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 aim of the research is to identify the adequacy of accounting disclosure in granting bank financing in explaining the role of accounting disclosure in granting bank financing by linking the concepts of full, comprehensive and adequate disclosure to bank financing. The impact of full accounting disclosure on granting bank financing, the existence of an impact of comprehensive accounting disclosure on granting bank financing, the existence of an impact of adequate accounting disclosure on granting bank financing, and the research relied on the descriptive approach, the deductive and inductive approach, the inferential analytical approach, a
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Abstract:
The internal control is the tool through which it is possible to verify and ensure the implementation of tasks in accordance with the established plans and programs and to evaluate the level of performance that is implemented within the different companies.
A guarantee from the supplier with the absence of a specialized technical committee that follows up the stages of implementing the contract and disbursing all amounts of financial dues to the supplier before completing the implementation of the contract and overlooking the non-implementation of some clauses of the contract by the committee in charge of
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The basic aim of this research is to study the interactional effect of investing information technology on the relationship between value added intellectual capital and financial performance as literature review suggested on the theoretical level, including previous studies, with the deduction of its trends strongly predicted by research hypotheses and their content associated with the investment in intellectual capital after information technology tools being employed in this direction to improve the financial performance of the studied companies at the levels of both industrial and service sectors, a non-random sample was chosen included (40) forty Iraqi Joint-Stoc
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RMK Al-Zaid, AT Al-Musawi, SJ Mohammad
Objectives: To assess the woman satisfaction with nursing care during labor.
Methodology: A descriptive analytic study about conducted for a purposive (non probability) sample of one hundred labor women interview validity and reliability of questionnaire are determined through panel of experts and pilot study. Descriptive and inferential statistical procedures were used to analyze the data, which collected by using interview technique.
Results: The study sample indicated that in general the women were satisfied in nursing care that provided during labor.
Recommendations: The study recommended educational tra
... Show MoreThis study investigates the role of Enterprise Resources Planning (ERP) systems in improving human resources management (HRM) processes. The rapid environmental changes led to increased demand on the ERP systems, which have changed the manual effort to technology-based processes, providing solutions focusing on the integration of all departments to achieve goals for the entire organization. HRM processes are mainly made up of two classes: strategic and operational HRM. An ERP system works to integrate both of them, making HRM processes more efficient, effective and feasible to provide support to the organization as a whole (inside and outside). In this article, a modest framework is proposed to describe HRM process integrity in relation to
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In light of the general inadequacy in the performance of the economic units operating in Iraq, and the contemporary developments in all the various sciences, Iraqi economic units have become obligated to use modern technologies applied around the world. Keeping abreast of these developments is done by moving away from traditional methods of evaluating performance and applying approved and accepted methods of evaluating performance. This will lead to an increase in the efficiency and effectiveness of the activities of economic units. In addition, this drives to reduce production costs. Accordingly, this study aims to clarify the application of the balanced scor
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