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.
This research seeks to study the role of military bases in activating defense diplomacy, with a focus on studying the case of France in the African continent, which relied on its military bases as a tool to implement its foreign policy. The research explains the concept of defense diplomacy and its relationship to military bases as an effective tool to strengthening bilateral relations between the state's parties. The research focuses on studying the effectiveness of military bases as a tool for activating French defense diplomacy, and studying the goals that French foreign policy seeks to achieve through its intervention or presence in the African continent. In addition to the geopolitical reasons that prompted France to move to
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The process of employing modern technology in a consistent manner is what the researcher is interested in, and the psychological role of the sound effect in enhancing psychopathic representations in cinematic characters, which had a wide resonance in the field of cinematic films, and after the predominance of digital technology in the production of contemporary films, the sound effect has a higher efficiency And a good level of advanced aesthetic and dramatic expression in film employment, so many directors resorted to this type of films by using various new and advanced techniques and technological programs in their industry, since the traditional construction does not achieve the dazzling that the viewer desires.
Accordingly, th
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The understanding exchange rate policy is fundamental in order to identify the mechanism by which works out macroeconomic, And the vital for macroeconomic analysis and empirical work to differentiate between the de facto regimes and de jure regimes, Where the proved surveys and studies issued by the international monetary fund that there is divergence between the de facto regime (Regime of exchange applied by the country actually) and between the de jure regime (Regime de jure through the documents and formal writings of officials of the central bank), And launched studies on the de facto regime (Being a the basis of evaluating monetary policy) Stabilized (peg-like)arrangements or
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The importance of the accounting profession in creating data and accounting information for economic resources and their sources and changes therein , through the effectiveness of this information and the degree of suitability and providing accurate and timely manner and in a form that makes it able to rationalize decisions and performance reporting , and there are several elements and behaviors control how the effectiveness of these reports and these behaviors work ethic that govern the work of management accountant when preparing performance reports , which are the ethics of the work of professional control principles and rules of accounting , legal, such as objectivity and reliability , neutrality and timeliness that must be a
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Research includes evaluation of projects implemented and which entered into trial operation period in accordance with the evaluation criteria and of (cost, quality and time) to determine the size deviations gap for the sample of projects during the years of assessment (2011-2012-2013-2014) of each of the three evaluation criteria, and then followed by a calculation the size of the overall gap to the problem based on the research problem to determine deviations from the specific implementation of each project by answering several questions to answer turns out the reasons for these deviations occur.
The importance of research Focus on the evaluation of received projects from contractors executing the projec
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Abstract : This research has tackled about the role of Russia in the international policies which concerning with energy , So the most important states in the world that possesses huge energy resources to be more able in the control over the reality and future production programs and the distribution of global energy alike , the latter had effectively influence on the economic and developmental aspects within many countries in the world and its impacts on political decisions and perhaps effected too much in the dimensions of strategic policies . In this context of research , Russia has been developed a high energy policy of strategic planning in order to restoring Russia position and its global role by using its potential powerful streng
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Fraud crimes, which is a form of crimes against the funds in public office, is one of the crimes of traditional and cutting-edge in the same time, but it took a distinct character from other traditional crimes because of what is based upon, behavioral fundamentals and foundations and expressive image of personal qualities, concentrated in the mental work, the inventive sophistication, and skillful abilities of the perpetrators of these crimes, in addition to what is owned by crooks today a behavioral ability represented in underestimating laws and instructions. Fraud is considered one of the organized crime methods It is the most important method of its methods, all crimes practiced by the cro
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This study aims to identify the concepts of financial crisis and its reasons of creation , also explain the effects of the accounting disclosure and the International Accounting Standards in current financial crisis, In addition to, indicate the role of accounting in the reform of the financial system from the impact of financial crisis.
The methodology of this study orientied to two main aspects, the first is an identifying approach through exploring the opinion of financial experts, the second aspect is based on an analytical approach to satisfy the requirements of experts to get there opi
... Show MoreThis study aimed to identify the role of digital transformation in improving the quality of the internal audit process. The researchers used the descriptive analytical approach, and the questionnaire was relied on as a study tool that was applied to the study population consisting of internal auditors working in banks listed on the Palestine Stock Exchange, and their number was (85). A checker and a comprehensive inventory method was used due to the small size of the community, where the response data of the questionnaire was analyzed and interpreted using the Statistical Packages Program (SPSS).
The results of the study showed that the use of digital transformation contributes to ensuring the quality of
... Show MoreAim: The purpose of this study is to compare the effect of epineurotomy of median nerve with just division of the transverse carpal ligament in the treatment of carpal tunnel syndrome. Patients & Methods: We conducted a prospective, random study to evaluate the effect of epineurotomy on the outcome of operative treatment of established median-nerve compression in the carpal canal. Fifty hands (forty-four patients) were selected randomly into two groups: group I had a release of the transverse carpal ligament alone, and group II had a release and adjuvant epineurotomy of the median nerve. The groups were similar with regard to age group, gender, duration of symptoms, and preoperative physical findings. All patients had electrophysiological e
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