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 tried to show the importance of Administrative Control being one of the important means in administrative work; they work on the review and audit work done and error handling explored in the work and prevent the occurrence and ascertain the extent of implementation of the planned targets, and therefore this is reflected in raising the efficiency of the performance of the tax examiner and complete the work as soon as possible and the highest efficiency and reduce the gaps that may occur between the parties of the tax settling accounts and dealt with in the theoretical side of the search to the research problem, namely with whether operating management oversight to improve the performance and increase the efficiency of t
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The Anticyclone Merge affects Iraq’s climate clearly through its impact on the different climatic elements. where it appears while they pass through special and distinctive weather . and most of this affection appears in temperatures, Therefore, this research study the relationship between the repetition and the survival period of the Anticyclone Merge and temperature average by using coefficient correlation (Pearson) that shows there’s strong inverse relationship between the integration of Anticyclones and temperatures average. &nbs
... Show MoreAll businesses seek to improve their levels of profits through various means, most notably their marketing channels, which ensure the delivery of their products to their customers in a safe manner in a timely manner. It considers losses to a minimum and that insurance companies place great interest in marine insurance losses because they often constitute huge amounts compared to other losses, hence the problem of research, which is centred on the type and size of the impact owned by the channel The Iraqi insurance company was chosen to be applied according to the intentional sample method because this company is closely related to the subject matter. The research has reached a set of conclusions, most notably that the choice of i
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Abstract
This study aims to identify the repercussions of the Corona pandemic (Covid 19) and its impact on the educational and psychological functions of the Omani family from the point of view of a number of fathers and mothers. Drive for a group of fathers and mothers, some of whom work in the government sector and others are mothers enrolled in graduate studies programs at the university, their ages range between (30-50 years) totally (28) mothers and fathers: 22 mothers and 6 fathers. The results showed that the repercussions of the transformation of e-learning, home quarantine, social distancing, and the challenges associated with them were among the most frequent responses that posed a real challenge to the
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Praise be to God, and may blessings and peace be upon the Messenger of God. As for:
The Noble Qur’an is the constitution of life, and a comprehensive educational approach that deals with individuals comprehensively, as it organizes worldly and eschatological life, and it is a curriculum concerned with organizing life starting with individuals and the family until the establishment of states, and from its comprehensiveness is reform, guidance and establishing boundaries. They have a disease in their hearts. They are exposed to this and are trying, by falsehood, to subjugate the Islamic world with man-made laws set by the West. Their aim is to distance people from
... Show MoreIFRS 17 aims to provide a unified basis for accounting for all types of insurance contracts, including reinsurance contracts, in a manner that benefits both investors and insurance companies and enhances the ability of the financial statements of insurance companies for comparison between companies listed in financial markets around the world. According to this standard, insurance contracts are accounted for on the basis of the Asset-Liability Approach and the use of fair values that the standard requires updating regularly in order to provide more useful information to the users of financial statements, as a result of the failure of reporting requirements for insurance contr
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Abstract
The current research aims to testing the impact of leadership styles (autocratic, democratic) in crises management (Making decision response, communications and information flows, Mobilization of resources) through strategic planning (Mission, objectives, and environmental analysis, and strategic choice) among managers of the Iraqi Ministry of electricity. Questionnaire has been adopted as a tool in data and information relating to research, as it had prepared on the basis of number of scales and finished using the included Likert quintet, which has been subjected to standards of validity and reliability and distributed to a sample consisting of (96) managers at the three departments of Min
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This research seeks to study the role of proactive leadership as an essential element that helps all federations that lead the wheel of sports, including the Iraqi Handball Federation, so that it builds a correct environment that helps manage the organizational errors that the Handball Federation may fall into, and this in turn helps in early detection of errors and obstacles that may occur. It is likely that the Federation will fall into the process of managing and organizing the Iraqi Handball League, in addition to increasing the clubs’ ability to assist the Iraqi Handball Federation by being proactive so as not to make mistakes. The research community included the administrative bodies of the clubs participating in the Iraqi E
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The service system has become a necessity of life in modern cities to be the most basic necessities of modern humans, they constitute a major base, which is based on the sustainability of life in the city and a standard measured through the degree of well-being and progress of civilized peoples and their interaction with the surrounding environment, making the services sector as a need not be an option, whenever the cities widened in population and space whenever provision of services and upgrading the quality and quantity more pressing, which made the subject of the services takes the biggest area of the trends and thinking of urban planners and those who in charge of drawing the cities policies. Consideri
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