bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of XbaI polymorphism of the estrogen receptor alpha in mexicans at early posmenopause
Authors: Lugo‐Martínez Gabriela , Jiménez‐Zamarripa Carlos Alberto , Madrigal‐Santillán Eduardo Osiris , Calzada‐Mendoza Claudia Camelia 
Published: June 2021

INTRODUCTIONMenopause is the cessation of menstrual cycle, is diagnosed after at least twelve consecutive months whitout bleeding, it occurs due to the reduced functioning of the ovaries, resulting in lower levels of ovarian hormones primarily estradiol (NAMS, 2012). Estrogen suppression has been correlated with higher incidence of cardiovascular and metabolic diseases observed in this age group.Estrogens exert its actions through their receptors, the most studied isoforms of these receptors are: the alpha (ER‐α), beta (Er‐β) and the a G coupled (GPR30). Due to its action and location, an important role in the preservation of cardiovascular and metabolic health has been attributed to ER‐ α (Raushember y Cols, 2016).Several ER‐α polymorphisms have been described, one of the most interesting due to its association with the etiology of cardiovascular pathologies, is the termed as XbaI (rs9340799A> G). This one, consists in the change of an adenine for a guanine, which modifies the affinity of the receptor for its ligand. The X allele has been linked to increased risk of bone demineralization, dyslipidemia, high body mass index (BMI), and oncologic diseases, such as breast cancer and ovarian tumors (chedrahui y Cols,2014; Lobo y Cols, 2014).The aim of this study was to identify the genotype of XbaI polymorphism in mexican posmenopausal women.MATERIALS AND METHODSA descriptive, observational, prospective, transversal, cohort study was carried out in 87 early posmenopausal women who attend to the climacteric clinic of “Hospital general Ignacio Zaragoza”. Clinical data, hormonal profile, blood pressure, antropometric parameters were evaluated. XbaI polymorphism was identified by restriction fragment length polymorphism (RFPL) method.RESULTSThe mean age was 53.01±5.08 years, the BMI average was 28.77±3.88 m/kg2. The averages of systolic, diastolic, and mean blood pressure were 116±10.44 mmHg, 78.7±9.39mmHg y 91.58±9.1 mmHg, respectively;27 patients had hypertension diagnostic under pharmacological treatment.We found 58.87%, 29.89% and 19.24% for xx, Xx and XX genotypes respectively (Graph 1).The averages of systolic, diastolic, mean blood pressure and BMI according XbaI genotype are showed in table 1, there was no statistical differences between groups.CONCLUSIONThe most common genotype in mexican posmenopausal women was xx.There was no differences in blood pressure and BMI according genotype.All patients had elevated values for BMI, independently of her XbaI genotypesSupport or Funding InformationnoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
EGR1 Interacts with TBX2 and Functions as a Tumor Suppressor in Rhabdomyosarcoma
Authors: Mohamad Trefa Salih , Davie Judith 
Published: June 2021

BackgroundEGR1, one of the immediate‐early response genes, can function as a tumor suppressor gene or as an oncogene in cancer. The function of EGR1 has not been fully characterized in rhabdomyosarcoma (RMS), a pediatric cancer derived from the muscle linage.MethodsEGR1 expression was characterized by RNA and protein analysis in RMS cells. EGR1 was ectopically expressed in RH30 cells by transfection of an EGR1 expression plasmid and selection of stable cell lines. A combination of techniques such as proliferation assays, scratch assays and soft agar assays were performed with RH30 cells expressing EGR1 to demonstrate the loss of oncogenic growth properties. Differentiation of RMS cells was detected by immunohistochemistry and RNA and protein analysis. Co‐immunoprecipitation studies were used to identify the interaction between EGR1 and TBX2 and gene expression changes were detected by RNA and protein analysis. TUNEL assays and RNA and protein analysis were used to characterize apoptosis in EGR1 expressing RH30 cells.ResultsWe found that EGR1 is downregulated in the alveolar RMS (ARMS) subtype but expressed at levels comparable to normal skeletal muscle in embryonal RMS (ERMS). We found that over expression of EGR1 in ARMS significantly decreased cell proliferation, mobility, and anchorage‐independent growth. EGR1 also promoted differentiation in RMS cells by inducing the expression of several genes involved in muscle differentiation including myosin heavy chain (MHC), MYOD1 and MYOG. We also found that EGR1 interacts with TBX2, which we have shown functions as an oncogene in RMS. The interaction inhibits EGR1 dependent gene expression, which includes the cell cycle regulators CDKN1A and PTEN as well as other important cell growth drivers such as NDRG1 and CST6. We also found that EGR1 induces apoptosis by triggering the intrinsic apoptosis pathway. EGR1 also sensitized RMS cells to chemotherapeutic agents.ConclusionsWe show that EGR1 is a potent tumor suppressor in RMS and that EGR1 and TBX2 antagonize each other's function. Our data suggest that activation of EGR1 may improve the therapeutic targeting of RMS.Support or Funding InformationHigher Committee for Education Development in Iraq (HCED)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Phosphoinositide Signaling Meets Heme Biochemistry
Authors: KHAN DANISH , Wofford Joshua , Gulten Gulcin , Sacchettini James , Lindahl Paul , Bankaitis Vytas 
Published: June 2021

