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https://www.readbyqxmd.com/read/30030544/the-effect-of-dextran-sulfate-as-model-glycosaminoglycan-analogue-on-membrane-lipids-dppc-cholesterol-and-dppc-cholesterol-mixture-the-monolayer-study
#1
Katarzyna Makyła-Juzak, Anna Chachaj-Brekiesz, Patrycja Dynarowicz-Latka, Paweł Dąbczyński, Joanna Zemla
Glycosaminoglycans (GAGs) are essential components of the extracellular matrices (ECMs) located on the outer surface of cellular membranes. They belong to the group of polysaccharides involved in diverse biological processes acting on the surface and across natural lipid membranes. Recently, particular attention has been focused on possible role of GAGs in the amyloid deposits. The amyloid formation is related to a disorder in protein folding, causing that soluble-in normal conditions-peptides become deposited extracellularly as insoluble fibrils, impairing tissue structure and its function...
July 20, 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/30030380/the-effect-of-truncation-on-prion-like-properties-of-%C3%AE-synuclein
#2
Makoto Terada, Genjiro Suzuki, Takashi Nonaka, Fuyuki Kametani, Akira Tamaoka, Masato Hasegawa
Increasing evidence suggests that α-synuclein (αS) aggregates in brains of individuals with Parkinson's disease and dementia with Lewy bodies can spread in a prion-like manner. Although the initial αS nuclei are pivotal in determining αS fibril polymorphs and resulting phenotypes, it is not clear how the initial fibril seeds are generated. Previous studies have shown that αS truncation might have an important role in αS aggregation. However, little is known about how this truncation influences αS's propagation properties...
July 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30029834/left-atrial-appendage-morphology-and-relative-contrast-agent-concentration-in-patients-undergoing-coronary-artery-cta
#3
M Korhonen, P Mustonen, M Hedman, J Vienonen, J Onatsu, R Vanninen, M Taina
AIM: To evaluate whether certain morphological features of the left atrial appendage (LAA) would influence the LAA/ascending aorta (AA) radiodensity ratio, as a reflection of the blood flow conditions in the LAA. MATERIALS AND METHODS: Eight-hundred and eight consecutive patients undergoing computed tomography angiography (CCTA) were evaluated. Of these, 749 had no history of atrial fibrillation and none had suffered acute stroke. The LAA/AA radiodensity ratio, and the length, lobe number, and morphological classification of LAAs were assessed...
July 17, 2018: Clinical Radiology
https://www.readbyqxmd.com/read/30029603/in-silico-prediction-of-novel-residues-involved-in-amyloid-primary-nucleation-of-human-i56t-and-d67h-lysozyme
#4
Jeddidiah W D Griffin, Patrick C Bradshaw
BACKGROUND: Amyloidogenic proteins are most often associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, but there are more than two dozen human proteins known to form amyloid fibrils associated with disease. Lysozyme is an antimicrobial protein that is used as a general model to study amyloid fibril formation. Studies aimed at elucidating the process of amyloid formation of lysozyme tend to focus on partial unfolding of the native state due to the relative instability of mutant amyloidogenic variants...
July 20, 2018: BMC Structural Biology
https://www.readbyqxmd.com/read/30029360/an-integrated-strategy-to-correlate-aggregation-state-structure-and-toxicity-of-a%C3%A3-1-42-oligomers
#5
Federica Bisceglia, Antonino Natalello, Melania Maria Serafini, Raffaella Colombo, Laura Verga, Cristina Lanni, Ersilia De Lorenzi
Despite great efforts, it is not known which oligomeric population of amyloid beta (Aß) peptides is the main neurotoxic mediator in Alzheimer's disease. In vitro and in vivo experiments are challenging, mainly because of the high aggregation tendency of Aß (in particular of Aß 1-42 peptide), as well as because of the dynamic and non covalent nature of the prefibrillar aggregates. As a step forward in these studies, an analytical platform is here proposed for the identification and characterization of Aß 1-42 oligomeric populations resulting from three different sample preparation protocols...
October 1, 2018: Talanta
https://www.readbyqxmd.com/read/30026696/homozygous-crem-ib%C3%AE-c-x-overexpressing-mice-are-a-reliable-and-effective-disease-model-for-atrial-fibrillation
#6
Frank T Stümpel, Juliane Stein, Kirsten Himmler, Beatrix Scholz, Matthias D Seidl, Boris V Skryabin, Frank U Müller
Background: Atrial fibrillation (AF) is a significant cause of morbidity and mortality with foreseeably increasing prevalence. While large animal models of the disease are well established but resource intensive, transgenic AF mouse models are not yet widely used to develop or validate novel therapeutics for AF. Hemizygous mice with a cardiomyocyte-specific overexpression of the human cAMP response element modulator (CREM) isoform IbΔC-X spontaneously develop AF on grounds of an arrhythmogenic substrate consisting of alterations in structure, conduction, and calcium handling...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30026014/structural-remodeling-and-conduction-velocity-dynamics-in-the-human-left-atrium-relationship-with-reentrant-mechanisms-sustaining-atrial-fibrillation
#7
Shohreh Honarbakhsh, Richard J Schilling, Michele Orini, Rui Providencia, Emily Keating, Malcolm Finlay, Simon Sporton, Anthony Chow, Mark J Earley, Pier D Lambiase, Ross J Hunter
BACKGROUND: Rate-dependent conduction velocity (CV) slowing is associated with atrial fibrillation (AF) initiation and reentry mechanisms. OBJECTIVES: Assess the relationship between bipolar voltage, CV dynamics and AF drivers. METHODS: Patients undergoing catheter ablation for persistent AF (<24 months) were enrolled. Unipolar electrograms were recorded with a 64-pole basket catheter during atrial pacing at four pacing intervals (PIs) during sinus rhythm...
July 16, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/30025208/binding-modes-of-a-glycopeptidomimetic-molecule-on-a%C3%AE-protofibrils-implication-in-its-inhibition-mechanism
#8
Linh Tran, Julia Kaffy, Sandrine Ongeri, Tâp Ha-Duong
We recently reported that a glycopeptidomimetic molecule significantly delays the fibrillization process of Aβ42 peptide involved in Alzheimer's disease. However the binding mode of this compound, named 3β, was not determined at the atomic scale, hindering our understanding of its mechanism of action and impeding structure-based design of new inhibitors. In the present study, we performed molecular docking calculations and molecular dynamics simulations to investigate the most probable structures of 3β complexed with Aβ protofibrils...
July 19, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30024984/amyloidogenic-cross-seeding-of-tau-protein-transient-emergence-of-structural-variants-of-fibrils
#9
Bartosz Nizynski, Hanna Nieznanska, Robert Dec, Solomiia Boyko, Wojciech Dzwolak, Krzysztof Nieznanski
Amyloid aggregates of Tau protein have been implicated in etiology of many neurodegenerative disorders including Alzheimer's disease (AD). When amyloid growth is induced by seeding with preformed fibrils assembled from the same protein, structural characteristics of the seed are usually imprinted in daughter generations of fibrils. This so-called conformational memory effect may be compromised when the seeding involves proteins with non-identical sequences leading to the emergence of distinct structural variants of fibrils (amyloid 'strains')...
2018: PloS One
https://www.readbyqxmd.com/read/30024736/conserved-s-t-residues-of-the-human-chaperone-dnajb6-are-required-for-effective-inhibition-of-a%C3%AE-42-amyloid-fibril-formation
#10
Cecilia Månsson, Remco T P van Cruchten, Ulrich Weininger, Xiaoting Yang, Risto Cukalevski, Paolo Arosio, Christopher M Dobson, Tuomas P J Knowles, Mikael Akke, Sara Linse, Cecilia Emanuelsson
The human molecular chaperone DNAJB6, an oligomeric protein with a conserved S/T-rich region, is an efficient suppressor of amyloid fibril formation by highly aggregation-prone peptides such as the Aβ and polyQ peptides associated with Alzheimer's and Huntington's disease, respectively. We previously showed that DNAJB6 can inhibit the processes through which amyloid fibrils are formed due to strong interactions with aggregated forms of Aβ42 that become sequestered. Here we report that the concentration-dependent capability of DNAJB6 to suppress fibril formation in ThT fluorescence assays decreases progressively with an increasing number of S/T substitutions, with an almost complete loss of suppression when 18 S/T-residues are substituted...
July 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/30024580/peripheral-cyclic-%C3%AE-amino-acids-balance-the-stability-and-edge-protection-of-%C3%AE-sandwiches
#11
Gábor Olajos, Anasztázia Hetényi, Edit Wéber, Titanilla Szögi, Lívia Fülöp, Tamás A Martinek
Engineering water-soluble stand-alone β-sandwich mimetics is a current challenge because of the difficulties associated with tailoring long-range interactions. In this work, single cis-(1R,2S)-2-aminocyclohexanecarboxylic acid mutations were introduced into the edge strands of the eight-stranded β-sandwich mimetic structures from the betabellin family. Temperature-dependent NMR and CD measurements, together with thermodynamic analyses, demonstrated that the modified peripheral strands exhibited an irregular and partially disordered structure but were able to exert sufficient shielding on the hydrophobic core to retain the predominantly β-sandwich structure...
July 19, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/30023834/structural-insight-of-amyloidogenic-intermediates-of-human-insulin
#12
Sandip Dolui, Anupam Roy, Uttam Pal, Achintya Saha, Nakul C Maiti
Engaging Raman spectroscopy as a primary tool, we investigated the early events of insulin fibrilization and determined the structural content present in oligomer and protofibrils that are formed as intermediates in the fibril formation pathway. Insulin oligomer, as obtained upon incubation of zinc-free insulin at 60 °C, was mostly spherical in shape, with a diameter of 3-5 nm. Longer incubation produced "necklace"-like beaded protofibrillar assembly species. These intermediates eventually transformed into 5-8 nm thick fibers with smooth surface texture...
February 28, 2018: ACS Omega
https://www.readbyqxmd.com/read/30023735/revealing-and-quantifying-the-three-dimensional-nano-and-microscale-structures-in-self-assembled-cellulose-microfibrils-in-dispersions
#13
Srivatssan Mohan, Jissy Jose, Anke Kuijk, Sandra J Veen, Alfons van Blaaderen, Krassimir P Velikov
Cellulose microfibrils (CMFs) are an important nanoscale building block in many novel biobased functional materials. The spatial nano- and microscale organization of the CMFs is a crucial factor for defining the properties of these materials. Here, we report for the first time a direct three-dimensional (3D) real-space analysis of individual CMFs and their networks formed after ultrahigh-shear-induced transient deagglomeration and self-assembly in a solvent. Using point-scanning confocal microscopy combined with tracking the centerlines of the fibrils and their junctions by a stretching open active contours method, we reveal that dispersions of the native CMFs assemble into highly heterogeneous networks of individual fibrils and bundles...
August 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/30023693/study-of-molecular-mechanisms-of-%C3%AE-synuclein-assembly-insight-into-a-cross-%C3%AE-structure-in-the-n-termini-of-new-%C3%AE-synuclein-fibrils
#14
Daniel Nir Bloch, Yifat Miller
Parkinson's disease is characterized by the self-assembly of α-synuclein (AS), in which its aggregates accumulate in the substantia nigra. The molecular mechanisms of the self-assembly of AS are challenging because AS is a relatively large intrinsically disordered protein, consisting of 140 residues. It is known that the N-termini of AS contribute to the toxicity of the proteins; therefore, it is important to investigate the self-assembly structure of the N-termini on AS as well. There have been extensive efforts to investigate the structural fibrils of AS(1-140), which have shown that the N-termini are disordered and do not participate in the fibrillary structure...
July 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/30023689/substituent-charge-and-size-effects-on-the-fluorogenic-performance-of-amyloid-ligands-a-small-library-screening-study
#15
Patrick L Donabedian, Mallory Evanoff, Florencia A Monge, David G Whitten, Eva Y Chi
Developing new molecular ligands for the direct detection and tracking of amyloid protein aggregates is key to understanding and defeating myriad neurodegenerative and other disorders including Alzheimer's and Parkinson's diseases. A crucial factor in the performance of an amyloid dye is its ability to detect the amyloid structural motif independent of the sequence of the amyloid-forming protomer. The current study investigates structure-function relationships of a class of novel phenyleneethynylene (PPE)-based dyes and fluorescent polymers using amyloid fibrils formed by two model proteins: lysozyme and insulin...
