bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Mitochondrial Dynamics Proteins Mitofusin‐2 and Drp‐1 in Myocardial Ischemia‐Reperfusion Injury Is Prevented by Matrix Metalloproteinase‐2 Preferring Inhibitors
Authors: Bassiouni Wesam , Seubert John M. , Schulz Richard 
Published: May 2022

ObjectiveMatrix metalloproteinase‐2 (MMP‐2) is a ubiquitous protease that cleaves several extracellular and intracellular proteins. MMP‐2 is activated intracellularly in response to enhanced oxidative stress resulting from myocardial ischemia/reperfusion (I/R) injury. Oxidative stress impairs mitochondrial function which is regulated by different proteins including mitofusin‐2 (Mfn‐2) and dynamin‐related protein‐1 (Drp‐1) which control mitochondrial dynamics involving fusion and fission, respectively. As both proteins are localized at the mitochondrial outer membrane and MMP‐2 is localized at the mitochondrial‐endoplasmic reticulum associated membrane we hypothesized that MMP‐2 may proteolyze Mfn‐2 and Drp‐1. We therefore investigated whether inhibition of MMP‐2 could protect against the loss of mitochondrial dynamics proteins during I/R injury.MethodsHearts isolated from 3 month old C57BL/6J mice were perfused according to Langendorff at constant pressure and subjected to I/R injury (30 min ischemia and 40 min reperfusion) in absence or presence of MMP‐2 preferring inhibitors ARP‐100 (10 µM) or ONO‐4817 (50 µM) or their vehicle (n=5 hearts per group). Effects on mechanical function were recorded. At the end of reperfusion, the hearts were homogenized and subcellular fractions were prepared. The degradation of troponin I (TnI), an intracellular MMP‐2 target, was measured in the cytosolic fraction as a marker of MMP‐2 activity. Levels of Mfn‐2 and Drp‐1 in the mitochondrial fraction were also measured using western blot. In silico analysis of potential MMP‐2 cleavage sites was performed using Procleave.ResultsARP‐100 or ONO‐4817 significantly increased left ventricular developed pressure compared to vehicle‐treated I/R hearts (% of pre‐ischemic baseline value at R40: IR+vehicle 25.5±3.2, IR+ARP 50.1±3.2, IR+ONO 57.3±1.6%, p<0.05). Similarly, both inhibitors significantly improved the rates of contraction and relaxation (+/‐dP/dt). TnI loss was increased in I/R hearts as shown by a significant reduction in TnI (~30 kDa) and the appearance of an ~22 kDa band. ARP‐100 or ONO‐4817 attenuated TnI loss, indicating MMP‐2 activation. Levels of Mfn‐2 and Drp‐1 in the mitochondrial fraction were significantly reduced in the I/R group and ARP‐100 or ONO‐4817 attenuated this reduction (p<0.05). Similar results were obtained using a different Mfn‐2 antibody that binds to its C‐terminus. In silico analysis of both mouse Mfn‐2 and Drp‐1 sequences showed several potential sites that could be targeted by MMP‐2.ConclusionsDuring myocardial I/R injury, MMP‐2 may affect mitochondrial dynamics by proteolysis of Mfn‐2 and Drp‐1. Inhibition of MMP‐2 activity could protect against cardiac contractile dysfunction in part by preserving these proteins affecting mitochondrial fusion and fission.
“What Bones And Bony Features Are You Teaching Your Students?” A Survey Of Skeletal System Coverage In Undergraduate Human Anatomy And Physiology Courses
Authors: Aryal Asmita , O'Loughlin Valerie D. 
Published: May 2022

