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Protein aggregation

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https://www.readbyqxmd.com/read/27933579/oligomerization-and-chaperone-like-activity-of-drosophila-melanogaster-small-heat-shock-protein-dmhsp27-and-three-arginine-mutants-in-the-alpha-crystallin-domain
#1
Mohamed Taha Moutaoufik, Geneviève Morrow, Halim Maaroufi, Céline Férard, Stéphanie Finet, Robert M Tanguay
The small Hsp DmHsp27 from Drosophila melanogaster is one of the few small heat shock proteins (sHsps) found within the nucleus. We report that its dimerization is independent of disulfide bond formation and seems to rely on salt bridges. Unlike metazoan sHsps, DmHsp27 forms two populations of oligomers not in equilibrium. Mutations at highly conserved arginine residues in mammalian sHsps have been reported to be associated with protein conformational defects and intracellular aggregation. Independent mutation of three highly conserved arginines (R122, R131, and R135) to glycine in DmHsp27 results in only one population of higher molecular weight form...
December 8, 2016: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/27932476/high-fat-diet-induced-lysosomal-dysfunction-and-impaired-autophagic-flux-contribute-to-lipotoxicity-in-the-kidney
#2
Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomonori Kimura, Tomoko Namba, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka
Excessive fat intake contributes to the progression of metabolic diseases via cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27932387/the-long-non-coding-rna-transcriptome-of-dictyostelium-discoideum-development
#3
Rafael D Rosengarten, Balaji Santhanam, Janez Kokosar, Gad Shaulsky
Dictyostelium discoideum live in the soil as single cells, engulfing bacteria and growing vegetatively. Upon starvation, tens of thousands of amoebae enter a developmental program that includes aggregation, multicellular differentiation, and sporulation. Major shifts across the protein-coding transcriptome accompany these developmental changes. However, no study has presented a global survey of long non-coding RNAs in D. discoideum To characterize the antisense and long intergenic non-coding RNA transcriptome, we analyzed previously published developmental time course samples using an RNA-sequencing library preparation method that selectively depletes ribosomal RNAs...
December 7, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27930828/integrin-and-cadherin-clusters-a-robust-way-to-organize-adhesions-for-cell-mechanics
#4
Rishita Changede, Michael Sheetz
Recent studies at the nanometer scale have revealed that relatively uniform clusters of adhesion proteins (50-100 nm) constitute the modular units of cell adhesion sites in both cell-matrix and cell-cell adhesions. Super resolution microscopy and membrane protein diffusion studies both suggest that even large focal adhesions are formed of 100 nm clusters that are loosely aggregated. Clusters of 20-50 adhesion molecules (integrins or cadherins) can support large forces through avidity binding interactions but can also be disassembled or endocytosed rapidly...
December 8, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27930817/assessment-of-virulence-factors-antibiotic-resistance-and-amino-decarboxylase-activity-in-enterococcus-faecium-mxvk29-isolated-from-mexican-chorizo
#5
Yenizey M Alvarez-Cisneros, Francisco J Fernández, Teresita Del Rosario Sáinz Espuñes, Edith Ponce-Alquicira
Enterococcus faecium MXVK29 has the ability to produce an antimicrobial compound that belongs to Class IIa of the Klaenhammer classification, and could be used as part of a biopreservation technology through direct inoculation of the strain as a starter or protective culture. However, Enterococcus is considered an opportunistic pathogen, so the purpose of this work was to study the food safety determinants of Enterococcus faecium MXVK29. The strain was sensitive to all of the antibiotics tested (penicillin, tetracycline, vancomycin, erythromycin, chloramphenicol, gentamicin, neomycin, kanamycin and netilmicin) and did not demonstrate histamine, cadaverine, or putrescine formation...
