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.
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Abstract
The issue of inequality in distribution of income and / or consumption expenditure is related to economic welfare because there is an inverse relationship between the economic welfare on the one hand, and the degree of inequality, on the other hand. Despite the fact that inequality is considered as normal phenomenon in every society, but if it exceeded certain limits it will lead to undesirable economic, social and political consequences. Therefore, the availability of indicators about inequality is a necessary tool for planning and evaluation of economic development programs. So, current study is aiming at measuring and analyzing the degree of inequality in distribution of consumpti
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In this work, a comparative analysis for the behavior and pattern of the variations of the IF2 and T Ionospheric indices was conducted for the minimum and maximum years of solar cycles 23 and 24. Also, the correlative relationship between the two ionospheric indices was examined for the seasonal periods spanning from August 1996 to November 2008 for solar cycle 23 and from December 2008 to November 2019 for solar cycle 24. Statistical calculations were performed to compare predicted values with observed values for the selected indices during the tested timeframes. The study's findings revealed that the behavior of the examined indices exhibited almost similar variations throughout the studied timeframe. The seasonal variations were
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This article discusses the change of values in urban family, because of various communication media and modern technologies as one of the most important factors affecting the changing family values in urban areas, this means becoming part of urban life. And focuses on the family in urban areas, for the privacy of the social, economic, demographic and cultural help to this effect, and because cities are the most friction and interaction with modern technologies.
This research attempts to evaluate the role of the information system by highlighting its importance in providing date and information to the tax administration the process of tax accounting for those who are subject to income tax whether they are individuals or companies where the effective information system provides accurate and reliable information in a timely manner.
At the theoretical part of the research, the research approaches the problem of the research represented in that whether the information system, applied in the General Commission for Taxes, is capable of achieving its role in reducing the phenomenon of tax evasion. The existence of a set of things which in the Commission may lead to increase tax evasion by taxpa
... Show MoreThere are certain dates in the history of nations that have their effects on them ,and the 25th of January 2011 is considered one of them in the history of the state of Egypt .Since this date Egypt has passed through many events that led to changes in the political life and its actors . New rolls has arisen for actors that didn't take part in the political life before so clearly ,like the military establishment which started to practice more prominent political roll, till it became the most important actor in the political life of Egypt .This establishment tried to institutionalize its roll through constitutional means ,considering that controlling the authority is the only alternative to safeguard the state which we are trying to study
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This study aims to study the inherited occupations which are considered to be a cultural, civilized and social legacy that effected by the Prevailing social and economic circumstances in the Iraqi society .
The study aimed to achieve several goals, including:
Identify the relationship between the urbanization and inherited occupations in the old city Al-Karkh.
Identify the relationship between the ecological construction and inherited occupations in the old city Al-Karkh.
Recognize the factors and motives inherited occupations in the study area .Identify the role of inherited occupations in promoting opportunities cohesion of the family system in the study area.
The field of the study had concentrated on a sample of famili
This study is concerned look at the role of satellite channels in the dissemination of
consumer culture that has become part of our everyday lives , which is a dangerous
phenomenon on society , so the study is aimed at introducing the concept of consumer culture
and the risks to individuals , which conducted a field study on a sample of students from the
University of Baghdad, as they represent an important category of the society they are a class
of young people to get to know the impact of satellite television on them through their various
programs and serials, films and ads may develop consumer culture they have , including in
respect of ideas and information , where the questionnaire was developed to ensure diffe
Massive multiple-input multiple-output (m-MIMO) is considered as an essential technique to meet the high data rate requirements of future sixth generation (6G) wireless communications networks. The vast majority of m-MIMO research has assumed that the channels are uncorrelated. However, this assumption seems highly idealistic. Therefore, this study investigates the m-MIMO performance when the channels are correlated and the base station employs different antenna array topologies, namely the uniform linear array (ULA) and uniform rectangular array (URA). In addition, this study develops analyses of the mean square error (MSE) and the regularized zero-forcing (RZF) precoder under imperfect channel state information (CSI) and a realist
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