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Guohua Lv, Ashutosh Kumar, Yun Huang, David Eliezer
Fibrillar α-synuclein (AS) is the major component of Lewy bodies, the pathological hallmark of Parkinson's disease. Using solid-state nuclear magnetic resonance (ssNMR), we previously reported a structural characterization of mouse AS (mAS) fibrils and found that the secondary structure of the mAS fibrils is highly similar to a form of human AS (hAS) fibrils. Recently, a three-dimensional structure of these same hAS fibrils was determined by ssNMR and scanning transmission electron microscopy. Using medium- and long-range distance restraints obtained from ssNMR spectra, we found that the single protofilament structure of mAS fibrils is also similar to that of the hAS fibrils...
June 19, 2018: Biophysical Journal
Lucas Brely, Federico Bosia, Nicola M Pugno
Contact unit size reduction is a widely studied mechanism as a means to improve adhesion in natural fibrillar systems, such as those observed in beetles or geckos. However, these animals also display complex structural features in the way the contact is subdivided in a hierarchical manner. Here, we study the influence of hierarchical fibrillar architectures on the load distribution over the contact elements of the adhesive system, and the corresponding delamination behaviour. We present an analytical model to derive the load distribution in a fibrillar system loaded in shear, including hierarchical splitting of contacts, i...
June 20, 2018: Soft Matter
Muhammad Uzair Lodhi, Tahira Sabeen Saleem, Muhammad Shariq Usman, Waliul Chowdhury, Aaron R Kuzel, Hafiz Imran Iqbal, Mustafa Rahim
Fibrillary glomerulonephritis (FGN) is an uncommon cause of primary glomerular disease. FGN is usually idiopathic; however, it has been associated with underlying malignancy or autoimmune diseases in some patients as well. The most commonly found autoimmune diseases in FGN patients include Graves' disease, systemic lupus nephritis, Chron's disease, and idiopathic thrombocytopenia purpura. FGN in a patient with underlying asymptomatic Sjogren's syndrome is very rare in the literature, with only two previously reported cases of this association...
April 15, 2018: Curēus
Ewelina Lulińska-Kuklik, Masouda Rahim, Daria Domańska-Senderowska, Krzysztof Ficek, Monika Michałowska-Sawczyn, Waldemar Moska, Mariusz Kaczmarczyk, Michał Brzeziański, Ewa Brzeziańska-Lasota, Paweł Cięszczyk, Alison V September
Collagen alpha-1(V) chain, encoded by the COL5A1 gene, plays a crucial role in abundant fibrillar collagens supporting many tissues in the body containing type I collagen and appears to regulate the association between heterotypic fibers composed of both type I and type V collagen occurring among others in muscles, tendons and ligaments. Taking this fact into consideration we decided to examine the association between COL5A1 rs12722 and rs13946 polymorphisms, individually and as inferred haplotypes, with anterior cruciate ligament rupture risk (ACLR) in professional soccer players...
June 2018: Journal of Human Kinetics
Daniel Wurmbrand, Jörg Wolfram Anselm Fischer, Rose Rosenberg, Klaus Boldt
A fibrillar, polymeric intermediate (Cd2Se)n was isolated from the synthesis of CdSe nanorods, which suggests that the reactants themselves can template anisotropic growth. It is shown that high monomer concentration is the principal factor favouring this reaction pathway. The intermediate is distinct from crystalline semiconductor or small clusters and is surprisingly temperature-stable below 250 °C.
June 18, 2018: Chemical Communications: Chem Comm
Tingting Li, Jin'e Liu, Hao Cai, Baomei Wang, Yunfeng Feng, Jun Liu
Cell-matrix interactions play critical roles in cell adhesion, tissue remodeling and cancer metastasis. Discoidin domain receptor 2 (DDR2) is a collagen receptor belonging to receptor tyrosine kinase (RTK) family. It is a powerful regulator of collagen deposition in the extracellular matrix (ECM). Although the oligomerization of DDR extracellular domain (ECD) proteins can affect matrix remodeling by inhibiting fibrillogenesis, it is still unknown how cellular DDR2 is incorporated into collagen matrix. Using 3-dimentional (3D) imaging for migrating cells, we identified a novel mechanism that explains how DDR2 incorporating into collagen matrix, which we named as posterior remnant tethering...
