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https://www.readbyqxmd.com/read/29032848/-ehlers-danlos-syndromes
#1
D-P Germain
Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inheritable connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and cutaneous fragility with delayed wound healing. Over and above these common features, they differ in the presence or absence of various organ and tissue abnormalities, and differences in genetic causal mechanisms and degree of severity. They are complex and multisystem diseases, with the majority being highly disabling because of major joint problems and neurosensory deficiencies, and in some cases, they may be life-threatening due to associated complications, especially vascular disorders...
October 9, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29032370/an-immunofluorescence-assay-for-extracellular-matrix-components-highlights-the-role-of-epithelial-cells-in-producing-a-stable-fibrillar-extracellular-matrix
#2
Omar S Qureshi, Hélène Bon, Breda Twomey, Gill Holdsworth, Kirsty Ford, Marianne Bergin, Linghong Huang, Mariusz Muzylak, Louise J Healy, Vanessa Hurdowar, Timothy S Johnson
Activated fibroblasts are considered major drivers of fibrotic disease progression through the production of excessive extracellular matrix (ECM) in response to signals from damaged epithelial and inflammatory cells. Nevertheless, epithelial cells are capable of expressing components of the ECM, cross-linking enzymes that increase its stability and are sensitive to factors involved in the early stages of fibrosis. We therefore wanted to test the hypothesis that epithelial cells can deposit ECM in response to stimulation in a comparable manner to fibroblasts...
October 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29031698/aggregation-of-a%C3%AE-17-36-in-the-presence-of-naturally-occurring-phenolic-inhibitors-using-coarse-grained-simulations
#3
Yiming Wang, David C Latshaw, Carol K Hall
Although some naturally-occurring polyphenols have been found to inhibit amyloid β fibril formation and reduce neuron cell toxicity in vitro, their exact inhibitory mechanism is unknown. In this work, discontinuous molecular dynamics (DMD) combined with the PRIME20 force field and a newly-built inhibitor model are performed to examine the effect of vanillin, resveratrol, curcumin and epigallocatechin-3-gallate (EGCG) on the aggregation of Aβ(17-36) peptides. Four sets of peptide/inhibitor simulations are performed in which inhibitors: (1) bind to Aβ(17-36) monomer; (2) interfere with Aβ(17-36) oligomerization; (3) disrupt a pre-formed Aβ(17-36) protofilament; (4) prevent the growth of Aβ(17-36) protofilament...
October 12, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29030187/not-only-tendons-the-other-architecture-of-collagen-fibrils
#4
REVIEW
Mario Raspanti, Marcella Reguzzoni, Marina Protasoni, Petra Basso
For many decades the fibrillar collagens have been the subject of a remarkable body of ultrastructural research. The vast majority of the studies, however, were carried out on tendon or on tendon-derived material. For many reasons this reflects an obvious choice but at the same time it also is an unfortunate circumstance, because this flooding of tendon-related data can easily encourage the false confidence that all connective tissues are similar. The reality is quite the opposite, and a different fibrillar structure has been long time observed on collagen fibrils from different tissues, the most notable example being offered by corneal fibrils...
October 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29023579/role-of-the-n-terminus-for-the-stability-of-an-amyloid-%C3%AE-fibril-with-three-fold-symmetry
#5
Christian A Söldner, Heinrich Sticht, Anselm H C Horn
A key player in Alzheimer's disease is the peptide amyloid-beta (Aβ), whose aggregation into small soluble oligomers, protofilaments, and fibrils finally leads to plaque deposits in human brains. The aggregation behavior of Aβ is strongly modulated by the nature and composition of the peptide's environment and by its primary sequence properties. The N-terminal residues of Aβ play an important role, because they are known to change the peptide's aggregation propensity. Since these residues are for the first time completely resolved at the molecular level in a three-fold symmetric fibril structure derived from a patient, we chose that system as template for a systematic investigation of the influence of the N-terminus upon structural stability...
