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 emergence of satellite channels has led to fundamental changes in the supposed role of television, making it a center of culture and an important tributary to social upbringing and influencing the attitudes and values of individuals and in making public opinion regarding various issues, some television programs target ordinary people at home by virtue of the nature of their subjects, where there is a large audience of viewers, who consume and absorb what is offered to them from the cultural production of those satellite channels that play with the aspirations of groups of society to find metaphysical or magic solutions to their social problems or psychological delusions. The media, through its various messages, contributes to brin
... Show More
This researchable paper aims to focus of the role & mechanism of market makers in Iraqi stock market through analyzing its role in other Arabian as well as global stock ones, especially in current period through activate the use of bonds, shares, and trying to create a continued price balance. Then decreasing the opportunity having gaps between highest and lowest level without reasonable causes. In addition trying to deactivate the common decision without supported information. Moreover, this paper aims to explain the rules of increasing liquidity and having balance to lead the market into positive direction. Thus, for achieving the above-mentioned requirements, such conditions should be underlined by market makers as well as t
... Show More
Abstract
The various countries seek to encourage their local investments through the various policies they follow. The most important of these is the monetary policy, which is a means and procedures taken by the monetary authority to control the supply of money and maintain its stability of its financial impact on economic activity.
The effect of monetary policy is to stimulate domestic investment through money supply that is inversely related to the interest rate and a direct relationship with domestic investment. When money supply increases, interest rates fall and local investment growth rates rise, but when the rise in money supply is high, Inflationary measure
The arise of Islam as a multidimensional changing phenomenon with its own revolutionary and comprehensive character was inherent with a lot of alterations in social aspects , and this is explicit particularly in the scope of urban life and town planning . Essentially, Islamic style of life has its own urban identity. The urbanization process in Islam has been developed across two integrated sides, the first one concerned on ideational and theoretical aspects , while the other associated with practice .Many urban centers emerged during the Islamic era since the erection of Basrah , the first Islamic town in the middle of the 7th. centaury. Some contemporary urban concepts , both environmental and social could be noticed in Islamic
... Show MoreABSTRACT The importance and objectives of the study were an attempt to understand the methodology of disseminating radical thought and the reasons of social acceptability that make young people embrace this thought. It also sheds light on the impact of this phenomenon on the regional role of Egypt and examines the strategic means and standards that the Egyptian state focuses on in immunization and prevention of extremism.
Banking institutions are considered one of development foundations,and they also performe active role in supporting national economey and itsinstitutions. Banks became diversed in their activities that specialized Banksbecame one of the constituents of developing work in any activity, especiallyin investiment sector .In view of the importance of insurance sector and thenecessity of developing its divices and its working instituments, studyinginsurance Banking reality became a necessity, because insurance Companies inIraq are suffering of weakness in the level of insurance service, in addition tothe existence of a problem in the relationship between Banks network andinsurance industry.So this research aims to define insurance reality; the
... Show MoreAbstract
In light of the great technological development and the emergence of globalization has increased global competition, where it became competitive exercise pressure on all sectors. In light of this companies mast enviorment depend on the means that keeps them on the competitive position through access to information about competitors in order to help them to draw a strategy that will achieve a competitive edge either through excellence or reduce the costs of their products and this means intelligence competitive and reverse engineering that help to gain information on competitors analyze and put of the decision-maker From this point formed the idea of research in the statement of the role of
... Show More
It is not long time since globalization has started along with knowledge economy and, communication media and technical information control on the world. As a result serious events appeared like failure in businesses, financial corruption and shortage of administration and control.
In spite of the great efforts held by international organizations and foundations to find organizational frames that adopt independence, que
... Show MoreThis study focuses on how tax administrations in Iraq use Artificial Intelligence (AI) techniques to monitor tax evasion for individuals and companies to achieve Tax Compliance (TC). AI was measured through four dimensions: Advanced Data Analytics Techniques (ADAT), Explainable AI (EAI), Machine learning (ML), and Robotic Process Automation (RPA). At the same time, TC was measured through registration, accounting, and tax payment stages. We relied on the questionnaire form to measure the variables. A sample of employees in the General Tax Authority in Iraq was selected, and a questionnaire was distributed to 132 people. The results indicated that the dimensions of AI affect achieving TC at all stages. This study provides evidence of using A
... Show More