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 aims to test the relationship of work pressure to its dimensions (role conflict, ambiguity of role, workload and nature of work) as an independent variable and its effect on organizational alienation by its dimensions (disability, lack of power, indifference, animosity, social isolation and self-alienation) (Restraint and confidence in negation, initiative, adaptation and living conscience) as a mediator variable, in some faculties of Baghdad University of Science (Medicine and Engineering) and Humanity (Education and Literature). The data was collected on the practical side, which was applied randomly (306) of the teachers and teachers of the colleges (56) items, which included the main research variables
... Show More
Central banks around the world typically use various financial indicators to evaluate performance. In Iraq, the indicators used by central banks to evaluate the performance of banks are of great importance to ensure that the banks operating within the Iraqi banking system comply with the regulatory and legal requirements issued by the Central Bank of Iraq or the Ministry of Finance. Given the need to study the profitability indicator to ensure its ability to evaluate the performance of specialized banks in Iraq, these banks carry out their banking activities and businesses through capital funded by the government. The use of profitability indicators in evaluating the performance of specialized banks provides information about the profitabil
... Show MoreBackground: As photochemical reaction that can stiffen the cornea, CXL is the only promising method of preventing progression of keratectasia such as KC and secondary ectasia following refractive surgery. The aim of CXL is to stabilize the underlying condition with a small chance of visual improvement. Objective: To show the sequences of changes in visual acuity and topographic outcomes during 1 year post CXL for patients with progressive Keratoconus.Type of the study: Cross sectional studyMethods: CXL procedure was done for 45 eyes with progressive KC. The following parameters had been monitored pre operatively, 1, 3, 6 and 12 months postoperatively: K apex, K2, corneal thickness at thinnest location, anterior and posterior elevation po
... Show MoreThe rapid development of information technology and its use in all areas has had a positive impact on all areas, and financial markets have had a share of this development through the use of an electronic trading system to settle transactions, enhance transparency and disclosure in all activities of these markets and revitalize their performance.
The reason for choosing this topic is that it is a very important topic for what modern technology addresses in trading operations in financial markets. It is worth noting that these innovations have eliminated the need for direct contact with people, but through the Internet and telephone networks, and the new technology has reduced the costs of building systems
... Show MoreThe research aims to identify the elements of performance supervisory good and effective and availability in the Governmental council through examination and analysis of the reality and practice of censorship in this Council through study and evaluate the characteristics of the regulatory effective upon which the Governmental council in the performance of his work and knowledge of their adequacy by comparing the established criteria , and determine the effect of characteristics supervisory the performance standards for the Governmental council, Based search to two assumptions key to check the level of the relationship and the influence of the dimensions of the con
... Show More
Interested in many scholars and reseachers the subject of the media and means varied his roleinfluential in the definition of the public of issues and political, cultural, social and because of its spread wide and ability to address the people of all levels effect them in the formation consciousness of those issues and types of this awareness is an awareness of the tax, contribute to media formation consciousness tax through the definition of people what tax and importance of the role of its revenues to supplement the state budget by posting tax laws and regulations of applied and all what respect process account tax, to be in charge of the tax familiar enough about this, which avoid being cheated taxmisleading when rev
... Show More
The tax policy is an important tool of fiscal policy tools which is usedasits multiple tools the State seeks to achieve objectives, such as theachievement of economic development.The importance of the research comes from the importance ofeconomic development resulting from economic policies and prudent fiscaland appropriate to the economic situation of Iraq at the moment is the mostimportant tax policy that taxes one of the most important financial instruments.The research aims to clarify the role of tax policy in developing of theIraqi economy.In an effort to achieve the goals researchers tried to prove thehypothesis ((The tax policy and through multiple tools that seeks to contributeto the achievement of economic development in Iraq)).
... Show MoreAbstract
The goal of the research is to diagnose some of the negative phenomena which was discovered through the period from (2010 to 2014) as determined by the national strategy to eliminate the corruption which was set out by the joint council of the corruption elimination in Iraq. And to measure the gap in applying the legal rules by the administration, concerning the misconducts and felonies upon the state employments made by the state employee and how far they are applied in the studied sample and to show the nature of the rules and their importance and their role when they are applied in scientific and expertise manner. And to encourage the offices of the general supervisors to adhere to them which will lead t
... Show More
The current research aims to measure the impact of the skills of human resources management professionals in information technology in Iraqi private banks, as the skills of human resources management professionals constitute the modern trend of banks' interest in employees with outstanding performance, and the presence of information technology in banks is a prerequisite for dealing with the huge amount of data. And converting it into information to support the decision-maker in light of a complex environment, and the field research problem was the presence of a clear lack of interest in the skills of human resource management professionals and the weak adoption of information technology, which was reflected negatively on the compet
... Show More
ABSTRACT:
The study aimed to identify the impact of the role of voluntary accounting disclosure in enhancing confidence in the informational content of financial reports. Correlation - Spearman to measure the degree of correlation, as well as the method of simple linear regression analysis, and the study reached several results, including: The level of enhancing the information content in the annual financial reports of the Palestinian banks listed on the Palestine Exchange under study reached the overall average (total) (94.1%), and also Voluntary Accounting Disclosure in Enhancing Confidence in the Informational Content of the List of Change in Ownership Equity of Listed
... Show More