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 imperative of achieving financial stability has transcended national boundaries, necessitating heightened attention from both researchers and policymakers. Consequently, this article delves into an examination of the impact of government debt and public debt on financial development within the context of Iraq. The study employs monetary policy, interest rate, inflation, and population growth as control variables to prognosticate financial development. Utilizing data extracted from the World Development Indicators (WDI) spanning the period from 1995 to 2022, the study employs the dynamic autoregressive distributed lag (DARDL) approach to scrutinize the associations under investigation. The findings underscore a negative association betwe
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Abstract
The research aims to identify the role played by the strategic mind of human resources managers in reducing the levels of strategic drift that can face the organization, as the problem of research to overlook the importance of this role in monitoring and follow-up all the changes that may face the organization during the implementation of its strategy, therefore highlights the importance Research in providing a set of solutions to the problems faced by the researched organization and as far as the research variables, the researchers have adopted the descriptive analytical approach in the applied side, as adopted the questionnaire as a main tool for data collection, which was prepared based on a number of ready me
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Background: Laparoscopic cholecystectomy (LC) has become the standard treatment for symptomatic cholelithiasis. Bile duct injury and accidental gallbladder perforation with spillage of bile and stone are common complications of LC. This study was carried out to assess the early complications of gallbladder perforation during LC, and identify the risk factor of that perforation.
Objectives: to evaluate the early complications which may occur after the perforation of the gallbladder during laparoscopic cholecystectomy and to determine the risk factors which are associated with the perforation of the gall bladder.
Subjects and methods: A prospective comparative study o
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The concept of insurance policy is one of the concepts that expresses a way to face the risks that a person is exposed to in the field of his life. It is a system that involves a prior agreement between two parties through which the risk is transferred from the second party (the insured) to the first party (the insurer) in return for paying an amount Calculated was able to cover the potential loss according to certain percentages agreed upon between the two parties, and that the main goal of any scientific analysis of the risk is to choose the most appropriate policy or method to confront it, by identifying the risks and ways to address them, and the main goal is to reduce losses and limit the possibility of their occurrence.
In
... Show MoreThe inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are heterogenous chronic inflammatory disorders of the gastrointestinal tract. The most widely accepted etiopathogenic hypothesis for these disorders suggests an immune mediated process.
Objective: This study was performed to evaluate the role of interleukine-33 in pathogenesis of inflammatory bowel disease and to correlate their levels with the disease activity and/or severity.
Methods: Fifty five subjects with inflammatory bowel disease (41 ulcerative colitis patients and 14 Crohn’s disease patients) their ages range from 16-65 years and 25 apparently healthy volunteers their ages and sexes were matched with the patients were participated i
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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A Forensic Accounting is represent science that deals with the application of knowledge in the areas of accounting, finance, tax and audit for the analysis, investigation, inquiry, inspection and testing issues in the civil law and criminal law in an attempt to reach the truth through which enable the Forensic Accountant to provide his Expert opinion , forensic accounting plays a major role by providing a range of important services in the field of investigation for fraud and litigation support, As one of the most important legal and accounting functions is to investigate allegations of alleged by the related parties, especially those allegations related to the existence of fraud, since the goal of judicial accountant will depend
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Agricultural development occupies an important position in the economies of developing countries, and its role is greater for the Arab countries. The first task is to provide food security for all the population through sustainable development, which includes the investment of available natural resources and employment opportunities for the rural population, As well as the provision of raw materials for agricultural processing in order to increase agricultural exports to reduce the balance of payments deficit. Sustainable development is linked to increased production and improvement, as well as to food security. On the one hand, it has to cope with the increase in population and if it is possible to achieve a surplus allocated for export, a
... 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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