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.
Began research of the foundations of Orientalist discourse based on force and metadata and authority, and the possibility of turning the West's view of the East as if made radical changes in the structure of the West or in a relationship of power and authority between it and the east. We have adopted in our paper on the research categories of Edward Said and visions in the field of Orientalism in general, and especially his book entitled the name of this area, not forgetting, or leave the expansion to other sources, a researcher in this field, to enrich the research.
We went to Orientalism as a concept and based cognitive, and the work of the Orientalist, and the meanings of Orientalism, which suggests Balastala which was c
... Show MoreDifferent Arabic and Islamic societies are free of evil instincts. Therefore, certain provisions of legitimacy came to stress the importance of the intentions of sharia to achieve the interests of all people that involve several aspects, including the five fundamental things: religion, oneself, offspring, mind and money. Almighty Allah has specified certain punishments on those who violate these things by imposing punishments on the part of the criminal to preserve souls. He imposes the penalty of theft to preserve property, the Hadd punishment for adultery to preserve the symptoms, the punishment on the drunk to preserve the mind, and the Hadd punishment for the apostate to preserve the religion. By the adherence to these punishments li
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Writing as a female playwright in theatre gives a deeper depiction of woman’s real- self. Beth Henley has succeeded in providing a new realist vision of women’s abilities to face their inevitable tragic fates and how to conquer their despair. In Crimes of the Heart, the playwright uses certain method to present the development of the heroines’ characters through blending the tragic events with a comic frame. In fact, Henley focuses on the simple humorous activities more that the importance of the tragic event to present her vision of how to survive and face the crisis of life.
Crimes of the Heart is a play that is concerned about three sisters whose lives are headed in distinctly different directions; howe
... Show MoreCommunicating effectively by gaining productive skills in a classroom setting is one of the critical goals of learning the English language. The current study was conducted to explore the correlation of EFL learners’ level of academic intelligence with their productive skills. The study tries to find an answer to what is the correlation between EFL learners’ academic intelligence and level of production skills. The study population represents EFL students at the departments of English language of the Iraqi Colleges of Education for the academic year (2022-2023). The sample includes 310 EFL students selected from the 3rd year of the Department of English of the College of Education, Ibn-Rushd for Human Sciences/University of Bagh
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The research dealt with the case stock repurchase policy of Emaar Real Estate Company one of listed companies in Dubai Stock exchange. The research has launched from the cognitive dimensions of repurchasing policy which took great concern in the literatures of financial management, and also this policy became as substitute for distributing the monitory profit in the last three decades in the international financial markets, but it did not get any importance in the Arab Markets such as that of the Arab Gulf in addition to the Iraqi Stock Exchange.
The research summarized a set of conclusions, the most important one was the consistence of analysis result with the test of the major two hypotheses (The first
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This research deals with the audio part of the cinematic film, which is the sound and its elements inside the space of the cinema picture. It also deals with the psychological side of the sound and the effects made by the sound on the audience through the carefully studied use of the film maker in employing the sound and the picture. For the importance of this element, most of the directors were aware of the seriousness that sound causes to the cinematography, and consequently working as a whole such as the indications, meanings, symbols, metaphors ,transitions…etc. The research included the methodological framework which consists of the research problem, in which the researcher ma
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