bluuebunny/crossref_metadata_2025_split huggingface dataset:
A summer physiology research program directed toward underrepresented students, UPRIME (Undergraduate Physiology Research In Medicine and Education), fosters and engages students into physiology research
Authors: Wu Steven , Anderson Lisa , Metzger Joseph , Barnett Vincent 
Published: May 2023

The Department of Integrative Biology and Physiology at the University of Minnesota is committed to supporting outstanding physiology majors interested in research and gaining research experience. We have created a program, UPRIME (Undergraduate Physiology Research In Medicine and Education), which has: 1) Foster young and aspiring undergraduates interested in physiology and biomedical research, and 2) Create unfettered opportunities for students that are both underrepresented in research and have strong interests in physiology research and education. UPRIME (Undergraduate Physiology Research In Medicine and Education) is a 10-week summer program hosted by the Department of Integrative Biology and Physiology at the University of Minnesota and sponsored by an American Heart Association award. Students (“UPRIME Scholars”) were either juniors or seniors that had just started working in physiology labs. They were selected on the basis of: 1) Scientific merit of their projects, 2) If they were underrepresented in research (as defined by NIH and/or especially in Minnesota), and 3) If they were from low socio-economic status. To meet our goals, UPRIME Scholars met once a week to discuss research and scientific methods. As the UPRIME Scholars were relatively inexperienced in research, we designed our meetings to be safe and open spaces for encouraging discussion, especially about their research projects. Discussion topics included techniques (e.g. qPCR, histology, and cell culture), experimental design (e.g. animal models, use of controls), and developing a hypothesis. In addition, we had UPRIME Scholars attend weekly “Graduate Student Colloquia” where our graduate students give formal presentations and chalk talks about their research. Here, UPRIME Scholars were tasked to identify and discuss the hypotheses tested, animal or experimental models used, and interpretation of results. In our first two years, UPRIME Scholars reported very positive experiences in their summer research and in the usefulness of the weekly meetings. They were able to better understand why they were doing their projects, how their projects were an important part of their mentor’s research, and how to troubleshoot the techniques they used. Taken together, the UPRIME program has been successful in the fostering of undergraduates in physiology research. The UPRIME program serves as our basis for future programs for undergraduates interested in research. American Heart Association 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.
A Systematic Review of the Historical Use of Sex and Gender in the American Journal of Physiology-Heart and Circulation
Authors: Vanden Noven Marnie , Anselmo Miguel , Tahsin Chowdhury Tasnova , Carter Jason , Keller-Ross Manda 
Published: May 2023

Females continue to be underrepresented in research despite the 1993 National Institute of Health (NIH) Revitalization Act and 2016 NIH mandate for inclusion of sex as a biological variable. Recently, the American Journal of Physiology-Cirulation and Heart (Am J Physiol Heart and Circ) issued a call and published several papers with the focus on sex as a biological variable in an effort to improve inclusion and representation of females in journal articles. To determine the progress Am J Physiol Heart and Circ has made in sex/gender reporting we conducted a systematic review of the first six months of each decade from 1980 to 2020 using PRISMA guidelines. METHODS: In the first six months of 1980 to 2020, 1,729 articles were published, of which 979 articles were reviewed. Articles were excluded if they did not include subjects, were editorials, methodology papers, or other special topics that did not include original research. RESULTS: From 1980 to 2020, human (H) studies increased and animal (A) studies decreased (1980: H=0.8%, A=89.3%; 1990: H=5.1%, A=81.7%; 2000: H=13.9%, A=69.9%; 2010: H=15.4%, A=68.4%; 2020: H=21.2%, A=58.7%). These studies (n=724, 74%) included 42,269 participants. In human studies, the number of males compared to females reported in the journal for each decade was consistently higher (1980: males n=5, females n=3; 1990: males n=199, females n=70; 2000: males n=355, females n=305; 2010: males n=472, females n=186; 2020: males n=1,222, females n=1,157). In animal studies, male animals were included consistently more than females (1980: males n=1,291, females n=58; 1990: males n=2,628, females n=447; 2000: males n=3,083, females n=590; 2010: males n=4,517, females n=663; 2020: males n=1,973, females n=1,372). CONCLUSIONS: While there has been improvement in the inclusion of female participants, this systematic review clearly demonstrates disparities in reporting sex as a biological variable in the Am J Physiol Heart and Circ. The underrepresentation of females in animal and human studies compromises our understanding of female physiology, directly impacting clinical care and outcomes. The call for using sex as a biological variable by the Am J Physiol Heart and Circ will likely contribute to closing the gap on this disparity and set new standards and expectations for the inclusion of females reported in research articles. Further, it is imperative that organizations such as the American Physiological Society and NIH ensure the use of sex as a biological variable as the norm instead of the exception. 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.
Identification of HMOX2 promoter variants linked to adaptation in Tibetans
Authors: Lin Andrew , Kong Mitchell , Gu Wanjun , Moya Esteban , Lawrence Elijah , Yu James , Simonson Tatum 
Published: May 2023

