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 measure the impact of knowledge management processes individually and in total in the innovative marketing.
We depart search of a problem expressed in a number of intellectual and practical questions, the application of this research in the General Company for Vegetable Oil Industry, represented composed a sample of (63) (Director General and Deputy Director General and Director of the Department and the Division) in the company researched, it has been designed measuring instrument to collect the necessary data either statistical means they are the percentage and the arithmetic mean and standard deviation and coefficient of variation and the coefficient of simple correlation and model
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Background: Insulin resistance is present in 50% or more of patients with primary hypothyroidism. Metformin can decrease TSH levels in these patients by a complex matter, this can be of great help in clinical practice.
Objective: This study was designed to evaluate the effect of metformin in reducing TSH levels in patients with primary hypothyroidism.
Methods: Hundred patients with primary hypothyroidism, 82 females, 18 males were included in this study, everyone was followed up for two months after adding metformin 850 mg twice daily in addition to thyroxin.
Results: 36 patients (36%) have a normal baseline TSH and no change after 2 months, 64 pa
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A Forensic Accounting is represent science that deals with the application of knowledge in the areas of accounting, finance, tax and audit for the analysis, investigation, inquiry, inspection and testing issues in the civil law and criminal law in an attempt to reach the truth through which enable the Forensic Accountant to provide his Expert opinion , forensic accounting plays a major role by providing a range of important services in the field of investigation for fraud and litigation support, As one of the most important legal and accounting functions is to investigate allegations of alleged by the related parties, especially those allegations related to the existence of fraud, since the goal of judicial accountant will depend
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There is substantial data supporting the importance of both endogenous and exogenous estrogen in maintaining reproductive health and preventing chronic disease, androgens in women's health are rarely discussed. This is one of the first researches to investigate correlates of blood testosterone concentrations in women with osteopenia, in anticipation of the growing interest in the role of androgens in women's health. A 65 volunteer women were enrolled in the current study, they were divided into two groups, 35 postmenopausal women with osteopenia were in the first group, and the second group contained 30 postmenopausal women without osteopenia as a control. Blood samples were collected from all participants and analyzed for testosterone l
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The idea of this research is the basis of the role exercised by the dimensions of performance management (Performance Planning- performance evaluation- improve the performance and development- feedback - Review and Performance Monitor) In order to achieve the success Organizational Is through the (strategic vision- the operational activity- development of the company- selection of personnel- the company's culture- Leadership and Management- Personal Development - Assessment and Review).And The research aims to identify the extent of the responsibility of performance management in achieving success Organizational through main hypotheses branched out by the sub-hypotheses to knowing out the&nbs
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The research addresses smart city concept as it is the latest urban design trends, by the investment of the capabilities of human, and artificial intelligence for the sake of the advancement of the city. The concept of a smart city is described as one of the most important manifestations of the information revolution, with the end of the twentieth, and the beginning of twenty – first century, The research attributes the emergence of the concept to: deficiencies of means, and traditional methods in building and development of cities, as well as The significant increase in the number of city and global metropolises dwellers. So, smart city approach has been adopted, along with innovative principles and methods which cons
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ABSTRACT
Background : The aim of this work is to assess the role of breast sonography and ductography in the evaluation of different causes of nipple discharge.
Methods : The study will be carried out on twenty-five female patients referred to the Radiodiagnosis department at Alexandria Main University Hospital presenting with nipple discharge.
They were divided into two groups:
Group I include 10 patients (40%) with surgically significant nipple discharge who were the patients with unilateral, uniorificial surgically significant colour type nipple discharge .They were investigated by mammography, sonography, and ductography.
Group II include 15 patients
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ABSTRACT
The research aims to study the effect of the commodity dumping phenomenon that Iraq suffered after 2003 on the consumption pattern of individuals, towards the acquisition of non-essential goods (luxury). To achieve our goal we relied on the questionnaire as a main tool for obtaining information related to the research, and it was distributed on a random sample of consumers in the city of Baghdad with 250 questionnaires. The answers of the research sample were analyzed using the statistical program (SPSS). The percentage weights and the factorial analysis method were used also to arrange the variables that affected on changing consumption patterns. The research reached a set of conclusions:
... Show MoreThis research aims to examine the relationship between learning organization and behavior of work teams. The variable of the learning organization took four dimensions depending on the study (sudhartna & Li, 2004): Common cultural values , communication, knowledge transfer and the characteristics of workers. The behavior of teams was identified on the basis of realizing of the respondents of their organization to work as a team where the research relied concepts applied in the study (Hakim , 2005) , and chose to research the case of a service organization for the study and relied on four dimensions of coordination , cooperation , sharing of information , the performance of the team, and was a curriculum approach and des
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