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.
Extemporization is the ability of the actor to reflect his internal being. It gives a sort of confidence and an ability to show the personal countenance of the role away from tension and rigidity. By extemporization, it is possible to deal with and criticize the real living life so it is an intellectual, emotional, sensual, and perceptive process connected with the psychological energy and the emotional memory and all this goes under the control of the director and his instigations and instructions depending on what the text involves of intellectual, social and psychological motivators so it primarily depends on talent, chance and discussion. The research involves four chapters; the first contains the problem
... Show MoreThe general approach of this research is to assume that the small nonlinearity can be separated from the linear part of the equation of motion. The effect of the dynamic fluid force on the pump structure system is considered vibrates at its natural frequency but the amplitude is determined by the initial conditions. If the motion of the system tends to increase the energy of the pump structure system, the vibration amplitude will increase and the pump structure system is considered to be unstable. A suitable MATLAB program was used to predict the stability conditions of the pump structure vibration. The present research focuses on fluid pump problems, namely, the role played by damping coefficient C, damping factor
... Show MoreTerrorist crime is considered a serious act that outweighs all other crimes in terms of impact and result, because it has a wide range on societies, and it also contains a great thing of danger represented in its purpose, and here describing terrorism as a crime is a description that does not give the full right to this behavior or that it It abbreviates it and does not show its actual reality, given that terrorism contains several different crimes and the roles of its contributors, and these roles are necessary to reach the result or the end. In which each episode is complementary to the other, it is not a single act, but rather several joint and complex actions that in turn all lead to the result, and the agreement in the terrorist pro
... Show MoreThankfully Thank meets the grace and pushes us Blaneh and a curse, peace and blessings be upon the Prophet after him, and his family and companions, and after:
This research deals with the subject of the provisions of the autistic in criminal penalties, one of the important issues, especially after the spread in abundance in our contemporary society, as the patient is characterized by autism in most of spaces of isolation and depression and aggressive behavior, and in some cases try autistic to commit suicide as a result of going through the psychological pressure , was this research to clarify what follows autistic criminal penalties as a result of the capital crime of self or without them, and the stat
... Show MoreThe movement is considered one of the important factors which attracts the receiver attention in designing artificial works in general, and especially in the advertisements, moreover the subject of the movement in the designing advertisements needs more care and study by the scholars. From this importance and from reaching to the basic streams of the research topic (the effect of the movement in the graphic design) the problem of the research has been set according to the following wonder:
- What is the designing process that establishes the movement in the commercial advertisements designs?
The researche
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The emergence of artistic movements in Western countries was after the period of modernity. They have introduced a great dialectical problem at the level of thought and discourse, which necessitated a change in the course of the aesthetic discourse into new visions. Thus, the present research aims to identify the aesthetic discourse of pop artists' Art and its representations in the outputs of the students of the Department of Art Education. The theoretical framework included two sections: the first one, what is the aesthetic discourse and the second is the educational bases of the students' outputs. The procedures of the current research included the analytical descriptive approach. The research sample consisted of (4) outputs chosen ac
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The capital banking foundation stone upon which the bank in the practice of business activities, the more capital a good financial adequacy of the increased bank's ability to grant credit and expand the various activities and provide a safety element for depositors and other sources of funding to achieve profits and increase the trading volume of the shares, causing the rise the rate of return for the shares of banks and have the Central Bank as head of the banking system by issuing instructions capital increase banking, according to the requirements of economic development and increase gross domestic product by supporting investment projects that are financed through banks, the research aims to show the extent of the banks commitment to
... Show MoreThe experiment was carried out in the field of botanical garden belonging to the Department of Biology Sciences, College of Education for Pure Science -Ibn AL-Haitham ,Baghdad University. for the growing season. 2014 -2013 to study the effect of the electromagnetic field which included five different intensities (0,5,10,15,20) MT and three periods of time, namely, (1,2,3) an hour and their interaction on some of the morphological characteristics of the safflower plant . designed experiment by Randomized Complete Block Design (RCBD) and three replicates per treatment, compared to the average using less significant difference at the level of probability (0.05) , the results showed the following:- 1-Exposing seeds to diffe
... Show Morethe digital public relations aim at make the workers getting the necessary information about the governmental institutions where they work and the enveronment surrounding them. it also tries to let the workers get the special knowlege of tthe publich relations and their jobs like the works of planning , arranging the active communication and executive skills needed in their writing , editing , special art skills for designing , production and technological skills to deal with the computer.
the problem of the research includes some questions as :
1- what are the uses achieved by degetal public relations workers at Iraqi universities (Baghdad, Mustansiriya, and Iraqi)
2- what are the tools used to apply digital public relations
(2)