The Phosphatidylinositol Transfer Proteins (PITPs) have emerged as central regulators of phosphoinositide signaling that that diversify signaling outcomes in cells. Sec14 is the prototype PITP in S. cerevisiae with five homologs (Sfh1‐Sfh5) involved in activities as diverse as trans‐ Golgi signaling and lipid droplet metabolism to phosphatidylethanolamine and ergosterol metabolism. Sfh5 is an orphan member of this family with unknown function with limited information about its genetic interactions or chemogenomic signatures. The surface potential map of Sfh5 indicated unusual electrostatics in the lipid‐binding domain of the protein. We purified recombinant Sfh5 protein from E. coli and subjected it to rigorous biochemical and biophysical analysis. We show that Sfh5 is a heme binding protein with a high spin ferric center as characterized by EPR and Mössbauer Spectroscopy. We solved the crystal structure of the heme‐bound protein to 2.6Å resolution and show that the lipid binding and heme binding sites overlap. We also identified a novel heme‐coordination motif that is conserved through fungal Sfh5s. Finally, we show that the lipid transfer ability of Sfh5 is enhanced when the protein is stripped of heme. We speculate that this protein is a heme‐transfer protein that delivers hemes within cell, particularly under conditions of oxidative stress. Taken together, this is for the first time phosphoinositide signaling proteins have been linked with bioinorganic chemistry involving heme.Support or Funding InformationThis work was funded in part by a grant from the National Institutes of Health (GM44530) and by the Robert A. Welch Foundation (BE0017).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Imaging and Quantifying Mitochondrial Morphology: a Focus on the 3D Freeware MitoGraph
Authors: Harwig Megan Cleland , Viana Matheus P , Egner John M , Harwig Jason , Widlansky Michael E , Rafelski Susanne M , Hill R. Blake 
Published: June 2021

Mitochondria are found in a variety of shapes, from small round punctate structures to a highly‐interconnected web. This morphological diversity is important for function, but complicates quantification. Consequently, early quantification efforts relied on various qualitative descriptors that understandably reduce the complexity of the network leading to challenges in consistency across the field. Recent application of state‐of‐the‐art computational tools have resulted in more quantitative approaches. This work focuses on MitoGraph, an open‐source image analysis platform for measuring mitochondrial morphology initially optimized for use with Saccharomyces cerevisiae. MitoGraph was used to assess mitochondrial morphology of five different mammalian cells types, all of which were accurately segmented by MitoGraph analysis. MitoGraph also successfully differentiated between distinct mitochondrial morphologies that ranged from entirely fragmented to hyper‐elongated.Support or Funding InformationThis was work was supported by the National Institutes of Health grants: R01‐GM067180, R01‐ HL128240 and R41‐AG056253.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
C‐terminal domain is responsible for a Kunitz‐type inhibitor uptake by tumor cells
Authors: Chudzinski‐Tavassi Ana Marisa , Morais Katia Luciano Pereira , Servent Denis , Sciani Juliana Mozer , Iqbal Asif 
Published: June 2021

