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https://www.readbyqxmd.com/read/28544119/common-fibril-structures-imply-systemically-conserved-protein-misfolding-pathways-in%C3%A2-vivo
#1
Karthikeyan Annamalai, Falk Liberta, Marie-Theres Vielberg, William Close, Hauke Lilie, Karl-Heinz Gührs, Angelika Schierhorn, Rolf Koehler, Andreas Schmidt, Christian Haupt, Ute Hegenbart, Stefan Schönland, Matthias Schmidt, Michael Groll, Marcus Fändrich
Systemic amyloidosis is caused by the misfolding of a circulating amyloid precursor protein and the deposition of amyloid fibrils in multiple organs. Chemical and biophysical analysis of amyloid fibrils from human AL and murine AA amyloidosis reveal the same fibril morphologies in different tissues or organs of one patient or diseased animal. The observed structural similarities concerned the fibril morphology, the fibril protein primary and secondary structures, the presence of post-translational modifications and, in case of the AL fibrils, the partially folded characteristics of the polypeptide chain within the fibril...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28543807/aromatic-interaction-mediated-inhibition-of-%C3%AE-amyloid-assembly-structures-and-cytotoxicity
#2
Hanyi Xie, Jiaxi Peng, Changliang Liu, Xiaocui Fang, Hongyang Duan, Yimin Zou, Yanlian Yang, Chen Wang
Abnormal aggregation of β-amyloid (Aβ) peptide plays an important role in the onset and progress of Alzheimer's disease (AD); hence, targeting Aβ aggregation is considered as an effective therapeutic strategy. Here, we studied the aromatic-interaction-mediated inhibitory effect of oligomeric polypeptides (K8Y8, K4Y8, K8W8) on Aβ42 fibrillization process. The polypeptides containing lysine as well as representative aromatic amino acids of tryptophan or tyrosine were found to greatly suppress the aggregation as evaluated by thioflavin T assay...
May 23, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28543036/self-assembly-of-two-hydrophobins-from-marine-fungi-affected-by-interaction-with-surfaces
#3
Paola Cicatiello, Principia Dardano, Marinella Pirozzi, Alfredo Maria Gravagnuolo, Luca De Stefano, Paola Giardina
Hydrophobins are amphiphilic fungal proteins endowed with peculiar characteristics, such as a high surface activity and an interface triggered self-assembly. Several applications of these proteins have been proposed in the food, cosmetics and biomedical fields. Moreover, their use as proteinaceous coatings can be effective for materials and nanomaterials applications. The discovery of novel hydrophobins with diverse properties may be advantageous from both the scientific and industrial points of view. Stressful environmental conditions of fungal growth may induce the production of proteins with peculiar features...
May 22, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28542244/a-quantitative-label-free-analysis-of-the-extracellular-proteome-of-human-supraspinatus-tendon-reveals-damage-to-the-pericellular-and-elastic-fibre-niches-in-torn-and-aged-tissue
#4
Osnat Hakimi, Nicola Ternette, Richard Murphy, Benedikt M Kessler, Andrew Carr
Tears of the human supraspinatus tendon are common and often cause painful and debilitating loss of function. Progressive failure of the tendon leading to structural abnormality and tearing is accompanied by numerous cellular and extra-cellular matrix (ECM) changes in the tendon tissue. This proteomics study aimed to compare torn and aged rotator cuff tissue to young and healthy tissue, and provide the first ECM inventory of human supraspinatus tendon generated using label-free quantitative LC-MS/MS. Employing two digestion protocols (trypsin and elastase), we analysed grain-sized tendon supraspinatus biopsies from older patients with torn tendons and from healthy, young controls...