Undergraduate (baccalaureate) human anatomy (HA) and anatomy and physiology (A&P) courses are offered globally, but how similar is their content coverage for each organ system? There has been a dearth of published research on this subject. Previously, some of the authors (Reynolds et al., 2018; submitted) surveyed instructors of stand‐alone HA as well as A&P courses to document comparability and variability in skeletal muscular system coverage in these courses. We now focus our attention on skeletal system coverage in these courses. A study by Sparacino et al., (2019) evaluated the undergraduate nursing anatomy curriculum at four institutions in the United Kingdom, but the study did not list the specific bone and its features students needed to know.Thus, a representative sample is required to be able to assess the variations in skeletal system coverage in both stand‐alone HA and A&P courses across different institutions.We have developed an online survey where undergraduate HA and A&P faculty can report on which skeletal elements (bones), and which features on these bones they require their students to know. The skeletal system coverage survey is made accessible to participants online via Qualtrics. Bones and their bony features listed in the survey are those listed and described in a typical undergraduate human anatomy textbook (Human Anatomy, 6th edition textbook by McKinley, O’Loughlin, and Pennefather‐O’Brien [2021]). This survey will also collect institutional demographic data such as the type of institution, course format, and geographic location of the institution, for comparison. We need to collect data from a large and representative sample of courses in order to accurately describe skeletal system coverage trends.This poster will provide both an in‐depth justification for the need for such a survey and serve to recruit participants to complete the survey. Additional recruitment will occur via recruitment emails to AAA (American Association for Anatomy), HAPS (Human Anatomy and Physiology Society), and AACA (American Association of Clinical Anatomists) listservs, as well as at the HAPS 2022 annual meeting. Thus, we will meet to speak about the formation of this survey, collect survey data from willing AAA participants, and have a critical conversation about skeletal system coverage in undergraduate human anatomy and physiology courses.
Role of stress granule activation in cardiomyocyte function in sepsis
Authors: Wang Yaqiao , Wu Kehan , Liu Runmin , Wang Hao , Rui Tao 
Published: May 2022

Sepsis is a life‐threatening organ dysfunction caused by a dysregulated host response to infection. It is the leading cause of mortality in Intensive Care Unit (ICU). Sepsis‐induced myocardial dysfunction (SIMD) is a major complication of the sepsis that contributes to high mortality of patients with sepsis. Stress granule (SG) is a cytoplasmic membraneless platform that is formed in response to cellular stresses. The role of SG in SIMD is unknown. The aim of present study is to understand whether activation of SG in cardiomyocytes (CM) plays a role in CM function in sepsis.MethodsCMs were treated with lipopolysaccharide (LPS). CM SG activation (eIF2α phosphorylation) and TNFα production were assessed with Western blot and ELISA, respectively. CM function was evaluated with intracellular cAMP. ISRIB or over‐expression of G3BP1 was employed interfering SG.ResultsChallenging CMs with LPS results in eIF2α phosphorylation, an increase in TNFα production, and a decrease in intracellular cAMP in response to dobutamine. Pharmacologically (ISRIB) or genetically inhibition (G3BP1 knock down) of SG leads to an exaggerated increase in TNFα expression. Further, SG inhibition results in enhanced decrease in CM function (decreased intracellular cAMP) in CM with LPS. Over‐expression of G3BP1 in CMs prevents LPS‐induced CM TNFα production and improves CM contractility.ConclusionOur results indicate that the cardiomyocyte stress granule activation plays a protective role of myocardial function in sepsis.
Bile Duct Ligation Changes the Inhibitory Control of Vasopressin Neurons in Male Rats
Authors: Aikins Ato O. , Brock Courtney , Little Joel T. , Farmer George E. , Cunningham J. T. 
Published: May 2022

Dilutional hyponatremia typically is caused by increased Arginine Vasopressin (AVP) secretion. This increases the risk of complications and mortality in patients with liver cirrhosis. Liver cirrhosis in male rats increases AVP release but the underlying mechanisms are still under investigation. In other models of chronic AVP release, changes in chloride homeostasis alters the inhibitory control of AVP neurons in the supraoptic nucleus (SON) causing GABA mediated excitation instead of inhibition. In the bile duct ligation (BDL) model of cirrhosis, changes in either intracellular chloride concentration or cell firing activity have not been directly tested. We hypothesize that liver cirrhosis increases intracellular chloride concentration leading to a decrease in GABA‐mediated inhibition of SON neurons from male rats.To test this hypothesis, we injected an adeno‐associated virus with a vasopressin promoter and a ratiometric chloride indicator, AAV2‐0VP1‐ClopHensorN into the SON of adult male Sprague‐Dawley rats. The rats either received BDL surgery, which was used to model liver cirrhosis, or a sham ligation surgery. All BDL rats had significantly higher liver weight to body weight ratio (n = 10‐20, p < 0.05), lower plasma osmolality (n = 10‐20, p < 0.001) and lower hematocrit (n = 10‐20, p < 0.05) as compared to sham rats. All rats were anesthetized with isoflurane (2‐3%), their brains were collected, and slices containing the SON were prepared. Loose‐cell patch recordings were made at 31±1oC using standard artificial cerebrospinal fluid. Labeled AVP cells and unlabeled SON cells were tested with focal application of muscimol (100µM), a GABAA receptor agonist.Cells from BDL rats showed impaired GABAA‐mediated inhibition in response to muscimol, as compared to those from sham rats. All putative AVP SON neurons from sham rats (4/4) showed decreased activity following muscimol while half of the putative AVP SON neurons (7/14) from BDL rats were excited (p < 0.001). Similar results were observed in experiments were the injections missed the SON. In these experiments, all SON neurons from sham rats were inhibited by muscimol (26/26) while thirty‐five percent of SON neurons from BDL rats (16/45) were excited by muscimol (p = 0.001). ClopHensorN based chloride imaging showed that muscimol application was associated with decreased intracellular chloride concentrations in putative AVP cells from BDL rats as compared to sham rats (n = 31‐32, p = 0.001). The results show that liver cirrhosis impairs the normal inhibitory response of SON neurons to GABAA receptor activation which could contribute to increased cell activity and dilutional hyponatremia in male rats.
The Glass Ceiling Thickens: How The COVID‐19 Pandemic Negatively Impacted Academic Medicine Faculty
Authors: McNulty Margaret A. , Lufler Rebecca S. 
Published: May 2022

