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https://www.readbyqxmd.com/read/28431576/enhanced-neuroinvasion-by-smaller-soluble-prions
#1
Cyrus Bett, Jessica Lawrence, Timothy D Kurt, Christina Orru, Patricia Aguilar-Calvo, Anthony E Kincaid, Witold K Surewicz, Byron Caughey, Chengbiao Wu, Christina J Sigurdson
Infectious prion aggregates can propagate from extraneural sites into the brain with remarkable efficiency, likely transported via peripheral nerves. Yet not all prions spread into the brain, and the physical properties of a prion that is capable of transit within neurons remain unclear. We hypothesized that small, diffusible aggregates spread into the CNS via peripheral nerves. Here we used a structurally diverse panel of prion strains to analyze how the prion conformation impacts transit into the brain. Two prion strains form fibrils visible ultrastructurally in the brain in situ, whereas three strains form diffuse, subfibrillar prion deposits and no visible fibrils...
April 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28425516/mechanical-and-vibrational-characterization-of-amyloid-like-het-s-nanosheets-based-on-the-skewed-plate-theory
#2
Hyun Joon Chang, Myeongsang Lee, Jae In Kim, Gwonchan Yoon, Sungsoo Na
Pathological amyloidogenic prion proteins have a toxic effect on functional cells in the human cerebrum because of poor degradability and the tendency to accumulate in an uncontrolled manner under physiological conditions. HET-s, a fungal prion protein, is known to undergo conformational variations from fibrillar to nanosheet structures during a change from low to high pH conditions. It has been said that this conformational change can lead to self-propagation by nucleating on the lateral surface of singlet fibrils...
April 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28424588/chaperones-as-suppressors-of-protein-misfolded-oligomer-toxicity
#3
REVIEW
Benedetta Mannini, Fabrizio Chiti
Chaperones have long been recognized to play well defined functions such as to: (i) assist protein folding and promote formation and maintenance of multisubunit complexes; (ii) mediate protein degradation; (iii) inhibit protein aggregation; and (iv) promote disassembly of undesired aberrant protein aggregates. In addition to these well-established functions, it is increasingly clear that chaperones can also interact with aberrant protein aggregates, such as pre-fibrillar oligomers and fibrils, and inhibit their toxicity commonly associated with neurodegenerative diseases without promoting their disassembly...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28424577/investigation-of-endocytic-pathways-for-the-internalization-of-exosome-associated-oligomeric-alpha-synuclein
#4
Marion Delenclos, Teodora Trendafilova, Divya Mahesh, Ann M Baine, Simon Moussaud, Irene K Yan, Tushar Patel, Pamela J McLean
Misfolding and aggregation of alpha-synuclein (αsyn) resulting in cytotoxicity is a hallmark of Parkinson's disease (PD) and related synucleinopathies. The recent body of evidence indicates that αsyn can be released from neuronal cells by nonconventional exocytosis involving extracellular vesicles (EVs) such as exosomes. The transfer of αsyn between cells has been proposed to be an important mechanism of disease propagation in PD. To date, exosome trafficking mechanisms, including release and cell-cell transmission, have not been fully described...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28417423/evaluation-of-the-expression-of-amyloid-precursor-protein-and-the-ratio-of-secreted-amyloid-beta-42-to-amyloid-beta-40-in-sh-sy5y-cells-stably-transfected-with-wild-type-single-mutant-and-double-mutant-forms-of-the-app-gene-for-the-study-of-alzheimer-s-disease
#5
Aslina Pahrudin Arrozi, Siti Nur Syazwani Shukri, Wan Zurinah Wan Ngah, Yasmin Anum Mohd Yusof, Mohd Hanafi Ahmad Damanhuri, Suzana Makpol
Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (Aβ). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations...
April 17, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28416568/pharmacological-and-toxicological-properties-of-the-potent-oral-%C3%AE-secretase-modulator-bpn-15606
#6
Steven L Wagner, Kevin D Rynearson, Steven K Duddy, Can Zhang, Phuong D Nguyen, Ann Becker, Uyen Vo, Deborah Masliah, Louise Monte, Justin B Klee, Corinne M Echmalian, Weiming Xia, Luisa Quinti, Graham Johnson, Jiunn H Lin, Doo Y Kim, William C Mobley, Robert A Rissman, Rudolph E Tanzi
Alzheimer's disease is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42 amino acid amyloid β peptide, as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance are postulated to initiate and drive the AD pathological process. We initially introduced a novel class of bridged aromatics referred to as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides...
