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 modern nation state, by virtue of its institutional nature, is divided into political and non-political institutions according to their respective jurisdictions. It is natural for non-political institutions to perform their functions under the control of the political establishment, for two reasons: first, Second: Ensuring the achievement of cooperation, harmony and integration between these different institutions in serving the stability of the society and its continuity and achieving its supreme objectives. The location of the military establishment is part of the non-political institutions of the state, since it carries out a non-political function that is based on defending the homeland against any threats that may threaten its s
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The process of discovering pharmaceuticals is of great importance in our contemporary life, in a way that without life becomes almost impossible, as this process is the first building block in the field of pharmaceutical industries to search for new methods and means of treatment and treatment. But in fact, the fact that talking about this process is not that simple and easy, because this process is complicated and difficult in a way that makes it take a time range that in some cases reaches what is permissible ten years to reach a chemical formula that can be used later in the manufacturing process Pharmacokinetics, and during this long period of time, this process will have a set of effects, some of which are specific to the researcher di
... Show MoreHardly a society is devoid of manifestations of imitating the opposite sex with the disparity between societies in quantity and quality, as imitating the opposite sex is an old phenomenon, and whoever follows what the old researchers wrote on this subject, finds various sayings, some of which lack evidence, being a kind of guesswork, A generalization that is not based on what is evidenced by it, and others consider resemblance to a behavior in which an animal resembles a human being. I will highlight in this research the resemblance to the opposite sex in the cultures of peoples, making the study into three sections. The manifestations of resembling men and women spread in Greek society greatly, and then the second study was devoted to the
... Show MorePsychology is one of the sciences that consciously overlap in terms of mutual influence with art forms in general and cinematic arts in particular. The psychological effect can be extrapolated into the visual image through the characters and their actions, especially the adoption of psychoanalytic ideas and proposals that came by (Freud), The cinema benefited from the concepts of psychology and participated in the process of creativity and the manufacture of events or the actions of characters, such as the concepts of consciousness and subconsciousness to express the psychological dimension of the film events, these data can be counted on the level of nightmares in the cinematic movies.
The methodological framework included the rese
The research tagged (the image of the soldier in contemporary Iraqi painting) dealt with the concept of the image as one of the basic concepts in the creative achievement, whether it is in the field of art, literature or beauty. Therefore, the concept of the image expanded to express the various aspects of human creativity, including the field of painting. To know the image of the soldier in contemporary Iraqi painting, the research included four chapters. The first chapter focused on the methodological framework of the research, while the second chapter included three sections. The first topic dealt with the philosophical and artistic concept of the image. The second topic was concerned with the representations of the soldier's image in
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The problem of medical waste over the past tow decades has emerged as one of the most important issues.
Which have negative effects on health and the environment ,and as a result specialists looked into the field.
Public health and research issues . This phenomenon in all its dimensions and efforts made For their containment through the development of health and environmental controls for the disposal of such wastes.
In a safe manner starting form the source of these wastes and the various health organizations are finished The final treatment ,and this is why the producers of hazardous medical waste. &nb
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The Mythical Reference in the Poetry of Nabil Yassin