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 present work focuses on the changing of the structural characteristics of the grown materials through different material characterization methods. Semiconductor CdSxSe 1-x nano crystallines have been synthesized by chemical vapor depostion. (X- ray Diffraction; XRD), (Field Emission Scanning Electron Microscopy; FESEM), measured the characterization of Semiconductor CdSxSe1-x nano crystallines. The optical properties of semiconductor CdSxSe1-x nanocrystallines have been studied by the photoluminescence (PL) (He-Cd pulsed ultraviolet laser at 325nm excitation wavelength) at room temperature. The results showed the change rule of photoluminsence peak at different S
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This study is concerned with the recent changes that occurred in the last three years (2017-2019) in the marshes region in southern Iraq as a result of the changes in the global climate, the study included all the water bodies in the five governorates that are located in the southern regions of Iraq (Wasit, Maysan, Dhi-Qar, Qadisiyah and Basrah), which represent the marshes lands in Iraq. Scenes of the Landsat 8 satellite are used to create a mosaic to cover the five governorates within a time window with the slightest difference between the date of the scene capture, not to exceed 8 days. The results of calculating the changes in water areas were obtained using the classifier support vector machine, where high accuracy ratios were recorded
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The trade balance is considered as a way to join the national economy with the world, So it is the mirror that reflect the economic center of the country and it is point to competitive ability of it, The tariff and the exchange rate perform a great role to motivate the domestic production and improve the trade balance if we direct them to achieve the same purpose. The Iraqi economic has trade balance which achieve overabundant during the years of studying because of the oil exports, while the other exports represent a small percentage it is hardly remember, and expansion in imports from other side causes exhaustion in oil revenues, and this make the trade balance in permanent
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The research consists of five chapters, and in the first chapter, it addresses the introduction and importance of the research, where the researcher explained the importance of bio-motor abilities and their role in achieving a high level through their connection to the skill performance of standing on the hands followed by the forward roll, and the research problem: Do these bio-motor abilities have an impact on the level of skill performance? Handstand followed by forward roll.
The research aims to measure the extent of the impact of Earnings quality in the continuity of the company for a sample of private commercial banks listed on the Iraq Stock Exchange. The research sample included (15) of the listed commercial banks that continue to issue their financial statements for the period from (2009-2018).The research relied on three main models of measurement and on four steps. The first step is to measure the Persistence (Earnings Quality) by Depending the sustainability model. While the second step included measuring the Predictability of accounting profits by deriving the square root of the disparity of the estimation error from the first model Persistence (Earnings Quality), and the third step included
... Show MoreThe study aimed to determine the impact of energy for the north and south magnetic poles on the the growth of bacteria isolated from cases of tooth decay, 68 swabs were collected from surfaces of faulty tooth, the detected of Staphylococcus aureus
... Show MoreThe waste sorting and recycling plant in the district of al- Mahmudiya (Yusufiya) is the only laboratory in Baghdad governorate. It is the only one in Iraq that collects and recycles waste. After sorting, we have packages of raw materials (aluminum cans, glass bottles, plastic bottles, Nylon bags) as well as natural fertilizers (food residues and others) and a sanitary landfill with specifications that meet international standards; However, the absence of a structure for the management of the plant (manager, assistant manager, accountant, etc.) in addition to the non-supply of waste on a daily and continuous basis and the lack of cooperation of the Municipality of Baghdad with the management of the plant led to delay in the work
... Show MoreThe exercise of activities and sports are of great importance to public health and to maintain the ideal health weight as well as the psychological and mental comfort of humans. The aim of this study is to determine the contribution and participation of educated females in physical activities at the University of Baghdad hall for the years 2011-2016, and to show the factors that influence women's contribution to physical activities at the university by selecting 100 students of males and 100 females' students randomly. During the questioning questions and statistical analysis of the questioning to find out the reasons for the discouraging contribution of the women to the various physical activities and try to find solutions and r
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