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 current research aims to identify the multiple intelligences in the fourth students’ acquisition of the literary processes of Arabic grammar and to identify the differences in multiple intelligence according to gender (males - females). The study was determined for students of the fourth literary preparatory Al-Hakim Preparatory (for males) and Rabat Preparatory (for females) of the Second Karkh Education Directorate, topics from the Arabic grammar subject (past tense, present tense, imperative, subject, and object) for the first semester of the academic year 2019-2020. The results showed that there were no statistically significant differences at the significance level (0.05) between the average scores of the students who were tau
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The importance of news broadcasts in society has increased after the domination of television over the mass media, especially after emerging the satellite channels, and spreading the satellite dishes among the public at large.
As well as the great role played by the modern technology in the transmission of news and events happening at once. Such role has contributed, significantly, in changing the concept and values of the news. The live broadcast of the events filmed is the news itself.
In the midst of the great transformations and circumstances that Iraq went through after 2003, which witnessed political and security instability, and the large increase in the number of media, especially satellite channels, in Iraq
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Establishing sustainable cities and residential neighborhoods requires the development of new planning strategies, as adopting sustainable planning strategies when planning urban land uses for residential neighborhoods is necessary due to the large number of urban land use problems that have emerged during urbanization. The most prominent modern concept concerned with the land was the concept of sustainability, as sustainable planning aspires to link knowledge with sustainability through measures to achieve it. Therefore, sustainable planning works to apply the principles of sustainability in planning.
And in view of the circumstances that our country went through, which negatively affected various sectors and aspects of life, in
... Show MoreScientists are investigating the efficacy of different biosorbents for promoting economic and environmental viability in purifying contaminants. Among the primary by-products of biodiesel production is waste microalgae biomass, which has the potential to be used as a cheap biosorbent for the treatment of pollution. In the present study, the biomass left over after extracting the chlorella vulgaris was used to test the potential biosorption of CIP from simulated aqueous solutions. Bisorbent's ability was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). Analysis with a Fourier Transform Infrared Spectrometer revealed that C
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This study was conducted to identify the impact of germination in the ratio Almaah of Chemical Constituents of Homs and in the organoleptic properties of the Biskt plant it and compare the results with the treatment control (seeds Almnepth) Adhrt results for a significant increase in the percentage of crude protein with the progress of the process of germination, reaching 24.5% in percentage of crude protein with the progress of the germination process Krbu hydrate college during the germination period, reaching 59.2% in the fourth day
The current study aims to investigate the effect of strategic knowledge management practices on an excellent performance at the Institution of Industrial Development and Research- the Ministry of Iraqi Industry (IDRMII). The present research is designed according to the descriptive method. To achieve the mentioned research objective, the researchers used the questionnaire as the main data collection tool. The research sample was 150 managers who are working at the top and middle management levels. To analyses the data gathered and reaching the results, several statistical techniques were used within AMOS.V25, SPSS.V21Software, This study reached a set of results, the most important of which is the existence of a positive correlat
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In the present research we the study the deposition of radioactive elements naturally and particularly radioactive radon gas in parts of the body of organisms which are of direct relevance to human life in the city of Baghdad as the samples which were collected from the bones and skin of some kinds of birds and chicken based on the principle that radioactive elements are concentrated always on the bones. We use of this as the exercise detector impact nuclear (CR-39), using the technology Cylindrical diffusion , the results indicated that the largest concentration of radon found in the bone bird Seagull tapered as it was (625 ± 37) Bq.cm-3, and less concentration of radon gas in the chicken bones of Al-kafeel as it was (105 ± 10) Bq.c
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