Populations living at high altitude have been subjected to the selective pressure of hypoxia due to low atmospheric pressure for hundreds of generations. Adaptive genetic signals are apparent in the genomes of present-day populations, but the links to physiological changes and underlying mechanisms are not completely understood. Our recent physiological studies revealed that Tibetans residing at intermediate altitude (2200 m; 13,780 ft) have lower hemoglobin concentration ([Hb]) and elevated carbon monoxide (CO) relative to other populations resident at the same altitude. Our previous genetic studies revealed that Tibetans residing at 4200 m (13,780 ft) exhibit a haplotype (20 kilobases) encompassing the Heme Oxygenase 2 (HMOX2) gene region. Heme oxygenase 2 protein produces carbon monoxide (CO) as a byproduct of hemoglobin breakdown. We hypothesize that HMOX2 underlies the observed CO levels at high altitude. We further hypothesize that regulatory variants could be linked to elevated heme oxygenase activity and, therefore, elevated CO levels in people of Tibetan ancestry.We measured carboxyhemoglobin (COHb) in Tibetan (n = 10) and Han Chinese (n = 8) male residents of Xining (2,200 m; 7,218 ft), China, using a co-oximeter and Tibetan (13 women, 8 men) and Han Chinese (6 women, 10 men) residents of Salt Lake City, Utah (1,413 m/4,637 ft) with a finger pulse oximeter. In the Xining cohort, COHb levels were 97% higher in Tibetans (1.01 ± 0.59 %) compared to their Han Chinese counterparts (0.51 ± 0.39 %, p < 0.048). This result was replicated in Salt Lake City, where Tibetans exhibited significantly higher COHb (4.31 ± 0.48%) compared to Han Chinese (2.00 ± 0.6%, p = 0.004).We also examined localized signals of natural selection (Composite of Multiple Signals test, CMS) from 27 previously published Tibetan genomes and identified single nucleotide variants (SNVs) within the selected haplotype with potential functional impacts on heme-oxygenase expression. Eleven variants were located within the promoter region of the HMOX2 gene. These variants exhibit significant delta allele frequencies (DAF) between Tibetans and Han Chinese (DAF > 0.2, p < 0.005) and are in high linkage disequilibrium (R2 > 0.9) in both populations. Literature and in-silico prediction tools (CIS-BP, JASPAR) indicate some of these variants have a potential gain-of-function roles as transcription factor binding sites.These results suggest adaptive, regulatory variants in HMOX2 may contribute to the observed increased endogenous CO in highland Tibetans, conferring protection from the selective stresses of high-altitude hypoxia. This project is funded by NIH R01HL145470. 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.
Hepatocyte PHB1 Deficiency Causes Sex-Specific Changes in Glycemic Control and Body Composition in Mice
Authors: Alowaisi Amany , Mahoney Jo , Berdaweel Islam , Anderson Ethan 
Published: May 2023