Amblyomin‐X is a recombinant Kunitz‐type FXa inhibitor that was identified through the transcriptome analysis of the salivary gland from Amblyomma sculptum tick. This protein triggers apoptosis in different tumor cell lines, and promotes regression of tumor growth and reduction of metastasis. In this regard, recently arose question about it structure‐fuction. Thereby, we investigated the effects of two truncated (synthetic) regions of Amblyomin‐X, which we termed Kunitz and C‐terminal domains. Here, using MTT and FXa chromogenic activity assay, we found that both domains have no cytotoxicity in human tumor cells (SK‐MEL‐ 28 and MIA PaCa‐2) and only Kunitz domain inhibit FXa slightly. Also, through confocal microscopy and high content analysis (ImageXpress Micro Confocal High‐Content, Molecular Devices), we observed C‐terminal domains (Alexa Fluor 488 conjugated) uptake by tumor cells previously than Amblyomin‐X (whole protein), but with similar intracellular trafficking and negligible nuclear translocation. Besides, circular dichroism analysis shown that Kunitz domain has quite a structure of α‐helix and β‐sheet, whereas the C‐terminal domain has the great part of random structure. Taken all results together, we can suggest that the C‐terminal domain is responsible for Amblyomin‐X uptake and could be an unusual cell penetrating peptide.Support or Funding InformationSupported by BNDES, Fapesp and União Química FarmacêuticaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Translation of Physiological Understanding (PhUn) Week Activities to a Larger Multi‐ Level Group of Students in a Scientific Environment Following Hurricane Maria
Authors: Rodriguez‐Flores Christine D. , Cruz Myrella , Gonzalez‐Charles Agnes P. , Brofen‐Quiñones Samuel , Rivera Raquel , Colon Maria , Ramos Dihna , Appleyard Caroline B. , Chompre Gladys 
Published: June 2021

Our previous PhUn week activities focused on students from similar grade levels in schools always achieved good learning outcomes. This year due to damaged school facilities after hurricane Maria devastated our island of Puerto Rico, we decided to introduce a Neuroscience theme in a larger combined activity held in a university laboratory environment.HypothesisHaving a larger number of students from different grade levels in a more scientific environment will promote learning and motivation.MethodsStudents from elementary (n=36), middle (n=33) and high school (n=33) attended an activity held at the local university. The activity was divided into three phases: a pre‐test, a teaching/interactive phase which included two conferences followed by rotating hands‐on activities, and a post‐test.ResultsAs in previous years, all students learned new information (elementary, middle school, and high school (39%, 5% and 11% increase vs. pre‐test). However, in contrast to previous years, students asked many questions related to research and laboratory safety, and wanted to know more about how they could work in that type of setting.ConclusionsEven in this larger group setting, all students gained knowledge about the nervous system, and the new environment produced higher levels of curiosity and excitement. Students were able to learn first‐hand what a physiologist is and what a career in this field might be.Support or Funding InformationSupported by PUCPRThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Induction of inward arterial remodeling is ameliorated in vivo by inhibition of actin polymerization dynamics in a mouse model of hypertension
Authors: Foote Christopher A , Castorena‐Gonzalez Jorge A , Padilla Jaume , Martinez‐Lemus Luis A 
Published: June 2021

Hypertension is associated with structural changes to the resistance vasculature leading to a reduction in resistance artery diameter. This process is termed inward remodeling and is defined as a reduction in lumenal diameter under passive conditions. We posit that inward remodeling involves dynamic changes to the actin cytoskeleton that facilitate the movement and rearrangement of vascular smooth muscle cells around a smaller vascular lumen. Ex vivo, prolonged exposure to vasoconstrictors has been demonstrated to induce remodeling via g‐protein coupled receptors (GPCR) that activate the Rho signaling pathway and subsequently promote actin polymerization. We report here that vascular smooth muscle cells, propagated on nanopatterned culture‐ware to maintain their contractile phenotype, increase their ratio of filamentous (F) to globular (G)‐actin in response to GPCR activation by Norepinephrine and Angiotensin (Ang) II. One of the enzymes in the Rho signaling pathway implicated in the increase in F/G‐actin following GPCR activation is Lim Kinase, which phosphorylates and inactivates the actin severing enzyme, cofilin. In isolated rat cremasteric arteries we demonstrate that inhibition of Lim Kinase blocks inward remodeling in the presence of GPCR agonists and this is coincident with a reduction in cofilin phosphorylation. To examine the process in vivo, we utilized a transgenic mouse line that expresses smooth muscle actin (SMA)‐GFP in vascular smooth muscle cells to measure proximal arterial diameter noninvasively within the outer ears using confocal microscopy. Exposure of these mice to 1000 ng/kg/min of Ang II for two weeks resulted in a significant increase in mean arterial blood pressure. Both ears were imaged prior to Ang II infusion (Day 0) and after 14 days of infusion to assess inward remodeling. Starting at day 0, the right ear was injected with a bolus of a Lim Kinase inhibitor (10 uM) and the left ear was injected with vehicle. Injections were repeated every 4 days for a total of four injections. The vehicle exposed ears significantly inwardly remodeled in contrast to those exposed to the Lim Kinase inhibitor (Vehicle diameter = −15.95 % +/− 1.79 versus Lim Kinase inhibitor diameter = −1.75% +/− 1.78, P<0.05). These data demonstrate that in vivo, Lim Kinase plays a necessary role in inward remodeling, and thus merits additional study as a potential therapeutic target in cardiovascular pathologies associated with inward remodeling.Support or Funding InformationNIH‐HL‐088105 to LAMThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impaired Coronary Collateral Growth in a Mouse Model of Diabetes
Authors: Cumpston Devan , Wan Weiguo , Chinchilla Sofia , McCabe Caige , Enrick Molly , Shoenbeck Sydney , Chilian William , Yin Liya 
Published: June 2021