INTRODUCTIONInequities faced by women in academic medicine before the COVID‐19 pandemic are well‐known, yet there are little formal data on exactly how the pandemic has affected faculty, particularly in academic medicine. The purpose of this cross‐sectional study was to elucidate the impact of the pandemic on faculty in academic medicine and identify whether it is disproportionately affecting populations, focusing specifically on responsibilities at home, work, and mental health according to gender identification, faculty rank, and faculty appointment.METHODSAn online questionnaire was distributed in February 2021 to faculty at academic medicine centers. This questionnaire asked respondents to provide demographic data, answer questions about their responsibilities at home and work, and indicate whether and how the pandemic has affected both. Respondents were also asked questions on self‐care and mental health and to document how their institution(s) can assist faculty in mitigating struggles associated with the pandemic. Responses were analyzed via quantitative (Pearson’s chi‐square tests) and qualitative (thematic analysis) means.RESULTSWomen, mid‐, and early‐career faculty were more likely to be responsible for the care of others (p=0.014), and the impact of the pandemic on caring for others was negative, especially for early career faculty (p=0.019). Research, teaching, and clinical practice were negatively impacted by the pandemic, with women feeling this more severely in clinical practice (p=0.003), as a result of an increased teaching load (p=0.042), and inadequate work environment (p=0.013). Women (p<0.01), early career‐faculty (p<0.01), and clinical faculty (p=0.029) were also more negatively impacted by the pandemic in the areas of self‐care and mental health. While there was no significant difference in who requested a leave of absence or tenure clock extension, early‐career and women faculty were more likely to fear retribution for such requests. Faculty provided actionable suggestions to combat these negative effects under five themes, including Flexible Expectations, Support, Mental Health, Compensation, and Communication.CONCLUSIONPre‐pandemic stress and burnout among faculty in academic medicine has been well documented, and this study demonstrates that academic medicine faculty, particularly women and early‐career faculty, continue to feel additional burdens secondary to the COVID‐19 pandemic. These data can be utilized by administrations and future studies to make informed decisions regarding policies and programs created to assist those populations who are most vulnerable to the effects of the pandemic.SIGNIFICANCETo the authors’ knowledge, this is the first study to provide both quantitative and qualitative data demonstrating a negative impact of the COVID pandemic on academic medicine faculty, particularly women and early career faculty. These data are necessary to create change to improve recruitment and retention of quality faculty.
Tac1‐expressing cells in the pre‐Bötzinger complex are potential targets to prevent opioid‐induced respiratory depression
Authors: Rousseau Jean‐Philippe , Scarpellini Carolina S. , Montandon Gaspard 
Published: May 2022

