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 problem with research in the question of whether art forms in the religious icon Byzantine, heiress docility and tradition craftsman arts civilizations of the above? ... And if you are well, you helped a quotation on the entry of strange ideas rampant within religious traditions, and are prompted to do Movement rejected prohibition, and the outbreak of the icons war? ... Or is it, in fact - and as researcher finds - the result of a need communication between the religious and the recipient organization in the establishment of a deliberative speech, be visible, along with reading it and audible? .. And lies the importance of this study is being added technical knowledge of the library that will enrich researchers and scholars in this
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The current report dealt with the effect of pesticides on the ecosystem through their impact on soil, water, and microorganisms and their impact on human health. As well as this study dealt with the biodegradation process of pesticides and the organisms involved in this process, even some previous studies proved that Bacillus spp. And Pseudomonas sp. Bacteria is the most efficient in the biodegradation of pesticides, at the same time, other previous studies dealt with the environmental factors that affect the biodegradation process of pesticides. It proved that each of the incubation periods, pH, and temperature have different effects on biodegradation. Most of the studies indicated that the best incubation period for biodegradation is 7-8
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The research is dealing with the color articulation and its significance in the poetry of Hana Al-bawab, who employed the “color” in a special technique in her poetry.The research is trying to deal with the identification of the color and its aesthetic significance and function in the poetic context, as it determines its indication and interaction with the words next to it in the context. The research will clarifies that the color is not only a visual phenomenon, but also an aesthetic, mental and emotional significance. The results that I have concluded, indicate that the poet has beseeched to display the color in her poetry with the plain and borrowed colors besides the inspired dark and bright colors. The color’s indication has b
... Show MoreTRIPS agreement was The first to apply protection by patents. However, this type of protection, which grants exclusive and monopoly rights to patent owners, came at the expense of developing countries which are considered rich in biodiversity and also at the expense of traditional and poor knowledge of modern technologies. The release of new plant varieties has led to the emergence of biopiracy and looting of the rights of developing countries without a license
The present research aims at recognizing the difficulties and problems which hamper teachers and educators alike when using the internet for educational purposes.It discusses the benefits of the internet as a source of information or publication and as a communicative tool.Arandom sample of (30) teachers working at schools in Baghdad / Second Risafa,was selected.Three of the sample members use the internet for student project plans via internet centers, whereas 16 of them use it for chatting, emailing and research purposes.The rest of the sample have limited knowledge of the internet. The researcher used the interviewing method to gather data from
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The study focused on the identification of the natural relation between the organizational components, and the most important is the organizational structure, which not hid its effect on each function and operation of the organizational structure through commanding the individual craters and its forms according to the requirement of these function, also it has relation with an organic synthesis that between the dimensions of the organic synthesis and the practice side in the commission of Integrity.
The problem of the research pensioned in some questions about hypothesis and theoretical parts, in which they go a mention about the hypothesis questions is to use all the knowledge's in this atmosphere and th
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The Intelligence of the Child in Relation to some Variables
The use of symbols is considered an important part of visual expression since ancient civilizations till the present time, and detecting the significance of these symbols is a communication means between the artwork and the recipient. The current study aims to detect the clarification of the concept of symbolic connotations, and to detect their importance in the works of the artist Eugene Delacroix, through description and technical analysis, and trying to monitor the technical aspects of these connotations and using them in forming the artwork; This shows the importance of the study in trying to benefit the scholars in the field of visual arts and the analysis of artworks in particular.
The study used the descriptive analytical appr