2017: PloS One
https://www.readbyqxmd.com/read/28539626/nano-assembly-of-amyloid-%C3%AE-peptide-role-of-the-hairpin-fold
#5
Sibaprasad Maity, Mohtadin Hashemi, Yuri L Lyubchenko
Structural investigations have revealed that β hairpin structures are common features in amyloid fibrils, suggesting that these motifs play an important role in amyloid assembly. To test this hypothesis, we characterized the effect of the hairpin fold on the aggregation process using a model β hairpin structure, consisting of two Aβ(14-23) monomers connected by a turn forming YNGK peptide. AFM studies of the assembled aggregates revealed that the hairpin forms spherical structures whereas linear Aβ(14-23) monomers form fibrils...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539446/infectious-prions-in-the-pregnancy-microenvironment-of-cwd-infected-reeves-muntjac-deer
#6
Amy V Nalls, Erin McNulty, Clare E Hoover, Laura A Pulscher, Edward A Hoover, Candace K Mathiason
Ample evidence exists for the presence of infectious agents at the maternal-fetal interface, often with grave outcomes to the developing fetus (i.e. zika virus, brucella, cytomegalovirus, toxoplasma). While less studied, pregnancy-related transmissible spongiform encephalopathies (TSEs) have been implicated in several species, including humans. Our previous work has shown that prions can be transferred from mother-to-offspring resulting in the development of clinical TSE disease in offspring born to CWD-infected muntjac dams (64)...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28537272/fibril-polymorphism-affects-immobilized-non-amyloid-flanking-domains-of-huntingtin-exon1-rather-than-its-polyglutamine-core
#7
Hsiang-Kai Lin, Jennifer C Boatz, Inge E Krabbendam, Ravindra Kodali, Zhipeng Hou, Ronald Wetzel, Amalia M Dolga, Michelle A Poirier, Patrick C A van der Wel
Polyglutamine expansion in the huntingtin protein is the primary genetic cause of Huntington's disease (HD). Fragments coinciding with mutant huntingtin exon1 aggregate in vivo and induce HD-like pathology in mouse models. The resulting aggregates can have different structures that affect their biochemical behaviour and cytotoxic activity. Here we report our studies of the structure and functional characteristics of multiple mutant htt exon1 fibrils by complementary techniques, including infrared and solid-state NMR spectroscopies...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28537000/advances-in-clinical-cardiology-2016-a-summary-of-the-key-clinical-trials
#8
REVIEW
Alastair Gray, Conor McQuillan, Ian B A Menown
INTRODUCTION: The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. METHODS: The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA)...
May 23, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28536002/actual-management-and-prognosis-of-severe-isolated-tricuspid-regurgitation-associated-with-atrial-fibrillation-without-structural-heart-disease
#9
Yusuke Takahashi, Chisato Izumi, Makoto Miyake, Miyako Imanaka, Maiko Kuroda, Shunsuke Nishimura, Yusuke Yoshikawa, Masashi Amano, Sari Imamura, Naoaki Onishi, Yodo Tamaki, Soichiro Enomoto, Toshihiro Tamura, Hirokazu Kondo, Kazuaki Kaitani, Yoshihisa Nakagawa
BACKGROUND: Patients with atrial fibrillation (AF) without structural heart diseases can show severe tricuspid regurgitation (TR), especially among aged people. The aim of this study was to clarify the actual management, prognosis, and prognostic factors for severe isolated TR associated with AF without structural heart diseases. METHODS AND RESULTS: We retrospectively investigated actual management in 178 consecutive patients with severe isolated TR associated with AF between 1999 and 2011 in our institution...
May 11, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28535056/solid-state-nmr-structure-based-inhibitor-design-to-achieve-selective-inhibition-of-the-parallel-in-register-%C3%AE-sheet-versus-antiparallel-iowa-mutant-%C3%AE-amyloid-fibrils
#10
Qinghui Cheng, Wei Qiang
Solid-state nuclear magnetic resonance (ssNMR) spectroscopy has been widely applied to characterize the high-resolution structures of β-amyloid (Aβ) fibrils. While these structures provide crucial molecular insights on the deposition of amyloid plaques in Alzheimer's diseases (AD), ssNMR structures have been rarely used so far as basis for designing inhibitors. It remains a challenge because the ssNMR-based Aβ fibrils structures were usually obtained with sparsely-isotope-labeled peptides with limited experimental constraints, where the structural models, especially the side-chain coordinates showed restricted precision...
