Search results for "ABO"
showing 10 items of 13628 documents
Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions.
2021
Summary VLGR1 (very large G protein-coupled receptor-1) is by far the largest adhesion G protein-coupled receptor in humans. Homozygous pathologic variants of VLGR1 cause hereditary deaf blindness in Usher syndrome 2C and haploinsufficiency of VLGR1 is associated with epilepsy. However, its molecular function remains elusive. Herein, we used affinity proteomics to identify many components of focal adhesions (FAs) in the VLGR1 interactome. VLGR1 is localized in FAs and assembles in FA protein complexes in situ. Depletion or loss of VLGR1 decreases the number and length of FAs in hTERT-RPE1 cells and in astrocytes of Vlgr1 mutant mice. VLGR1 depletion reduces cell spread and migration kinetic…
Comparing Targeted vs. Untargeted MS2 Data-Dependent Acquisition for Peak Annotation in LC-MS Metabolomics
2020
One of the most widely used strategies for metabolite annotation in untargeted LCMS is based on the analysis of MSn spectra acquired using data-dependent acquisition (DDA), where precursor ions are sequentially selected from MS scans based on user-selected criteria. However, the number of MSn spectra that can be acquired during a chromatogram is limited and a trade-off between analytical speed, sensitivity and coverage must be ensured. In this research, we compare four different strategies for automated MS2 DDA, which can be easily implemented in the frame of standard QA/QC workflows for untargeted LC&ndash
Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10+ phenotype
2017
Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire…
Serum Amino Acid Profiles in Childhood Predict Triglyceride Level in Adulthood: A 7-Year Longitudinal Study in Girls.
2016
AbstractContext:Branched-chain and aromatic amino acids are associated with high risk of developing dyslipidemia and type II diabetes in adults.Objective:This study aimed to examine whether serum amino acid profiles associate with triglyceride concentrations during pubertal growth and predict hypertriglyceridemia in early adulthood.Design:This was a 7.5-year longitudinal study.Setting:The study was conducted at the Health Science Laboratory, University of Jyväskylä.Participants:A total of 396 nondiabetic Finnish girls aged 11.2 ± 0.8 years at the baseline participated in the study.Main Outcome Measures:Body composition was assessed by dual-energy x-ray absorptiometry; serum concentrations o…
Human Achilles tendon glycation and function in diabetes
2016
Diabetic patients have an increased risk of foot ulcers, and glycation of collagen may increase tissue stiffness. We hypothesized that the level of glycemic control (glycation) may affect Achilles tendon stiffness, which can influence gait pattern. We therefore investigated the relationship between collagen glycation, Achilles tendon stiffness parameters, and plantar pressure in poorly ( n = 22) and well ( n = 22) controlled diabetic patients, including healthy age-matched (45–70 yr) controls ( n = 11). There were no differences in any of the outcome parameters (collagen cross-linking or tendon stiffness) between patients with well-controlled and poorly controlled diabetes. The overall effe…
Unsaturated Oral Fat Load Test Improves Glycemia, Insulinemia and Oxidative Stress Status in Nondiabetic Subjects with Abdominal Obesity.
2016
Aims To evaluate the changes in glycemia, insulinemia, and oxidative stress markers during an oral fat load test in nondiabetic subjects with abdominal obesity and to analyze the association between postprandial oxidative stress markers and postprandial glucose and insulin responses. Methods We included 20 subjects with abdominal obesity (waist circumference > 102 cm for men and > 88 cm for women) and 20 healthy lean controls (waist circumference < 102 cm for men and < 88 cm for women). After 12 hours of fasting we performed a standardized fat load test (0–8 hours) with supracal® (50 g/m2). We determined metabolic parameters, oxidized and reduced glutathione, and malondialdehyde. Results In…
Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.
2016
Abstract Background and aims Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity. Methods and results As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric haz…
Low level activity thresholds for changes in NMR biomarkers and genes in high risk subjects for type 2 diabetes
2017
AbstractOur objectives were to determine if there are quantitative associations between amounts and intensities of physical activities (PA) on NMR biomarkers and changes in skeletal muscle gene expressions in subjects with high risk for type 2 diabetes (T2D) performing a 3-month PA intervention. We found that PA was associated with beneficial biomarker changes in a factor containing several VLDL and HDL subclasses and lipids in principal component analysis (P = <0.01). Division of PA into quartiles demonstrated significant changes in NMR biomarkers in the 2nd - 4th quartiles compared to the 1st quartile representing PA of less than 2850 daily steps (P = 0.0036). Mediation analysis of PA-…
Decreased consumption of branched-chain amino acids improves metabolic health
2016
Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino…
Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women
2016
AbstractInsulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain …