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 study of triples seeks to deal with the comprehensive nature of the Qur’an texts, and the choice fell on the trilogy of great torment, pain, and humiliation in the Noble Qur’an - an objective study, the title of this research, in which I tried to shed light on these terms, and the nuances between them, and in particular torment The eschatological terminology varied, which can be summed up in three terms, namely the great, the painful, and the offensive. The types of torment, the pain is the painful one that is described by the severity of pain and its horror, as for the humiliating punishment, it is that which humiliates the one who has fallen on it, and the diversity of torment is due to the diversity of sins.
Abstract
The image of the soldier, as a hero who sacrifices everything to defend his
country and values, is no longer depicted in modern drama. With two World Wars
and many regional wars and civil wars, the soldier becomes a victim, not a hero.
Authors present the character of the soldier as a man who suffers a lot as he is
victimized by his own government and its politics that forces him to be in such a
position. Dramatists express their views about race, oppression and war through
their characters, such as the character of the soldier, as in the two selected plays for
this research: The Hostage by Brendan Behan and A Soldier's Play by Charles
Fuller.
The Hostage depicts, through its events, the Irish oppre
The research aims to measure the net nominal protection coefficients for the products table eggs and poultry meat and the extent of its impact on domestic production volume for the period of 1990- 2013 has been the use of mathematical formulas simplified in the calculation of the transaction process with a view to the extent of support and protection offered by the state pricing policy for products Resources Sector Animal in Iraq and reach search Highlights and most important, there are volatile price state policy with regard to eggs and poultry meat, as it ranged net nominal protection coefficients between the larger and less than the right one, which means that values are unstable to support local producers or consumers, and can be The
... Show MoreThe research aims at identifying the organizational performance of the kindergarten teachers and defines the educational environment of kindergarten children. To achieve the objectives of the research, the researcher adopted the organizational performance scale for (Saadi, 2016), which was applied to kindergarten teachers. The scale consists of (43) paragraphs, and has good reliability and validity, as the coefficient of reliability (84.0) in a retest method, and (87.0) using the formula Alpha Kronbach. Additionally, the researcher adopted the educational environment scale for (Radam, 2015); the scale consists of (66) paragraphs, and it enjoys a good reliability and validity, as the coefficient of reliability (89.0) method of reliability
... Show MoreVocational stresses and their relation with the level of ambition among the lecturers of the university In general , vocational stresses affect the attention and the process of focusing making individual busy with solving of his daily problems instead of his job. The vocational stresses , anxiety and tension are factors effecting the physical and psychological ability of the individual. This study aims to measure the vocational stresses among the lecturers of the university , to measure the level of ambition among them, to identify the statistical differences significant among them according to sex variable, to identify the differences significant in level of ambition among them according to sex variable and to identify the correlation r
... Show MoreThis research deals with the effect of constructive conflict of the organizational identification .These relatively recent subjects have relative importance in the field of administration and they have strong effect in the success of organizations .The objective of this research is to detect the level of the constructive conflict and the organizational identification in the center of The Ministry of Planning. So, two major hypotheses were formulated The first are searched the correlation between the constructive conflict and the organizational identification and it emerged with four sub-hypotheses searched the correlation among every dimension of the constructive conflict with the organizational identification .The second major h
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The use analysis value chain such information in the provision as financial so information quality meet and satisfy the needs of users such information , particularly investors and lenders as the identification needs financial information and the knowledge as their behavior influenced by that information can be based on the accounting profession to focus on improving their function in order to achieve its goal that satisfying their needs and rationalize their decisions . In accounting thought discovered fertile ground for users preferences as one of the entrances theorising positive which is based on the need to include knowledge on accounting hypothesis that explain the
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In the theory of cinema genre, horror films are at the forefront of the list. It is one of the oldest genres that saw the light with the early emergence of cinema, taking advantage of literary works, especially Gothic literature and it continues to this day, but the third millennium has seen a marked increase in the number of films and recipients alike. There were many types within the same genre and there are many authors and varied topics, all seeking to spread terror and panic and fear in the hearts of viewers who are passionate about the type of horror. Although the fear and horror have been, throughout the ages, a challenge to the psychological balance and stability, as well as being a rejection and an opposition to the aesthetic ta
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When we try to navigate the experiment in search of the repressed and to find the dream of creativity by changing the modularity of the presentation, and the relationship of the characters with the rest of the elements according to a visual vision that reflects the product of the presentation system through the formation of visions and ideas within the textual structure.
We find that the expression of the theatrical act may need to exclude narrative dialogues and turn them into a tangible visual language. Physical and visual expression, and movement review, thus producing a “picture language” through which it is possible to form a new vision, and this is called (image theater), which translates the language of dialogue through lig
Sloped solar chimney system is a solar chimney power plant with a sloped collector. Practically, the sloped collector can function as a chimney, then the chimney height can be reduced and the construction cost would be reduced.The continuity, Naver-stockes, energy and radiation transfer equations have been solved and carried out by Fluent software. The governing equations are solved for incompressible, 3-D, steady, turbulent standard model with Boussiuesq approximation to develop for the sloped solar chimney system in this study and evaluate the performance of solar chimney power plant in Baghdad city of Iraq numerically by Fluent (14) software with orking conditions such as solar radiation intensity (30
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