The Role of the Deubiquitylase MYSM1 During Alphavirus Infection Amer Nubgan The members of the genus Alphavirus are positive-sense RNA viruses and it is one of two within the family Togaviridae. Most alphaviruses are predominantly transmitted to susceptible vertebrates by a mosquito vector. Alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly life threatening symptoms. Chikungunya virus (CHIKV) is the aetiological agent represents a substantial health burden to affected populations, with clinical symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. In recent years, CHIKV has received significant attention from public health authorities as a consequence of the dramatic emergence infections in the Indian Ocean islands and the Caribbean as well as the recent emergence of CHIKV in the Americas. Infections have also been reported around Europe such as in Italy, France and Greece. Currently, no safe, approved or effective vaccine or treatment exists for CHIKV infection. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates different kinds of cellular processes, which may be targeted by viruses to aid their replication within cells. In recent years it has been well established that both the forward reaction of ubiquitination, and the reverse reaction of deubiquitination are targeted during virus infection to enhance their replication, either by targeting of cellular proteins or encoding viral homologues of key pathway proteins. The reverse reaction is undertaken by a large family of enzymes termed deubiquitylases or DUBs, and many of these have been shown to play a crucial role, not only in virus replication but also in the regulation of the immune system and vesicle trafficking. The DUBs are attractive drug targets and have increasingly been implicated in cellular processes germane to malignancy which makes the continued characterisation of the role of DUBs during virus infection a worthwhile objective. In on-going experiments in the research group a DUB siRNA pools library screen identified 12 DUBs (USP1, USP4, USP5, USP34, USP45, USP46, OTUD6A, UCHL1, JOSD2, BRCC3 and MYSM1). Depletion of these hits in HeLa cells lead to an increase in cell viability following Semiliki Forest Virus (SFV) infection (and predicted to be pro-viral) and thus could potential be candidate antiviral targets. Inroads into understanding the role of the DUB hits during the alphavirus infection, focusing initial on the BSL2 model virus SFV, and extending this to CHIKV (at BSL3). In the present study, further screening focused on the deconvolution siRNA pools for the DUB hits. Investigation of the subsequent follow up experiments with one strong candidate DUB from this list, MYSM1. Two different approaches were taken. Firstly, the effect of depletion of MYSM1 by siRNA treatment was further investigated in HeLa cells. Secondly, the analysis was extended to investigate the role of MYSM1 in fibroblasts utilising MYSM1 genetic knockout murine embryo fibroblasts. Results from this study indicate that depletion of MYSM1 in HeLa cells by siRNAs resulted in a reduction in both SFV and CHIKV replication, as assayed by measuring RNA levels and plaque formation. It was also found that MYSM1 genetic knockout in MEF cells lead to increase in both SFV and CHIKV replication. In addition, depletion of MYSM1 by siRNAs in MRC-5 cells lead to increase in SFV replication. In conclusion, MYSM1 generated interesting data, implying a role during virus infection that appeared to depend on the cell type being infected. Up to now it is unclear what the effector mechanisms are that contribute to these observations, subject to further mechanistic and functional studies, may increase the options available for targeting this vital DUB during Alphavirus infections.
This contribution provides an atomistic understanding into the impact of W, Nb, and Mo co-substitution at Hf-site of cubic HfO2 lattice to produce Hf1−xTMxO2 system at x = 25%. The calculations have been performed under the framework of density functional theory supported by Habbured parameter (DFT+U). Structural analysis demonstrates that the recorded lattice constants is in good coherence with the previously published results. For the lattice parameters, contraction by 1.33% comparing with the host system has been reported. Furthermore, the doping effect of TM on the band gap leads to its reduction in the resulting Hf0.75TM0.25O2 configurations. The partial density of states (PDOS) indicate that hybridization through localized electroni
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The current research is summarized by studying and understanding the imagination and what resulted from it in postmodern arts, specifically Pop Art. The research was focused spatially (America) between the year 1950-1975 AD and it defined the research problem by asking about what factors and variables that established the social imagination in culture Al-Gharbia, which in turn crystallized the Western cultural product to appear in its form, which is historically called "pop art". Two studies were adopted in the second chapter. The first one was the cultural structure of the social imagination. The second topic was concerned with the stylistic diversity of pop art, and the third chapter included research and accreditation procedures. Ther
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The effect of air injection angle on the performance of airlift pump used for water pumping has been studied analytically and experimentally. An airlift pump of dimensions 42mm diameter and 2200 mm length with conventional and modified air injection device was considered. A modification on conventional injection device (normal air-jacket type) was carried out by changing injection angle from 90 (for conventional) to 45 and 22.5 (for modified). Continuity and one-dimensional momentum balance for the flow field with basic principle of two-phase flow and expressions of slip ratio and friction factor as function of flow rates were formulated. The analytical and experimental investigations were carried out f
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THE PROBLEM OF TRANSLATING METAPHOR IN AN ARTISTIC TEXT (ON THE MATERIAL OF RUSSIAN AND ARABIC LANGUAGES)
In this research we present An idea of setting up same split plots experiments in many locations and many periods by Latin Square Design. This cases represents a modest contribution in area of design and analysis of experiments. we had written (theoretically) the general plans, the mathematical models for these experiments, and finding the derivations of EMS for each component (source) of sources of variation of the analysis of variance tables which uses for the statistical analysis for these expirements
Toxoplasma gondii is a unique intracellular parasite, which infect a large proportion of the world population, but uncommonly causes clinically significant disease. The present study was performed to estimate the prevalence of toxoplasmosis in 400 apparently healthy blood donor males, their ages were between 18 and 57 years using enzyme linked immunosorbent assay, and to examine the effects of infection on total testosterone, free testosterone and follicle stimulating hormone (FSH) levels in their sera. Seroprevalence showed 10 (2.5 %) and 121 (30 %) of them had IgM and IgG antibodies respectively. Both acute and chronic toxoplasmosis in males recorded higher significant (P < 0.05) mean concentration for total and free testosterone hormone,
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When sites of new communication occurs which represents the merit of the development of communication technology which is characterized by the services of ( facebook-twiter-corapora-youtube-mass space-friendster-flicker-willnecked in addition to the direct services for viber-whatsup-telgram-and chat on) play important role in changing the infrastructure of Arabic societies which are consideredas closed and not changeable societies during near period and the significance of this study comes from the importounce of this subject which is considered as anew trend of the age on the field of media and public response and acceptance inspite of what is known about Arabic society-it doesn’t accept change-this occurance is associated with terms
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The assessment of a river water’ quality is an essential procedure of monitor programs and is used to collect basic environmental data. The management of integrated water resources in a sustainable method is also necessary to allow future generations to meet their water needs. The main objective of this research is to assess the effect of the Diyala River on Tigris River water quality using Geographic Information System (GIS) technique. Water samples have been collected monthly from November 2017 to April 2018 from four selected locations in Tigris and Diyala Rivers using the grab sampling method. Fourteen parameters were studied which are Turbidity, pH, Dissolved Oxygen, Biological Oxygen Demand, Electrical Conductivi
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