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.
Assessing performance efficiency is critical to the management need for oversight, planning, and continuous periodic evaluation of the multiple activities of Northern Cement State Company in order to determine the level of achievement of the objectives set, and to correct the deviations and delays that the evaluation shows and limitation of liability. What cannot be measured cannot be managed. The aim of this research is to highlight the impact of using BSC, financial and non-financial, to give comprehensive and clear picture of the company's performance and to measure the quality of its performance by using six-sigma and the level of deviations in achieving the planned goals. Therefore, four-key hypotheses were formulated for th
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Background: The styloid process is a cylindrical bone (protrusion). It situated above the common carotid artery between the external and internal branches immediately proximal to the internal jugular vein and facial nerves. The styloid process varies in length also it may be absent as well as elongated. Classically, an elongated styloid process and calcified of stylohyoid ligament causes Eagle’s syndrome. The aim of this study was to examine the styloid process using 3 dimensional multi-detector computed tomography (3D-MDCT) to detect the presence of Eagle’s syndrome that causes severe headache and migraine. Materials and methods: One hundred patients with severe headache and migraine were exposed to 3D- multi-detector CT with special
... Show MoreThis study aims to identify the role of forensic accounting in resolving banking disputes in the Iraqi environment, and to achieve this goal, the fiel
d survey method was used, as it is the most appropriate for studying the phenomenon in question and achieving its objectives. A sample of (50) male and female employees was selected, distributed among five banks listed on the Iraq Stock Exchange in the Baghdad governorate. The questionnaire tool prepared for this purpose was applied to them, which consisted of two main axes. The first axis included paragraphs of questions related to the importance of forensic accounting. The second axis relates to disputes At the end of the research, we reached a set of conclusions, the most import
... Show MoreThis study aims to identify the role of forensic accounting in the Iraqi environment, banking stability, and to achieve this goal, we used the field survey method, as it is the most appropriate for studying the phenomenon in question and achieving its objectives.
Where we selected a sample consisting of (50) male and female employees, distributed among five private banks in Baghdad governorate, namely (Ashur International Bank, Development Investment Bank, Iraqi Middle East Investment Bank, Hammurabi Commercial Bank, Khaleej Commercial Bank), and the questionnaire tool was applied to them Designed for this purpose, which consisted of
... Show MoreThe aim of the research is to identify the role of public relations in promoting tourism by the Palestinian tourism and travel companies in Gaza from the public relations officer’s point of view in those companies.
The researcher used the descriptive analytical method as the most appropriate for such studies and implemented the questionnaire as a tool to obtain the required data from the respondents.
The Researcher reached several conclusions:
1- There is a low percentage of women working in the field of public relations in Palestinian tourism establishments in the Gaza Strip, where the percentage did not exceed 5%.
2- The interpersonal communication counted as one of the elements of integra
The issue of intellectual capital is a critical issue in the success and excellence of organizations, especially if it is linked to the management of customer experience, and because of the characteristic of the Iraqi environment, which affected all sectors, including the banking sector, it was important to discuss the types of intellectual capital and its relationship to the management of customer experience, especially when managers private banks, the importance of research lies in the linking of its variables to build the strategic capabilities of banks to achieve excellence and sustainability, it aims to diagnose the extent of interest in the types of intellectual capital and management of customer experience in the Iraqi ban
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The Iranian nuclear program was one of the most prominent issues in the international arena, in light of Iran's insistence on using it in various ways, and according to international changes, it came under pressure from the American side to impose packages of sanctions, which continued to our time, as it went to Russia and China to gain support in developing its nuclear activities. And, by virtue of the common interests that are linked between them, Iran has received great support from the last two countries in all fields to reach the final agreement in 2015, regarding asserting the peace of these activities, in addition to lifting all restrictions represented in the previous sanctions according to the Security Council resolutions, Aldo
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The research problem is that most of the construction projects exceed the planned value, due to the failure to implement the plans on time. The current study aims to monitor the implementation of the project and for each of the executed tasks of the table of quantities in order to detect deviations at the time they occur, evaluate the time and cost performance, and then identify the areas of waste and analyze the implementation of each task in order to diagnose the underlying problems and find possible and applicable solutions in the environment Iraqi. The research was applied in one of the companies specialized in the field of construction projects, and one of the most important conclusions reached is the possibility of applying
... Show MoreAn experimental and theoretical analysis was conducted for simulation of open circuit cross flow heat
exchanger dynamics during flow reduction transient in their secondary loops. Finite difference
mathematical model was prepared to cover the heat transfer mechanism between the hot water in the
primary circuit and the cold water in the secondary circuit during transient course. This model takes under
consideration the effect of water heat up in the secondary circuit due to step reduction of its flow on the
physical and thermal properties linked to the parameters that are used for calculation of heat transfer
coefficients on both sides of their tubes. Computer program was prepared for calculation purposes which
cover a
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