fibril structure

BACKGROUND: Structural remodeling is critical to the initiation and maintenance of atrial fibrillation (AF). IGF1, insulin like growth factor 1, has been recognized as contributor to fibrosis. However, the roles and mechanisms of IGF1 in structural remodeling during AF is still unclear. METHODS: We investigated the transcriptional expression profiles of left atria in AF and non-AF rat models by using microarray analysis. And quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the accuracy...

The aggregation of α-synuclein (α-syn) into amyloid fibrils is a major pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. The mechanisms underlying the structural transition of soluble and innocuous α-syn to aggregated neurotoxic forms remains largely unknown. The disordered nature of α-syn has hampered the use of structure-based protein engineering approaches to elucidate the molecular determinants of this transition. The recent 3D structure of a pathogenic α-syn fibril provides a template for this kind of studies...

An injectable bone may serve as a minimally invasive therapy for large orthopedic defects and osteoporosis and an alternative to allografting and surgical treatment. However, conventional bone substitutes lack the desirable biodegradability, bioresponsibility, and functionality to regulate the bone regeneration process. Here, we report an injectable, bioresponsive bone composed of bisphosphonate-modified nanocellulose (pNC) as a bone substitute for bone regeneration. Composites composed of nano-fibrillated cellulose and β-tricalcium phosphate (β-TCP) mimic bone structures in which apatite reinforces collagen fibrils...

BACKGROUND: Cardiac involvement in myotonic dystrophy type 1 (MD1) includes conduction disease, arrhythmias, and left-ventricular (LV) systolic dysfunction leading to an increased sudden cardiac death risk. An understanding of the interplay between electrical and structural myocardial changes could improve the prediction of adverse cardiac events. We aimed to explore the relationship between signs of cardiomyopathy by conventional and advanced cardiovascular magnetic resonance (CMR), and electrical abnormalities in MD1...

Atrial fibrillation (AF) can be initiated from arrhythmogenic foci within the muscular sleeves that extend not only into the pulmonary veins but also into both vena cavae. Patients with SVC-derived AF have the common clinical and genetic risk factors. Bayesian network analysis is a probabilistic model in which a qualitative dependency relationship among random variables is represented by a graph structure and a quantitative relationship between individual variables is expressed by a conditional probability...

β-lactoglobulin (BLG) is a well characterized milk protein and a model for folding and aggregation studies. Rutin is a quercetin based-flavanoid and a famous dietary supplement. It is a potential protector from coronary heart disease, cancers, and inflammatory bowel disease. In this study, amyloid fibrillation is reported in BLG at pH 2.0 and temperature 358 K. It is inhibited to some extent by rutin with a rate of 99.3 h-1  M-1 . Amyloid fibrillation started taking place after 10 h of incubation and completed near 40 h at a rate of 16...

The purpose of this study was to explore the influence of Er:YAG laser irradiation with different pulse durations on the organic matrix, micromorphology of the hybrid layer (HL), and bond strength over time. Sixty caries-free human molars were cut to obtain flat dentin surfaces which were randomly divided into 4 groups: control (not irradiated-G1) and laser groups (80 mJ/2 Hz) with pulse duration ranging between 50 (G2), 300 (G3), and 600 μs (G4). A self-etch adhesive system (Universal 3M ESPE) was applied on pre-treated dentin surfaces and cylinders of resin composite were built up and stressed in a universal testing machine (μSBS) at 24 h and after12 months (n = 12)...

Background Chronic intermittent hypoxia ( CIH ) is a distinct pathological mechanism of obstructive sleep apnea ( OSA ), which is recognized as an independent risk factor for cardiovascular diseases. The aims of this study were to ascertain whether CIH induces atrial fibrillation ( AF ), to determine whether cardiac sympathetic denervation ( CSD ) can prevent it and suppress blood pressure, and to explore the potential molecular mechanisms involved. Methods and Results Sixty Sprague-Dawley male rats were randomly divided into 4 groups: sham, CSD , CIH , CIH + CSD ...

Obesity, defined as a Body Mass Index (BMI) of ≥30 kg/m2, is the most common chronic metabolic disease worldwide and its prevalence has been strongly increasing. Obesity is associated with various diseases such as cardiovascular disease, type 2 diabetes and hypertension. Regarding heart rhythm disorders, obesity is associated with an increase in atrial fibrillation (AF), the most common arrhythmia in clinical practice. AF is associated with an increased cardiovascular morbidity and mortality. Obesity, a novel risk factor, is responsible for a 50%-increased incidence of AF...

Amyloid formation occurs via numerous complex mechanisms, often involving intermediates. This study examines the mechanism of amyloidogenesis in two N-terminal fragments of serum amyloid A (SAA), which are known to exhibit dramatically different amyloid structures. Fibrillization kinetics by these peptides are found to exhibit two unusual features: slower rates at higher peptide concentration, and complete insensitivity to addition of pre-formed seed. Additionally, we find that these peptides form micelle-like oligomers in solution...