2018: International Journal of Biological Sciences
L Xi, P De Falco, E Barbieri, A Karunaratne, L Bentley, C T Esapa, N J Terrill, S D M Brown, R D Cox, G R Davis, N M Pugno, R V Thakker, H S Gupta
Glucocorticoid-induced osteoporosis (GIOP) is a major secondary form of osteoporosis, with the fracture risk significantly elevated - at similar levels of bone mineral density - in patients taking glucocorticoids compared with non-users. The adverse bone structural changes at multiple hierarchical levels in GIOP, and their mechanistic consequences leading to reduced load-bearing capacity, are not clearly understood. Here we combine experimental X-ray nanoscale mechanical imaging with analytical modelling of the bone matrix mechanics to determine mechanisms causing bone material quality deterioration during development of GIOP...
June 11, 2018: Acta Biomaterialia
Yibo Jin, Yunxiang Sun, Jiangtao Lei, Guanghong Wei
Alzheimer's disease (AD) is associated with the aggregation of amyloid-β (Aβ) peptides into toxic fibrillar aggregates. Finding effective inhibitors of Aβ aggregation is a crucial step for the development of drugs against AD. Recent experiments reported that dihydrochalcone (Dih), a compound extracted from the daemonorops draco tree, could effectively inhibit Aβ fibrillization and reduce Aβ cytotoxicity. However, the influence of Dih molecules on preformed Aβ fibrils and the atomic-level details of interactions between Dih and Aβ fibrils are largely unknown...
June 14, 2018: Physical Chemistry Chemical Physics: PCCP
Sabrina M Peviani, Vinicius Guzzoni, Clara M Pinheiro-Dardis, Yara P da Silva, Alisson C R Fioravante, Adriana H Sagawa, Gabriel B Delfino, João L Q Durigan, Tania F Salvini
Stretching is a common method used to prevent muscle shortening and improve limited mobility. However, the effect of different time periods on stretching-induced adaptation of the extracellular matrix and its regulatory elements have yet to be investigated. We aimed to evaluate the expression of fibrillar collagens, sarcomerogenesis, metalloproteinase (MMP) activity and gene expression of the extracellular matrix (ECM) regulators in the soleus (SOL) muscle of rats submitted to different stretching periods. The soleus muscles were submitted to 10 sets of passive stretching over 10 (St 10d) or 15 days (St 15d) (1 min per set, with 30 seconds' rest between sets)...
June 13, 2018: Scientific Reports
Priya Govindaraju, Leslie Todd, Snehal Shetye, James Monslow, Ellen Puré
Cutaneous wound healing consists of three main phases: inflammation, re-epithelialization, and tissue remodeling. During normal wound healing, these processes are tightly regulated to allow restoration of skin function and biomechanics. In many instances, healing leads to an excess accumulation of fibrillar collagen (the principal protein found in the extracellular matrix - ECM), and the formation of scar tissue, which has compromised biomechanics, tested using ramp to failure tests, compared to normal skin (Corr and Hart, 2013 [1])...
June 9, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Lina Nilsson, Annelie Pamrén, Tohidul Islam, Kristoffer Brännström, Solmaz A Golchin, Nina Pettersson, Irina Iakovleva, Linda Sandblad, Anna L Gharibyan, Anders Olofsson
The pathological Aβ aggregates associated with Alzheimer's disease follow a nucleation-dependent path of formation. A nucleus represents an oligomeric assembly of Aβ peptides that acts as a template for subsequent incorporation of monomers to form a fibrillar structure. Nuclei can form de novo or via surface-catalyzed secondary nucleation, and the combined rates of elongation and nucleation control the overall rate of fibril formation. Transthyretin (TTR) obstructs Aβ fibril formation in favor of alternative non-fibrillar assemblies, but the mechanism behind this activity is not fully understood...
June 8, 2018: Journal of Molecular Biology
Jason Greenwald, Witek Kwiatkowski, Roland Riek
How life can emerge from non-living matter is one of the fundamental mysteries of the universe. A bottom-up approach to this problem focuses on the potential chemical precursors of life, in particular the nature of the first replicative molecules. Such thinking has led to the currently most popular idea: that a RNA-like molecule played a central role as the first replicative and catalytic molecule. Here, we review an alternative hypothesis that has recently gained experimental support, focusing on the role of amyloidogenic peptides rather than nucleic acids, in what has been by some termed "the amyloid-world" hypothesis...
June 8, 2018: Journal of Molecular Biology
Annette Eva Langkilde, Fátima Herranz-Trillo, Pau Bernadó, Bente Vestergaard
Structural investigation of intermediately formed oligomers and pre-fibrillar species is of tremendous importance in order to elucidate the structural principles of fibrillation, and because intermediate species have been suggested as the pathogenic agents in several amyloid diseases. Structural investigations are however greatly complicated by the dynamic changes between structural states of very different sizes and life-times. Small angle X-ray scattering (SAXS) is an ideal method to handle this challenge...
