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 researcher seeks to know the extent of applying the concept of design by Iraqi electronic press sites to provide media product with the acceptance of their browsers and ensure their repeated visits to such sites in the framework of the guiding rules for laser browsing. The researcher uses analytical study on a sample of six Iraqi electronic newspaper sites to identify the general features of their design and the methods of distribution of the structural elements of the pages. The researcher also conducts a field study on a sample of the surfers of electronic newspaper sites to see the extent of their evaluation to their design and the degree of their satisfaction.
Smart cities are using innovative technological solutions to improve the quality of life and service that citizens and visitors receive. Defined as a digital or ecological city, its services depend on information and communication technology infrastructure, such as intelligent automated traffic systems, advanced security management Services, building systems, and the use of automation in offices and homes. The global trend now towards smart cities, sustainable and green cities and other cities, with different nomenclature, the common denominator is the comfort of the individual and the preservation of natural resources. Adopting smart, sustainable, green, or healthy cities is either t
Disabled people are among the most important groups that need attention, care, and financial and moral care. They cannot fulfill the requirement of life normally without care from a person to meet their special needs. The disability is either mental or physical. The Iraqi government has paid attention to this category by adopting a law for this category, represented by Law No. (38) for the year (2013), which keeps their rights and duties in Iraqi society by establishing institution of persons with disabilities and special needs of the Ministry of Labor and Social Affairs to create a modern society politically, socially, culturally or economically. In view of the importance of this group in society, the media reinforces the communit
... Show MoreThe purpose of this study is to assess the performance of government units (Iraqi hospitals) by trying to determine the possibility of the current governmental accounting system to provide information on the performance reports of government units. In order to improve the efficiency of hospital resources management, the services provided by the hospital should be subject to performance measurement and evaluation The importance of the health sector in the provision of services, in order to raise the efficiency of the performance of services provided by government units has reached the researcher a set of conclusions, the most important
- The financial reports produced by the accounting s
After the information revolution that occurred in the Western world, and the developments in all fields, especially in the field of education and e-learning, from an integrated system based on the effective employment of information and communication technology in the teaching and learning processes through an environment rich in computer and Internet applications, the community and the learner were able to access information sources and learning at any time and place, in a way that achieves mutual interaction between the elements of the system and the surrounding environment. After the occurrence of the phenomenon of Covid 19, it led to a major interruption in all educational systems that had never happened before, and the disrupt
... Show MoreThis research sought to detect the level of organizational culture prevailing in the Integrity Commission as well as the level of the organizational citizenship behavior of staff of the Commission and the impact of organizational culture in these behaviors. To achieve the objectives of the research and test the validity of hypotheses have been used questionnaire derived from measurements ready modern researchers foreigners have been adapted to suit the Iraqi environment, have been distributed (189) questionnaire on the number of employees from the Integrity Commission, which represented the research sample where the research community has a number is (1365) employees in the Baghdad was the use of a number of statistical met
... Show MoreThe current research seeks to identify the role of the marketing intelligence system in its dimensions (customer intelligence, market intelligence, competitor intelligence, insurance product intelligence, sales representatives) and its reflection on improving the quality of the insurance service provided by the National Insurance Company represented in its dimensions (reliability, response, tangibility, Safety, the spirit of empathy, communication) adopted in the current research, and based on that, the research came as an attempt to find out the extent to which the research sample company can apply the approach of the marketing intelligence system and its impact on improving the quality of the insurance service provided to custo
... Show MoreThe current research aims to verify the role of strategic intelligence as an explanatory variable in organizational success as a respondent variable in the colleges of the University of Fallujah, the research community. (Dean, Associate Dean, Section Head, Division Officer, Unit Officer), The researcher used the questionnaire as the main tool to collect data that included (50) items, in addition to using personal interviews and field observations as aids in data collection. The researcher relied on statistical programs (SPSS V.25; Excel V (16) In the treatment and analysis of data through the use of the most appropriate statistical methods (arithmetic mean, standard deviation, difference coefficient, determinatio
... Show MoreThe research aims at a statement Internal Debt options during shocks and the impact of this borrowing in the volume of the foreign reserve, using induction and deduction with available data analysis. During the period (2004-2013) did not require the use of borrowing across (financial institutions, discounted transfers, bonds); it was only sufficient by transfer with commercial banks that can finance of temporary budget deficits: rose and decline of volume of foreign reserve according to the changes of oil prices and the volume of purchases and sales of the Central Bank of Iraq. Central Bank of Iraq (CBI) has significantly contributed to Internal Debt through bond and discounted transfers in the secondary market; thus, funding the
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