT near the vesicles (ENDO, n=3; ENDO-EX, n=3; SHAM, n=4; SHAM-EX, n=4). Results: The vesicles from ENDO-EX animals had significantly decreased average weight (p<0.05) and smaller average total area (p<0.01) compared with the ENDO group. UCP-1 staining shows a trend to increase in exercise groups when compared to non-exercise groups. Interestingly, there is a moderate negative correlation between UCP-1 expression and vesicle size (r=-.69). Conclusions: Exercise is related to increasing the UCP-1 pathways in MAT that may be associated with decreasing the size of the endometrial vesicle implants. Supported by R15AT009915 and HRD-2008186. 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.
Impact of Plant-Derived Dietary Fibers on Energy and Glucose Homeostasis
Authors: Howard Elizabeth , Meyer Rachel , Weninger Savanna , Kangath Archana , Duca Frank 
Published: May 2023

The gut microbiota contributes to the development of metabolic disease, and it is well known that diet shapes the gut microbiota, emphasizing the need to better understand how diet impacts metabolic disease via alterations in the gut microbiota. Dietary fiber intake is linked with improvements in metabolic homeostasis in humans, and specific fibers beneficially alter the gut microbiota, promote weight loss, and improve glucose homeostasis. In a previous study, we found that specific plant-based flours, including wheat and barley, supplemented into a high-fat diet (HFD) reduced body weight and adiposity and improved glucose tolerance in rats. However, whether this was due to specific fibers within the flours remains unknown. To test the impact of various dietary fibers on energy and glucose homeostasis, we supplemented HFD-fed mice with 5 different fibers (beta-pectin, beta-glucan, wheat dextrin, resistant starch, or cellulose as a control) at 10% (w/w) for 18 weeks (n=12/group), measuring body weight, adiposity, indirect calorimetry, and glucose tolerance. We found that only beta-glucan supplementation in a HFD decreased adiposity and body weight gain and improved oral glucose tolerance compared to HFD with cellulose, while all other dietary fibers failed to improve metabolic homeostasis. Supplementation with beta-glucan increased energy expenditure and locomotor activity in mice compared to HFD-cellulose. Despite a lack of metabolic effect for most dietary fibers, all fibers supplemented into a HFD shifted the cecal microbiota composition and exhibited increased SCFA levels. However, only beta-glucan supplemented mice specifically exhibited an increase in Ileibacterium relative abundance, as well as higher cecal butyrate levels compared to HFD-cellulose. These findings demonstrate that beta-glucan is a promising therapeutic option for diet-induced obesity and glucose tolerance, possibly via increased energy expenditure. Future studies will investigate the role of the gut microbiota and butyrate in the metabolic improvements observed with beta-glucan supplementation in HFD-feeding. USDA National Institute of Food and Agriculture 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.
ADAM17 overexpression improves cerebrovascular vasoreactivity and cognitive function in the APP/PS1 mouse model of Alzheimer's disease
Authors: Fopiano Katie Anne , Tian Yanna , Suggs Hayden , Buncha Vadym , Lang Liwei , Wang Rongrong , Filosa Jessica , Bagi Zsolt 
Published: May 2023

The disintegrin and metalloproteinase 17 (ADAM17) exhibits α-secretase activity, whereby it can prevent the production of neurotoxic amyloid precursor protein-α (APP). ADAM17 is abundantly expressed in vascular endothelial cells and may act to regulate vascular homeostatic responses, including vascular growth and vasomotor function. We hypothesized that cerebrovascular ADAM17 plays a role in the pathogenesis of Alzheimer’s disease (AD). Here we found that 8-10 months old APP/PS1 mice (expressing transgenes for APP Swedish mutation and PSEN1 with L166P mutation) with significant cognitive deficits display a markedly reduced expression of ADAM17 in cerebral microvessels. Systemic delivery and AAV-mediated re-expression of ADAM17 in APP/PS1 mice improved cognitive functioning, without affecting β-amyloid plaque density. Moreover, we found that the endothelium-dependent vasodilator function of isolated and pressurized cerebral arteries in APP/PS1 mice was impaired, which was restored to normal levels by the ADAM17 re-expression. The cerebral microvascular network density in the APP/PS1 mice before or after ADAM17 re-expression was not affected. In addition, proteomic analysis identified several differentially expressed molecules involved in AD neurodegeneration and repair that were reversed by ADAM17 re-expression. Thus, we propose that a reduced ADAM17 expression in cerebral microvessels impairs vasodilator function, whereby it contributes to the development of cognitive dysfunction in APP/PS1 mice, and that ADAM17 can potentially be targeted for therapeutic intervention in AD. T32HL155011; 20PRE35211126 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.
Glucocorticoid Receptor-beta (GRb) is a driver of adiposity via PPARgamma in adipose tissue: Lessons learned from the first CRISPR GRb KO animals
Authors: Martinez Genesee , Kipp Zachary , Stec David , Hinds Terry 
Published: May 2023

