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.
To deduct the childhood status in Iraq, it was important manner to use statistical tools and approaches concerned with interpreting the causal relationships and their attitudes and use classification method for the important effects (variables) to draw an obvious picture of the phenomena under study in order to make it useful through investing, updating and improving it in by demographic studies in the future. Two statistical methods had been used in the field of analyzing data of multivariate analysis namely, Cluster Analysis and Factor Analysis.
The present study focuses on four fundamental axes .The nutrition axis, health axis, Educational axis, and the social axis. The study has ca
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After the internal audit as a tool of internal control in any organization, and helps in the evaluation of all internal control activities, as a tool to ensure compliance with the plans and policies to achieve the goals of the institution as much as possible of the efficiency, effectiveness, and should have the Internal Audit full independence and is linked to senior management, and aims to get the credibility and accuracy of information and data, and keep abreast of modern developments.
The practical side includes the preparation of the questionnaire, which included a set of questions that fit the hypothesis of the research, was Tozeiha the research sample consisting of employees of the Internal Audit Department an
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The Role of Japan in the Reconstruction of Iraq
This study aims to suggest a technique for soil properties improvement of AL- Kadhimin shrine Minaret and to support the foundation, which has a tilt of roughly 80 cm from the vertical axis. The shrine of the AL- Kadhimin is made up of four minarets with two domes set in a large courtyard. The four minarets have skewed to varying degrees due to uncontrolled dewatering inside the shrine in recent years. However, the northeast minaret was the most inclined due to its proximity to the well placed inside shrine courtyard. When the well near the minaret is operated, the water level drops, increasing the effective stresses of the soil and causing differential settling of the minaret foundation. To maintain the minaret's foundation from potenti
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Abstract
This study cares for the economic living conditions in Mosul City. Its importance lies in the critical period that has been covered
(2002-2007), which was dominated by far–reaching events at political economic and social levels. Among the main results that have been revealed are the following: the rate of economic growth in the City has been the lowest among major urban centers in Iraq. Besides, real income per capita in the City has stayed stagnant during the period of the study. However, the inequality in distribution of income has decreased. The main bulk of the city's population rely on their income from wages and salari
Abstract
Financing is one of the important pillars for activating and activating the agricultural sector, through which we can see an agricultural project on the ground. However, supplying the agricultural sector with financial resources requires a credit policy that is capable of making the right financing decision, because the financial resources are limited. The credit policy, and the financing decision, must be the best use not only to provide the necessary money, but to work to provide everything that would develop and activate the agricultural sector.
The transformation of the Agricultural Cooperative Bank of Iraq from specialized banking to the overall would lead to a decrease in the volume
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The construction project is a very complicated work by its nature and requires specialized knowledge to lead it to success. The construction project is complicated socially, technically and economically in its planning, management and implementation aspects due to the fact that it has many variables and multiple stakeholders in addition to being affected by the surrounding environment. Successful projects depend on three fundamental points which are cost-time, performance and specifications. The project stakeholder's objective to achieve best specifications and the cost-time frame stipulated in the contract.
The question is, was the optimum implementation accomplished? The provision for the success of the project
... Show MoreThe features of strategic thought transformation in Russia based on attempt confirm the Russian influenced on Region of Eastern Europe through series of common defense treaties and mutual security between USSR and another states this treaties emphasis size on direct Russian supervision on these states in addition, Russia in trusted to formation communism regimes in its vital space, Russia inherited the status of former USSR in political and economic levels.
Shortly we can see that Russia witnessed large Transformation in political strategic thought as a result of change in internal strategic environment and change of nature understanding which influenced on Russia. This
... Show MoreThe tourism activity is one of the pillars on which the economy of any country is based , the importance of the tourism sector is reflected in its potential to become an effective development alternative in many countries, especially Iraq ,this has a direct impact on the national economy as an important source in attracting hard currency and eliminating unemployment. Adding the Iraqi Marshlands to the list of effects makes it contribute to diversification of sources of income and stimulating rest of the economic sectors, the potentials and qualifications possessed by Iraq in the field of tourism and monuments have a significant impact on the state budget if they were exploited optimally. The research aims at identifying the contr
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To determine the relationship between hepatitis C virus infection and Diabetic mellitus type 2 , twenty patient's with diabetic mellitus type 2 aged (30-61) years old have been investigated from 01/11/2014 to 01/02/2015 and compared with fifteen parentally healthy individuals. All the studies groups were carried out to measure anti-HCV Abs by enzyme linked immunosorbent assay (ELISA), There was significant elevation (P≤0.05) in the HCV Abs compared with control groups .The percentage of HCV Abs was 15% and there was highly significant (P≤0.01) differences between studied group, while there was non-significant differences (P≥0.05) between patients groups according to age and gender compared with control groups. These results indicated
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