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https://www.readbyqxmd.com/read/28729665/identification-of-proteins-that-specifically-recognize-and-bind-protofibrillar-aggregates-of-amyloid-%C3%AE
#1
Elisabet Wahlberg, M Mahafuzur Rahman, Hanna Lindberg, Elin Gunneriusson, Benjamin Schmuck, Christofer Lendel, Mats Sandgren, John Löfblom, Stefan Ståhl, Torleif Härd
Protofibrils of the 42 amino acids long amyloid-β peptide are transient pre-fibrillar intermediates in the process of peptide aggregation into amyloid plaques and are thought to play a critical role in the pathology of Alzheimer's disease. Hence, there is a need for research reagents and potential diagnostic reagents for detection and imaging of such aggregates. Here we describe an in vitro selection of Affibody molecules that bind to protofibrils of Aβ42cc, which is a stable engineered mimic of wild type Aβ42 protofibrils...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729192/butyrylcholinesterase-knockout-reduces-fibrillar-%C3%AE-amyloid-and-conserves-18-fdg-retention-in-5xfad-mouse-model-of-alzheimer-s-disease
#2
D R DeBay, G A Reid, I R Macdonald, G Mawko, S Burrell, E Martin, C V Bowen, S Darvesh
Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia. One hallmark of the AD brain is the deposition of β-amyloid (Aβ) plaques. AD is also a state of cholinergic dysfunction and butyrylcholinesterase (BChE) associates with Aβ pathology. A transgenic mouse (5XFAD) is an aggressive amyloidosis model, producing Aβ plaques of which BChE also associates. A derived strain (5XFAD/BChE-KO), with the BChE gene knocked out, has significantly lower fibrillar Aβ than 5XFAD mice at the same age...
July 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28727845/emergent-multisystemic-enterococcus-infection-threatens-endangered-christmas-island-reptile-populations
#3
Karrie Rose, Jessica Agius, Jane Hall, Paul Thompson, John-Sebastian Eden, Mukesh Srivastava, Brendan Tiernan, Cheryl Jenkins, David Phalen
Multisystemic infections with a morphologically unusual bacterium were first observed in captive critically endangered Lister's geckos (Lepidodactylus listeri) on Christmas Island in October 2014. Since then the infection was identified in another captive critically endangered lizard species, the blue-tailed skink (Cryptoblepharus egeriae) and two species of invasive geckos; the four clawed gecko (Gehyra mutilata) and Asian house gecko (Hemidactylus frenatus), in a wide geographic range across the east side of the island...
2017: PloS One
https://www.readbyqxmd.com/read/28725967/%C3%AE-synuclein-transfer-between-neurons-and-astrocytes-indicates-that-astrocytes-play-a-role-in-degradation-rather-than-in-spreading
#4
Frida Loria, Jessica Y Vargas, Luc Bousset, Sylvie Syan, Audrey Salles, Ronald Melki, Chiara Zurzolo
Recent evidence suggests that disease progression in Parkinson's disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28723155/inhibiting-the-fibrillation-of-serum-albumin-proteins-in-presence-of-surface-active-ionic-liquids-sails-at-low-ph-a-spectroscopic-and-microscopic-study
#5
Sangita Kundu, Chiranjib Banerjee, Nilmoni Sarkar
One of the key necessary steps to prevent human neurological disorders is the efficient disruption of protein aggregation or amyloid fibril. In this article, we have explored the effect of three amphiphilic surface active ionic liquids (SAILs) namely 1-methyl-3-octylimidazolium chloride ([C8mim]Cl), 1-dodecyl-3-methyllimidazolium chloride ([C12mim]Cl) and 1-hexadecyl-3-methyllimidazolium chloride ([C16mim]Cl) having concentration of 5.8 mM, 0.29 mM and 0.08 mM respectively on bovine serum albumin (BSA) and human serum albumin (HSA) fibril...