July 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/30021107/direct-evidence-for-the-effect-of-glycerol-on-protein-hydration-and-thermal-structural-transition
#16
Mitsuhiro Hirai, Satoshi Ajito, Masaaki Sugiyama, Hiroki Iwase, Shin-Ichi Takata, Nobutaka Shimizu, Noriyuki Igarashi, Anne Martel, Lionel Porcar
The mechanisms of protein stabilization by uncharged solutes, such as polyols and sugars, have been intensively studied with respect to the chemical thermodynamics of molecular crowding. In particular, many experimental and theoretical studies have been conducted to explain the mechanism of the protective action on protein structures by glycerol through the relationship between hydration and glycerol solvation on protein surfaces. We used wide-angle x-ray scattering (WAXS), small-angle neutron scattering, and theoretical scattering function simulation to quantitatively characterize the hydration and/or solvation shell of myoglobin in aqueous solutions of up to 75% v/v glycerol...
July 17, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/30019205/role-of-ion-channels-in-heart-failure-and-channelopathies
#17
REVIEW
Ann-Kathrin Rahm, Patrick Lugenbiel, Patrick A Schweizer, Hugo A Katus, Dierk Thomas
Heart failure (HF) is a complication of multiple cardiac diseases and is characterized by impaired contractile and electric function. Patients with HF are not only limited by reduced contractile function but are also prone to life-threatening ventricular arrhythmias. HF itself leads to remodeling of ion channels, gap junctions, and intracellular calcium handling abnormalities that in combination with structural remodeling, e.g., fibrosis, produce a substrate for an arrhythmogenic disorders. Not only ventricular life-threatening arrhythmias contribute to increased morbidity and mortality but also atrial arrhythmias, especially atrial fibrillation (AF), are common in HF patients and contribute to morbidity and mortality...
July 17, 2018: Biophysical Reviews
https://www.readbyqxmd.com/read/30018137/amyloid-%C3%AE-fibrils-assembled-on-ganglioside-enriched-membranes-contain-both-parallel-%C3%AE-sheets-and-turns
#18
Teruhiko Matsubara, Hanaki Yasumori, Koichiro Ito, Takafumi Shimoaka, Takeshi Hasegawa, Toshinori Sato
Some protein and peptide aggregates, such as those of amyloid β protein (Aβ) are neurotoxic and have been implicated in several neurodegenerative diseases. Ab accumulates at nanoclusters enriched in neuronal lipids called gangliosides in the presynaptic neuronal membrane, and the resulting oligomeric and/or fibrous forms accelerate the development of Alzheimer's disease. Although the presence of Aβ deposits at such nanoclusters is known, the mechanism of their assembly and the relationship between Aβ secondary structure and topography are still unclear...
July 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30017527/extent-and-magnitude-of-low-voltage-areas-assessed-by-ultra-high-density-electroanatomical-mapping-correlate-with-left-atrial-function
#19
F Hohendanner, I Romero, F Blaschke, F R Heinzel, B Pieske, L-H Boldt, A S Parwani
INTRODUCTION: The extent of left atrial (LA) adverse remodeling as a cardiac disease marker has become increasingly important. In patients with atrial fibrillation (AF), atrial remodeling (AR) is accompanied by increased mortality. The relation between LA function and the extent of low-voltage areas (LVAs) has not yet been systematically investigated. METHODS: In patients with AF undergoing catheter-ablation, LA was studied using echocardiography and ultra-high-density mapping (Rhythmia®)...
July 9, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/30014287/region-specific-microstructure-in-the-neonatal-ventricles-of-a-porcine-model
#20
F Ahmad, S Soe, N White, R Johnston, I Khan, J Liao, M Jones, R Prabhu, I Maconochie, Peter Theobald
The neonate transitions from placenta-derived oxygen, to supply from the pulmonary system, moments after birth. This requires a series of structural developments to divert more blood through the right heart and onto the lungs, with the tissue quickly remodelling to the changing ventricular workload. In some cases, however, the heart structure does not fully develop causing poor circulation and inefficient oxygenation, which is associated with an increase in mortality and morbidity. This study focuses on developing an enhanced knowledge of the 1-day old heart, quantifying the region-specific microstructural parameters of the tissue...
July 16, 2018: Annals of Biomedical Engineering
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