May 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28534025/atrial-fibrillation-dynamics-and-ionic-block-effects-in-six-heterogeneous-human-3d-virtual-atria-with-distinct-repolarization-dynamics
#11
Carlos Sánchez, Alfonso Bueno-Orovio, Esther Pueyo, Blanca Rodríguez
Atrial fibrillation (AF) usually manifests as reentrant circuits propagating through the whole atria creating chaotic activation patterns. Little is yet known about how differences in electrophysiological and ionic properties between patients modulate reentrant patterns in AF. The goal of this study is to quantify how variability in action potential duration (APD) at different stages of repolarization determines AF dynamics and their modulation by ionic block using a set of virtual whole-atria human models...
2017: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/28533591/long-term-histopathological-developments-in-knee-joint-components-in-a-rat-model-of-osteoarthritis-induced-by-monosodium-iodoacetate
#12
Ikufumi Takahashi, Taro Matsuzaki, Masahiro Hoso
[Purpose] This study was performed to evaluate the long-term histopathological changes in knee-joint components including synovial membrane and joint capsule in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA). [Subjects and Methods] Fifty male rats were used. OA was induced through intra-articular injection of MIA, and ten rats were randomly allocated to each of five groups induced with OA for 1, 2, 4, 6, or 8 weeks. At the end of each period, the knee components were examined histopathologically...
April 2017: Journal of Physical Therapy Science
https://www.readbyqxmd.com/read/28532586/the-role-of-genetics-in-primary-ventricular-fibrillation-inherited-channelopathies-and-cardiomyopathies
#13
Lia Crotti, Maria-Christina Kotta
Sudden cardiac death (SCD) has a strong familial component; however, our understanding of its genetic basis varies significantly according to the underlying causes. When coronary artery disease is involved, the predisposing genetic background is complex and despite some interesting findings it remains largely unknown. Quite different is the case of monogenic structural and non-structural heart diseases, in which a number of disease-causing genes have been established and are being used in clinical practice...
June 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28531354/monomeric-polyglutamine-structures-that-evolve-into-fibrils
#14
David Punihaole, Ryan S Jakubek, Riley James Workman, Lauren E Marbella, Patricia Campbell, Jeffry D Madura, Sanford A Asher
We investigate the solution and fibril conformations and structural transitions of the polyglutamine (polyQ) peptide, D2Q10K2 (Q10), by synergistically using UV Resonance Raman (UVRR) spectroscopy and Molecular Dynamics (MD) simulations. We show that Q10 adopts two distinct, monomeric solution conformational states, a collapsed β-strand and a PPII-like structure that do not readily interconvert. This clearly indicates a high activation barrier in solution that prevents equilibration between these structures...
May 22, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28527712/insulin-fibrillation-the-influence-and-coordination-of-zn-2
#15
Christian Grundahl Frankær, Pernille Sønderby, Maria Blanner Bang, Ramona Valentina Mateiu, Minna Groenning, Jens Bukrinski, Pernille Harris
Protein amyloid fibrillation is obtaining much focus because it is connected with amyloid-related human diseases such as Alzheimer's disease, diabetes mellitus type 2, or Parkinson's disease. The influence of metal ions on the fibrillation process and whether it is implemented in the amyloid fibrils has been debated for some years. We have therefore investigated the influence and binding geometry of zinc in fibrillated insulin using extended X-ray absorption fine-structure and X-ray absorption near-edge structure spectroscopy...