July 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28722658/the-golgi-localized-gamma-ear-containing-arf-binding-gga-protein-family-alters-alpha-synuclein-%C3%AE-syn-oligomerization-and-secretion
#6
Bjoern von Einem, Judith Eschbach, Martin Kiechle, Anke Wahler, Dietmar R Thal, Pamela J McLean, Jochen H Weishaupt, Albert C Ludolph, Christine A F von Arnim, Karin M Danzer
Several age-related neurodegenerative disorders are associated with protein misfolding and aggregation of toxic peptides. α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinson's disease (PD) as well as dementia with Lewy bodies. Rising evidence points to oligomeric and pre-fibrillar forms as the pathogenic species, and oligomer secretion seems to be crucial for the spreading and progression of PD pathology. Recent studies implicate that dysfunctions in endolysosomal/autophagosomal pathways increase α-syn secretion...
July 15, 2017: Aging
https://www.readbyqxmd.com/read/28720779/mimicking-paracrine-tgf%C3%AE-1-signals-during-myofibroblast-differentiation-in-3d-collagen-networks
#7
Michael Ansorge, Jiranuwat Sapudom, Marina Chkolnikov, Martin Wilde, Ulf Anderegg, Stephanie Möller, Matthias Schnabelrauch, Tilo Pompe
TGFβ1 is a key regulator for induction of tissue remodeling after dermal wounding. We present a model of paracrine delivery of TGFβ1 for differentiation of dermal fibroblasts based on a fibrillar 3D collagen matrix and embedded TGFβ1 releasing microparticles. We found differentiation into myofibroblasts was achieved in a TGFβ1 dependent manner at much lower doses than systemic delivery. This effect is accounted to the slow and sustained TGFβ1 release mimicking paracrine cell signals.
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715636/backbone-engineered-%C3%AE-peptide-amphitropic-gels-for-immobilization-of-semiconductor-quantum-dots-and-2d-cell-culture
#8
Rajkumar Misra, Aman Sharma, Anjali Shiras, Hosahudya N Gopi
We are reporting a spontaneous supramolecular assembly of backbone engineered γ-peptide scaffold and its utility in the immobilization of semiconductor quantum dots and in cell culture. The stimulating feature of this γ-peptide scaffold is that it efficiently gelate both aqueous phosphate buffers as well as aromatic organic solvents. A comparative and systematic investigation reveals that the greater spontaneous self-aggregation property of γ-peptide over the α-, and β-peptide analogues is mainly due to the backbone flexibility, increased hydrophobicity and "π-π stacking of γ-phenylalanine residues...
July 17, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28714118/body-wall-structure-in-the-starfish-asterias-rubens
#9
Liisa M Blowes, Michaela Egertová, Yankai Liu, Graham R Davis, Nick J Terrill, Himadri S Gupta, Maurice R Elphick
The body wall of starfish is composed of magnesium calcite ossicles connected by collagenous tissue and muscles and it exhibits remarkable variability in stiffness, which is attributed to the mechanical mutability of the collagenous component. Using the common European starfish Asterias rubens as an experimental animal, here we have employed a variety of techniques to gain new insights into the structure of the starfish body wall. The structure and organisation of muscular and collagenous components of the body wall were analysed using trichrome staining...
July 16, 2017: Journal of Anatomy
https://www.readbyqxmd.com/read/28711595/a%C3%AE-truncated-species-implications-for-brain-clearance-mechanisms-and-amyloid-plaque-deposition
#10
Erwin Cabrera, Paul Mathews, Emiliya Mezhericher, Thomas G Beach, Jingjing Deng, Thomas A Neubert, Agueda Rostagno, Jorge Ghiso
Extensive parenchymal and vascular Aβ deposits are pathological hallmarks of 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. In spite of the numerous studies focusing in Aβ, the relevance of N- and C-terminal truncated species for AD pathogenesis remains largely understudied. In the present work, using novel antibodies specifically recognizing Aβ species N-terminally truncated at position 4 or C-terminally truncated at position 34, we provide a clear assessment of the differential topographic localization of these species in AD brains and transgenic models...