December 8, 2016: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/27930341/analysis-of-138-pathogenic-mutations-in-presenilin-1-on-the-in-vitro-production-of-a%C3%AE-42-and-a%C3%AE-40-peptides-by-%C3%AE-secretase
#6
Linfeng Sun, Rui Zhou, Guanghui Yang, Yigong Shi
A hallmark of Alzheimer's disease (AD) is the aggregation of β-amyloid peptides (Aβ) into amyloid plaques in patient brain. Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase produces Aβ of varying lengths, of which longer peptides such as Aβ42 are thought to be more harmful. Increased ratios of longer Aβs over shorter ones, exemplified by the ratio of Aβ42 over Aβ40, may lead to formation of amyloid plaques and consequent development of AD. In this study, we analyzed 138 reported mutations in human presenilin-1 (PS1) by individually reconstituting the mutant PS1 proteins into anterior-pharynx-defective protein 1 (APH-1)aL-containing γ-secretases and examining their abilities to produce Aβ42 and Aβ40 in vitro...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27930322/casitas-b-cell-lymphoma-cbl-proteins-protect-mammary-epithelial-cells-from-proteotoxicity-of-active-c-src-accumulation
#7
Chandrani Mukhopadhyay, Aleata Triplett, Tom Bargar, Carol Heckman, Kay-Uwe Wagner, Mayumi Naramura
Casitas B-cell lymphoma (Cbl) family ubiquitin ligases negatively regulate tyrosine kinase-dependent signal transduction by promoting degradation of active kinases. We and others previously reported that loss of Cbl functions caused hyperproliferation in lymphoid and hematopoietic systems. Unexpectedly, Cbl deletion in Cbl-b-null, Cbl-c-null primary mouse mammary epithelial cells (MECs) (Cbl triple-deficiency) induced rapid cell death despite enhanced MAP kinase and AKT activation. Acute Cbl triple-deficiency elicited distinct transcriptional and biochemical responses with partial overlap with previously described cellular reactions to unfolded proteins and oxidative stress...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929735/development-of-adsorptive-hybrid-filters-to-enable-two-step-purification-of-biologics
#8
Nripen Singh, Abhiram Arunkumar, Michael Peck, Alexei M Voloshin, Angela M Moreno, Zhijun Tan, Jonathan Hester, Michael C Borys, Zheng Jian Li
Recent progress in mammalian cell culture process has resulted in significantly increased product titers, but also a substantial increase in process- and product-related impurities. Due to the diverse physicochemical properties of these impurities, there is constant need for new technologies that offer higher productivity and improved economics without sacrificing the process robustness required to meet final drug substance specifications. Here, we examined the use of new synthetic adsorptive hybrid filters (AHF) modified with the high binding capacity of quaternary amine (Emphaze™ AEX) and salt-tolerant biomimetic (Emphaze™ ST-AEX) ligands for clearance of process-related impurities like host cell protein (HCP), residual DNA, and virus...
December 8, 2016: MAbs
https://www.readbyqxmd.com/read/27929117/cct-complex-restricts-neuropathogenic-protein-aggregation-via-autophagy
#9
Mariana Pavel, Sara Imarisio, Fiona M Menzies, Maria Jimenez-Sanchez, Farah H Siddiqi, Xiaoting Wu, Maurizio Renna, Cahir J O'Kane, Damian C Crowther, David C Rubinsztein
Aberrant protein aggregation is controlled by various chaperones, including CCT (chaperonin containing TCP-1)/TCP-1/TRiC. Mutated CCT4/5 subunits cause sensory neuropathy and CCT5 expression is decreased in Alzheimer's disease. Here, we show that CCT integrity is essential for autophagosome degradation in cells or Drosophila and this phenomenon is orchestrated by the actin cytoskeleton. When autophagic flux is reduced by compromise of individual CCT subunits, various disease-relevant autophagy substrates accumulate and aggregate...
December 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27929047/caveolin-1-is-an-aggresome-inducing-protein
#10
Ajit Tiwari, Courtney A Copeland, Bing Han, Caroline A Hanson, Krishnan Raghunathan, Anne K Kenworthy
Caveolin-1 (Cav1) drives the formation of flask-shaped membrane invaginations known as caveolae that participate in signaling, clathrin-independent endocytosis and mechanotransduction. Overexpression or mutations of Cav1 can lead to its mistrafficking, including its accumulation in a perinuclear compartment previously identified as the Golgi complex. Here, we show that in the case of overexpressed Cav1-GFP, this perinuclear compartment consists of cytoplasmic inclusion bodies generated in response to the accumulation of aggregates of misfolded proteins, known as aggresomes...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928935/taking-the-stock-of-granule-cargo-platelet-releasate-proteomics
#11
Oliver Pagel, Elena Walter, Kerstin Jurk, René P Zahedi
Human platelets are key players in a multitude of physiological and pathological processes. Upon activation they release cargo from different types of granules as well as microparticles in an apparently well-regulated and orchestrated manner. The resulting specific platelet releasates create microenvironments of biologically active compounds and proteins during platelet aggregation and thrombus formation, allowing efficient delivery of growth factors and immune modulators to their sites of effect and enhancing the coagulative response in a positive feedback loop...
December 8, 2016: Platelets
https://www.readbyqxmd.com/read/27928708/withania-somnifera-reverses-transactive-response-dna-binding-protein-43-proteinopathy-in-a-mouse-model-of-amyotrophic-lateral-sclerosis-frontotemporal-lobar-degeneration
#12
Kallol Dutta, Priyanka Patel, Reza Rahimian, Daniel Phaneuf, Jean-Pierre Julien
Abnormal cytoplasmic mislocalization of transactive response DNA binding protein 43 (TARDBP or TDP-43) in degenerating neurons is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous work suggested that nuclear factor kappa B (NF-κB) may constitute a therapeutic target for TDP-43-mediated disease. Here, we investigated the effects of root extract of Withania somnifera (Ashwagandha), an herbal medicine with anti-inflammatory properties, in transgenic mice expressing a genomic fragment encoding human TDP-43(A315T) mutant...
December 7, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27928652/enhanced-proteostasis-in-post-ischemic-stroke-mouse-brains-by-ubiquilin-1-promotes-functional-recovery
#13
Yanying Liu, Fangfang Qiao, Hongmin Wang
Stroke is pathologically associated with oxidative stress, protein damage, and neuronal loss. We previously reported that overexpression of a ubiquitin-like protein, ubiquilin-1 (Ubqln), protects neurons against ischemia-caused brain injury, while knockout of the gene exacerbates cerebral ischemia-caused neuronal damage and delays functional recovery. Although these observations indicate that Ubqln is a potential therapeutic target, transgenic manipulation-caused overexpression of Ubqln occurs before the event of ischemic stroke, and it remains unknown whether delayed Ubqln overexpression in post-ischemic brains within a clinically relevant time frame is still beneficial...
December 7, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27928571/diffusion-dynamics-of-latex-nanoparticles-coated-with-ssdna-across-a-single-nanopore
#14
Sébastien Balme, Mathilde Lepoitevin, Ludovic F Dumée, Mikhael Bechelany, Jean-Marc Janot
The fundamental understanding of the transport mechanisms of objects across a single nanopore is one key point to develop Coulter counters at the nanoscale for macromolecule or nanoparticle detection. In this area, nanoparticles have been less investigated than biomacromolecules such as DNA or proteins due to their self-aggregation in the presence of salts. In this work, the transport of modified latex nanoparticles across solid-state nanopores was investigated. To prevent their aggregation, their surface was modified with a low molecular weight single strand DNA coating...
December 8, 2016: Soft Matter
https://www.readbyqxmd.com/read/27928512/extracellular-vesicle-associated-a%C3%AE-mediates-trans-neuronal-bioenergetic-and-ca-2-handling-deficits-in-alzheimer-s-disease-models
#15
Erez Eitan, Emmette R Hutchison, Krisztina Marosi, James Comotto, Maja Mustapic, Saket M Nigam, Caitlin Suire, Chinmoyee Maharana, Gregory A Jicha, Dong Liu, Vasiliki Machairaki, Kenneth W Witwer, Dimitrios Kapogiannis, Mark P Mattson
Alzheimer's Disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs) are small 50-150 nanometer membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient CSF and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca(2+) homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity...
2016: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/27927963/inhibition-of-prolyl-oligopeptidase-restores-spontaneous-motor-behavior-in-the-%C3%AE-synuclein-virus-vector-based-parkinson-s-disease-mouse-model-by-decreasing-%C3%AE-synuclein-oligomeric-species-in-mouse-brain
#16
Reinis Svarcbahs, Ulrika H Julku, Timo T Myöhänen
: Decreased clearance of α-synuclein (aSyn) and aSyn protein misfolding and aggregation are seen as major factors in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies that leads to disruption in neuronal function and eventually to cell death. Prolyl oligopeptidase (PREP) can accelerate the aSyn aggregation process, while inhibition of PREP by a small molecule inhibitor decreases aSyn oligomer formation and enhances its clearance via autophagy in different aSyn overexpressing cell types and in transgenic PD animal models...
December 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27927214/antiplatelet-and-antithrombotic-effects-of-cordycepin-enriched-wib-801ce-from-cordyceps-militaris-ex-vivo-in-vivo-and-in-vitro
#17
Hyuk-Woo Kwon, Jung-Hae Shin, Deok Hwi Lim, Woo Jeong Ok, Gi Suk Nam, Min Ji Kim, Ho-Kyun Kwon, Jun-Hee Noh, Je-Young Lee, Hyun-Hong Kim, Jong-Lae Kim, Hwa-Jin Park
BACKGROUND: A species of the fungal genus Cordyceps has been used as a complementary and alternative medicine of traditional Chinese medicine, and its major component cordycepin and cordycepin-enriched WIB-801CE are known to have antiplatelet effects in vitro. However, it is unknown whether they have also endogenous antiplatelet and antithrombotic effects. In this study, to resolve these doubts, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from Cordyceps militaris-hypha, then evaluated its ex vivo, in vivo, and in vitro antiplatelet and antithrombotic effects...
December 7, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27927196/the-topology-structure-and-pe-interaction-of-litaf-underpin-a-charcot-marie-tooth-disease-type-1c
#18
Anita K Ho, Jane L Wagstaff, Paul T Manna, Lena Wartosch, Seema Qamar, Elspeth F Garman, Stefan M V Freund, Rhys C Roberts
BACKGROUND: Mutations in Lipopolysaccharide-induced tumour necrosis factor-α factor (LITAF) cause the autosomal dominant inherited peripheral neuropathy, Charcot-Marie-Tooth disease type 1C (CMT1C). LITAF encodes a 17 kDa protein containing an N-terminal proline-rich region followed by an evolutionarily-conserved C-terminal 'LITAF domain', which contains all reported CMT1C-associated pathogenic mutations. RESULTS: Here, we report the first structural characterisation of LITAF using biochemical, cell biological, biophysical and NMR spectroscopic approaches...
December 7, 2016: BMC Biology
https://www.readbyqxmd.com/read/27926845/membrane-bound-alpha-synuclein-clusters-induce-impaired-lipid-diffusion-and-increased-lipid-packing
#19
Aditya Iyer, Nathalie Schilderink, Mireille M A E Claessens, Vinod Subramaniam
The aggregation of membrane-bound α-synuclein (αS) into oligomers and/or amyloid fibrils has been suggested to cause membrane damage in in vitro model phospholipid membrane systems and in vivo. In this study, we investigate how αS interactions that precede the formation of well-defined aggregates influence physical membrane properties. Using three truncated variants of αS with different aggregation propensities and comparable phospholipid membrane binding affinities we show, using fluorescence recovery after photobleaching (FRAP) and fluorescence anisotropy measurements, that formation of αS clusters on supported lipid bilayers (SLBs) impairs lateral lipid diffusion and increases lipid packing beneath the αS clusters...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926837/the-significance-of-the-location-of-mutations-for-the-native-state-dynamics-of-human-lysozyme
#20
Minkoo Ahn, Christine L Hagan, Ana Bernardo-Gancedo, Erwin De Genst, Francisco N Newby, John Christodoulou, Anne Dhulesia, Mireille Dumoulin, Carol V Robinson, Christopher M Dobson, Janet R Kumita
The conversion of human lysozyme into amyloid fibrils is associated with a rare but fatal hereditary form of nonneuropathic systemic amyloidosis. The accumulation of large amounts of aggregated protein is thought to be initiated by the formation of transient intermediate species of disease-related lysozyme variants, essentially due to the loss of global cooperativity under physiologically relevant conditions. Interestingly, all five naturally occurring, amyloidogenic, single-point mutations are located in the β-domain of lysozyme, the region that is predominantly unfolded during the formation of the transient intermediate species...
December 6, 2016: Biophysical Journal
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