Prohibitin 1 (PHB1) is a dynamic lipid raft associated protein that is located in plasma membrane and in the inner mitochondrial membrane complexed with its homolog PHB2 in a tight 1:1 stoichiometric ratio. The PHB1/2 ‘supercomplex’ has been linked to many cellular processes including proliferation, apoptosis, transcription, inflammation, signaling and metabolism. Previous studies have shown that PHB1 plays a role in modulation of insulin signaling via PIP3→AKT pathway. Moreover, a recent report showed that male and female mice with adipocyte-specific PHB1 overexpression developed obesity, while only the obese males developed glucose intolerance and fatty liver. These and other findings strongly implicate a sex-specific role for adipocyte PHB1 as a key mediator in glucose metabolism, although mechanisms remain obscure and it is further unclear whether this sex-specific effect is exclusive to adipocytes. Here, we examined the role of hepatocyte PHB1 in regulating glucose metabolism with diet induced obesity. Mice with hepatocyte specific PHB1 deficiency (hPHB1def) were generated by crossing homozygous PHB1 floxxed mice (PHB1fl/fl) with Albumin-Cre (Alb-Cre+/+) mice. Male and female mice were randomly assigned to normal chow diet (CTL diet) or high fat high sucrose diet (HFHS) for 20 weeks. Female hPHB1def mice were found to have a lower body weight compared with WT in both diet groups. However, male hPHB1def mice had increased body fat (gonadal fat) and decreased lean mass compared with WT males, even on CTL diet. At the same time, female hPHB1def mice had reduced brown fat mass compared to WT females on HFHS diet, but not CTL diet. Male hPHB1def mice on CTL diet are insulin resistant compared with WT males; however, female hPHB1def mice have improved glucose tolerance compared with WT females, due in part to decreased gluconeogenic capacity in female hPHB1def mice. Surprisingly, circulating PHB1 levels decreased with diet induced obesity in both males and females, with hPHB1def having lower hepatocyte-PHB1 content compared with WT, regardless of diet. Collectively, these findings reveal that hepatocyte-PHB1 is an important regulator of systemic glucose metabolism and adiposity in a sexually dimorphic manner. American Heart Association (AHA) 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.
Acute Radiation Exposure Increases Mortality to Traumatic Hemorrhage
Authors: Torres Luciana , Niland Casey , Ybarra Jennifer , Marshall Stephanie , Ryan Kathy 
Published: May 2023

It is anticipated that both ionizing radiation and traumatic injury may occur simultaneously in future terrorist attacks and battlefield scenarios. However, it is not known how radiation combined with injuries (RCI) will impact physiological compensatory responses to traumatic hemorrhage and survival. We hypothesized that the addition of radiation to our established traumatic hemorrhage model (Klemcke et al., J Appl Physiol 2021) would increase mortality. Male rats (n=6/group) were randomly assigned to 1 of 4 groups: sham (no injury; no radiation); radiation injury (RI) only; traumatic hemorrhage alone (CI); or RI combined with traumatic hemorrhage (RCI). For RI and RCI rats, whole-body irradiation was performed with a single, sub-lethal X-ray dose of 5.5 Gy delivered at 1 Gy/min (MultiRad 350). CI consisted of extremity trauma (fibular fracture + penetrating and soft tissue injury, performed under isoflurane anesthesia) followed by conscious hemorrhage of 37% of blood volume. Rats were monitored for 14 days following injury or sham procedures. Sham rats had 100% survival to Day 14, while RI and CI rats had 50% and 50% mortality, respectively, at this point. RCI rats, however, demonstrated 100% mortality at Day 14; differences in survival proportions were significant (P=0.005). We therefore developed a new rat model of RCI by combining X-ray irradiation with traumatic hemorrhage which allows acute (hours) as well as chronic (days) observations. While RI alone produced significant mortality, the addition of traumatic hemorrhage increased mortality to 100%. Future work will elucidate physiological mechanisms potentiating the lethal effect of either RI or CI alone. Biomedical Advanced Research and Development Authority (BARDA). 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.
Physiological characterization of instrumental learning in the spinal cord using the Paw Withdrawal Learning paradigm
Authors: Aldana Efren , Araiza James , Wang Y. Curtis , Zhong Hui , Tillakaratne Niranjala , Edgerton V Reggie , Joseph Michael 
Published: May 2023

Following spinal cord injury (SCI), sensory and motor functions are severely disrupted yet the spinal circuitry below the injury site continues to maintain active and functional neuronal properties (Edgerton, 2004). The spinal cord is endogenously capable of several forms of adaptive plasticity, including functional re-training with exercise, instrumental, and Pavlovian learning. The paw withdrawal learning (PaWL) paradigm represents a simple spinal instrumental learning model (Jindrich 2019). Briefly, in mice whose spinal cords are completely transected (ST) at mid-thoracic (T7-T9) level, the tibialis anterior (TA) muscle is given a sub maximal threshold shock to a hind leg when the leg is extended below a 1mm imposed threshold from a baseline starting position. The contingent group mice learn to maintain the shocked leg, in a flexed position while the experimentally coupled noncontingent group of mice do not acquire the flexed position. To demonstrate the acquisition of the flexed paw hold is mediated through muscle-specific proprioceptive inputs and a time dependent modification of the spinal interneuronal network associated with the TA motor pool, we measured the TA muscle activity using acute EMG during PaWL in both Contingent stim and non-contingent stim groups. To demonstrate that TA specific sensory afferents are critical in PaWL, we blocked the proprioceptive muscle and the cutaneous afferents using Lidocaine. During PaWL, the TA muscle showed significant EMG activity when compared to medial gastrocnemius and vastus lateralis muscles. We detected greater TA muscle activity in the Contingent stim compared to the non-contingent groups. The significant increase in the EMG amplitude in the TA muscle and time-frequency and power relationships in the contingent group, but not the non-contingent group, suggests that the successful learning requires a temporal engagement of the spinal sensorimotor network. CSULA Mini-Grant 2020 and Joseph/Gomez-Pinilla R01NS056413 (Diversity Supplement) 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.
Vagal C-fibers mediate HDM induced airway hyperreactivity via PAR1 receptors
Authors: Patil Mayur , Pavelkova Nikoleta , Taylor-Clark Thomas , Akopian Armen 
Published: May 2023

Airway hyperreactivity (AHR) is a hallmark of allergic asthma, and the major cause of exacerbations. Although acute bronchospasm can be mitigated by bronchodilators and corticosteroids, no therapeutics effectively target AHR. Recent studies have shown that airway afferent/sensory nerves play a critical role in AHR, but the mechanisms are not well understood. Here we show employing two-photon ex vivo imaging of the vagal ganglia of PirtCre;R26 ‐ GCaMP6s mice, HDM extract caused a robust activation of the majority of naïve airway-specific C-fibers. Importantly, diphtheria toxin-mediated ablation of C-fibers using Nav1.8Cre, caused a significant reduction in HDM induced AHR in mice. HDM extract is made up of proteases and can activate PARs, the G-protein coupled receptors (GPCR). We analyzed PAR receptor expression in airway specific C-fibers using single neuron RT-PCR and found that all airway C-fibers expressed PAR1 and only 5% expressed PAR2 receptors. Ex vivo imaging of the vagal ganglia of PirtCre;R26 ‐ GCaMP6s mice we observed that pretreatment (10mins) with an antagonist (FR171113, 15μM) to PAR1 but not PAR2 receptors, significantly blocked the stimulatory effect of HDM on C-fibers. We created sensory neuronal conditional knockout of PAR1 and PAR2 using the PirtCre mice crossed with PAR1 and PAR2 floxed mice to generate experimental PirtCre/PAR1fl/fl and PirtCre/PAR2fl/fl CKO mice. We found that PirtCre/PAR1fl/fl (CKO) mice exposed to HDM over a period of 12 days had significantly reduced HDM-induced AHR. Our data suggests that direct activation of airway vagal C-fiber afferent PAR1 receptors by HDM allergens leads to HDM-induced airway hyperreactivity. Supported by AHA predoctoral grant 14PRE18490009 and Warren Alpert Foundation grant 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 Role of Acetyl-CoA Synthetase Short Chain Family Member-1 on Adipocyte Thermogenic Capacity
Authors: Zhang David , Chocron Sandra , Mota Linda , Brey Eric , Gius David , Gonzalez Porras Maria 
Published: May 2023