RationalOpioids are extensively used for their analgesic properties but present a variety of unwanted side effects, including tolerance, dependence and respiratory depression. The analgesic effect of opioids is due to activation of µ‐opioid receptors (MOR) in the central nervous system and no treatments are currently available to prevent respiratory depression without reducing their analgesic properties. The neural circuits and mechanisms regulating respiratory depression, sedation, and analgesia by opioids often overlap, therefore making challenging the identification of the mechanisms regulating respiratory depression. Neurons expressing tachykinin precursor 1 peptide (Tac1) located in the pre‐Bötzinger complex (preBötC) also co‐express neurokinin‐1 receptors (NK1R) and MORs. NK1R neurons are preferentially inhibited by opioids and play an essential role in mediating opioid‐induced respiratory depression.ObjectiveHere, we tested the hypothesis that optogenetic activation of Tac1‐expressing preBötC cells in freely behaving mice will modulate breathing and prevent respiratory depression by opioids.MethodsUsing a Cre‐loxP recombination approach, we injected in Tac1 Cre recombinase mice the adeno‐associated virus containing the gene cassette of the excitatory channelrhodopsin‐2 ChETA flanked between loxP sites. A 200 µm optical fiber was then fixed above the preBötC for laser stimulation with blue light (wavelength: 480 nm). After a four weeks period to allow ChETA expression in targeted cells, the mouse was placed in a plethysmographic chamber and breathing was measured while laser stimulations were performed under baseline conditions (30 Hz). Following baseline measurements, the clinically relevant µ‐opioid drug fentanyl was administered by intraperitoneal injection (0.3 mg/Kg). About 5 minutes after fentanyl injection, targeted preBötC cells were activated using laser stimulations (30 Hz).ResultsData show that stimulation of Tac1‐expressing cells increased respiratory frequency under baseline conditions. Fentanyl depressed breathing in 5 minutes and stimulation of Tac1 cells prevented opioid‐induced respiratory depression; an effect that was reversible.ConclusionTac1‐expressing preBötC cells may constitute a target to prevent depression of breathing by opioids. These results will help identify the cells mediating opioid‐induced respiratory depression, an essential step toward the development of therapeutic targets to reduce the risk of opioids overdose and associated mortality.
Ameliorative potential of D‐Ribose‐L‐Cysteine in male Wistar rats with metabolic syndrome
Authors: Ojetola Abodunrin A. , Fasanmade Adesoji A. 
Published: May 2022

Metabolic Syndrome (MS) refers to cluster of cardiometabolic risk factors which include obesity, insulin resistance, dyslipidaemia, hyperglycaemia and hypertension. Although, oxidative stress is implicated in its aetiology, protocols in MS management have not included the use of antioxidants. D‐ribose‐L‐cysteine (DRLC) is a potent antioxidant which has been suggested to be useful in the management of dyslipidaemia. This study was designed to investigate the effects of DRLC in rats with MS.Twenty male Wistar rats (190‐200g) were assigned into four groups (n=5). Groups I and II were fed with standard diet (SD) for eight weeks and were subsequently treated orally with: 10mL/kg distilled water and 250mg/kg DRLC daily for another eight weeks respectively. Groups III and IV were fed with a modified standard diet (MSD) consisting of 17% fructose and 20% lard with additional 10% fructose solution, given ad‐libitum for eight weeks to induce MS in rats. They were subsequently treated orally with: 10mL/kg distilled water (group III) and 250mg/kg DRLC (group IV) daily for another eight weeks respectively. Animals were weighed and Blood Pressure (BP) measured using rat tail cuff method. They were euthanized, and blood and heart were collected for biochemical analysis. Fasting Blood Glucose (FBG) was determined through glucose oxidase method. Serum C‐reactive Protein (CRP), Tumour Necrosis Factor alpha (TNFα) and insulin were determined through ELISA. Cardiac reduced Glutathione (GSH), Glutathione Peroxidase (GPx), Superoxide Dismutase (SOD), Xanthine Oxidase (XO), malondialdehyde; serum triglycerides, Total Antioxidants Capacity (TAC), High Density Lipoprotein (HDL) and Total Cholesterol (TC) were determined by spectrophotometry. Low Density Lipoprotein (LDL) was determined using Friedwald’s formula. Data were expressed as mean ± SEM and compared by ANOVA at p < 0.05.Body weight, systolic BP, FBG and TNFα of group IV (255.8±10.8g, 167.8±8.6mmHg, 84.3±6.0mg/dL, 433.0±54.8pg/mL, respectively) were significantly reduced compared to group III (318.9±12.7g, 219.0±9.8mmHg, 140.9±9.9mg/dL, 577.8±31.8pg/mL, respectively). Also, insulin, TC, LDL and heart XO of group IV were significantly reduced compared to group III. The serum levels of CRP, triglycerides and malondialdehyde in group II were significantly reduced compared to group I. There were significant increases in serum TAC, cardiac GPx, SOD, GSH; and serum HDL of group IV (1.2±0.3mmol/mL, 2.4±0.5U/L, 1.1±0.1U/L, 11.3±9.7mM, 13.4±1.6mg/dL, respectively) compared to group III (0.6±0.2mmol/mL, 1.1±0.2U/L, 0.7±0.1U/L, 0.8±0.2mM, 7.7±1.4mg/dL, respectively).The D‐ribose‐L‐cysteine ameliorated dyslipidaemia, hyperglycaemia and hypertension by decreasing oxidative stress and pro‐inflammatory cytokines in male rats with metabolic syndrome.
D230025D16Rik: A Novel Regulator of Muscle Cell Differentiation
Authors: Chaffer Tomer J. , Moamer Alaa , Leduc‐Gaudet Jean‐Philippe , Broering Felipe E. , Mayaki Dominique , Huck Laurent , Sandri Marco , Gouspillou Gilles , Hussain Sabah 
Published: May 2022

