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 purpose of this research is to study the organic planning in the United Industry Alliance, focusing on an applied model. It takes the concept of good planning, and its importance in the overall picture, well into political, economic, and military policy. It also analyzes how the United States has used this year to address the challenges that nationalism targets. The research draws on typical examples to illustrate the differences between researcher and decision effectiveness. It also discusses the factors that lead to the success or failure of dynamic planning, and draws lessons from it in other countries. Finally, the researcher begins to help in planning the goal as a basic tool in enhancing effectiveness.
The research sheds light on an important religious sect that played a fundamental role in the structure of the Iraqi society in general and the Baghdadi society in particular, in which the Jews in general and the Jewish women in particular played an active role in the culture and heritage of Baghdadi society. The educational, cultural and artistic activity of Jewish literacy is a model for study.
The research addresses smart city concept as it is the latest urban design trends, by the investment of the capabilities of human, and artificial intelligence for the sake of the advancement of the city. The concept of a smart city is described as one of the most important manifestations of the information revolution, with the end of the twentieth, and the beginning of twenty – first century, The research attributes the emergence of the concept to: deficiencies of means, and traditional methods in building and development of cities, as well as The significant increase in the number of city and global metropolises dwellers. So, smart city approach has been adopted, along with innovative principles and methods which cons
... Show MoreThe research aims to measure the impact of knowledge management processes individually and in total in the innovative marketing.
We depart search of a problem expressed in a number of intellectual and practical questions, the application of this research in the General Company for Vegetable Oil Industry, represented composed a sample of (63) (Director General and Deputy Director General and Director of the Department and the Division) in the company researched, it has been designed measuring instrument to collect the necessary data either statistical means they are the percentage and the arithmetic mean and standard deviation and coefficient of variation and the coefficient of simple correlation and model
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Ajloun reserve is the most important reserved areas set up by the Jordanian government to encourage development and ecotourism, is located on the green mountains of Ajloun north of Jordan, was founded in 1989 and follow The Royal Society for the conservation of the natur, an area of 13 km2, and covered with thick forests of oak trees and Butm, maple and others, characterized by the diversity of vital consists of 319 species of medicinal and aromatic plants and wild flowers, and where there are 40 species of birds, 14 species of mammals, 16 reptiles, 5 species of plants registered in the world. The Reserve has a great importance in Jordan ,it is the most reservations attractive to tourists, both internally and externally, and prov
... Show MoreThe Egyptian labor movement is the oldest trade union movement in the Arab region. Beside, the labor movement in any society is, in fact, only a reflection of the extent of awareness of that class in that society. Such a comparison is based on the degree of social growth the working class has reached. Moreover, the Egyptian working class was characterized by modernity in its inception compared to other social forces and classes. In addition, its development is linked to the level of industrial development of the country. The peasants and craftsmen were the mainstay of production in the Egyptian society over several centuries. The labor union movement also represents the human aspect of the labor force when it encounters and interacts wit
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The idea of this research is the basis of the role exercised by the dimensions of performance management (Performance Planning- performance evaluation- improve the performance and development- feedback - Review and Performance Monitor) In order to achieve the success Organizational Is through the (strategic vision- the operational activity- development of the company- selection of personnel- the company's culture- Leadership and Management- Personal Development - Assessment and Review).And The research aims to identify the extent of the responsibility of performance management in achieving success Organizational through main hypotheses branched out by the sub-hypotheses to knowing out the&nbs
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In order to specify the features of higher education process and its quantitative and qualitative development in Iraq ; one should look back at its historical process and the need of interesting with it .
Accordingly , there will be a chance for verifying the demand of the Iraqi society according to the political , social , and cultural changes especially during the national governance (1932 – 1958 ) .
For depicting the most important quantitative and qualitative development of this kind of education the period of 1932 -1958 , and since there is no previous study that tackled this topic , here comes the need of writing this paper .
After historical
... Show MoreThe purpose of this study was to evaluate the anesthetic effectiveness of a buccal infiltration technique combined with local massage (using 2% lidocaine) in the extraction of mandibular premolars to be utilized as an alternative to the conventional inferior alveolar nerve block.
Patients eligible included any subject with a clinical indication for tooth extraction of the mandibular 1st or 2nd premolars. All patients were anesthetized buccally by local infiltration technique followed by an external pressure applied for 1 min directly over the injection area. In each case, another local
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