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.
The research aims to test the correlation relationships between wise leadership, and the business model, and to demonstrate its influence (wise leadership) on the business model. Therefore, two main hypotheses were put forward. The research was applied to a sample consisting of (87) managers and deputy managers, some of them are members on the board of directors of the researched company. The questionnaire was adopted as a basic tool for collecting data, in addition to personal interviews. A number of statistical methods were used to analyze the data and obtain results. The researcher showed a set of results, including: There is a significant correlation between wise leadership and business model. There is an influence of wise leadership on
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The present study was designed to indicate the influence of the feeding plate on the nutritional and general health problems of the isolated cleft palate infants. For this study fourteen infants were taken, their ages between one day to one week, refered from cosmetic surgery and palate center to cleft lip and palate rehabilitation center in institute of technical medical / Baghdad for feeding plate purpose . Four infants put them as normal group; all those infants were subjected during (6th) month to evaluate the body weight, feeding problem and the respiratory infection. According to tables and figures this study showed a gradual improvement in nutritional problem including (feeding problem, body weight) and health problem (such as respir
... Show Moreالغرض من البحث دراسة تأثير ادارة المعرفة (استراتيجية الشخصنة والترميز) في تحقيق التفوق الاستراتيجي في بيئة المصارف الاهلية العراقية ، وتم اعتماد منهج البحث الوصفي والتحليلي ، لذا اعتمد الباحث الفلسفة الوضعية وفق المنهج الاستنباطي لغرض اشتقاق فرضية البحث الاولى من الجانب النظري وتوصل البحث الى مجموعة من النتائج اهمها ان استراتيجية الشخصنة حققت تقدماً كبيراً في قدرتها على التأثير في التفوق الاستراتيجي بوصف
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The Voluntary Obedience has great importance for the modern taxes systems and its management and this is meant the taxpayer whom in charge to pay of his taxes obligations voluntarily , he is very known of himself whereas he prepared his finishing accountings and present them as samples prepared by taxes management and settle the tax sum directly according to specified income , which has an impact to find end to tax evasion as result lead to increase the tax income and achieve the justice for the taxpayer and the state treasury
At different stages of the evolution of the modern Iraqi state ears last century did not receive the industrial sectors importance in great domestic production (GDP) and that the limited resources available in the initial stage and the dominance of public sector industry in the late stage , so the continued decline in the contribution of the private industrial sector in GDP , and this is why imbalance in the labor market and reduced demand for manpower in this sector despite the high rates of labor supply and the various skills and levels of investments, their human and the different geographical distribution , and direction of labor to other economic sectors most requested of the l
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The purpose of the research is to study the impact of knowledge management (personalization and coding strategy) in achieving strategic excellence in the environment of Iraqi private banks, and the descriptive and analytical research approach has been adopted, so the researcher adopted positive philosophy according to the deductive approach for the purpose of deriving the first research hypothesis from the theoretical side and the research reached a group of The most important results are that the personalization strategy has made great progress in its ability to influence strategic superiority as a responsive variable, as the civil bank departments were successful in employing the changes that occurred in the personalization str
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Moisture-induced damage is a serious problem that severely impairs asphaltic pavement and affects road serviceability. This study examined numerous variables in asphalt concrete mixtures to assess their impact on moisture damage resistance. Mix design parameters such as the asphalt content (AC) and aggregate passing sieve No. 4 (PNo. 4) were considered as variables during this study. Additionally, hydrated lime (HL) was utilized as a partial substitute for limestone dust (LS) filler at 1.5% by weight of the aggregate in asphalt concrete mixtures for the surface layer. This study also investigated the potential enhancement of traditional asphalt binders and mixtures by adding nano-additives, specifically nano-silica oxide (NS) and na
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