2017: PloS One
https://www.readbyqxmd.com/read/29019918/protein-misfolding-and-aggregation-as-a-therapeutic-target-for-polyglutamine-diseases
#6
REVIEW
Toshihide Takeuchi, Yoshitaka Nagai
The polyglutamine (polyQ) diseases, such as Huntington's disease and several types of spinocerebellar ataxias, are a group of inherited neurodegenerative diseases that are caused by an abnormal expansion of the polyQ tract in disease-causative proteins. Proteins with an abnormally expanded polyQ stretch undergo a conformational transition to β-sheet rich structure, which assemble into insoluble aggregates with β-sheet rich amyloid fibrillar structures and accumulate as inclusion bodies in neurons, eventually leading to neurodegeneration...
October 11, 2017: Brain Sciences
https://www.readbyqxmd.com/read/29017973/modulating-microfibrillar-alignment-and-growth-factor-stimulation-to-regulate-mesenchymal-stem-cell-differentiation
#7
Dinorath Olvera, Binulal N Sathy, Simon F Carroll, Daniel J Kelly
The ideal tissue engineering (TE) strategy for ligament regeneration should recapitulate the bone - calcified cartilage - fibrocartilage - soft tissue interface. Aligned electrospun-fibers have been shown to guide the deposition of a highly organized extracellular matrix (ECM) necessary for ligament TE. However, recapitulating the different tissues observed in the bone-ligament interface using such constructs remains a challenge. This study aimed to explore how fiber alignment and growth factor stimulation interact to regulate the chondrogenic and ligamentous differentiation of mesenchymal stem cells (MSCs)...
October 7, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28994248/maldi-mass-spectrometry-imaging-a-novel-tool-for-the-identification-and-classification-of-amyloidosis
#8
Martin Winter, Andreas Tholey, Arnt Kristen, Christoph Röcken
Amyloidosis is a group of diseases caused by extracellular accumulation of fibrillar polypeptide aggregates. So far, diagnosis is performed by Congo red staining of tissue sections in combination with polarization microscopy. Subsequent identification of the causative protein by immunohistochemistry harbors some difficulties regarding sensitivity and specificity. Mass spectrometry-based approaches have been demonstrated to constitute a reliable method to supplement typing of amyloidosis, but still depend on Congo red staining...
October 10, 2017: Proteomics
https://www.readbyqxmd.com/read/28994181/age-associated-dysregulation-of-protein-metabolism-in-the-mammalian-oocyte
#9
Francesca E Duncan, Susmita Jasti, Ariel Paulson, John M Kelsh, Barbara Fegley, Jennifer L Gerton
Reproductive aging is characterized by a marked decline in oocyte quality that contributes to infertility, miscarriages, and birth defects. This decline is multifactorial, and the underlying mechanisms are under active investigation. Here, we performed RNA-Seq on individual growing follicles from reproductively young and old mice to identify age-dependent functions in oocytes. This unbiased approach revealed genes involved in cellular processes known to change with age, including mitochondrial function and meiotic chromosome segregation, but also uncovered previously unappreciated categories of genes related to proteostasis and organelles required for protein metabolism...
October 10, 2017: Aging Cell
https://www.readbyqxmd.com/read/28993166/heating-treatments-affect-the-thermal-behaviour-of-doxorubicin-loaded-in-pegylated-liposomes
#10
Diego R Perinelli, Marco Cespi, Giulia Bonacucina, Filippo Rendina, Giovanni Filippo Palmieri
Doxil(®) is a stealth marketed PEGylated liposomal formulation, containing the anticancer drug doxorubicin. After loading via a pH gradient, fibrillar supramolecular structures of doxorubicin sulfate originates inside the core of the liposomes. Recently, the crystallinity of doxorubicin sulfate has been confirmed by high-resolution calorimetry. However, no detailed information are available on the nature of doxorubicin sulfate nanocrystals and on the effect of different thermal treatments. Thus, the aim of this work was to characterize the thermal behaviour of Doxil(®) in comparison to the unloaded liposomes using microcalorimetry, dynamic light scattering and high-resolution ultrasound spectroscopy (HR-US)...