Cardiovascular disease is the leading cause of death in the United States, Ischemic Heart Disease (IHD) accounts for one in seven cardiovascular related deaths. Patients with poorly developed coronary collateral networks have a poorer prognosis after a cardiovascular event than those with well‐developed collaterals. Furthermore, coronary collateral growth is impaired in metabolic syndromes such as diabetes, and obesity. The underlying mechanism(s) that is (are) causal for growth are unknown. In an attempt to elucidate a mechanistic understanding, we developed a murine model that allows us to use genetically modified mice to study the coronary collateral growth spatially and temporally.Methodsa pneumatic snare was implanted and situated around the LAD (open chest surgery during anesthesia). After mice recovered from surgery, the snare was periodically inflated to occlude the LAD; thus producing episodes of ischemia or repetitive ischemia (RI). Coronary collateral growth (CCG) was measured by myocardial blood flow with contrast echocardiography and by collateral numbers by micro‐CT.Results1) No native coronary collaterals were found in mice. 2) After the RI stimulation, extensive coronary collaterals grew. 3) Diabetic mice failed to grow coronary collaterals after RI stimulation. 4) Moreover, the coronary blood flow increased in the ischemic area when there was coronary collateral growth. 5) The quantification of vessel density by tree analysis showed an increase after RI stimulation. Figure 1 (A–C) shows the microfil pictures of the wild type mouse heart without CCG (A), the wild type mouse heart with CCG (B), and the diabetic heart without CCG (C). We believe this murine model of coronary collateral growth is very useful for future studies to investigate the mechanism of regulation of coronary collateral growth. Figure 1 (D–F) shows the micro‐CT pictures of the wild type mouse heart without CCG (D), the wild type mouse heart with CCG (E) and the diabetic heart without CCG (F).Support or Funding Information2R01HL103227‐05( Zhang, Yin), 1R01HL135110‐01 (WMC, LY), 1 R01 HL137008‐01A1 (LY), 1R15HL115540‐01 (LY) and14BGIA18770028 from American Heart AssociationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
O‐GlcNAc Transferase Regulates Phenotypic Transformation of Vascular Smooth Muscle Cells in Response to Hyperglycemia
Authors: Raman Priya , Mathias Amy , Patel Aakaash , Singh Daman , Storm Kyle 
Published: June 2021

