957 resultados para Amyloid-p Component


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The present study aimed to investigate interactions of components in the high solids systems during storage. The systems included (i) lactose–maltodextrin (MD) with various dextrose equivalents at different mixing ratios, (ii) whey protein isolate (WPI)–oil [olive oil (OO) or sunflower oil (SO)] at 75:25 ratio, and (iii) WPI–oil– {glucose (G)–fructose (F) 1:1 syrup [70% (w/w) total solids]} at a component ratio of 45:15:40. Crystallization of lactose was delayed and increasingly inhibited with increasing MD contents and higher DE values (small molecular size or low molecular weight), although all systems showed similar glass transition temperatures at each aw. The water sorption isotherms of non-crystalline lactose and lactose–MD (0.11 to 0.76 aw) could be derived from the sum of sorbed water contents of individual amorphous components. The GAB equation was fitted to data of all non-crystalline systems. The protein–oil and protein–oil–sugar materials showed maximum protein oxidation and disulfide bonding at 2 weeks of storage at 20 and 40°C. The WPI–OO showed denaturation and preaggregation of proteins during storage at both temperatures. The presence of G–F in WPI–oil increased Tonset and Tpeak of protein aggregation, and oxidative damage of the protein during storage, especially in systems with a higher level of unsaturated fatty acids. Lipid oxidation and glycation products in the systems containing sugar promoted oxidation of proteins, increased changes in protein conformation and aggregation of proteins, and resulted in insolubility of solids or increased hydrophobicity concomitantly with hardening of structure, covalent crosslinking of proteins, and formation of stable polymerized solids, especially after storage at 40°C. We found protein hydration transitions preceding denaturation transitions in all high protein systems and also the glass transition of confined water in protein systems using dynamic mechanical analysis.

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Cloud services provide its users with flexible resource provisioning. But in the current market, a user has to choose from a limited set of configurations at a fixed price. This paper presents an autonomous negotiation system termed CloudNeg for negotiating cloud services. CloudNeg provides buyers and sellers of cloud services with autonomous agents to negotiate on the specifications of a cloud instance, including price, on their behalf. These agents elicit their buyers’ time preferences and use them in negotiations. Further, this paper presents two artifacts: a negotiation algorithm and a prototype which together form CloudNeg.

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BACKGROUND: The majority of total ankle arthroplasty (TAA) systems use extramedullary alignment guides for tibial component placement. However, at least 1 system offers intramedullary referencing. In total knee arthroplasty, studies suggest that tibial component placement is more accurate with intramedullary referencing. The purpose of this study was to compare the accuracy of extramedullary referencing with intramedullary referencing for tibial component placement in total ankle arthroplasty. METHODS: The coronal and sagittal tibial component alignment was evaluated on the postoperative weight-bearing anteroposterior (AP) and lateral radiographs of 236 consecutive fixed-bearing TAAs. Radiographs were measured blindly by 2 investigators. The postoperative alignment of the prosthesis was compared with the surgeon's intended alignment in both planes. The accuracy of tibial component alignment was compared between the extramedullary and intramedullary referencing techniques using unpaired t tests. Interrater and intrarater reliabilities were assessed with intraclass correlation coefficients (ICCs). RESULTS: Eighty-three tibial components placed with an extramedullary referencing technique were compared with 153 implants placed with an intramedullary referencing technique. The accuracy of the extramedullary referencing was within a mean of 1.5 ± 1.4 degrees and 4.1 ± 2.9 degrees in the coronal and sagittal planes, respectively. The accuracy of intramedullary referencing was within a mean of 1.4 ± 1.1 degrees and 2.5 ± 1.8 degrees in the coronal and sagittal planes, respectively. There was a significant difference (P < .001) between the 2 techniques with respect to the sagittal plane alignment. Interrater ICCs for coronal and sagittal alignment were high (0.81 and 0.94, respectively). Intrarater ICCs for coronal and sagittal alignment were high for both investigators. CONCLUSIONS: Initial sagittal plane tibial component alignment was notably more accurate when intramedullary referencing was used. Further studies are needed to determine the effect of this difference on clinical outcomes and long-term survivability of the implants. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

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To investigate the neural systems that contribute to the formation of complex, self-relevant emotional memories, dedicated fans of rival college basketball teams watched a competitive game while undergoing functional magnetic resonance imaging (fMRI). During a subsequent recognition memory task, participants were shown video clips depicting plays of the game, stemming either from previously-viewed game segments (targets) or from non-viewed portions of the same game (foils). After an old-new judgment, participants provided emotional valence and intensity ratings of the clips. A data driven approach was first used to decompose the fMRI signal acquired during free viewing of the game into spatially independent components. Correlations were then calculated between the identified components and post-scanning emotion ratings for successfully encoded targets. Two components were correlated with intensity ratings, including temporal lobe regions implicated in memory and emotional functions, such as the hippocampus and amygdala, as well as a midline fronto-cingulo-parietal network implicated in social cognition and self-relevant processing. These data were supported by a general linear model analysis, which revealed additional valence effects in fronto-striatal-insular regions when plays were divided into positive and negative events according to the fan's perspective. Overall, these findings contribute to our understanding of how emotional factors impact distributed neural systems to successfully encode dynamic, personally-relevant event sequences.

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Physarum polycephalum is a well-studied microbial eukaryote with unique experimental attributes relative to other experimental model organisms. It has a sophisticated life cycle with several distinct stages including amoebal, flagellated, and plasmodial cells. It is unusual in switching between open and closed mitosis according to specific life-cycle stages. Here we present the analysis of the genome of this enigmatic and important model organism and compare it with closely related species. The genome is littered with simple and complex repeats and the coding regions are frequently interrupted by introns with a mean size of 100 bases. Complemented with extensive transcriptome data, we define approximately 31,000 gene loci, providing unexpected insights into early eukaryote evolution. We describe extensive use of histidine kinase-based two-component systems and tyrosine kinase signaling, the presence of bacterial and plant type photoreceptors (phytochromes, cryptochrome, and phototropin) and of plant-type pentatricopeptide repeat proteins, as well as metabolic pathways, and a cell cycle control system typically found in more complex eukaryotes. Our analysis characterizes P. polycephalum as a prototypical eukaryote with features attributed to the last common ancestor of Amorphea, that is, the Amoebozoa and Opisthokonts. Specifically, the presence of tyrosine kinases in Acanthamoeba and Physarum as representatives of two distantly related subdivisions of Amoebozoa argues against the later emergence of tyrosine kinase signaling in the opisthokont lineage and also against the acquisition by horizontal gene transfer.

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The objective of this work is to present a new scheme for temperature-solute coupling in a solidification model, where the temperature and concentration fields simultaneously satisfy the macro-scale transport equations and, in the mushy region, meet the constraints imposed by the thermodynamics and the local scale processes. A step-by-step explanation of the macrosegregation algorithm, implemented in the finite volume unstructured mesh multi-physics modelling code PHYSICA, is initially presented and then the proposed scheme is validated against experimental results obtained by Krane for binary and a ternary alloys.

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Field-collected specimens of three species of Laminaria and three species of subtidal red algae (Delesseria sanguinea, Plocamium cartilagineum and Phyllophora pseudoceranoides) were exposed to natural summer sunlight on Helgoland (southern North Sea) for up to 4 h at 15 °C. Dark-adapted variable fluorescence (Fv : Fm) was measured immediately after these treatments, and following 6, 24 and 48 h of recovery in moderate irradiances of white light. The response of plants to the full spectrum of natural sunlight was compared with that to PAR alone, UV-A + visible, UV-A + UV-B, or UV-A alone. The Fv : Fm values of all species were reduced to minimal values after 4 h in all of these treatments, but those of the more resistant species (Laminaria spp. and P. pseudoceranoides) were higher after shorter exposures to UV radiation alone than to PAR with or without UV. The recovery of Fv : Fm in all species was also more rapid in the two treatments that contained UV radiation alone than in those that included PAR. These results suggest that it is the high irradiances of PAR in natural sunlight which are responsible for the photoinhibition of photosynthesis of subtidal seaweeds and that the current ambient irradiances of UV radiation (either UV-B or UV-A) in northern temperate latitudes would not contribute significantly to this photoinhibition.

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There is increasing evidence of an interaction between cholesterol dynamics and Alzheimer's disease (AD), and amyloid ß-peptide may play an important role in this interaction. Aß destabilizes brain membranes and this action of Aß may be dependent on the amount of membrane cholesterol. We tested this hypothesis by examining effects of Aß1-40 on the annular fluidity (i.e., lipid environment adjacent to proteins) and bulk fluidity of rat synaptic plasma membranes (SPM) of the cerebral cortex, cerebellum, and hippocampus using the fluorescent probe pyrene and energy transfer. Amounts of cholesterol and phospholipid of SPM from each brain region were determined. SPM of the cerebellum were significantly more fluid as compared with SPM of the cerebral cortex and hippocampus. Aß significantly increased (P 0.01) annular and bulk fluidity in SPM of cerebral cortex and hippocampus. In contrast, Aß had no effect on annular fluidity and bulk fluidity of SPM of cerebellum. The amounts of cholesterol in SPM of cerebral cortex and hippocampus were significantly higher (P 0.05) than amount of cholesterol in SPM of cerebellum. There was significantly less (P 0.05) total phospholipid in cerebellar SPM as compared with SPM of cerebral cortex. Neuronal membranes enriched in cholesterol may promote accumulation of Aß by hydrophobic interaction, and such an interpretation is consistent with recent studies showing that soluble Aß can act as a seed for fibrillogenesis in the presence of cholesterol.

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Despite progress in defining a pathogenic role for amyloid beta protein (Abeta) in Alzheimer's disease, orally bioavailable compounds that prevent its effects on hippocampal synaptic plasticity and cognitive function have not yet emerged. A particularly attractive therapeutic strategy is to selectively neutralize small, soluble Abeta oligomers that have recently been shown to mediate synaptic dysfunction. METHODS: Using electrophysiological, biochemical, and behavioral assays, we studied how scyllo-inositol (AZD-103; molecular weight, 180) neutralizes the acutely toxic effects of Abeta on synaptic function and memory recall. RESULTS: Scyllo-inositol, but not its stereoisomer, chiro-inositol, dose-dependently rescued long-term potentiation in mouse hippocampus from the inhibitory effects of soluble oligomers of cell-derived human Abeta. Cerebroventricular injection into rats of the soluble Abeta oligomers interfered with learned performance on a complex lever-pressing task, but administration of scyllo-inositol via the drinking water fully prevented oligomer-induced errors. INTERPRETATION: A small, orally available natural product penetrates into the brain in vivo to rescue the memory impairment produced by soluble Abeta oligomers through a mechanism that restores hippocampal synaptic plasticity.

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Synucleins are small proteins that are highly expressed in brain tissue and are localised at presynaptic terminals in neurons. alpha-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms of alpha-synuclein have been associated with autosomal-dominant Parkinson's Disease. A fragment of alpha-synuclein has also been identified as the non-Abeta component of Alzheimer's Disease amyloid. In this review we describe some structural properties of alpha-synuclein and the two mutant forms, as well as alpha-synuclein fragments, with particular emphasis on their ability to form beta-sheet on ageing and aggregate to form amyloid-like fibrils. Differences in the rates of aggregation and morphologies of the fibrils formed by alpha-synuclein and the two mutant proteins are highlighted. Interactions between alpha-synuclein and other proteins, especially those that are components of amyloid or Lewy bodies, are considered. The toxicity of alpha-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases.