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 Ilkhanid Mongols (651-756 AH / 1253-1355 AD) were interested in urbanization and construction in keeping with civilized countries and to have an architectural imprint that competed with the neighboring nations. The Ilkhan Öljeitü Muḥammad Khudābandeh (703-716 AH / 1303-1316 AD), known for his love of building and construction, wanted to have a capital that would immortalize his name and history, so he ordered its construction to compete with contemporary cities, and he summoned workers and engineers from all over the world to contribute to its construction. The city has several educational and service institutions such as schools, ribats, khanqas, mosques, hospitals, markets, and baths, as well as a mausoleum for him, which
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A total of 320 samples of vaginal swabs was obtained from women complaining of vaginal infection and attending two hospitals in Al-Sader city, Baghdad, namely Ibn AlBaladi Hospital for Pediatrics and Gynecology and Fatimat Al-Zahraa Hospital for Obstetrics in Al-Habibia district during the period from Desember 1997 till July 1998. Results of direct smear and culture showed that Trichomonas vaginalis infection occurred in 19.1%, in addition to some microorganisms. The most common infection was by Candida spp. (24.7%), followed by Gardnerella vaginalis (13.8%) and Staph. aureus (10.9%). Infection with Escherichia coli, Klebsiella spp. and Prote
... Show MoreThe worsening of environmental problems has led to them being addressed by many entities, the most important of which are the top regulators. Federal Board of supreme audit Office is one of the most important regulators in Iraq. The problem of the research was the fundamental question of the extent to which the Federal Financial Supervisory Office was committed to implementing and exercising environmental control over the audited ones. The refore, the research was based on the main objective of questioning the role of the Federal Financial Supervisory Office in the exercise of environmental control and the compliance of those under its control, by identifying the antosai standards for environmental control, particularly the stand
... Show MoreThe Security Council has an active role in addressing international crises and dealing with their causes. The Libyan crisis is one of the most important real tests of the Security Council and its role in maintaining international peace and security, as the Council has proven so far an ineffective role in resolving the crisis and dealing withtheir causes, which has prolonged its duration and increased its complexities and dangerous repercussions, perhaps the most prominent of which is the threat of the recently achieved cease-fire and the formation of a new transitional government led by Abdel Hamid al-Dabaiba, the growing significant obstacles facing the political process, foremost of which is the continued presence of foreign forces , m
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Despite the multiplicity of institutions contributing to the decision-making process in the United States of America, they interact to crystallize positions regarding international and strategic situations. The formulation of the national security policy depends on a number of institutions that complement each other in order to achieve an advanced security situation. Thus, the decision reflects the process of interaction of the existing regulatory institutions. This is because the essence of the national security and achieving its requirements also stems from the existence of a coherent system of shared beliefs and principles in the American society. Besides, these elements are the bases for achieving
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Sports risk has become a threat to the sports sector in general and the impact on an efficient player and the old stadiums in particular. So have such a thing fertile ground of global insurance companies to exploit it optimally exploited through the development and marketing of insurance lids for the provision of protection for athletes of different risks they may face, which contributed to the growth and development of the performance of these companies and helped in the emergence of sports insurance specialist firms. And through the insurance process in the field of sports and where the insurance is a type of social solidarity. The main problem is this spirit manifested search in question is whether to embrace sports institutions sport
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I have studied the relationship between blood groups in humans and disease Cutaneous injury for the first time in Iraq study showed the presence of a significant statistical relationship between them leather Bmsoy in hospitals in Baghdad and its suburbs
A total of 37 Staphylococcus epidermidis isolates, isolated from corneal scraping of patients with bacterial keratitis and 20 isolates from healthy eyes (as control) (all isolates, isolated from, Ibn Al- Haietham eye hospital / Baghdad), were tested for slime production, 52.63% of all isolates were positive-slime production (23 isolates from patients and 7 isolates from controls). It was found that positive-slime producing S. epidermidis were exhibited a high resistance to antibiotics as compared to negative-slime producing isolates.
The human perception of science and knowledge is affected by the personal point of view, thus giving it its religious, mental and emotional dimensions to make that perception an effective tool for realizing the truth comprehensively in the delivery of knowledge to the depths of the human soul. The later is composed of multiple factors, which contributes to the human self-development with dimensions beyond the limits of mental logic and the perception of material and emotional situations. That knowledge in the perception of Islamic virtue, which must characterize each Muslim.
Human beings have been striving for knowledge and the understanding of the universe in which they live. For centuries, mankind has acquired knowledge directly an