October 7, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28988881/comprehensive-proteomic-profiles-of-mouse-aapoaii-amyloid-fibrils-provide-insights-into-the-involvement-of-lipoproteins-in-the-pathology-of-amyloidosis
#11
Hiroki Miyahara, Jinko Sawashita, Eri Ishikawa, Mu Yang, Xin Ding, Yingye Liu, Naomi Hachiya, Fuyuki Kametani, Masahide Yazaki, Masayuki Mori, Keiichi Higuchi
Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs. We previously reported that R1.P1-Apoa2(c) mice provide a reproducible model of AApoAII amyloidosis...
October 6, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28987870/the-critical-size-of-focal-articular-cartilage-defects-is-associated-with-strains-in-the-collagen-fibers
#12
A Heuijerjans, W Wilson, K Ito, C C van Donkelaar
The size of full-thickness focal cartilage defect is accepted to be predictive of its fate, but at which size threshold treatment is required is unclear. Clarification of the mechanism behind this threshold effect will help determining when treatment is required. The objective was to investigate the effect of defect size on strains in the collagen fibers and the non-fibrillar matrix of surrounding cartilage. These strains may indicate matrix disruption. Tissue deformation into the defect was expected, stretching adjacent superficial collagen fibers, while an osteochondral implant was expected to prevent these deformations...
September 28, 2017: Clinical Biomechanics
https://www.readbyqxmd.com/read/28987163/cellular-reactions-of-the-central-nervous-system
#13
Gabor G Kovacs
Major cell types of the central nervous system comprise neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells, and microglia), choroid plexus cells, cells related to blood vessels and coverings. These cells show a wide range of reactions to various noxious agents, which can be detected in routine stainings. Some of these reactions are nonspecific to different injuries; however some, such as the appearance of inclusion bodies, can be highly disease-specific. Immunohistochemical markers are widely used in neuropathologic diagnostic practice and help to understand the pathogenesis of diseases...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28986385/the-role-of-halofuginone-in-fibrosis-more-to-be-explored
#14
REVIEW
Yin Luo, Xiaoyan Xie, Di Luo, Yuan Wang, Yijun Gao
Fibrosis, which can be defined as an abnormal or excessive accumulation of extracellular matrix (ECM), particularly fibrillar collagens, is a key driver of progressive organ dysfunction in many inflammatory and metabolic diseases, including idiopathic pulmonary fibrosis (IPF), cirrhosis, nephropathy, and oral submucous fibrosis (OSF). It has been estimated to contribute to ∼45% of deaths in the developed world. Therefore, agents that target specific fibrotic pathways, with the consequence of slowing, arresting, or even reversing the progression of tissue fibrogenesis, are urgently needed...
October 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28986145/peptides-for-targeting-%C3%AE-b2-crystallin-fibrils
#15
Mehdi Ghaffari Sharaf, Sibel Cetinel, Valentyna Semenchenko, Karim F Damji, Larry D Unsworth, Carlo Montemagno
Crystallins are a major family of proteins located within the lens of the eye. Cataracts are thought to be due to the formation of insoluble fibrillar aggregates, which are largely composed of proteins from the crystallin family. Today the only cataract treatment that exists is surgery and this can be difficult to access for individuals in the developing world. Development of novel pharmacotherapeutic approaches for the treatment of cataract rests on the specific targeting of these structures. βB2-crystallin, a member of β-crystallin family, is a large component of the crystallin proteins within the lens, and as such was used to form model fibrils in vitro...
