78 research outputs found

    Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease

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    Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer’s disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins. We correlate this with the use of an in silico analysis tool VisANT to elucidate possible pathways through which the involvement of Keratin 9 may take place. We identify possible links with Dickkopf-1, a negative regulator of the wnt pathway, and propose that the abnormal expression of Keratin 9 in AD blood and cerebrospinal fluid may be a result of blood brain barrier dysregulation and disruption of the ubiquitin proteasome system. Our findings suggest that dysregulated Keratin 9 expression is a consequence of AD pathology but, as it interacts with a broad range of proteins, it may have other, as yet uncharacterized, downstream effects which could contribute to AD onset and progression

    Analysis of protein carbonylation - pitfalls and promise in commonly used methods

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    Abstract Oxidation of proteins has received a lot of attention in the last decades due to the fact that they have been shown to accumulate and to be implicated in the progression and the patho-physiology of several diseases such as Alzheimer, coronary heart diseases, etc. This has also resulted in the fact that research scientist became more eager to be able to measure accurately the level of oxidized protein in biological materials, and to determine the precise site of the oxidative attack on the protein, in order to get insights into the molecular mechanisms involved in the progression of diseases. Several methods for measuring protein carbonylation have been implemented in different laboratories around the world. However, to date no methods prevail as the most accurate, reliable and robust. The present paper aims at giving an overview of the common methods used to determine protein carbonylation in biological material as well as to highlight the limitations and the potential. The ultimate goal is to give quick tips for a rapid decision making when a method has to be selected and taking into consideration the advantage and drawback of the methods

    Comparative study of the implementation of tin and titanium oxide nanoparticles as electrodes materials in Li-ion batteries

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    Transition metal oxides potentially present higher specific capacities than the current anodes based on carbon, providing an increasing energy density as compared to commercial Li-ion batteries. However, many parameters could influence the performance of the batteries, which depend on the processing of the electrode materials leading to different surface properties, sizes or crystalline phases. In this work a comparative study of tin and titanium oxide nanoparticles synthesized by different methods, undoped or Li doped, used as single components or in mixed ratio, or alternatively forming a composite with graphene oxide have been tested demonstrating an enhancement in capacity with Li doping and better cyclability for mixed phases and composite anodes

    Comprehensive Profiling of N‑Linked Glycosylation Sites in HeLa Cells Using Hydrazide Enrichment

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    The adenocarcinoma cell line HeLa serves as a model system for cancer research in general and cervical cancer in particular. In this study, hydrazide enrichment in combination with state-of-the art nanoLC−MS/MS analysis was used to profile N-linked glycosites in HeLa cells. N-Linked glycoproteins were selectively enriched in HeLa cells by the hydrazide capture method, which isolates all glycoproteins independent of their glycans. Nonglycosylated proteins were removed by extensive washing. N-Linked glycoproteins were identified with the specific NXT/S motif and deamidated asparagine (N). Deglycosylation was carried out in both H_2 (^16)O and H_2 ^(18)O to confirm the deamidation. NanoLC−MS/MS analysis indicated that the method selectively enriched at least 100 fold N-linked glycosites in HeLa cells. When both the membrane and cytosolic fractions were used, a total of 268 unique N-glycosylation sites were identified corresponding to 106 glycoproteins. Bioinformatic analysis revealed that most of the glycoproteins identified are known to have an impact on cancer and have been proposed as biomarkers

    Deep Phenotyping of Post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

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    Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention

    On the Design Flow of the Fractional-Order Analog Filters Between FPAA Implementation and Circuit Realization

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    This work explicitly states the design flows of the fractional-order analog filters used by researchers throughout the literature. Two main flows are studied: the FPAA implementation and the circuit realization. Partial-fraction expansion representation is used to prepare the approximated fractional-order response for implementation on FPAA. The generalization of the second-order active RC analog filters based on opamp from the integer-order domain to the fractional-order domain is presented. The generalization is studied from both mathematical and circuit realization points of view. It is found that the great benefit of the fractional-order domain is that it adds more degrees of freedom to the filter design process. Simulation and experimental results match the expected theoretical analysis

    Improvement of Chitosan Films Properties by Blending with Cellulose, Honey and Curcumin

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    Chitosan is a natural biopolymer that can be used in biomedical applications, tissue engineering, and wound dressing because of its biodegradability, biocompatibility, and antibacterial activity. The blending of chitosan films with natural biomaterials such as cellulose, honey, and curcumin was studied at different concentrations in order to improve their physical properties. Fourier transform infrared (FTIR) spectroscopy, mechanical tensile properties, X-ray diffraction (XRD), antibacterial effects, and scanning electron microscopy (SEM) were studied for all blended films. The XRD, FTIR, and mechanical results showed that films blended with curcumin were more rigid and compatible and had higher antibacterial effects than other blended films. In addition, XRD and SEM showed that blending chitosan films with curcumin decreases the crystallinity of the chitosan matrix compared to cellulose and honey blending films due to increased intermolecular hydrogen bonding, which reduces the close packing of the CS matrix

    Etude des proprietes rheologiques de melanges de poudres d'oxyde d'uranium

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    International audienceLe combustible nucléaire envisagé pour les réacteurs à neutrons rapides refroidis au sodium est constitué de pastilles céramiques fabriquées à partir d’UO2_2 et de PuO2_2, suivant un procédé de type métallurgie des poudres. Ce combustible est différent du combustible actuel des réacteurs à eau pressurisée. Il présente des caractéristiques spécifiques (géométrie, microstructure…) qui nécessitent un processus de fabrication adapté. En particulier, les propriétés rhéologiques de la poudre alimentant le poste de pressage doivent être appropriées pour un remplissage reproductible de moules de presse annulaires
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