April 17, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28407447/hierarchical-micro-nanofibrous-bioscaffolds-for-structural-tissue-regeneration
#7
Yun Xu, Wenguo Cui, Yanxia Zhang, Pinghui Zhou, Yong Gu, Xiaofeng Shen, Bin Li, Liang Chen
Various biomimetic scaffolds with hierarchical micro/nanostructures are designed to closely mimic native extracellular matrix network and to guide cell behavior to promote structural tissue generation. However, it remains a challenge to fabricate hierarchical micro/nanoscaled fibrous scaffolds with different functional components that endow the scaffolds with both biochemical and physical features to exert different biological roles during the process of tissue healing. In this study, a biomimetic designed micro/nanoscaled scaffold with integrated hierarchical dual fibrillar components is fabricated in order to repair dura mater and prevent the formation of epidural scars via collagen molecule self-assembly, electrospinning, and biological interface crosslinking strategies...
April 13, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28407005/c1q-ablation-exacerbates-amyloid-deposition-a-study-in-a-transgenic-mouse-model-of-attrv30m-amyloid-neuropathy
#8
Elena Panayiotou, Eleni Fella, Revekka Papacharalambous, Stavros Malas, Maria Joao Saraiva, Theodoros Kyriakides
ATTRV30M amyloid neuropathy is a lethal autosomal dominant sensorimotor and autonomic neuropathy, caused by deposition of amyloid fibrils composed of aberrant transthyretin (TTR). Ages of onset and penetrance exhibit great variability and genetic factors have been implicated. Complement activation co-localizes with amyloid deposits in amyloidotic neuropathy and is possibly involved in the kinetics of amyloidogenesis. A candidate gene approach has recently identified C1q polymorphisms to correlate with disease onset in a Cypriot cohort of patients with ATTRV30M amyloid neuropathy...
2017: PloS One
https://www.readbyqxmd.com/read/28398045/conformational-effects-through-hydrogen-bonding-in-a-constrained-%C3%AE-peptide-template-from-intraresidue-seven-membered-rings-to-a-gel-forming-sheet-structure
#9
Hawraà Awada, Claire M Grison, Florence Charnay-Pouget, Jean-Pierre Baltaze, François Brisset, Régis Guillot, Sylvie Robin, Ali Hachem, Nada Jaber, Daoud Naoufal, Ogaritte Yazbeck, David J Aitken
A series of three short oligomers (di-, tri-, and tetramers) of cis-2-(aminomethyl)cyclobutane carboxylic acid, a γ-amino acid featuring a cyclobutane ring constraint, were prepared, and their conformational behavior was examined spectroscopically and by molecular modeling. In dilute solutions, these peptides showed a number of low-energy conformers, including ribbonlike structures pleated around a rarely observed series of intramolecular seven-membered hydrogen bonds. In more concentrated solutions, these interactions defer to an organized supramolecular assembly, leading to thermoreversible organogel formation notably for the tripeptide, which produced fibrillar xerogels...
April 21, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28397888/graphene-quantum-dots-for-detecting-monomeric-amyloid-peptides
#10
Huan Huang, Ping Li, Min Zhang, Yue Yu, Yuhao Huang, Huaiyu Gu, Chen Wang, Yanlian Yang
Detection of the concentration of amyloid monomers is of great importance in the diagnosis of amyloidogenesis. Herein, we propose a method to detect the concentration of amyloid β (Aβ) peptide monomers by utilizing the fluorescence characteristics of graphene quantum dots (GQDs). The linear dependence of the photoluminescence (PL) intensity of GQDs on the Aβ monomer concentration can be identified. It can be further illustrated that both monomeric and fibrillar Aβ peptides can be monitored by using GQDs...
April 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28392383/fibrillar-assembly-of-bacterial-cellulose-in-the-presence-of-wood-based-hemicelluloses
#11
Paavo A Penttilä, Tomoya Imai, Junji Sugiyama
Composite materials mimicking the plant cell wall structure were made by culturing cellulose-producing bacteria together with secondary-wall hemicelluloses from wood. The effects of spruce galactoglucomannan (GGM) and beech xylan on the nanoscale morphology of bacterial cellulose were studied in the original, hydrated state with small-angle X-ray scattering (SAXS). The SAXS intensities were fitted with a model covering multiple levels of the hierarchical structure. Additional information on the structure of dried samples was obtained using scanning and transmission electron microscopy and infra-red spectroscopy...
April 6, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28386328/kallistatin-protects-against-bleomycin-induced-idiopathic-pulmonary-fibrosis-by-inhibiting-angiogenesis-and-inflammation
#12
Xiaoping Huang, Xiao Wang, Xiaolan Xie, Shulan Zeng, Zhaofa Li, Xianxiang Xu, Huiyong Yang, Fei Qiu, Junsheng Lin, Yong Diao
Aberrant angiogenesis and vascular remodeling are the main features of idiopathic pulmonary fibrosis. Kallistatin is an anti-angiogenic peptide with known effects on endothelial cells. This study aimed to demonstrate that kallistatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in a rat model by inhibiting angiogenesis. Twenty-five rats were randomly divided into five experimental groups: (A) Saline only (SA)-as the negative control, (B) BLM only (BLM)-as the model group, (C) BLM and 0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28381645/effect-of-position-specific-single-point-mutations-%C3%A2-and-%C3%A2-biophysical-characterization-of-amyloidogenic-peptide-fragments-identified-from-lattice-corneal-dystrophy-%C3%A2-patients
#13
Venkatraman Anandalakshmi, Elavazhagan Murugan, Eunice Tze Leng Goh, Lim Wei Ting, Shyam S Chaurasia, Toshio Yamazaki, Toshio Nagashima, Benjamin Lawrence George, Gary Swee Lim Peh, Konstantin Pervushin, R Lakshminarayanan, Jodhbir S Mehta
Corneal stromal dystrophies are a group of genetic disorders that may be caused by mutations in the TGFBI gene which results in the aggregation and deposition of mutant proteins in various layers of the cornea. The type of amino acid substitution dictates the age of onset, anatomical location of the deposits, morphological features of deposits (amyloid, amorphous powder or a mixture of both forms) and the severity of disease presentation. It has been suggested that abnormal turn over and aberrant proteolytic processing of the mutant proteins results in the accumulation of insoluble protein deposits...
April 5, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28379242/aggregation-behavior-of-novel-heptamethine-cyanine-dyes-upon-their-binding-to-native-and-fibrillar-lysozyme
#14
Kateryna Vus, Ulyana Tarabara, Atanas Kurutos, Olga Ryzhova, Galyna Gorbenko, Valeriya Trusova, Nikolai Gadjev, Todor Deligeorgiev
Two newly synthesized symmetrical heptamethine cyanine dyes, AK7-5 and AK7-6, absorbing in the region of low autofluorescence of biological samples, have been tested for their ability to detect proteins aggregated into amyloid fibrils. In aqueous solution these probes possess three absorption bands corresponding to the monomer, dimer and H-aggregate species. The association of the dye with fibrillar lysozyme was followed by the enhancement of the monomer band and the reduction of the H-band. The absorption spectra measured at various fibril concentrations were analyzed in terms of the model allowing for the shift of equilibria between various dye species due to the binding of monomers and dimers of AK7-5 and AK7-6 to amyloid fibrils...
April 5, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28378128/effects-of-water-chemistry-and-surface-contact-on-the-toxicity-of-silver-nanoparticles-to-bacillus-subtilis
#15
Jun Yi, Jinping Cheng
The growing use of silver nanoparticles (AgNPs) has created concerns about its potential impacts on natural microbial communities. In this study, the physicochemical properties of AgNPs and its toxicity on natural bacteria Bacillus subtilis (B. subtilis) were investigated in aqueous conditions. The characterization data showed that AgNPs highly aggregated in aqueous conditions, and the hydrodynamic diameter of AgNPs in aqueous conditions was larger than its primary size. The studied AgNPs was less toxic to B...