October 3, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28981200/soluble-fibrin-causes-an-acquired-platelet-glycoprotein-vi-signaling-defect-implications-for-coagulopathy
#16
Mei Yan Lee, Christopher C Verni, Bradley A Herbig, Scott L Diamond
BACKGROUND: In coagulopathic blood, circulating thrombin may drive platelet dysfunction. METHODS/RESULTS: Using calcium dye-loaded platelets, the effect of thrombin exposure and soluble fibrin generation on subsequent platelet GPVI function was investigated. Exposure of apixaban-treated platelet-rich plasma (12% PRP) to thrombin (1-10 nM), but not ADP or thromboxane mimetic U46619 exposure, dramatically blocked subsequent GPVI activation by convulxin, collagen-related peptide, or fibrillar collagen...
October 5, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28972786/absolute-quantification-of-amyloid-propagons-by-digital-microfluidics
#17
Manuela Pfammatter, Maria Andreasen, Georg Meisl, Christopher G Taylor, Jozef Adamcik, Sreenath Bolisetty, Antoni Sanchez-Ferrer, David Klenerman, Christopher M Dobson, Raffaele Mezzenga, Tuomas P J Knowles, Adriano A Aguzzi, Simone Hornemann
The self-replicating properties of numerous proteins into amyloid fibrils is a common phenomenon and underlies several neurodegenerative diseases. Because propagation-active fibrils are chemically indistinguishable from innocuous aggregates and monomeric precursors, their detection requires measurements of their replicative capacity. In the present study, we pre-sent a digital amyloid quantitative assay (d-Aqua) with insulin as amyloid model for the absolute quantification of single replicative units, propagons...
October 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28971683/hydroxylamine-chemical-digestion-for-insoluble-extracellular-matrix-characterization
#18
Alexander S Barrett, Matthew J Wither, Ryan C Hill, Monika Dzieciatkowska, Angelo D'Alessandro, Julie A Reisz, Kirk C Hansen
The extracellular matrix (ECM) is readily enriched by decellularizing tissues with non-denaturing detergents to solubilize and deplete the vast majority of cellular components. This approach has been used extensively to generate ECM scaffolds for regenerative medicine technologies and in 3D cell culture to model how the ECM contributes to disease progression. A highly enriched ECM fraction can then be generated using a strong chaotrope buffer that is compatible with downstream bottom-up proteomic analysis or 3D cell culture experiments after extensive dialysis...
October 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28971419/exploring-amyloidogenicity-of-clusterin-a-structural-and-bioinformatics-analysis
#19
Paraskevi L Tsiolaki, Katerina C Nastou, Nikolaos N Louros, Stavros J Hamodrakas, Vassiliki A Iconomidou
Clusterin, a multitasking glycoprotein, is a protein highly conserved amongst mammals. In humans, Clusterin is mainly a secreted protein, described as an extracellular chaperone with the capability of interacting with a broad spectrum of molecules. In neurodegenerative diseases, such as Alzheimer's disease, it is an amyloid associated protein, co-localized with fibrillar deposits in amyloid plaques in systemic or localized amyloidoses. An 'aggregation-prone' segment (NFHAMFQ) was located within the Clusterin α-chain sequence using AMYLPRED, a consensus method for the prediction of amyloid propensity, developed in our lab...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28970886/pyroglutamate-modified-a%C3%AE-3-42-affects-aggregation-kinetics-of-a%C3%AE-1-42-by-accelerating-primary-and-secondary-pathways
#20
C Dammers, M Schwarten, A K Buell, D Willbold
The aggregation into amyloid fibrils of amyloid-β (Aβ) peptides is a hallmark of Alzheimer's disease. A variety of Aβ peptides have been discovered in vivo, with pyroglutamate-modified Aβ (pEAβ) forming a significant proportion. pEAβ is mainly localized in the core of plaques, suggesting a possible role in inducing and facilitating Aβ oligomerization and accumulation. Despite this potential importance, the aggregation mechanism of pEAβ and its influence on the aggregation kinetics of other Aβ variants have not yet been elucidated...
July 1, 2017: Chemical Science
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