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Protein aggregation

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https://www.readbyqxmd.com/read/28735144/entorhinal-tau-pathology-disrupts-hippocampal-prefrontal-oscillatory-coupling-during-associative-learning
#1
Stephanie E Tanninen, Bardia Nouriziabari, Mark D Morrissey, Rami Bakir, Robert D Dayton, Ronald L Klein, Kaori Takehara-Nishiuchi
A neural signature of asymptomatic preclinical Alzheimer's disease (AD) is disrupted connectivity between brain regions; however, its underlying mechanisms remain unknown. Here, we tested whether a preclinical pathologic feature, tau aggregation in the entorhinal cortex (EC) is sufficient to disrupt the coordination of local field potentials (LFPs) between its efferent regions. P301L-mutant human tau or green fluorescent protein (GFP) was virally overexpressed in the EC of adult rats. LFPs were recorded from the dorsal hippocampus and prelimbic medial prefrontal cortex while the rats underwent trace eyeblink conditioning where they learned to associate 2 stimuli separated by a short time interval...
July 6, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28734976/structural-basis-of-the-substrate-specificity-and-instability-in-solution-of-a-glycosidase-from-lactobacillus-plantarum
#2
Iván Acebrón, Laura Plaza-Vinuesa, Blanca de Las Rivas, Rosario Muñoz, J Cumella, F Sánchez-Sancho, José Miguel Mancheño
Statistics from structural genomics initiatives reveal that around 50-55% of the expressed, non-membrane proteins cannot be purified and therefore structurally characterized due to solubility problems, which emphasized protein solubility as one of the most serious concerns in structural biology projects. Lactobacillus plantarum CECT 748(T) produces an aggregation-prone glycosidase (LpBgl) that we crystallized previously. However, this result could not be reproduced due to protein instability and therefore further high-resolution structural analyses of LpBgl were impeded...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734135/folding-while-bound-to-chaperones
#3
REVIEW
Scott Horowitz, Philipp Koldewey, Frederick Stull, James Ca Bardwell
Chaperones are important in preventing protein aggregation and aiding protein folding. How chaperones aid protein folding remains a key question in understanding their mechanism. The possibility of proteins folding while bound to chaperones was reintroduced recently with the chaperone Spy, many years after the phenomenon was first reported with the chaperones GroEL and SecB. In this review, we discuss the salient features of folding while bound in the cases for which it has been observed and speculate about its biological importance and possible occurrence in other chaperones...
July 19, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28733985/lalf32-51-e7-a-hpv-16-therapeutic-vaccine-candidate-forms-protein-body-like-structures-when-expressed-in-nicotiana-benthamiana-leaves
#4
Romana J R Yanez, Renate Lamprecht, Milaid Granadillo, Isis Torrens, Elsa Arcalís, Eva Stöger, Edward P Rybicki, Inga I Hitzeroth
High-risk Human papillomaviruses (HPVs) cause cervical cancer, and while there are good prophylactic vaccines on the market, these are ineffective against established infections, creating a clear need for therapeutic vaccines. The HPV E7 protein is one of the essential oncoproteins for the onset and maintenance of malignancy, and is therefore an ideal therapeutic vaccine target. We fused the HPV-16 E7 protein to the Limulus polyphemus anti-lipopolysaccharide factor (LALF32-51 ), a small hydrophobic peptide that can penetrate cell membranes and that has immunomodulatory properties...
July 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28733960/a-review-of-fluid-biomarkers-for-alzheimer-s-disease-moving-from-csf-to-blood
#5
REVIEW
Kaj Blennow
A set of core cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) includes total tau (T-tau), phosphorylated tau (P-tau) and β-amyloid 42 (Aβ42). These biomarkers reflect some of the key aspects of AD pathophysiology, including neuronal degeneration, tau phosphorylation with tangle formation, and Aβ aggregation with deposition of the peptide into plaques. The core AD CSF biomarkers have been validated clinically in numerous studies, and found to have a very high diagnostic performance to identify AD, both in the dementia and in the mild cognitive impairment stages of the disease...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28733840/identification-of-a%C3%A2-rare-coch-mutation-by-whole-exome-sequencing-implications-for-personalized-therapeutic-rehabilitation-in-an-austrian-family-with-non-syndromic-autosomal-dominant-late-onset-hearing-loss
#6
Thomas Parzefall, Alexandra Frohne, Martin Koenighofer, Andreas Kirchnawy, Berthold Streubel, Christian Schoefer, Wolfgang Gstoettner, Klemens Frei, Trevor Lucas
BACKGROUND: Non-syndromic autosomal dominant hearing impairment is characteristically postlingual in onset. Genetic diagnostics are essential for genetic counselling, disease prognosis and understanding of the molecular mechanisms of disease. To date, 36 causative genes have been identified, many in only individual families. Gene selection for genetic screening by traditional methods and genetic diagnosis in autosomal dominant patients has therefore been fraught with difficulty. Whole-exome sequencing provides a powerful tool to analyze all protein-coding genomic regions in parallel, thus allowing the comprehensive screening of all known genes and associated alterations...
July 21, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28733623/crystal-structure-of-a-low-molecular-weight-activator-blm-pep-with-yeast-20s-proteasome-insights-into-the-enzyme-activation-mechanism
#7
Julia Witkowska, Małgorzata Giżyńska, Przemysław Grudnik, Przemysław Golik, Przemysław Karpowicz, Artur Giełdoń, Grzegorz Dubin, Elżbieta Jankowska
Proteasomes are responsible for protein turnover in eukaryotic cells, degrading short-lived species but also removing improperly folded or oxidatively damaged ones. Dysfunction of a proteasome results in gradual accumulation of misfolded/damaged proteins, leading to their aggregation. It has been postulated that proteasome activators may facilitate removal of such aggregation-prone proteins and thus prevent development of neurodegenerative disorders. However, the discovery of pharmacologically relevant compounds is hindered by insufficient structural understanding of the activation process...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733489/interaction-of-misfolded-proteins-and-mitochondria-in-neurodegenerative-disorders
#8
REVIEW
Andrey Y Abramov, Alexey V Berezhnov, Evgeniya I Fedotova, Valery P Zinchenko, Ludmila P Dolgacheva
The number of the people affected by neurodegenerative disorders is growing dramatically due to the ageing of population. The major neurodegenerative diseases share some common pathological features including the involvement of mitochondria in the mechanism of pathology and misfolding and the accumulation of abnormally aggregated proteins. Neurotoxicity of aggregated β-amyloid, tau, α-synuclein and huntingtin is linked to the effects of these proteins on mitochondria. All these misfolded aggregates affect mitochondrial energy metabolism by inhibiting diverse mitochondrial complexes and limit ATP availability in neurones...
July 21, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28733286/the-regulator-ldhr-and-the-d-lactate-dehydrogenase-ldha-of-burkholderia-multivorans-play-a-role-in-carbon-overflow-and-in-planktonic-cellular-aggregates-formation
#9
Inês N Silva, Marcelo J Ramires, Lisa A Azevedo, Ana R Guerreiro, Andreia C Tavares, Jörg D Becker, Leonilde M Moreira
LysR-type transcriptional regulators (LTTR) are the most commonly found regulators in Burkholderia cepacia complex, comprising opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. Despite LTTRs being global regulators of pathogenicity in several bacteria, few have been characterized in Burkholderia Here, we showed that gene ldhR of B. multivorans encoding a LTTR is co-transcribed with ldhA encoding a d-lactate dehydrogenase, and evaluate their implication in virulence traits like exopolysaccharide (EPS) synthesis and biofilm formation...
July 21, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28733250/sphingosine-kinase-1-protects-renal-tubular-epithelial-cells-from-renal-fibrosis-via-induction-of-autophagy
#10
Chunyang Du, Yunzhuo Ren, Fang Yao, Jialiang Duan, Hui'er Zhao, Yunxia Du, Xia Xiao, Huijun Duan, Yonghong Shi
Autophagy is an important homoeostatic mechanism for the lysosomal degradation of protein aggregates and damaged cytoplasmic components. Recent studies suggest that autophagy which is induced by TGF-β1 suppresses kidney fibrosis in renal tubular epithelial cells (RTECs) of obstructed kidneys. Sphingosine kinase 1(SK1), converting sphingosine into endogenous sphingosine-1-phosphate (S1P), was shown to modulate autophagy and involved in the processes of fibrotic diseases. Since SK1 activity is also up-regulated by TGF-β1, we explored its effect on the induction of autophagy and development of renal fibrosis in this study...
July 18, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28732975/high-intensity-ultrasound-treatment-of-protein-isolate-extracted-from-dephenolized-sunflower-meal-effect-on-physicochemical-and-functional-properties
#11
Mudasir Ahmad Malik, Harish Kumar Sharma, Charanjiv Singh Saini
The influence of high intensity ultrasound (HIUS) on physicochemical and functional properties of sunflower protein isolates was investigated. Protein solutions (10% w/v) were treated with ultrasound probe (20kHz) and ultrasound bath (40kHz) for 5, 10, 20 and 30min. Thermal stability of protein isolates was reduced as indicated by differential scanning calorimetry. Minimum thermal stability was observed at 20min of sonication and increased further with increase in treatment time indicating aggregation at prolonged sonication...
November 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28732351/tropomyosin-isoform-tpm2-1-regulates-collective-and-amoeboid-cell-migration-and-cell-aggregation-in-breast-epithelial-cells
#12
HyeRim Shin, Dayoung Kim, David M Helfman
Metastasis dissemination is the result of various processes including cell migration and cell aggregation. These processes involve alterations in the expression and organization of cytoskeletal and adhesion proteins in tumor cells. Alterations in actin filaments and their binding partners are known to be key players in metastasis. Downregulation of specific tropomyosin (Tpm) isoforms is a common characteristic of transformed cells. In this study, we examined the role of Tpm2.1 in non-transformed MCF10A breast epithelial cells in cell migration and cell aggregation, because this isoform is downregulated in primary and metastatic breast cancer as well as various breast cancer cell lines...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732135/synovial-immunophenotype-and-anti-citrullinated-protein-antibodies-in-ra-patients-relationship-to-treatment-response-and-radiological-prognosis
#13
Carl Orr, Aurelie Najm, Monika Biniecka, Trudy McGarry, Chin-Teck Ng, Francis Young, Ursula Fearon, Douglas J Veale
OBJECTIVE: Serum anti-citrullinated peptide antibodies (ACPA) may be present before development of rheumatoid arthritis (RA) and may predict more severe, erosive disease. This study examines synovial tissue immunophenotype according to ACPA status in RA patients, response to treatment and erosive status. METHODS: Consecutive RA patients were prospectively recruited and underwent clinical and serological assessment before and after treatment. Radiological assessment was performed at the time of clinical follow up...
July 21, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28731428/development-of-nasal-lipid-nanocarriers-containing-curcumin-for-brain-targeting
#14
Gustavo Richter Vaz, Gabriela Hädrich, Juliana Bidone, Jamile Lima Rodrigues, Mariana Corrêa Falkembach, Jean-Luc Putaux, Mariana Appel Hort, José Maria Monserrat, Antônio Sergio Varela Junior, Helder Ferreira Teixeira, Ana Luiza Muccillo-Baisch, Ana Paula Horn, Cristiana Lima Dora
BACKGROUND: Curcumin (CUR) has properties that can be useful for the treatment of Alzheimer's disease. Such properties are the inhibition of amyloid-β-protein (Aβ) aggregation, Aβ-induced inflammation, and activities of β-secretase and acetylcholinesterase. However, previous studies have revealed that CUR exhibited low bioavailability and difficulties in reaching the brain. OBJECTIVE: To overcome such drawbacks, this study aims at developing nasal lipid nanocarriers loaded with CUR to effectively target the brain...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731321/conjugation-dependent-interaction-of-folic-acid-with-folate-binding-protein
#15
Rachel Leah Merzel, Carolina Frey, Junjie Chen, Rachel Garn, Mallory A van Dongen, Casey A Dougherty, Ananda Kandaluru, Philip S Low, E Neil G Marsh, Mark M Banaszak Holl
Serum proteins play a critical role in the transport, uptake, and efficacy of targeted drug therapies, and here we investigate the interactions between folic acid-polymer conjugates and serum folate binding protein (FBP), the soluble form of the cellular membrane-bound folate receptor. We demonstrate that both choice of polymer and method of ligand conjugation affect the interactions between folic acid-polymer conjugates and serum FBP, resulting in changes in the folic acid-induced protein aggregation process...
July 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28731279/influence-of-l-amino-acids-on-aggregation-and-biofilm-formation-in-azotobacter-chroococcum-and-trichoderma-viride
#16
Velmourougane Kulandaivelu, Radha Prasanna
AIM: The effects of L-amino acids on growth and biofilm formation in Azotobacter chroococcum (Az) and Trichoderma viride (Tv) as single (Az, Tv) and staggered inoculated cultures (Az-Tv, Tv-Az) was investigated. METHODS AND RESULTS: A preliminary study using a set of twenty L-amino acids, identified six amino acids (L-Glu, L-Gln, L-His, L-Ser, L-Thr, and L-Trp) which significantly enhanced growth and biofilm formation. Supplementation of these amino acids at different concentrations revealed that 40 mmol l(-1) was most effective...
July 21, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28731091/developing-force-fields-when-experimental-data-is-sparse-amber-gaff-compatible-parameters-for-inorganic-and-alkyl-oxoanions
#17
Sadra Kashefolgheta, Ana Vila Verde
We present a set of Lennard-Jones parameters for classical, all-atom models of acetate and various alkylated and non-alkylated forms of sulfate, sulfonate and phosphate ions, optimized to reproduce their interactions with water and with the physiologically relevant sodium, ammonium and methylammonium cations. The parameters are internally consistent and are fully compatible with the Generalized Amber Force Field (GAFF), the AMBER force field for proteins, the accompanying TIP3P water model and the sodium model of Joung and Cheatham...
July 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28731040/er-stress-and-the-unfolded-protein-response-in-neurodegeneration
#18
REVIEW
Claudio Hetz, Smita Saxena
The clinical manifestation of neurodegenerative diseases is initiated by the selective alteration in the functionality of distinct neuronal populations. The pathology of many neurodegenerative diseases includes accumulation of misfolded proteins in the brain. In physiological conditions, the proteostasis network maintains normal protein folding, trafficking and degradation; alterations in this network - particularly disturbances to the function of endoplasmic reticulum (ER) - are thought to contribute to abnormal protein aggregation...
July 21, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28729861/comparative-omics-and-trait-analyses-of-marine-pseudoalteromonas-phages-advance-the-phage-otu-concept
#19
Melissa B Duhaime, Natalie Solonenko, Simon Roux, Nathan C Verberkmoes, Antje Wichels, Matthew B Sullivan
Viruses influence the ecology and evolutionary trajectory of microbial communities. Yet our understanding of their roles in ecosystems is limited by the paucity of model systems available for hypothesis generation and testing. Further, virology is limited by the lack of a broadly accepted conceptual framework to classify viral diversity into evolutionary and ecologically cohesive units. Here, we introduce genomes, structural proteomes, and quantitative host range data for eight Pseudoalteromonas phages isolated from Helgoland (North Sea, Germany) and use these data to advance a genome-based viral operational taxonomic unit (OTU) definition...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28729832/the-role-of-microglia-in-retinal-neurodegeneration-alzheimer-s-disease-parkinson-and-glaucoma
#20
REVIEW
Ana I Ramirez, Rosa de Hoz, Elena Salobrar-Garcia, Juan J Salazar, Blanca Rojas, Daniel Ajoy, Inés López-Cuenca, Pilar Rojas, Alberto Triviño, José M Ramírez
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions...
2017: Frontiers in Aging Neuroscience
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