Obesity and its associated comorbidities are major contributors to deaths worldwide. This has led to increasing rates of multiple obesity-associated comorbidities, such as type II diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. A conundrum exists in that short-term glucocorticoid therapy reduces body weight, but the long-term chronic treatment causes weight gain and adiposity. Because of these effects observed clinically, we are interested in better understanding the complex role of glucocorticoid receptor (GR) isoforms in lipid and glucose metabolism. We hypothesized that the conundrum is related to an imbalance of the GRα and GRβ isoforms. They arise from a single GR gene ( Nr3c1) due to the alternative splicing of exon 9 and are antagonists to one another. To test this hypothesis, we developed specialized GRβ CRISPR knockout (KO) technology to target GRβ for KO in mice, and these animals only express the GRα isoform. The GRβ homozygous knockout (KO) mice seem to be lethal. However, the heterozygous KO (GRβHetKO) mice are viable, with no observable phenotypes on standard chow. Therefore, we used GRβHetKO mice to study the effects of this isoform on adiposity. We placed the GRβHetKO and GRβWT mice on a high-fat diet (HFD) for 8 weeks. We found that the GRβHetKO mice fed HFD had significantly reduced body weights (p-value <0.05) and adiposity (p-value <0.01) compared to their littermates, which was paralleled with significantly reduced PPARγ (p-value <0.01) expression in inguinal white adipose tissue (iWAT) but not in eWAT or liver tissues. The liver histology sections showed decreased lipid accumulation. Molecular analysis of GRβ-PPARγ signaling indicates that GRβ positively affects PPARγ transcriptional activity. We conclude that GRβ drives PPARγ expression and activity in adipose to induce adiposity in iWAT, which might affect fat accumulation in the liver. Our studies here indicate that future studies of GRβ might explain differences observed in the clinic for short- and long-term glucocorticoid therapies, and a better understanding of the GR isoforms could benefit patients with obesity and possibly improve obesity-associated comorbidities. 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.
Distinct effects of cell-free hemoglobin on oxygen pressure dynamics of fast vs. slow twitch muscle
Authors: Lemke Aviv , Calvo Nainoa , Hirai Daniel , Ferguson Scott 
Published: May 2023

Hemolysis occurs following exposure to environmental stressors (e.g., microgravity) and in hemolytic diseases (e.g., sickle cell disease). When released from the red blood cell, cell-free hemoglobin (Hb) reduces nitric oxide (NO) availability and impacts skeletal muscle microvascular oxygen pressure (PO2 mv) dynamics during contractions in mixed fiber type muscle. However, the impact of cell-free Hb on fast- vs. slow twitch muscles remains unknown. Thus, the purpose of this investigation was to test the hypothesis that cell free Hb would lower the PO2 mv in slow, but not fast, twitch muscle. Phosphorescence quenching was used on two groups of young-adult male Sprague-Dawley rats to measure PO2 mv of the gastrocnemius (n=10) and soleus (n=8) muscles. Measurements were made at rest and during 180 s of 1-Hz contractions (6-8 v) under control conditions and following 50 mg of Hb infusion (tail-artery catheter). Mean arterial pressure (MAP) was monitored via a femoral artery catheter. Cell-free Hb increased MAP by 48% in the gastrocnemius and soleus groups (gastrocnemius, control: 93 ± 14, Hb: 138 ± 15; soleus, control: 89 ± 10, Hb: 132 mmHg, p<0.01 for both). Hb resulted in a shorter time delay (control: 10.29 ± 6.38, Hb: 3.88 ± 3.06 s) and faster mean response time (control: 22.03 ± 5.82, Hb: 14.29 ± 4.18 s) at the onset of contractions for the gastrocnemius (p<0.05 for both). There were no significant Hb induced differences in any kinetic parameter in the soleus (p>0.05 for all). Contrary to our original hypothesis and despite significant increases in MAP, cell-free Hb did not alter the kinetic response or the contracting steady-state PO2 mv in the slow-twitch soleus muscle. However, the kinetic response during the crucial rest-exercise transition in the gastrocnemius was significantly faster following Hb infusion, suggesting that Hb disrupts QO2/VO2 matching in fast-twitch muscle. Given the ~48% greater MAP following Hb infusion, these results suggest that cell-free Hb may disrupt skeletal muscle vascular conductance during contractions but may not impact PO2 mv in a fiber-type specific manner. Robert C. Perry fund of the Hawai'i Community Foundation 21ADVC-109518 and NIH-L60HL134123 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.
Early program seminar to promote learning physiology via a core concepts approach
Authors: Sweeney Terrence , Sweeney Terrence 
Published: May 2023

Spurred by the foundational work of Michaels, McFarland, Modell and others 1,2 in establishing and promoting a consensus collection of core concepts in physiology that facilitate learning, an increasingly broad collection of physiology educators have begun to embrace the employment of a core concepts approach to teaching and learning physiology. That said, challenges remain in the classroom in convincing students to forego the siloed and highly specific approach to learning physiology that has carried them through their earliest years of science education, and instead adopt a more general and conceptual approach that ultimately advances their level of learning. To help promote this effort in our Bachelors-level Physiology degree program, we have developed a Core Concepts in Physiology Seminar – a required, one-credit course delivered as part of our program's second year curriculum. The seminar immerses students in the core concepts approach, unfettered by the content-heavy demands of the typical anatomy & physiology survey courses. Delivered while the students are co-enrolled in the second half of a year-long anatomy & physiology lecture and laboratory sequence, the seminar can draw on the foundational content of those course while placing its emphasis on student creation of general models2, and allow students to share and discuss the application of critical core concepts such as flow down gradients, energy, cell-cell communication, and homeostasis. While the core concepts are also being introduced in the anatomy & physiology courses, the seminar provides a low-risk environment for challenging students' approach to learning, with the desired outcome of increasing student adoption of the more integrative and general core concepts approach. 1 Modell, H., Adv. Physiol. Educ. 23: 101-107, 2000. 2 Michaels, J et al. The core concepts of physiology: A new paradigm for teaching physiology. DOI 10.1007/978-1-4939-6909-8, Springer, 2017. Supported by The University of Scranton 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.