July 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28711409/nortriptyline-inhibits-aggregation-and-neurotoxicity-of-alpha-synuclein-by-enhancing-reconfiguration-of-the-monomeric-form
#11
Timothy J Collier, Kinshuk R Srivastava, Craig Justman, Tom Grammatopoulous, Birgit Hutter-Paier, Manuela Prokesch, Daniel Havas, Jean-Christophe Rochet, Fang Liu, Kevin Jock, Patrícia de Oliveira, Georgia L Stirtz, Ulf Dettmer, Caryl E Sortwell, Mel B Feany, Peter Lansbury, Lisa Lapidus, Katrina L Paumier
The pathology of Parkinson's disease and other synucleinopathies is characterized by the formation of intracellular inclusions comprised primarily of misfolded, fibrillar α-synuclein (α-syn). One strategy to slow disease progression is to prevent the misfolding and aggregation of its native monomeric form. Here we present findings that support the contention that the tricyclic antidepressant compound nortriptyline (NOR) has disease-modifying potential for synucleinopathies. Findings from in vitro aggregation and kinetics assays support the view that NOR inhibits aggregation of α-syn by directly binding to the soluble, monomeric form, and by enhancing reconfiguration of the monomer, inhibits formation of toxic conformations of the protein...
July 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28710429/the-a2v-mutation-as-a-new-tool-for-hindering-a%C3%AE-aggregation-a-neutron-and-x-ray-diffraction-study
#12
Laura Cantu', Laura Colombo, Tatiana Stoilova, Bruno Demé, Hideyo Inouye, Rachel Booth, Valeria Rondelli, Giuseppe Di Fede, Fabrizio Tagliavini, Elena Del Favero, Daniel A Kirschner, Mario Salmona
We have described a novel C-to-T mutation in the APP gene that corresponds to an alanine to valine substitution at position 673 in APP (A673V), or position 2 of the amyloid-β (Aβ) sequence. This mutation is associated with the early onset of AD-type dementia in homozygous individuals, whereas it has a protective effect in the heterozygous state. Correspondingly, we observed differences in the aggregation properties of the wild-type and mutated Aβ peptides and their mixture. We have carried out neutron diffraction (ND) and x-ray diffraction (XRD) experiments on magnetically-oriented fibers of Aβ1-28WT and its variant Aβ1-28A2V...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710275/a-ph-dependent-switch-promotes-%C3%AE-synuclein-fibril-formation-via-glutamate-residues
#13
Gina M Moriarty, Michael P Olson, Tamr B Atieh, Maria K Janowska, Sagar D Khare, Jean Baum
Alpha-synuclein (αS) is the primary protein associated with Parkinson's disease, and undergoes aggregation from its intrinsically disordered monomeric form to a cross-β fibrillar form. The closely related homolog beta-synuclein (βS) is essentially fibril resistant under cytoplasmic physiological conditions. Toxic gain of function by βS has been linked to dysfunction, but the aggregation behavior of βS under altered pH is not well understood. In this work, we compare fibril formation of αS and βS at pH 7...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28708370/in-situ-formation-of-microfibrillar-crystalline-superstructure-achieving-high-performance-polylactide
#14
Chunhai Li, Ting Jiang, Jianfeng Wang, Hong Wu, Shaoyun Guo, Xi Zhang, Jiang Li, Jiabin Shen, Rong Chen, Ying Xiong
As one biobased and biodegradable polyester, polylactide (PLA) is widely applied in disposable products, biomedical devices and textile. Nevertheless, due to its inherent brittleness and inferior strength, simultaneously reinforcing and toughening of PLA without sacrificing its biodegradability is highly desirable. In this work, a robust assembly consisting of compact and well-ordered microfibrillar crystalline superstructure (FCS) surrounded by slightly oriented amorphism, is achieved by a combined external force field...
July 14, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28705830/molecular-and-ultrastructural-studies-of-a-fibrillar-collagen-from-octocoral-cnidaria
#15
Joseph P R O Orgel, Ido Sella, Rama S Madhurapantula, Olga Antipova, Yael Mandelberg, Yoel Kashman, Dafna Benayahu, Yehuda Benayahu
We report here the biochemical, molecular and ultrastructural features of a unique organization of fibrillar collagen extracted from the octocoral Sarcophyton ehrenbergi Collagen, the most abundant protein in the animal kingdom, is often defined as a structural component of extra-cellular matrices in metazoans. In the present study, collagen fibers were extracted from the mesenteries of S. ehrenbergi polyps. These fibers are organized as filaments and further compacted as coiled fibers. The fibers are uniquely long, reaching an unprecedented length of tens of centimeters...