April 4, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28373589/tissue-inhibitor-of-matrix-metalloproteinase-1-promotes-myocardial-fibrosis-by-mediating-cd63-integrin-%C3%AE-1-interaction
#16
Abhijit Takawale, Pu Zhang, Vaibhav B Patel, Xiuhua Wang, Gavin Oudit, Zamaneh Kassiri
Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis is a key feature of various cardiomyopathies and compromises cardiac systolic and diastolic performance. TIMP1 (tissue inhibitor of metalloproteinase-1) is consistently upregulated in myocardial fibrosis and is used as a marker of fibrosis. However, it remains to be determined whether TIMP1 promotes tissue fibrosis by inhibiting extracellular matrix degradation by matrix metalloproteinases or via an matrix metalloproteinase-independent pathway...
April 3, 2017: Hypertension
https://www.readbyqxmd.com/read/28367383/multiple-calcifying-pseudoneoplasms-of-the-neuraxis
#17
Leonardo B Brasiliense, Dennis W Dickson, Raouf E Nakhleh, Rabih G Tawk, Robert Wharen
Calcifying pseudoneoplasms of the neuraxis (CAPNONs) are extremely rare tumors that are frequently misdiagnosed and overlooked by clinicians. To date, only 40 intracranial lesions have been reported, and in all instances, they were found as a solitary calcified mass. To our knowledge, the current case report is the first to illustrate the development of multiple intraaxial CAPNONs and shed more light on the origin of these lesions. We discuss the case of a 67-year-old woman who presented with a six-year history of recurrent seizures...
February 21, 2017: Curēus
https://www.readbyqxmd.com/read/28361953/cell-to-cell-transfer-of-saa1-protein-in-a-cell-culture-model-of-systemic-aa-amyloidosis
#18
Stephanie Claus, Ioana Puscalau-Girtu, Paul Walther, Tatiana Syrovets, Thomas Simmet, Christian Haupt, Marcus Fändrich
Systemic AA amyloidosis arises from the misfolding of serum amyloid A1 (SAA1) protein and the deposition of AA amyloid fibrils at multiple sites within the body. Previous research already established that mononuclear phagocytes are crucial for the formation of the deposits in vivo and exposure of cultures of such cells to SAA1 protein induces the formation of amyloid deposits within the culture dish. In this study we show that both non-fibrillar and fibrillar SAA1 protein can be readily transferred between cultured J774A...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28358996/multiple-viral-plaques-with-sebaceous-differentiation-associated-with-an-unclassified-papillomavirus-type-in-a-cat
#19
J S Munday, S Marshall, N A Thomson, M Kiupel, R W Heathcott, A French
CASE HISTORY AND CLINICAL FINDINGS A 15-year-old neutered male domestic short-haired cat was presented due to multiple 0.5-2 cm-diameter crusting plaques in the left preauricular region, over the bridge of nose, and in the right periocular region. The plaques did not appear to cause discomfort. HISTOPATHOLOGICAL FINDINGS Biopsy samples of four plaques were examined histologically. Three plaques consisted of well-demarcated foci of mild epidermal hyperplasia overlying markedly hyperplastic sebaceous glands...
April 20, 2017: New Zealand Veterinary Journal
https://www.readbyqxmd.com/read/28356893/alzheimer-s-toxic-amyloid-beta-oligomers-unwelcome-visitors-to-the-na-k-atpase-alpha3-docking-station
#20
Thomas DiChiara, Nadia DiNunno, Jeffrey Clark, Riana Lo Bu, Erika N Cline, Madeline G Rollins, Yuesong Gong, David L Brody, Stephen G Sligar, Pauline T Velasco, Kirsten L Viola, William L Klein
Toxic amyloid beta oligomers (AβOs) are known to accumulate in Alzheimer's disease (AD) and in animal models of AD. Their structure is heterogeneous, and they are found in both intracellular and extracellular milieu. When given to CNS cultures or injected ICV into non-human primates and other non-transgenic animals, AβOs have been found to cause impaired synaptic plasticity, loss of memory function, tau hyperphosphorylation and tangle formation, synapse elimination, oxidative and ER stress, inflammatory microglial activation, and selective nerve cell death...
March 2017: Yale Journal of Biology and Medicine
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