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 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
... Show More
This research aims to identify the nature effect of some mechanisms governance in the Accounting Conservatism for a sample of the practices of companies (banks) in the Iraq Stock Exchange and identify any of this mechanics most effects in the accounting Conservatism. To achieve this objective the use of all of it (the size of the board of directors, management ownership, ownership concentration, the auditor's report) as independent variables was used model Basu revised to measure the Accounting Conservatism , which was considered a variable follower with taking into account the effect of the control variables represented by the (company size and leverage) of a sample of listed on the Iraq Stock Exchange companies for the pe
... Show More
The Trump administration asserts that the actions of the United States are neither constrained by international organizations nor international controls, as they strive to seek a leadership position in a competitive manner, advance the reform of the United Nations in order to gain strength and support for US interests, and promote conservative social values. This negative policy is the result of the influence and mutual influence of long-term isolationism, the "American exception" and popular trends in the United States, as well as the result of the Trump administration's attempt to employ powerful means to revitalize the United States' strong position in the United Nations. However, the Trump administration’s policy toward the United
... Show More
Advertising is an important and influential tool in various commercial operations, as it represents a means of communication that depends on influencing individuals or society as a whole, working on a link between the producer and the consumer, so the importance of advertising appears in two dimensions, the first is economic represented in its role in achieving economic growth for the facility, while the social dimension lies in its role By influencing the behaviors and ideas of individuals, and from here it appears to us the importance of formulating, organizing and designing the advertising message that advertising agencies resort to in their advertising campaigns. Orientation, definition, and raising the level of the advertising messa
... Show More
Objectives: To determine the impact of the household hazardous waste’s aspects upon the environment
pollution .and to identify the relationship between the households’ demographic characteristics and the aspects
of household hazardous waste.
Methodology: A descriptive study is conducted between December 14th 2004 to October 20th 2005that uses of
an assessment tool. A probability (simple random sampling) of (336) principal’s households which is selected
from the zones around the (14) primary health care centers as focal points, (8) in the urban and (6) in the rural
areas of Baghdad Governorate. After reliability and validity were determined Data are collected through the use
of an assessment tool that is consist
Talking about the importance of the imagination in sculptural works has a role in shaping the collective memory and moving it, whether it is an artistic, social, religious or historical imagination. Because it documents the cultural heritage of any country through the structural structure of the sculptural form, and its connotations and symbols, which are considered an effective aesthetic image in the crystallization of various intellectual concepts and contents.
Therefore, the study aimed to know the employment of the popular imagination in the artistic works of the sculptor (Muhammad Ghani Hikmat), as well as to reveal the artistic and aesthetic features of the folklore and its reflection on its artistic style. And the references
The bifurcation of the constitutional rights of one of the techniques used by the constitutional court to expand the scope of the constitutional right to explicit, and access to the fact that guarantees constitutional rights, and establishes the constitutional elimination of this technique on a particular bond is the constitutional terms of reference, and in the light of his discretion in the exercise of the constitutional powers of , and tends at times To the adoption of a broad branching approach, which confers on the constitutional text containing constitutional rights a wider scope than the scope of an explicit right.