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 need for an intellectual understanding of the context from many aspects' dictates understanding the ways through which the graphic designer walks in simulating the intent of the design process and elevating it to levels of communicative perception that leads to communicating the idea to the recipient, and it is thus a need closely related to the context, if it is historical. Culturally or socially, and between the mechanisms of selecting and operating the elements and units of the graphic and design achievement. On this basis, the role of context in graphic design can be studied.
The research included four chapters, the first chapter of the research problem and the need for it, and the aim of the research was (discovering the
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This study was carried out to measure the percentage of heavy metals pollution in the water of the Diyala river and to measure the percentage of contamination of these elements in the leafy vegetables grown on both sides of the Diyala river, which are irrigated by the contaminated river water (celery, radish, lepidium, green onions, beta vulgaris subsp, and malva). Laboratory analysis was achieved to measure the ratio of heavy element contamination (Pb, Fe, Ni, Cd, Zn and Cr) using flame atomic absorption spectrophotometer during the summer months of July and August for the year 2017. The study showed that the elements of zinc, chromium, nickel and cadmium were high concentrations and exceeded. The maximum concentration of these
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The research aims to study the role of e-government in enhancing institutional performance. The dimensions of e-government are: (support and commitment of senior management, technical structures, organization and human resources, knowledge and information, work procedures, attention to citizens' satisfaction, and client parties),while the dimensions of institutional performance are: (Service improvement, innovation, efficiency and effectiveness).
The research used electronic questionnaire as a main tool for data collection, The questionnaire included all the employees in the e-government project in Department of Government Coordinate and Citizen Affairs at the General Secretariat of the C
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This research discusses the developmental role of the social worker in providing care for children at risk. The research is desicriptive in nature include both the theoretical and field aspects. The theoretical aspect focuses on the characteristics and requirements of these children and what forms and implications are exposed to them by society, what is the developmental role of the social worker in the rehabilitation of this group. As for the field aspect, the study sample took a (40) social workers who working in Aiwa institutions inside Baghdad. A questionnaire of (14) questions was used as tool to collect the needed data.
لم تعد ظاهرة غسل الأموال ظاهرةً محلیة أو إقلیمیة، فكل دولة معرضة لهذه الظاهرة لانتأثیراتها تستهدف الإنسان أینما كان باستهدافها الأوضاع الاقتصادیة والمالیة والاجتماعیة وحتىالأخلاقیة، سواء على المستوى الوطني أم على المستوي الدولي، فضلاً عن استغلال الاندماج الحاصلفي أسواق المال الدولیة والتطور التقني في الأنظمة المالیة لنقل الأموال المراد غسلها وتحریكها إلى إيمكان في العالم، وهو ما
The intervention in the military institute represents a great role in the Nigerian
political life since 1960. There are many reasons behind this domination. The First is that
many African militants participated in liberating their countries from colonization. The
second is that they tried to stay in power as long as they could stay through the rule of one
party.
There fore, they depend on the process of political and economic reform to get rid of
military rule that dominated the Nigerian Political life to be a civilian state
Housing finance is considered to be an important and basic element in housing market, so it’s very important to aid individuals and particular institutions to built or buy new housing units.Inadequate finance system for housing is capable of supporting families to fulfill their needs and helping them to buy and built houses represented a big gap between the need to housing units and available stock. The most important finance institutions in Iraq nowa days are the Real Estate Bank and Housing Fund.Althoughthe role played byeach ofthese institutions, but thattheir roleis stilllimited in thehousing financeat the level ofindividuals orinstitutions. the adoption of the real estate Bank and housing fund to the amount allocated by th
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Characteristic of money laundering phenomenon is a compound and complex nature like the style of regular crimes . These operations are planned and excuted with those who have high quality experiences to hide the evidences of their deeds so They ask the help of financials ,economicals and legists to plan for money laundering. Banks are important and suitable places for illegal circulation of money because of the different types of accounts , rapidity and overlap which emphasis of its main duty to dislocate illegal money which comes from illegal sources without adding legal characteristic to it . Here we should explain the important role of banks in striving the phenomenon –Bank should try to show and analyze inward proced
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This research is a modest contribution to Put the finishing touches on therole of managerial leaders represented by static companies belonging to theministry of transport and communication/ [iraq] . the research has adopted thedescriptive. Analytical methodology and field study technique, using thequestionnaire as a tool for data collection [58] forms Nar, been distributed tothe research sample. The sample has been deliberately selected {generalmanager, as assistant general manager and heads of department}. Thequestionnaires and the main hypotheses of represented by the existence ofsignificant correlation and impact between successful managerial leadershipand crisis management using the software {SPSS}, were analyzed. Resultswere identic
... Show MoreThis research is an initial attempt to explore the reality of education and its concept in Islam, and to describe the presence of educational practices in the Arab-Islamic heritage. The importance of this research lies in addressing a set of important issues related to the contemporary Islamic educational system. The research revealed the extent of the need for authentic educational values that draw their reference from the origins of Islam, and it emphasized the analysis of the reality of education in the Islamic world and the identification of its problems and the finding of solutions through a quick and comprehensive look at the diverse contributions of Muslimthinkers to Islamic educational thought, and their active ro
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