Obesity is characterized by an increase in adipose mass and is the leading risk factor for type 2 diabetes. Recent research suggests that activation of brown or beige fat and white adipose tissue browning represent a new therapeutic strategy for metabolic diseases. Fatty acid oxidation is required for the browning of white adipose tissue (WAT) and the induction of uncoupling protein 1 (UCP1) in WAT. The Acyl-CoA Synthetase Short Chain Family Member-1 (ACSS1), an established SIRT3 deacetylation target, is central to fatty acid oxidation (FAO) and mitochondrial bioenergetics by converting acetate and CoA to acetyl-CoA. However, the biological function of ACSS1 acetylation (ACSS1-Ac) in thermogenic adipose tissue and how it contributes to metabolic changes in adipocytes has not been investigated. We have generated a novel acetylation mimic mouse where lysine 635 (K635) was mutated to glutamine (K635Q), representing constitutive ACSS1-K635-Ac. Male mice expressing Acss1K635Q/K635Q exhibited a reduction in size and body weight. Upon 48-hour fasting, these mice exhibited hypothermia as well as decreased ATP and lactate levels. Interestingly, UCP1 gene expression was upregulated in brown adipose tissue (BAT) of the Acss1K635Q/K635Q compared to WT and also in WAT from fasted animals. Differentiated beige adipocytes also showed higher UCP1, PGC1a and adiponectin gene expression in cells isolated from Acss1K635Q/K635Q mice compared to WT cells. Oxygen consumption rate of these cells was lower with lower basal and ATP-coupled respiration. Acss1K635Q/K635Q beige adipocytes failed to respond to beta-adrenergic stimulation and did not increase their respiration capacity when compared to WT cells. No differences were observed in glucose uptake and lipolysis functional assays. These results suggest that the mutation leads to a disruption of downstream signaling of UCP1. In conclusion, ACSS1-K635-Ac is a novel thermoregulator in adipose tissue that could lead to further development of new therapies for metabolic diseases. 1. Mays Cancer Center CCSG (P30 CA054174); 2. National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, under Award Number F32-0DK122754 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 Heat Index as a Measure of Future Heat Stress with Climate Change
Authors: Romps David , Lu Yi-Chuan 
Published: May 2023

The wet-bulb temperature and wet-bulb globe temperature (WBGT) have been widely used to forecast the physiological consequences of extreme heat associated with climate change. Unfortunately, those metrics are not based in any physiological model of thermoregulation, which means their values do not map one-to-one onto physiological states. In contrast, the widely used heat index is based on a model of human thermoregulation: each value of the heat index maps onto a unique state of the human body. This mapping is obscured in practical applications of the heat index, which use the National Weather Service's empirical fit to values tabulated in Robert Steadman's seminal 1979 paper. In addition, that empirical fit is used, without scientific justification, to extrapolate the heat index to high heat and humidity, where Steadman's paper gave no values because of an apparent failure in the underlying physiological model. In recent work, Steadman's model has been extended, allowing the heat index to be calculated for extreme heat and humidity while retaining full backward compatibility. This reveals that the extrapolation used by the National Weather Service underestimates the heat index during severe US heat waves by as much as 10 degrees Celsius. For example, the peak heat index at Chicago's Midway International Airport was underreported by 9 degrees Celsius during the July 1995 heat wave, which killed hundreds of people. This correction has important implications for physiology: these corrected values reveal that even walking in the shade would have brought a healthy person close to the point of hyperthermia. This highlights how close global warming is to making the most severe US heat waves a fatality risk for even young and healthy adults. Department of Energy's Atmospheric System Research 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.