2018: Methods in Molecular Biology
Serene W Chen, Nunilo Cremades
Amyloid assemblies of certain proteins, including the Parkinson disease-related protein α-synuclein, are commonly associated with the development and spreading of neurodegenerative diseases, although the nature of the most toxic forms and the mechanisms by which they trigger neurodegeneration remain largely unknown. This is at least in part due to the inherent challenges involved in the preparation of stable and structurally homogeneous samples of amyloid assemblies that could be used in toxicity experiments...
2018: Methods in Molecular Biology
Agueda Rostagno, Thomas A Neubert, Jorge Ghiso
Amyloid β (Aβ) is the major constituent of the brain deposits found in parenchymal plaques and cerebral blood vessels of patients with Alzheimer's disease (AD). Besides classic full-length peptides, biochemical analyses of brain deposits have revealed high degree of Aβ heterogeneity likely resulting from the action of multiple proteolytic enzymes. This chapter describes a sequential extraction protocol allowing the differential fractionation of soluble and deposited Aβ species taking advantage of their differential solubility properties...
2018: Methods in Molecular Biology
Lisa D Muiznieks, Simon Sharpe, Régis Pomès, Fred W Keeley
Liquid-liquid phase separation resulting in formation of colloidal droplets has recently attracted attention as a mechanism for rapid and transient assembly of intracellular macromolecules into functional units. Phase separation also appears to be a widespread and evolutionarily ancient mechanism for organization of proteins of the extracellular matrix into fibrillar, polymeric assemblies. Elastin, which provides the physical properties of extensibility and elastic recoil to large arteries, lungs and other tissues, is the best characterized extracellular matrix protein whose polymeric assembly is initiated by phase separation...
June 7, 2018: Journal of Molecular Biology
Josephine L Morris, Stephen J Cross, Yinhui Lu, Karl E Kadler, Yongbo Lu, Sarah L Dallas, Paul Martin
Fibrillar collagen is a major component of many tissues but has been difficult to image in vivo using transgenic approaches because of problems associated with establishing cells and organisms that generate GFP-fusion collagens that can polymerise into functional fibrils. Here we have developed and characterised GFP and mCherry collagen-I fusion zebrafish lines with basal epidermal-specific expression. We use these lines to reveal the dynamic nature of collagen-I fibril deposition beneath the developing embryonic epidermis, as well as the repair of this collagen meshwork following wounding...
June 5, 2018: Developmental Biology
Lilia Rodriguez, Maria M Marano, Anurag Tandon
In Parkinson's disease, intracellular α-synuclein (α-syn) inclusions form in neurons and are referred to as Lewy bodies. These aggregates spread through the brain following a specific pattern leading to the hypothesis that neuron-to-neuron transfer is critical for the propagation of Lewy body pathology. Here we review recent studies employing pre-formed fibrils generated from recombinant α-syn to evaluate the uptake, trafficking, and release of α-syn fibrils. We outline methods of internalization as well as cell surface receptors that have been described in the literature as regulating α-syn fibril uptake...
2018: Frontiers in Neuroscience
Glen M DeLoid, Ikjot Singh Sohal, Laura R Lorente, Ramon M Molina, Georgios Pyrgiotakis, Ana Stevanovic, Ruojie Zhang, David Julian McClements, Nicholas K Geitner, Douglas W Bousfield, Kee Woei Ng, Say Chye Joachim Loo, David C Bell, Joseph Brain, Philip Demokritou
Engineered nanomaterials are increasingly added to foods to improve quality, safety, or nutrition. Here we report the ability of ingested nanocellulose (NC) materials to reduce digestion and absorption of ingested fat. In the small intestinal phase of an acellular simulated gastrointestinal tract, the hydrolysis of free fatty acids (FFA) from triglycerides (TG) in a high-fat food model was reduced by 48.4% when NC was added at 0.75% w/w to the food, as quantified by pH stat titration, and by 40.1% as assessed by fluorometric FFA assay...
June 6, 2018: ACS Nano
Jeremy D Eekhoff, Fei Fang, Spencer P Lake
The hierarchical structure of tendon allows for attenuation of mechanical strain down decreasing length scales. While reorganization of collagen fibers accounts for microscale strain attenuation, cross-linking between collagen molecules contributes to deformation mechanisms at the fibrillar and molecular scales. Divalent and trivalent enzymatic cross-links form during the development of collagen fibrils through the enzymatic activity of lysyl oxidase (LOX). By establishing connections between telopeptidyl and triple-helical domains of adjacent molecules within collagen fibrils, these cross-links stiffen the fibrils by resisting intermolecular sliding...
June 6, 2018: Connective Tissue Research
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