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.
Women's rights in social studies and national textbooks in the secondary stage in the light of the international charters of women's rights and the cultural specificity of the Saudi society Abstract The current study focuses on exploring women rights that required to be involved in social studies and national textbooks in the secondary stage in the light of international conventions on women's rights and cultural specificity of the Saudi society, as well as to reveal the teachers and educational supervisors' estimation about the degree of importance of those components included in the books, and then build a matrix of the range and sequence of women's rights in the books of social studies and national in the secondary stage. The study us
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This research’s goal is to restore and to revive the jurisprudence of Mother of Believers (Um alMuaamineen) “Um Salmah” "may God bless her", and to highlight her outstanding assimilation and understanding of religion and her conscious thought. The current research is a comparative scientific theoretical study represented in the comparison of jurisprudence of “Um Salamah” with Hadiths of fasting and pilgrimage rules as well as the duration mentioned in jurisprudence of for doctrines( 4 schools of thought )to identify these hadiths with the inclusion and discussion of their evidence.
The current research included two topics: the first one is to identify and introduce
... Show MoreThis paper aimed to test random walking through the ISX60 market index for the ability to judge market efficiency at a weak level. The study used Serial Correlation Test, the Runs Test, the Variance Ratio Test, as well as the Rescaled Range Test.The population of the study represents of Iraq Stock Exchange. The study concluded accepting the hypothesis of the study that the returns of the ISX60 market index in the Iraqi market for securities does not follow the random walking in general and as a result the Iraq market for securities is inefficient within the weak level of efficiency and the study recommended need a supervisors work in the Iraqi market for securities to activate all means a which will work to communication with information
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China is moving towards building the largest economic power in the world, so what does this mean economically and politically for Europe, America, the Middle East and the Arab world? This project is called the expansionist Chinese Marshall Plan which is a revival of the old Silk Road in a new way. It represents the aspirations of the Chinese people and their president, Xi Jinping, to build a transport route from Asia to Europe and a railway plan to transport goods. The purpose of this is to develop the economic growth model, expand into new markets, promote the Chinese currency, and expand economic and political influence in the areas covered by the Chinese initiative. Equal opportunities in distributing investments to these countries, a
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Although cinema is moving towards art, it has dealt with the character since the beginning of the discovery of cinematic art in films such as (Doctor Caligari's cabin) and most German expressive films in the third decade of the twentieth century, but the interest of cinema is growing in the estranged human personality, meaning that this character It lives by its alienation from the environment and society that surrounds it, because our present days have witnessed on the material and moral level more social breakdowns such as wars and disasters, and the sharp contradiction in the social and economic level of people themselves or between different societies, or between the individual and his community, and new social relations have increas
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This study was conducted to determine the relationship between two most common diseases in Iraqis patients , which are Diabetic mellitus (DM) and Rheumatoid Arthritis (RA); seeking rheumatoid factor in hyperglycemic sera. The results revealed that ; 62.5% of hyperglycemic (HG) patients had positive rheumatoid factor (RF) . No difference in number between both gender of HG patients (20 males and 20 females ) , RF reaction was nearly similar in males and females of HG patients ( 12 &13 respectively ) . Only 40% out of patient controls had positive RF . None of the apparently healthy subjects had positive RF .
The study aims to identify the impact of the round-robin strategy on the logical thinking of fourth-year middle school students in chemistry. Two groups were employed: an experimental group consisted of (30) students who were taught according to the round-robin strategy, and the control group consisted of (30) students who were taught according to the traditional method. The researcher adopted the experimental design with partial control by preparing the visual thinking test tool, which consists of (20) multiple-choice items, it was applied as a post-test on the research sample. The result showed that there was a statistically significant difference in favor of the experimental group, which was taught according to the Round Robin s
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The conflict between the fundamentalist and news theory in the methodology that each of the two schools pursued with the Twelver Shi'a Imamiyyah in deriving the legal rulings from the sources of legislation, especially in the second source, which is the noble hadith and narration after the Holy Qur’an, which is the first source has gone through multiple and complex stages that led This struggle to excess, stress, exaggeration, negligence, neglect and indulgence by each of the two schools in dealing with the noble hadith and narration and in the manufacture of rules and laws and fundamentalist and juristic theories of the process of jurisprudential development of legal rulings where every school believed and proceed
... Show Moreeclaration has become today has an important and active and influential role in the recipient public life، and are concentrated advertising on the creativity component manufacture to attract his attention toward what to be announced from a variety products ، and is dominated by television commercials tempo and imagination، and display them a variety of ways catches the attention and an impressive simulates the their senses of hearing and sight ، to influence in the receiver and the public paid for purchase. Through it crystallization the subject of our research on the importance of creativity in television advertising and effective for attracting the attention of the public towards the receiver advertised products، and in
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