Search results for "Fibril"
showing 10 items of 836 documents
Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE.
2019
Background Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved. Aims We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial. Patients and Methods A total of 3,874 patients were included in the primary analysis (day 31–180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding. Results The rates of recurrent VTE and bleeding events we…
The collagen type I segment long spacing (SLS) and fibrillar forms: Formation by ATP and sulphonated diazo dyes.
2016
The collagen type I segment long spacing (SLS) crystallite is a well-ordered rod-like molecular aggregate, ∼300nm in length, which is produced in vitro under mildly acidic conditions (pH 2.5-3.5) in the presence of 1mM ATP. The formation of the SLS crystallite amplifies the inherent linear structural features of individual collagen heterotrimers, due to the punctate linear distribution and summation of the bulkier amino acid side chains along the length of individual collagen heterotrimers. This can be correlated structurally with the 67nm D-banded collagen fibril that is found in vivo, and formed in vitro. Although first described many years ago, the range of conditions required for ATP-in…
Ranolazine-Mediated Attenuation of Mechanoelectric Feedback in Atrial Myocyte Monolayers.
2020
[EN] Background Mechanical stretch increases Na(+)inflow into myocytes, related to mechanisms including stretch-activated channels or Na+/H(+)exchanger activation, involving Ca(2+)increase that leads to changes in electrophysiological properties favoring arrhythmia induction. Ranolazine is an antianginal drug with confirmed beneficial effects against cardiac arrhythmias associated with the augmentation ofI(NaL)current and Ca(2+)overload. Objective This study investigates the effects of mechanical stretch on activation patterns in atrial cell monolayers and its pharmacological response to ranolazine. Methods Confluent HL-1 cells were cultured in silicone membrane plates and were stretched to…
High-Pressure-Driven Reversible Dissociation of α-Synuclein Fibrils Reveals Structural Hierarchy
2017
The analysis of the α-synuclein (aS) aggregation process, which is involved in Parkinson's disease etiopathogenesis, and of the structural feature of the resulting amyloid fibrils may shed light on the relationship between the structure of aS aggregates and their toxicity. This may be considered a paradigm of the ground work needed to tackle the molecular basis of all the protein-aggregation-related diseases. With this aim, we used chemical and physical dissociation methods to explore the structural organization of wild-type aS fibrils. High pressure (in the kbar range) and alkaline pH were used to disassemble fibrils to collect information on the hierarchic pathway by which distinct β-sh…
Recombinant anthrax protective antigen: Observation of aggregation phenomena by TEM reveals specific effects of sterols.
2017
Abstract Negatively stained transmission electron microscope images are presented that depict the aggregation of recombinant anthrax protective antigen (rPA83 monomer and the PA63 prepore oligomer) under varying in vitro biochemical conditions. Heat treatment (50 °C) of rPA83 produced clumped fibrils, but following heating the PA63 prepore formed disordered aggregates. Freeze-thaw treatment of the PA63 prepore generated linear flexuous aggregates of the heptameric oligomers. Aqueous suspensions of cholesterol microcrystals were shown to bind small rPA83 aggregates at the edges of the planar bilayers. With PA63 a more discrete binding of the prepores to the crystalline cholesterol bilayer ed…
Antibody-mediated blockade of JMJD6 interaction with collagen I exerts antifibrotic and antimetastatic activities
2017
JMJD6 is known to localize in the nucleus, exerting histone arginine demethylase and lysyl hydroxylase activities. A novel localization of JMJD6 in the extracellular matrix, resulting from its secretion as a soluble protein, was unveiled by a new anti-JMJD6 mAb called P4E11, which was developed to identify new targets in the stroma. Recombinant JMJD6 binds with collagen type I (Coll-I), and distinct JMJD6 peptides interfere with collagen fibrillogenesis, collagen-fibronectin interaction, and adhesion of human tumor cells to the collagen substrate. P4E11 and collagen binding to JMJD6 are mutually exclusive because the amino acid sequences of JMJD6 necessary for the interaction with Coll-I ar…
Back to the oligomeric state: pH-induced dissolution of concanavalin A amyloid-like fibrils into non-native oligomers
2016
The subtle interplay between long range electrostatic forces, hydrophobic interactions and short range protein-protein interactions regulates the onset/evolution of protein aggregation processes as well as the stability of protein supramolecular structures. Using a combination of FTIR spectroscopy, light scattering and advanced imaging, we present evidence on the main role of electrostatic forces in the formation and stability of amyloid-like fibrils formed from concanavalin A (ConA), a protein showing structural homology with the human serum amyloid protein. At high protein concentration, where protein-protein interactions cannot be neglected, we highlight a thermal-induced aggregation pat…
Lipid levels, atrial fibrillation and the impact of age:Results from the LIPIDOGRAM2015 study
2020
Background and aims: An inverse relationship between lipid levels and atrial fibrillation (AF) has been suggested, but whether the association is upheld for all age groups remains unclear. The aim of the study was to examine associations between lipid levels and AF by age groups in a nationwide study in Poland. Methods: Multivariate Poisson regression models were used to estimate prevalence ratios (PRs) for AF by lipid levels. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), non-HDL-C and LDL-C/HDL-C ratios were grouped into quartiles. Results: Of the 13,724 participants, 5.2% (n = 708) had AF. People with…
Physiological and Molecular Adaptations to Strength Training
2018
High muscle contraction forces that lead to gains in muscle function, size, and strength characterize resistance exercise training. The purpose of this chapter is to outline the adaptations in myofiber size and metabolism that occur by stimuli of hormones and local growth factors, mechanical and metabolic stress of muscle tissue, and myofibrillar disruptions induced by a resistance exercise bout. The chapter will highlight the network of intracellular pathways (including mTOR signaling) that ultimately lead to increases in gene expression and protein synthesis. Accumulation of acute exercise responses by systematic training over time modulate the muscle proteome that can be observed as chan…
Myelin changes in Alexander disease
2018
Introduction: Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic inclusions in astrocytes. Mutations in the gene coding for glial fibrillary acidic protein (GFAP) have been identified as a genetic basis for AxD. However, the mechanism by which these variants produce the disease is not understood. Development: The most widespread hypothesis is that AxD develops when a gain-of-function mutation causes an increase in GFAP. However, this mechanism does not explain myelin loss, given that experimental models in which GFAP expression is normal or mutated do not exhibit myelin disorders. …