148 research outputs found

    Novel phylogenetic algorithm to monitor human tropism in Egyptian H5N1-HPAIV reveals evolution toward efficient human-to-human transmission

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    Years of endemic infections with highly pathogenic avian influenza (HPAI) A subtype H5N1 virus in poultry and high numbers of infections in humans provide ample opportunity in Egypt for H5N1-HPAIV to develop pandemic potential. In an effort to better understand the viral determinants that facilitate human infections of the Egyptian H5N1-HPAIVvirus, we developed a new phylogenetic algorithm based on a new distance measure derived from the informational spectrum method (ISM). This new approach, which describes functional aspects of the evolution of the hemagglutinin subunit 1 (HA1), revealed a growing group G2 of H5N1-HPAIV in Egypt after 2009 that acquired new informational spectrum (IS) properties suggestive of an increased human tropism and pandemic potential. While in 2006 all viruses in Egypt belonged to the G1 group, by 2011 these viruses were virtually replaced by G2 viruses. All of the G2 viruses displayed four characteristic mutations (D43N, S120(D,N), (S,L)129Δ and I151T), three of which were previously reported to increase binding to the human receptor. Already in 2006–2008 G2 viruses were significantly (p<0.02) more often found in humans than expected from their overall prevalence and this further increased in 2009–2011 (p<0.007). Our approach also identified viruses that acquired additional mutations that we predict to further enhance their human tropism. The extensive evolution of Egyptian H5N1-HPAIV towards a preferential human tropism underlines an urgent need to closely monitor these viruses with respect to molecular determinants of virulence

    Towards a Numerical Procedure for Composite Slab Assessment

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    Composite slab design relies upon adequate shear bond resistance between the steel and concrete. This is achieved by friction between the materials and the mechanical interlock of embossments pressed in the steel. The behaviour of this shear bond resistance is complex and is obtainable only from model tests. This paper explores the potential for numerical modelling to provide the required design information

    Značaj atestiranja uređaja za aplikaciju sredstava za zaštitu bilja

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    In Serbia, since 1999, the Law on providing services in the field of plant protection which regulates mandatory inspection of sprayers and mist blowers in use. Plant protection law is to regulate the field of pesticide application. Pass laws are harmonized with the EU directive 91/414/EEC, and shall also include the article on mandatory inspection of sprayers and mist blowers. The main aim of the work is to inform and prepare the machines for users of plant protection products and control of the equipment and devices to pass the required control of technical accuracy of machines. The ways are given, organization and the results of mandatory inspection of sprayers in the developed European countriesU Srbiji od 1999 godine Zakonom o pružanju usluga u oblasti zaštite bilja predviđa se obavezna provera prskalica i orošivača kao i Zakonom o zaštiti bilja oblast primene pesticida se detaljnije reguliše. Doneti zakoni su usklađeni sa EU 91/414EEZ, i odnose se na obaveznu kontrolu prskalica i orošivača. Cilj rada je da informiše i pripremi korisnike mašina za zaštitu bilja, na obaveznu kontrolu tehničke ispravnosti. Navedeni su načini organizacije i neki rezultati obaveznog pregleda prskalica u razvijenim evropskim zemljama

    Cyclic Voltammetric Determination of Antioxidant Capacity of Cocoa Powder, Dark Chocolate and Milk Chocolate Samples: Correlation with Spectrophotometric Assays and Individual Phenolic Compounds

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    Phenolic antioxidants in cocoa powder, dark chocolate and milk chocolate samples are quantified electrochemically using cyclic voltammetry with a glassy carbon electrode. Cyclic voltammograms were recorded from 0 to 800 mV at a scan rate of 100 mV/s. Phenolics with an ortho-diphenol group show the first oxidation peak in the potential range between 370 and 460 mV (vs. Ag/AgCl) in 0.1 mol/L of the acetate buffer, pH=4. The first and third anodic current peaks, close to 670 mV, can be ascribed to the first and second oxidation of the catechin-type flavonoids that are present at a high concentration in samples. The second peak at around 560 mV can be ascribed to phenolic acids. Procyanidins B1, B2, B3 and B4 did not have any visible waves. Strong positive correlation was established between antioxidant activities deduced from cyclic voltammograms with those determined using spectrophotometric assays. HPLC method was used for the quantification of individual phenolic compounds

    Modulation of CP2 Family Transcriptional Activity by CRTR-1 and Sumoylation

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    CRTR-1 is a member of the CP2 family of transcription factors. Unlike other members of the family which are widely expressed, CRTR-1 expression shows specific spatio-temporal regulation. Gene targeting demonstrates that CRTR-1 plays a central role in the maturation and function of the salivary glands and the kidney. CRTR-1 has also recently been identified as a component of the complex transcriptional network that maintains pluripotency in embryonic stem (ES) cells. CRTR-1 was previously shown to be a repressor of transcription. We examine the activity of CRTR-1 in ES and other cells and show that CRTR-1 is generally an activator of transcription and that it modulates the activity of other family members, CP2, NF2d9 and altNF2d9, in a cell specific manner. We also demonstrate that CRTR-1 activity is regulated by sumoylation at a single major site, residue K30. These findings imply that functional redundancy with other family members may mask important roles for CRTR-1 in other tissues, including the blastocyst stage embryo and embryonic stem cells

    Endocytosis of plasma-derived factor V by megakaryocytes occurs via a clathrin-dependent, specific membrane binding event

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    Megakaryocytes were analyzed for their ability to endocytose factor V to define the cellular mechanisms regulating this process. In contrast to fibrinogen, factor V was endocytosed by megakaryocytes derived from CD34 + cells or megakaryocyte-like cell lines, but not by platelets. CD41 + ex vivo -derived megakaryocytes endocytosed factor V, as did subpopulations of the megakaryocyte-like cells MEG-01, and CMK. Similar observations were made for fibrinogen. Phorbol diester-induced megakaryocytic differentiation of the cell lines resulted in a substantial increase in endocytosis of both proteins as compared to untreated cells that did not merely reflect their disparate plasma concentrations. Factor IX, which does not associate with platelets or megakaryocytes, was not endocytosed by any of the cells examined. Endocytosis of factor V by megakaryocytes proceeds through a specific and independent mechanism as CHRF-288 cells endocytosed fibrinogen but not factor V, and the presence of other plasma proteins had no effect on the endocytosis of factor V by MEG-01 cells. Furthermore, as the endocytosis of factor V was also demonstrated to occur through a clathrin-dependent mechanism, these combined data demonstrate that endocytosis of factor V by megakaryocytes occurs via a specific, independent, and most probably receptor-mediated, event.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75473/1/j.1538-7836.2005.01190.x.pd

    Impact of DNA methylation on trophoblast function

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    The influence of epigenetics is evident in many fields of medicine today. This is also true in placentology, where versatile epigenetic mechanisms that regulate expression of genes have shown to have important influence on trophoblast implantation and placentation. Such gene regulation can be established in different ways and on different molecular levels, the most common being the DNA methylation. DNA methylation has been shown today as an important predictive component in assessing clinical prognosis of certain malignant tumors; in addition, it opens up new possibilities for non-invasive prenatal diagnosis utilizing cell-free fetal DNA methods. By using a well known demethylating agent 5-azacytidine in pregnant rat model, we have been able to change gene expression and, consequently, the processes of trophoblast differentiation and placental development. In this review, we describe how changes in gene methylation effect trophoblast development and placentation and offer our perspective on use of trophoblast epigenetic research for better understanding of not only placenta development but cancer cell growth and invasion as well
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