Metabolomics Workbench ST000763 - GNPS - Untargeted metabolomics and lipidomics of scleroderma PAH discovery cohort
Ontology highlight
ABSTRACT:
INSTRUMENT(S): QTOF - NEGATIVE, QTOF - POSITIVE
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Maureen Kachman
PROVIDER: MSV000082744 | GNPS | Thu Aug 02 18:01:00 BST 2018
REPOSITORIES: GNPS
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Project description:This experiment was performed using the following cohorts: 1) healthy controls, 2) patients with scleroderma at low risk for pulmonary hypertension, 3) pateints with scleroderma at high risk for pulmonary hypertension who underwent a catheterization and were found to have normal pressures, borderline elevated pressures or pulmonary arterial hypertensino (PAH). Whole blood was drawn directly into EDTA tubes at rest and again at peak exercise for each human subject. The samples were processed to plasma by MCRU and stored at -80 in the Biorepository.
2017-06-19 | ST000763 | MetabolomicsWorkbench
Project description:This experiment was performed using the following cohorts: 1) healthy controls, 2) patients with scleroderma at low risk for pulmonary hypertension, 3) pateints with scleroderma at high risk for pulmonary hypertension. Whole blood was drawn directly into stop soilution (1:1 ratio) at rest and again at peak exercise for each human subject.
2015-01-20 | ST000283 | MetabolomicsWorkbench
Project description:This experiment was performed using the following cohorts: 1) healthy controls, 2) patients with scleroderma at low risk for pulmonary hypertension, 3) pateints with scleroderma at high risk for pulmonary hypertension. Whole blood was drawn directly into stop soilution (1:1 ratio) at rest and again at peak exercise for each human subject.
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Project description:This experiment was performed using the following cohorts: 1) healthy controls, 2) patients with scleroderma at low risk for pulmonary hypertension, 3) pateints with scleroderma at high risk for pulmonary hypertension (SSc Cath). Whole blood was drawn directly into stop soilution (1:1 ratio) at rest and again at peak exercise for each human subject. The samples were processed to plasma by MCRU and stored at -80 in the Biorepository.
2017-06-19 | ST000762 | MetabolomicsWorkbench
Project description:Full title: Eccentric exercise activates novel transcriptional regulation of hypertrophic signaling pathways not affected by hormone changes. Unaccustomed eccentric exercise damages muscle tissue stimulating mechanisms of recovery and remodeling that may be affected by cellular protection by the sex hormone 17β-estradiol (E2). Using cDNA microarrays, we screened for differences in mRNA expression caused by E2 and eccentric exercise. After randomly assignment to 8 days of either placebo (CON) or E2 (EXP), eighteen men performed 150 single-leg eccentric contractions. Muscle biopsies were collected at baseline (BL), following supplementation (PS), +3 hours (3H) and +48 hours (48H) after exercise. Serum E2 concentrations increased significantly with supplementation (P < 0.001) but did not affect microarray results. Exercise led to early transcriptional changes in striated muscle activator of Rho signaling (STARS), Rho family GTPase 3 (RND3), mitogen activated protein kinase (MAPK) regulation and the downstream transcription factor FOS. Targeted RT-PCR analysis identified concurrent induction of negative regulators of calcineurin signaling RCAN (P < 0.001) and HMOX1 (P = 0.009). Protein contents were elevated for RND3 at 3H (P = 0.02) and FOS at 48H (P < 0.05). These findings indicate that early RhoA and NFAT signaling and regulation are altered following exercise for muscle remodeling and repair, but are not affected by E2. Eighteen young healthy men volunteered as participants in this study. All subjects were pre-screened to ensure that they were healthy, fit and had not regularly participated in resistance exercise in the preceding 6 months. Body composition was measured using dual energy x-ray absorptiometry (DEXA) scans (Hologic QDR 1000W, Waltham, MA). Thigh muscle cross-sectional area was calculated using anthropomorphic measurements of mid-thigh circumference and skinfold thickness. The subject demographics were (mean ± SD): age, 21 ± 2 y; height, 181 ± 5 cm; weight, 76.9 ± 12.8 kg. Subjects were assigned in a randomized, double-blind manner to either a control (CON, N=9) or experimental (EXP, N=9) group. CON subjects consumed 400 mg glucose polymer (Polycose; Abbott Laboratories, Ross Division, St. Laurent, Quebec, Canada) for 10 days. EXP subjects consumed ~300 mg glucose with 1 mg E2 (Estrace; Shire BioChem, Inc., St. Laurent, Quebec, Canada) for 2 days followed by 2 mg E2 for 8 days. On the morning of the ninth day, subjects reported to the laboratory and performed the exercise protocol. Supplementation continued until the day of the final biopsy and blood collection to maintain serum E2 concentrations throughout the collection protocol. Subjects in both groups were instructed to take one pill at the same time each day and return any unused pills. On the testing day, following a short warm-up (10 min of light cycling), subjects were seated in a Biodex isokinetic dynamometer (System 3, Biodex Medical Systems Inc., Ronkonkoma, NY) with their right leg strapped to a lever arm. The lever arm was programmed to extend their leg to 150º of flexion (where 180º is full extension) at a moderate speed (30º/s), then flex their leg to 90°of flexion at a faster speed (120°/s). During the flexion phase, subjects were instructed to attempt to maximally resist flexion of the knee (i.e. voluntary ‘maximal’ contraction) against the descending lever arm throughout the entire range of motion. The complete test consisted of 15 sets of 10 repetitions, each set separated by 1 minute of rest. Prior to each tissue collection, subjects abstained from any other form of physical exertion (within 72 h), avoided alcohol (within 48 h), ate their habitual diet (within 48 h), and abstained from caffeine (within 12 h). Each subject consumed a 350 Kcal defined formula diet (57% carbohydrates, 15% protein and 28% fat) two hours before each muscle biopsy and did not eat again until after the final biopsy of each session was taken. Muscle biopsies were taken from the vastus lateralis of the control (left) leg during the familiarization session (baseline, BL) and after 8 days of supplementation (post supplementation, PS) and the exercised (right) leg 3 hours (3H) and 48 hours (48H) after exercise, in anatomically distinct sites approximately 6 cm apart. Blood was drawn from the antecubital vein at the same collection times. Muscle and blood samples were processed and stored for future measurements.
2009-12-16 | E-GEOD-19062 | biostudies-arrayexpress
Project description:Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease. However, the pathogenic mechanisms of SSBP are still uncertain. Thus, ceRNA microarray was applied to identify differentially expressed lncRNAs and mRNAs. The whole blood samples from 10 hypertensives and 10 normotensives were collected by professional nurses in community health centers using EDTA blood tube. The samples were classified according to the salt sensitivity (SS, salt sensitivity; SR, salt resistant) and hypertension (H, hypertensives; N, normotensives). QRT-PCR and cell experiments would be also implemented to validate the reliability of the results.
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Project description:Sodium-lithium countertransport activity (SLC) is an intermediate phenotype for salt sensitive hypertension; elevated SLC corresponds to increased risk of hypertension. Genetic epidemiology studies indicate that SLC is heritable in humans and nonhuman primates; however, little is known about genetic determinants explaining variation in SLC. In this study we identified dietary salt-responsive gene networks in baboon kidneys and salt-responsive networks that differ between baboons with normal and high blood pressure phenotypes.
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Project description:A single bout of exercise induces changes in gene expression in skeletal muscle. Regular exercise results in an adaptive response involving changes in muscle architecture and biochemistry, and is an effective way to manage and prevent common human diseases such as obesity, cardiovascular disorders and type II diabetes. Our study is a transcriptome-wide analysis of skeletal muscle tissue in a large cohort of untrained Thoroughbred horses before and after a bout of high-intensity exercise and again after an extended period of training. We hypothesized that regular high-intensity exercise training primes the transcriptome for the demands of high-intensity exercise.
2018-08-07 | E-MTAB-5447 | biostudies-arrayexpress
Project description:This file describes the SBML version of the mathematical model in the following journal article: Linking Pulmonary Oxygen Uptake, Muscle Oxygen Utilization and Cellular Metabolism during Exercise, Ann Biomed Eng. 2007 Jun;35(6):956-69. (Pubmed ID: 17380394). This mathematical model simulates oxygen transport and metabolism in skeletal muscle in response to a step change from a warm-up steady state to a higher work rate corresponding to exercise at different levels of intensity: moderate (M), heavy (H) and very heavy (VH). The model parameter values are listed in the tables of this article. The parameter values that are independent of the exercise level are reported in Table 2. The parameter values that depend on the exercise level are reported in Tables 1A, 3 and 4.
The model simulations (Figures 2, 3, 4 and 5) were obtained for a representative subject with a set of parameter values different from those in Table 1A, 3 and 4. In the sbml model, these model parameters are used to simulate exercise at a very heavy (VH) intensity for the representative subject. Additionally, the parameter values needed to simulate exercise at moderate (M) and heavy (H) intensity are reported in the list of parameters of the file. The model simulates dynamics of (1) the concentrations of free (F) and total (T) oxygen concentration in blood (CFcap, CTcap) and tissue (CFtis, CTtis), Adenosine Triphosphate (ATP), Adenosine Diphosphate (ADP), Phosphocreatine (PCr) and Creatine (Cr); (2) the metabolic flux of oxidative phosphorylation, creatine kinase and ATPase; (3) the oxygen uptake in blood and oxygen transport rate from blood to tissue during exercise. The simulation also computes muscle oxygen saturation (StO2m) and relative muscle oxygen saturation (RStO2m) in order to compare simulated and experimental responses of human muscle oxygenation during exercise.
The model was successfully tested with Roadrunner of the Systems Biology Workbench (SBW). The model simulations obtained with Roadrunner match those obtained with the mathematical model represented in Fortran and Matlab for relative and absolute tolerance smaller than 10-7.
To allow for simulations at varying levels of exercise, the parameter exercise_level was introduced. A value of 1 means medium, 2 heavy and 3 very heavy exercise. Setting this parameter assigns the parameters Vmax, KatpaseE, dQMm and tauQm with the relevant parameters. The warmup steady state is influenced by the parameter changes for this representative subject and the model has to be brought into steady state after each change of exercise level.
This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Nov��re N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.
2009-10-16 | BIOMD0000000248 | BioModels
Project description:Hypertension-induced damage to the hippocampus not only leads to behavioral changes, but also to various brain diseases, but the mechanisms underlying hippocampal lesions are still unclear.
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