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 research aims to determine the effectiveness of auditing in light of the relationship between the governance of investment policy and the cost of debt in companies listed on the Iraqi Stock Exchange. The problem of the research is to raise the question about the effect of the governance of investment policy and the cost of debt on the effectiveness of auditing and auditors. During the research, the most important of them were: the existence of an impact relationship on the effectiveness of auditing through the relationship between the governance of investment policy and the cost of debt. The companies listed in the Iraqi Stock Exchange lack an effective proposed guide or framework dealing with the governance of investment policy desp
... Show MoreOral swab samples were collected from 120 children (ages between one month- 10 years) who were infected with oral thrush and 30 healthy children. The percentages of isolated yeasts and Bacteria were 66.6% and 96.6% respectively. The dominate yeast and bacteria were Candida albicans and Staphylococcus aureus with of 78.7% and 34.4% respectively. Results revealed that the highest percent of infection with oral thrush disease was 32.5% in children within the age of 1-2 months.
Cardiovascular disease (CVD) is a class of diseases that involve the blood vessels or heart. Chlamydia pneumoniae has been considered as the most reasonable; also, it is able to increase and persevere inside vascular cells and to make the chronic inflammation in atherosclerosis. In this study, blood samples were subjected for molecular detection of Chlamydia pneumoniae by using conventional polymerase chain reaction (PCR) depending on 16S rRNA. Seventy patients who suffer from cardiovascular diseases (angina, myocardial infarction and atherosclerosis) aged between 33-86
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The last ten years observed a shift enormous scientific in the method and way that it deals professional with the cost accounting and reflected the result those shift enormous scientific of increase the competitive environmental that accompanied the emergence of a modern manufacturing environmental on surface the long roductive life and emergence advanced information technology that give a central focus of his important on client with growing global markets growth on a large scale.
The research aim to define the concept of cost awareness, the concept and methods of strategic cost management and the role of cost awareness for managers of industrial units in strategic of cost managem
... Show MoreAccording to the importance of the subject of research, and the importance of the surveyed organization as a dynamic sector of the country in general , The research attempts to suggest to service organizations in general reconsidering the currently adopted mechanisms in the redesign of its functions , and in the services provided industry . The data was collected from (98) Director Mangers , head of department and head of division . The research tool is the questionnaire , which included (50) items . The results show Significant Effect & Correlation relationship between the two variables due to their dimensions . These lead to he application of job enrichment technology will increase the organization's ability to possess efficient hu
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Ajloun Governorate is considered the smallest governorate in Jordan in terms of area, and its population density rises to 472.2 people/ km2 and is distributed among five municipalities. The Al-Shafa municipality is one of these municipalities. Al-Shafa is rich in its natural and human resources, and the first municipal council was established in it in 2001.
This study seeks to achieve the following general objective: inventory the natural and human resources that Al-Shafa enjoys, and highlight the role of Al-Shafa municipality in achieving and settling sustainable development for the local community. Certain content, which are: the comprehensive approach to geographical reality, the descriptive
... Show MoreIn a world of fierce competition companies of different activities strive to strengthen their competitiveness in order to be able to deliver greater value to their customers and gain a distinct sites in competition with other companies in the market at the local and international levels. Every company seeks to focus on one or more of the competitive capabilities in order to turn it into an obvious advantage or a number of competitive advantages to contribute in improving the performance and superiority over its competitors. Therefore, the management of companies no longer need only useful information for the internal aspects of the environment, but also need to include the external environment that includes various and constantly changin
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Diverting river flow during construction of a main dam involves the construction of cofferdams, and tunnels, channels or other temporary passages. Diversion channels are commonly used in wide valleys where the high flow makes tunnels or culverts uneconomic. The diversion works must form part of the overall project design since it will have a major impact on its cost, as well as on the design, construction program and overall cost of the permanent works. Construction costs contain of excavation, lining of the channel, and construction of upstream and downstream cofferdams. The optimization model was applied to obtain optimalchannel cross section, height of upstream cofferdam, and height of downstream cofferdamwith minimum construction cost
... Show MoreThe experiment was conducted in Al- Mahaweel Research Station in Babel Governorate, Ministry of Agriculture during autumn season 2016-2017 to determine the role of irrigation management processes and micronutrient fertilization in growth and productivity of two varieties of wheat IPA 99 and Al-Rasheed 22 in clay loam soil classified as Typic Torriflovent. The experiment included four irrigation treatments and six fertilization treatments. The experiment was designed under randomized complete block design (RCBD) with three replications. Wheat grain IPA 99 and Al-Rasheed 22 varieties were planted in 23/11/2016 and harvested in 13/5/2017. The amount and periods of irrigation depended on sensors reading of volumetric water content was measured
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