RationaleLoss of skeletal muscle mass and function is a common clinical feature and poor prognostic indicator in various diseases. A promising therapeutic approach of regenerative medicine for repair of skeletal muscle is through the delivery of cellular therapies targeting regulators of muscle regeneration (myogenesis). However, not all the proteins involved in this process have been identified. To address the gap in knowledge of proteins involved in myogenesis, we recently identified a novel gene, D230025D16Rik, which has never been characterized within the context of skeletal muscle growth and repair.MethodsThe role of D230025D16Rik in a C2C12 murine model of myoblast differentiation was assessed by using an siRNA loss‐of‐function approach. Differentiation of C2C12 myoblasts into myotubes in cells with intact D230025D16Rik and those with D230025D16Rik knockdown (KD) was determined by various experimental techniques, such as RT‐qPCR, microarray, immunofluorescence staining, and immunoblotting.ResultsD230025D16Rik has a mainly nuclear localization in myoblasts, whereas in myotubes, D230025D16Rik has both a nuclear and cytosolic localization. D230025D16Rik expression level is induced at the onset of differentiation (i.e., Day 1) and steadily increases as myoblasts fuse into myotubes. In response to D230025D16Rik KD, the expression of transcription factors MyoD1 and Myogenin and muscle‐specific transcripts Myosin Heavy Chain (MyHC) and Muscle Creatine Kinase (MCK) were upregulated such that a significant acceleration of myogenesis was observed. This observation was further confirmed by an analysis of transcriptomes of control and D230025D16Rik KD myoblasts that revealed an upregulation of myogenesis‐related transcripts in cells with D230025D16Rik KD. Phenotypically, we observe hypertrophic myotube formation at days 0 and 1 in response to D230025D16Rik KD, as indicated by immunofluorescence staining for MyHC. Finally, the presence of nuclear aggregates on D230025D16Rik KD myotubes indicates that D230025D16Rik is essential for proper myotube formation.ConclusionAltogether, these findings highlight, for the first time, the potential regulatory functions of D230025D16Rik during myogenesis.
Sentiment Analysis Machine Learning Model Congruence: A Case Study Using Neuroscience Module Evaluations
Authors: Plochocki Jeffrey , Kibble Jonathan 
Published: May 2022

IntroductionMedical school faculty and administrators regularly assess sentiment in student‐generated textual data, such as instructor and course evaluations. Machine learning models (MLMs) that automate and systematize sentiment analysis are commercially available. However, the congruency of MLMs has not been extensively tested. We compare sentiment polarity derived from human analysis and five MLMs to test the hypothesis they yield significantly correlated output.MethodsStudent evaluations (n=116) of the neuroscience module at the UCF College of Medicine were collected and anonymized. Students were asked to evaluate the strengths of the module (n=108) and provide suggestions for improvement (n=102). Responses were subjected to sentiment analysis by five commercially available MLMs and two module faculty reviewers. Sentiment was classified as either positive (1), neutral (0), or negative (‐1).ResultsSentiment polarity as assessed by the reviewers was significantly correlated (r=0.66, p<0.05). Reviewer assessments were congruent for 73.8% (n=155) of responses. Congruence was greatest for responses on strengths of the module (92.6%, n=100) compared to suggestions for improvement (54.4%, n=103). Congruency among the MLMs was 38.1% (n=80) for all responses, 60.1% (n=80) for module strengths (n=65), and 14.7% (n=15) for suggestions for improvement. Correlation matrix showed moderate correlations among the reviewers and MLMs (range of r=0.41‐0.62, p<0.05). Congruence among all reviewers and MLMs occurred for 34.3% (n=72) responses, with maximal incongruence occurring for only 2.4% (n=5) of responses. Again, congruence was greatest for responses on module strengths (58.3%, n=63) compared to suggestions for improvement (8.8%, n=9). All methods assessed the responses on strength of the module to be more positive than suggestions for improvement. With all methods combined, responses on strengths of the module scored an average of 0.79 compared to suggestions for improvement, which scored ‐0.34.ConclusionSentiment polarity derived from human analysis and MLMs is significantly correlated, although the coefficients reflect only modest linear relationships. MLMs are less congruent than the human observers. All methods demonstrate greater congruence when assessing responses as more positive (i.e., module strengths) than negative (i.e., suggestions for improvement). Additional refinement of MLMs may be necessary before for they can be applied with consistency in medical education settings.