July 13, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28701686/congestive-heart-failure-with-preserved-ejection-fraction-in-a-patient-with-light-chain-al-amyloidosis-and-multiple-myeloma
#16
Edgar Francisco Carrizales-Sepúlveda, Alejandro Ordáz-Farías, Raymundo Vera-Pineda, Mario Alberto Benavides-González, Ramiro Flores-Ramírez
BACKGROUND Amyloidosis is characterized by tissue deposition of insoluble fibrillar proteins and it affects almost every organ; there are many types and the heart can be affected in all of them. CASE REPORT Our report describes a middle-aged man who presented to the Emergency Department with congestive heart failure. Clinical, electrocardiographic, and echocardiographic findings suggested the presence of an infiltrative disease, so an abdominal fat tissue biopsy was performed. A final diagnosis of systemic amyloidosis with heart involvement was made...
July 13, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28699302/runx3-inhibits-melanoma-cell-migration-through-regulation-of-cell-shape-change
#17
Xin Zhang, Linghui Wang, Xianlu Zeng, Takashi Fujita, Wenguang Liu
The transcription factor Runx3 is a known tumor suppressor gene, and its expression is frequently lost in melanoma. However, the potential contribution of the loss of Runx3 expression to melanoma development and progression remains unclear. In this in vitro study, we demonstrated that ectopic Runx3 re-expression in B16-F10 melanoma cells changed the cell shape from elongated and branched to spread and unbranched, which enhanced stress fiber formation, increased the number of mature and fibrillar focal adhesions, and up-regulated fibronectin expression...
July 12, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28698377/monomeric-and-fibrillar-%C3%AE-synuclein-exert-opposite-effects-on-the-catalytic-cycle-that-promotes-the-proliferation-of-a%C3%AE-42-aggregates
#18
Sean Chia, Patrick Flagmeier, Johnny Habchi, Veronica Lattanzi, Sara Linse, Christopher M Dobson, Tuomas P J Knowles, Michele Vendruscolo
The coaggregation of the amyloid-β peptide (Aβ) and α-synuclein is commonly observed in a range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. The complex interplay between Aβ and α-synuclein has led to seemingly contradictory results on whether α-synuclein promotes or inhibits Aβ aggregation. Here, we show how these conflicts can be rationalized and resolved by demonstrating that different structural forms of α-synuclein exert different effects on Aβ aggregation. Our results demonstrate that whereas monomeric α-synuclein blocks the autocatalytic proliferation of Aβ42 (the 42-residue form of Aβ) fibrils, fibrillar α-synuclein catalyses the heterogeneous nucleation of Aβ42 aggregates...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28698049/tensins-bridging-amp-activated-protein-kinase-with-integrin-activation
#19
REVIEW
Maria Georgiadou, Johanna Ivaska
Integrin activation is essential for cell adhesion and for connecting the extracellular matrix to the actin cytoskeleton. Thus, inappropriate integrin activation has been linked to several diseases, including cancer. Recent insights demonstrate that the main fibrillar adhesion component tensin maintains β1-integrin active in these mature adhesions. Depletion or silencing of AMP-activated protein kinase (AMPK), the energy sensor involved in maintaining the energy balance of the cell, enhances integrin activity by increasing the expression of tensin and thereby promoting cell adhesion, matrix formation, and mechanotransduction...
July 8, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28696657/a-3d-structural-model-of-high-performance-non-fullerene-polymer-solar-cells-as-revealed-by-high-resolution-afm
#20
Shaowei Shi, Xiaofeng Chen, Xubo Liu, Xuefei Wu, Feng Liu, Zhi-Guo Zhang, Yongfang Li, Thomas P Russell, Dong Wang
Rapid improvements in non-fullerene polymer solar cells (PSCs) have brought power conversion efficiencies to over 12%. To further improve device performance, a fundamental understanding of the correlations between structure and performance is essential. In this paper, based on a typical high performance system consisting of J61(one donor-acceptor (D-A) copolymer of benzodithiophene and fluorine substituted benzotriazole) and ITIC (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']-dithiophene), a 3D-structural model is directly imaged by employing high resolution atomic force microscopy (AFM)...
July 11, 2017: ACS Applied Materials & Interfaces
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