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.
Organizations nowadays, whether public or private organizations, productive or service (such as banks), face major challenges as a result of rapid and continuous changes, and in front of these challenges traditional management operations and tools become unable to make the organization able to work, which makes it imperative for these organizations to follow the methods and management practices, including the proposed knowledge risk management and strategic direction so that it can elevate its actions at the level of developments in reality, in the sense that these organizations and in the light of environmental developments to characterize their strategic direction as an intellectual approach characterized by mo
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This study is designed to detect the level of cytokine IFN-γ concentration, and some antioxidants, including super oxide dismutase (SOD) and Vitamin C, and to estimate the level of sex hormones (FSH and LH), and to determine auto-antibodies (antiphospholipid antibodies (APA) IgG\IgM, and anticardiolipin antibodies (ACA) IgG\IgM) and to estimate the blood parameters in 51 miscarriage women infected with T.gondii distributed depending on the type of antibodies. Additionally, 39 volunteers non-infected with T.gondii included (19 miscarriage women, 10 pregnant women and 10 non-pregnant women). ELISA and spectrophotometer method were used in this study. The results of IFN-γ showed a significant increase)p<0.05) in the l
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Biomarkers such as Interleukin-6 (IL-6), Procalcitonin (PCT), C-reactive protein (CRP) and Neutrophil-Lymphocyte Ratio (NLR) have a role in the pathogenesis of severe coronavirus disease 2019 (COVID-19). The aim of this study was to explore the differences between serum levels of such biomarkers in severe and non-severe COVID-19 cases and compare them with normal people and to evaluate the sociodemographic variables and chronic diseases effect on the severity of COVID-19. The study included 160 subjects, divided into two groups, a case group of 80 patients, and a control group of 80 normal persons. The case group was divided into two subgroups: 40 severe COVID-19 patients and 40 patients with non-severe disease. Blood IL-6 was asses
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The research aims to identify the most important concerns that led to the increase of interest in the topic of corporate governance and specifically highlighting the role of the audit committees of the Administration Board in reducing the risk of the auditor and the rationalization of professional judgments، in particular about accepting the assignment and setting the fees of the audit process by extrapolating global experience in this area ، and a field study is conducted for a sample of private Iraqi banks to evaluate the role of audit committees constituted currently per with bank law no. (94) of 2004 and to be acknowledged with actual performance of these committees and their role in recommending the n
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Each of the countries that make up the international community and active in international and regional relations has specific elements and tools. Their roles differ according to those components and tools. There are countries that play an effective and effective international role, while others play an effective and effective regional role. The international or regional role in order to be effective and influential must be based on a set of conditions that will give it a degree of credibility and achieve the objectives of the role. The state affects the decisions of other countries because of its ability, and the ability of the state to influence is not limited to military power only, but political, economic, demographic, technical, geo
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This study aims to analyze the messages of a number of global news outlets on Twitter. In order to clarify the news outlets tactics of reporting, the subjects and focus during the crisis related to the spread of the Covid-19 virus. The study sample was chosen in a deliberate manner to provide descriptive results. Three news sites were selected: two of the most followed, professional and famous international news sites: New York Times and the Guardian, and one Arab news site: Al-Arabiya channel.
A total of 18,085 tweets were analyzed for the three accounts during the period from (1/3/2020) to (8/4/2020). A content analysis form was used to analyze the content of the news coverage. The results indicate an increase in th
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Background: Ruptured posterior communicating artery (PCoA) aneurysms are common; they usually present with subarachnoid haemorrhage (SAH) and oculomotor nerve palsy. The aneurysmal dome projection may influence the safety access and aneurysmal neck clipping. Here, we discuss additional intraoperative steps that may be required to widen the surgical field to ensure safe surgical clipping of a rupture pure posteriorly directed PCoA aneurysm. Case description: A previously healthy 38-year-old male reported sudden severe headache and disturbed level of consciousness with a Glasgow coma scale (GCS) of 13. His initial computed tomography (CT) scan of the head showed SAH in the basal cistern. 3D-constructed CT angiography (CTA) revealed a
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There is no doubt that Agricultural Policy is the main responsible for the degrading in Agricultural sector in Iraq during the period 2003-2013, and that was very clear from magnitude of indicators because of little sharing of each of agricultural product in GDP because it was (9.38%) in average during the study period and the annual changing of it was negative (-5.82%), and there is increasing in deficit of trade balance in Agriculture during the study period about (4185.73) million US$, and the percentage of agricultural exports from total exports was (0.14%) in average only. The foreign trade policy in Agricultural products also cannot determine map of Revealed Comparative Advantage (RCA) of Agricultural products and crops. The study sh
... Show MoreObjectives: To assess nurses-midwives' knowledge about pain management during labor before and after implementation of educational program and to determine the effectiveness of educational program on nurses-midwives' knowledge about pain management during labor in Baghdad Maternity Hospitals.
Methodology: A quasi-experimental design has been conducted during the period of (February 27th 2019 through 2nd June 2019) on non-probability sample (purposive) consists of (44 Nurses/midwives') who are work in delivery room, the sample was exposed to pretest, educational program, posttest. The study was conducted in three Directories, (Baghdad Teaching Hospital) at medical city health
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