fibril structure

Amyloid plaques composed of fibrils of misfolded Aβ peptides are pathological hallmarks of Alzheimer's disease (AD). Aβ fibrils are polymorphic in their tertiary and quaternary molecular structures. This structural polymorphism may carry different pathologic potencies and can putatively contribute to clinical phenotypes of AD. Therefore, mapping of structural polymorphism of Aβ fibrils and structural evolution over time is valuable to understanding disease mechanisms. Here, we investigated how Aβ fibril structures in situ differ in Aβ plaque of different mouse models expressing familial mutations in the AβPP gene...

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To enhance M-mode echocardiography's utility for measuring cardiac structures, we developed and evaluated an artificial intelligence (AI)-based automated analysis system for M-mode images through the aorta and left atrium [M-mode (Ao-LA)], and through the left ventricle [M-mode (LV)]. Our system, integrating two deep neural networks (DNN) for view classification and image segmentation, alongside an auto-measurement algorithm, was developed using 5,958 M-mode images [3,258 M-mode (LA-Ao), and 2,700 M-mode (LV)] drawn from a nationwide echocardiographic dataset collated from five tertiary hospitals...

Assemblies of peptides and proteins through specific intermolecular interactions set the basis for macroscopic materials found in nature. Peptides provide easily tunable hydrogen-bonding interactions, which can lead to the formation of ordered structures such as highly stable β-sheets that can form amyloid-like supramolecular peptide nanofibrils (PNFs). PNFs are of special interest, as they could be considered as mimics of various fibrillar structures found in nature. In their ability to serve as supramolecular scaffolds, they could mimic certain features of the extracellular matrix to provide stability, interact with pathogens such as virions, and transduce signals between the outside and inside of cells...

UNLABELLED: A man in his 70s with a history of mitral valve replacement (MVR) and long-standing persistent atrial fibrillation (AF) presented with effort angina. Coronary angiography revealed severe stenosis of the left main coronary artery (LMCA). As it was an emergent case, PCI (percutaneous coronary intervention) was selected for treatment. Intravascular ultrasonography revealed no atherosclerotic lesions in the LMCA. The LMCA was effectively dilated by the drug-eluting stent. No elevation in intracardiac pressure was observed in cardiac catheterization after PCI...

Prion-like protein aggregation is characteristic of numerous neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. This process involves the formation of aggregates ranging from small and potentially neurotoxic oligomers to highly structured self-propagating amyloid fibrils. Various approaches are used to study protein aggregation, but they do not always provide continuous information on the polymorphic, transient, and heterogeneous species formed. This review provides an updated state-of-the-art approach to the detection and characterization of a wide range of protein aggregates using nanopore technology...

The current challenge in effectively treating atrial fibrillation (AF) stems from a limited understanding of the intricate structure of the human atria. The objective and quantitative interpretation of the right atrium (RA) in late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) scans relies heavily on its precise segmentation. Leveraging the potential of artificial intelligence (AI) for RA segmentation presents a promising solution. However, the successful implementation of AI in this context necessitates access to a substantial volume of annotated LGE-MRI images for model training...

BACKGROUND: The accumulation of ordered protein aggregates, amyloid fibrils, accompanies various neurodegenerative diseases (such as Parkinson's, Huntington's, Alzheimer's, etc.) and causes a wide range of systemic and local amyloidoses (such as insulin, hemodialysis amyloidosis, etc.). Such pathologies are usually diagnosed when the disease is already irreversible and a large amount of amyloid plaques have accumulated. In recent years, new drugs aimed at reducing amyloid levels have been actively developed...

INTRODUCTION: Concomitant left bundle branch area pacing (LBBAP) with atrioventricular (AV) nodal ablation is emerging as a viable management option in atrial fibrillation refractory to medical management. Its viability in patients with pulmonary disease and atrial fibrillation is unknown. METHODS AND RESULTS: This is a retrospective, observational cohort study in consecutive patients who underwent concomitant LBBAP with AV nodal ablation with advanced pulmonary disease at the Cleveland Clinic Fairview Hospital between January 2019 and January 2023...

Prions, the misfolding form of prion proteins, are contagious proteinaceous macromolecules. Recent studies have shown that infectious prion fibrils formed in the brain and non-infectious fibrils formed from recombinant prion protein in a partially denaturing condition have distinct structures. The amyloid core of the in vitro-prepared non-infectious fibrils starts at about residue 160, while that of infectious prion fibrils formed in the brain involves a longer sequence (residues ∼90-230) of structural conversion...

Pauling and Corey expected that a racemic mixture would result in a rippled β-sheet, however, it has been known from experiments that the racemic mixtures of triphenylalanine lead to a herringbone structure. Because of the theoretical limitations concerning crystal structures such as rippled β-sheet, it is inevitable to understand how the interplay of the amino acids prefers a specific structural motif. In this paper we use molecular dynamics to understand the sequence- and enantiomer-dependent structures by comparisons between rippled β-sheet and pleated β-sheet, solvated and anhydrous rippled β-sheet, and rippled β-sheet and the herringbone structure, based on thermodynamics and structures at the atomic level...

BACKGROUND: For the majority of patients with atrial fibrillation (AF), disease management has improved in recent years. However, there are still populations underrepresented or excluded in current registries and randomized controlled trials. HERA-FIB (Heidelberg Registry of Atrial Fibrillation) was planned to assess real-world evidence for the prevalence, demographic characteristics and management of patients with the diagnosis of AF presenting consecutively to a chest pain unit. METHODS AND RESULTS: HERA-FIB is a retrospective, observational, single-center study on patients with a diagnosis of AF presenting to a chest pain unit from June 2009 until March 2020...

BACKGROUND: The relationship of serial NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurements with changes in cardiac features and outcomes in heart failure (HF) remains incompletely understood. We determined whether common clinical covariates impact these relationships. METHODS AND RESULTS: In 2 nationwide observational populations with HF, the relationship of serial NT-proBNP measurements with serial echocardiographic parameters and outcomes was analyzed, further stratified by HF with reduced versus preserved left ventricular ejection fraction, inpatient versus outpatient enrollment, age, obesity, chronic kidney disease, atrial fibrillation, and attainment of ≥50% guideline-recommended doses of renin-angiotensin system inhibitors and β-blockers...

BACKGROUND: The medial knee structures have a primary role in stabilizing valgus and rotational stress, which makes them important in assessing the ligament-injured knee globally and choosing the most adequate treatment. PURPOSE: To conduct a layer-by-layer dissection of the knee's anteromedial side and provide a qualitative and quantitative description of the anatomy and histology of a ligament in the anteromedial region of the knee, which we have termed the anterior oblique ligament (AOL)...

Parkinson's disease arises from protein misfolding, aggregation, and fibrillation and is characterized by LB (Lewy body) deposits, which contain the protein α-synuclein (α-syn) as their major component. Another synuclein, γ-synuclein (γ-syn), coexists with α-syn in Lewy bodies and is also implicated in various types of cancers, especially breast cancer. It is known to seed α-syn fibrillation after its oxidation at methionine residue, thereby contributing in synucleinopathy...

Exenatide, a promising cardioprotective agent, protects against cardiac structural remodeling and diastolic dysfunction. Combined blockade of sodium and potassium channels is valuable for managing atrial fibrillation (AF). Here, we explored whether exenatide displayed anti-AF effects by inhibiting human Kv1.5 and Nav1.5 channels. We used the whole-cell patch-clamp technique to investigate the effects of exenatide on hKv1.5 and hNav1.5 channels expressed in human embryonic kidney 293 cells and studied the effects of exenatide on action potential (AP) and other cardiac ionic currents in rat atrial myocytes...

Calcium-binding S100A8 and S100A9 proteins play a significant role in various disorders due to their pro-inflammatory functions. Substantially, they are also relevant in neurodegenerative disorders via the delivery of signals for the immune response. However, at the same time, they can aggregate and accelerate the progression of diseases. Natively, S100A8 and S100A9 exist as homo- and heterodimers, but upon aggregation, they form amyloid-like oligomers, fibrils, or amorphous aggregates. In this study, we aimed to elucidate the aggregation propensities of S100A8, S100A9, and their heterodimer calprotectin by investigating aggregation kinetics, secondary structures, and morphologies of the aggregates...

Fluorinated non-natural amino acids are attracting considerable research interest, especially in the biomedical field and in materials science, thanks to their ability to self-assemble into peculiar supramolecular structures. The conformational changes induced by the presence of fluorine atoms obviously affect their functions, as well as the biological activity of the deriving peptides and proteins. Here, we will briefly describe the main effects of fluorination on the aggregation behavior of such building blocks, focusing in particular on their improved tendency to form fibrils, and gels therefrom...

OBJECTIVE: We aimed to examine the potential association between migraine and vascular dementia (VaD) using a nationwide population database. BACKGROUND: Migraine and VaD showed similar structural and functional changes in pathophysiology process and shared common risk factors, However, whether migraine prevalence increases VaD incidence remains controversial. METHODS: This retrospective population-based cohort study used the medical records from the Korean National Health Insurance System database...

BACKGROUND: Cardiac arrhythmias are very common in patients with obstructive sleep apnea (OSA), especially atrial fibrillation (AF) and nonsustained ventricular tachycardia (NVST). Cardiac autonomic dysfunction and structural remodeling caused by OSA provide the milieu for cardiac arrhythmia development. This study aimed to determine whether OSA is associated with various cardiac arrhythmias and investigate potential pathophysiologic pathways between them. METHODS: The analysis covered 600 patients with clinical suspicion of OSA hospitalized in Renmin Hospital of Wuhan University between January 2020 and May 2023...