May 17, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28526838/thioflavin-t-fluoresces-as-excimer-in-highly-concentrated-aqueous-solutions-and-as-monomer-being-incorporated-in-amyloid-fibrils
#16
Anna I Sulatskaya, Andrey V Lavysh, Alexander A Maskevich, Irina M Kuznetsova, Konstantin K Turoverov
Fluorescence of thioflavin T (ThT) is a proven tool for amyloid fibrils study. The correct model of ThT binding to fibrils is crucial to clarify amyloid fibrils structure and mechanism of their formation. Although there are convincing evidences that ThT has molecular rotor nature, implying it's binding to fibrils in monomer form, speculations concerning ThT binding to fibrils in aggregated forms appear in literature so far. The elaborated approach for fluorescence intensity correction on the inner filter effects applied to ThT aqueous solutions with a wide range of concentration allowed characterizing ThT excimers fluorescence and showing its difference from that of ThT bound to fibrils...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28525683/multilayer-microstructure-of-idiopathic-epiretinal-macular-membranes
#17
Claudio Azzolini, Terenzio Congiu, Simone Donati, Alberto Passi, Petra Basso, Eliana Piantanida, Cesare Mariotti, Francesco Testa, Simona M Caprani, Jennifer Cattaneo, Riccardo Vinciguerra
PURPOSE: To identify the ultramicroscopic structure of idiopathic epiretinal macular membranes (iEMMs) by scanning electron microscopy (SEM). METHODS: We examined 28 iEMMs surgically removed from 28 eyes of 28 patients. All specimens, previously observed at stereomicroscope, were treated with an osmium maceration technique. Fine resolution of iEMMs' 3D architecture and their interaction with the retina were studied using a Philips SEM-FEG XL-30 microscope. RESULTS: The specimens appeared as laminar connective structures partially or completely adherent to the inner limiting membrane (ILM)...
May 19, 2017: European Journal of Ophthalmology
https://www.readbyqxmd.com/read/28524623/upper-gastrointestinal-complications-following-ablation-therapy-for-atrial-fibrillation
#18
S-Y Park, M Camilleri, D Packer, K Monahan
BACKGROUND: Following ablation therapy for cardiac arrhythmias, patients may develop upper gastrointestinal (UGI) symptoms. The vagus nerve is close to the atria and may be affected by ablating energy. AIM: To identify structural or functional complications in UGI tract following ablation for atrial fibrillation (AF) and clinical outcomes and association with vagal dysfunction. METHODS: Using natural language processing of electronic medical records and an AF ablation database of 5380 patients treated during 17 years, we identified 40 patients with UGI complications...
May 19, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28524190/establishing-the-link-between-fibril-formation-and-raman-optical-activity-spectra-of-insulin
#19
Jiří Kessler, Shigeki Yamamoto, Petr Bouř
Folding of proteins into insoluble amyloidal fibrils is implicated in a number of biological processes. Optical spectroscopy represents a convenient tool to monitor such structural variations. Recently, characteristic changes in Raman optical activity (ROA) spectra of insulin during a pre-fibrillar stage were reported but not supported by a theoretical model. In the present study, molecular dynamics and the density functional theory are used to simulate the spectra and understand the connection between the structure, and ROA and Raman spectral intensities...
May 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28522397/cellulose-acetate-poly-lactic-acid-coaxial-wet-electrospun-scaffold-containing-citalopram-loaded-gelatin-nanocarriers-for-neural-tissue-engineering-applications
#20
Mahdi Naseri-Nosar, Majid Salehi, Shahriar Hojjati-Emami
The current study aimed to develop a biodegradable three-dimensional drug-loaded scaffold with the core-shell structured fibrils using coaxial wet-electrospinning for neural tissue engineering application. Poly lactic acid was wet-electrospun as the core, whereas cellulose acetate was fabricated into the fibril's shell. The scaffold then was coated with citalopram-loaded gelatin nanocarriers (CGNs) produced by nanoprecipitation. Scanning electron microscope observation revealed that the fibrils formed a nonwoven structure with the average diameter of ∼950nm...
May 15, 2017: International Journal of Biological Macromolecules
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