α-Synuclein (AS) is an intrinsically disordered protein highly expressed in dopaminergic neurons. Its amyloid aggregates are the major component of Lewy bodies, a hallmark of Parkinson's disease (PD). AS is particularly exposed to oxidation of its methionine residues, both in vivo and in vitro. Oxidative stress has been implicated in PD and oxidized α-synuclein has been shown to assemble into soluble, toxic oligomers, rather than amyloid fibrils. However, the structural effects of methionine oxidation are still poorly understood...

Atrial fibrillation (AF), the most common type of cardiac arrhythmia, is thought to be regulated by changes in microRNA (miRNA) expression. However, the evidence for this is inconsistent. The high stability and expression of circulating exosomal miRNAs may allow their use as candidate biomarkers. For the discovery phase, exosomes were isolated from the serum of patients with supraventricular tachycardia (SVT) as the controls ( n = 5) and with paroxysmal AF ( n = 4) and persistent AF ( n = 5) for microarray analysis of miRNAs...

Atrial fibrillation has caused severe burden for people worldwide. Differentiation of fibroblasts into myofibroblasts, and consequent progress in atrial structural remodeling have been considered the basis for persistent atrial fibrillation, yet little is known about the molecular mechanisms underlying the process. Here, we show that cyclin-dependent kinase 1 (CDK1) is activated in atrial fibroblasts from patients with atrial fibrillation (AFPAF) and in platelet derived growth factor BB (PDGF-BB)-treated atrial fibroblasts from patients with sinus rhythm (AFPSR)...

The presence of αSN fibrils indisputably associates with the development of synucleinopathies. However, while certain fibril morphologies have been linked to downstream pathological phenotypes, others appear less harmful, leading to the concept of fibril strains, originally described in relation to prion disease. Indeed, the presence of fibrils does not associate directly with neurotoxicity. Rather, it has been suggested that the toxic compounds are soluble amyloidogenic oligomers, potentially co-existing with fibrils...

Amyloid fibril deposits observed in Alzheimer's disease comprise amyloid-β (Aβ) protein possessing a structured hydrophobic core and a disordered N-terminal domain (residues 1-16). The internal flexibility of the disordered domain is likely essential for Aβ aggregation. Here, we used 2 H static solid-state NMR methods to probe the dynamics of selected side chains of the N-terminal domain of Aβ(1-40) fibrils. Line shape and relaxation data suggested a two-state model, in which the domain's free state undergoes a diffusive motion that is quenched in the bound state, likely because of transient interactions with the structured C-terminal domain...

BACKGROUND: Our aim was to provide an evidence-based assessment of the relationship between pulmonary vein variants and atrial fibrillation (AF). METHODS: A comprehensive systematic search was performed on the databases PubMed, EMBASE, Cochrane library and Science Direct. Following assessment of eligibility and methodologic quality, data on PV variants were extracted and pooled into a meta-analysis. RESULTS: A total of 12 studies (1337 cases and 1250 controls) were included...

A 56-year-old man without any structural heart disease underwent a second ablation procedure for a recurrent atrial tachycardia (AT). He had undergone cryoballoon pulmonary vein isolation, left atrial roof, and mitral isthmus linear ablation of atrial fibrillation 2 years prior. This article is protected by copyright. All rights reserved.

Lysyl oxidase-generated intermolecular cross-links are essential for the tensile strength of collagen fibrils. Two cross-linking pathways can be defined, one based on telopeptide lysine aldehydes and another on telopeptide hydroxylysine aldehydes. Since the 1970s it has been accepted that the mature cross-linking structures on the lysine aldehyde pathway, which dominates in skin and cornea, incorporate histidine residues. Here, using a range of MS-based methods, we reexamined this conclusion and  found that telopeptide aldol dimerization is the primary mechanism for stable cross-link formation...

Tendinopathies are common chronic injuries that occur when damage accumulation caused by sub-rupture fatigue loading outpaces repair. Studies have linked fatigue loading with various mechanical, structural, and biological changes associated with pathology. However, the multiscale progression of damage accumulation with respect to area, severity and the distinct contributions of strain level and number of cycles has not been fully elucidated. The objective of this study was to investigate multiscale mechanisms underlying fatigue damage accumulation and their effect on the cellular environment...

Importance: Severe aortic stenosis causes pressure overload of the left ventricle, resulting in progressive cardiac dysfunction that can extend beyond the left ventricle. A staging system for aortic stenosis has been recently proposed that quantifies the extent of structural and functional cardiac changes in aortic stenosis. Objectives: To confirm the reproducibility of a proposed staging system and expand the study findings by performing a survival analysis and to evaluate the association of aortic stenosis staging with both cardiac and noncardiac post-transcatheter aortic valve replacement (TAVR) readmissions...