Risks of vascular complications are enhanced two‐to‐four fold in diabetes, accounting for increased morbidity and mortality in these patients. Hyperglycemia is an important risk factor for macrovascular complications associated with diabetes. Diabetic patients exhibit an increased incidence of vascular smooth muscle cell (VSMC) migration and proliferation, a hallmark of VSMC phenotypic switching from the quiescent contractile state to a synthetic proliferative phenotype. Hyperglycemia increases glucose flux through the hexosamine biosynthetic pathway triggering an enhanced signaling via O‐linked N‐acetylglucosamine (O‐GlcNAc) transferase (OGT), the key enzyme catalyzing addition of O‐GlcNAc moieties to proteins. Protein O‐GlcNAcylation is a unique post‐translational protein modification implicated in diabetes and related cardiovascular complications. Previous studies have suggested both cardio‐protective and cardio‐detrimental effects of protein O‐GlcNAcylation in diabetes. However, the precise role of OGT in the etiology of diabetic atherogenesis remains incompletely understood. The goal of the current study was to investigate whether OGT modulates VSMC transition to a de‐differentiated phenotype under hyperglycemic conditions. Immunoblotting experiments revealed that in primary cultures of human aortic smooth muscle cells (HASMC) in vitro, benzyl 2‐deoxy α‐D‐galactopyranoside (BG), a pharmacological inhibitor of OGT, decreased high glucose‐induced OGT and O‐GlcNAc protein expression, and this was accompanied with attenuated PCNA (proliferation marker), reduced vimentin (SM synthetic marker) and increased SM‐MHC (SM contractile marker) expression. Consistent with these findings, deletion of OGT using siRNA gene silencing significantly lowered protein O‐GlcNAc and PCNA expression in glucose‐stimulated HASMC compared with glucose‐treated cells transfected with control siRNA. Notably, under glucose‐stimulated conditions, OGT knockdown enhanced calponin (SM contractile marker) expression in HASMC transfected with OGT siRNA vs cells transfected with control siRNA. Finally, electrophoretic mobility shift assay (EMSA) revealed that specific OGT inhibitors (BG and ST045849) attenuated high glucose‐induced DNA‐binding activity of YY1 and Elk1 (transcriptional repressors of SM contractile phenotype) in HASMC compared to cells treated with glucose alone. Taken together, these data clearly demonstrate that loss of OGT inhibits VSMC phenotypic de‐differentiation in response to hyperglycemia, suggesting OGT as a potential therapeutic target in diabetic atherosclerosis.Support or Funding InformationAmerican Heart Association ‐ Grant‐in‐Aid 16GRNT31200034This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Butanol extract of Morinda Lucida (BEML) protects against Isoproterenol‐induced myocardial infarction in Wistar rats
Authors: Adenipekun Kehinde , Omóbòwálé Temidayo , Oyagbemi Ademola , Adedapo Adeolu , Ashafa Anofi , Yakubu Momoh , Adejumobi Olumuyiwa , Ola‐Davies Olufunke , Ajibade Temitayo 
Published: June 2021

With the rising rates of cardiovascular diseases, increase cost of modern therapeutic drugs, as well as the adverse effects of the modern medicine on the users; there is a surge in the need to search for herbs with excellent antioxidant properties for use in preventive medicine. Morinda Lucida, commonly found in the Tropics, precisely in the rain forest of West Africa; it is an important medicinal plant known for its antioxidant and therapeutic uses. The aim of this study was to investigate the cardioprotective effects of the Butanol extract of Morinda Lucida (BEML) against Isoproterenol‐induced myocardial infarction in Wistar rats. Male albino Wistar rats (n=60) were pre‐treated with BEML for a period of 10 days. Group A (control) received food and water ad‐libitum. Group B was challenged with 70 mg/kg Isoproterenol (ISO) alone. Group C: Isoproterenol + 100 mg/kg BEML. Group D: Isoproterenol + 200 mg/kg BEML Group E: 100 mg/kg BEML alone and Group F: 200 mg/kg BEML alone. Groups B, C and D were challenged with ISO on the 11th day. This study found out that ISO induced severe myocardial injuries associated with significant increase in markers of oxidative stress, as confirmed by elevated Malondialdehyde (MDA), as well as decreased reduced Glutathione (GSH), Glutathione peroxidase (GPx), Glutathione, Glutathione‐S‐transferase (GST), Catalase (CAT), Superoxide dismutase (SOD) relative to ISO alone. Pre‐treatment with BEML prior to administration of ISO significantly reduced serum Creatinine kinase myocardial band (CK‐MB) and Lactate dehydrogenase (LDH and also suppressed the expressions of Cardiac troponin I (CTnI), and nuclear factor kappa beta (NF‐κB), respectively. Pre‐treatment with BEML reduced infarct size and restored cardiac ultrastructural integrity. Gas Chromatography Mass Spectrometry (GCMS) analysis revealed the presence of Phytol, 11‐Eicosenoic acid, Palmitoleic acid, Nonacosylic acid, Methyl Palmitoleate, Stearic acid, Vitamin E (alpha‐Tocopherol), Tocopheryl acetate, 17α‐Hydroxyprogesterone, β‐Amyrin acetate, Alpha‐Amyrin acetate, lupenone, and Sclareol in BEML. Together, we conclude that BEML act as potential protective agent against myocardial infarction and other cardiac conditions through its antioxidant, anti‐inflammatory and free radical scavenging activity. The observed cardio‐protective effect might be due to the presence of arrays of phytonutrients.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.