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.
Background: The use of the cone beam computed tomography for analysing the position of the greater palatine foramen in relation to various anatomical landmarks is crucial in dentistry. The aims of the current study, firstly is to determine the greater palatine foramen position in relation to various anatomical landmarks by using cone beam computed tomography and secondly is to make a comparison of the measurements according to side, gender, and age. Materials and methods: This prospective study included 60 Iraqi patients (28males and 32 females) who selected according to availability of Inclusion criteria, which include age range (21 - 60 years), with no dentofacial deformities or pathological lesion at the maxilla. All patients had inform
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The research Reviews the sides of highlight importance of the Nano-Accounting which doing the accounting performance functions fully computerized without the intervention of an accountant, to solve the problem of not keeping up the rationalization of recording and accounting systems, with the rationalization of production which fully computerized.(be invisible and hidden accounting), resulting by linking or interaction of the accounting, additive production system represented three-dimensional printers, open source and recycling. That which result the rationalizing the facilities of production, organization and self-control which derived nanotechnology idea, which aims to minimize materials and change it properties, then view the a
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The research stems from the problem that focuses on a number of questions. They are as follows: What is the extent of interest in the topic of efficiency by the banks and their role in raising the efficiency of the banking business and its development? Is the banking efficiency used in Iraqi banks clear and specific for the Iraqi banking sector? How the banking sector efficiency is measured and what are the approaches adopted in determining the banking inputs and outputs? What is the level of efficiency in the research sample of the banks and what are the causes of its decline or rise in private banks individually and in the Iraqi banking sector in general?
The re
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ABSTRACT
The purpose of the research is to identify the role of drinking water quality in achieving customer satisfaction in one of the formations of the Ministry of Construction, Housing and Public Municipalities (Diwaniyah Water Directorate), as they are important service organizations that have a fundamental role in serving the community. Faced many administrative challenges, as a result of the continuous and accelerating environmental changes, environmental pollution and immaturity of social awareness and social responsibility, as these contributed to and affected the quality of drinking water, Therefore, it is necessary to know the role of quality, specifically "drinking water and its effect o
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The role of specific amino acids namely cysteine, methionine, threonine and asparagine in the protection provided by vamin solution against B-lactam inhibition to E. coli was evaluated in vitro In minimal medium, cells were treated with 32 ug/ml of penicillin G, carbenciLlin, hostacillin, cloxacillin and cephalotin in the presence of specific amino acid supplementation. Deletion of specific amino acids from the media abolished the protection provided by vamin. Threonine was essential for the protection of cells against all tested antibiotics, while cysteine was essential for protection against carbencillin and sephalotin. Deletion of methionine or asparagine abolished the protection against carbencillin and to a less extent cephalotin.
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Nowadays, the world adopts a philosophy that relates to environmental conservation. This philosophy can be achieved through providing environmentally friendly products while satisfying customers' needs as well. To attain that, a new systems and programs need to be applied in a scientific manner, and total quality environmental management (TQEM) is among these concepts. The research aimed to analyze the Relationship between (TQEM) Practices and its effect on Flexible Manufacturing in Badush factory. The research sample includes managers and head of divisions at top, middle and front line management levels which were (27) working in Badush factory. To achieve the objectives of the study, the descriptive anal
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The importance of the study lies in highlighting the role of smartwatches as a modern tool for analyzing training load based on functional indicators, such as heart rate and calorie consumption. This allows coaches to monitor individual players’ responses during different training periods, helping to improve physical performance efficiency and reduce the risk of overload-induced fatigue. The study aimed to analyze calorie consumption at different heart rate levels between the special preparation and competition periods for youth football players, with the goal of determining the effect of physiological adaptation on energy efficiency. To achieve this objective, the researcher adopted the descriptive method due to its suitability f
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The current research focuses on a major problem: the weak role of disclosing corporate information in the application of laws, regulations and instructions related to the application of corporate governance principles weakens the ability to protect the rights of shareholders and investors in companies listed on the Iraqi Stock Exchange and the study aims to study and analyze the role of disclosure and transparency in achieving the necessary protection to ensure the rights of shareholders. The study was applied to a sample of (42) analysis samples representing (84%) of the total questionnaires distributed to investors and shareholders in all listed companies in the Iraqi Stock Exchange. The results confirm the shareholder's right to obtai
... Show MoreThe importance of the research comes from dealing with the problem of lack of traffic awareness, which causes accidents and the occurrence of human and material losses, and the research aims to study the role of satellite channels in forming traffic awareness among the public, and a sample was chosen from Baghdad consisting of (280) individuals, male and female, and used the questionnaire tool. To obtain the data, which included several questions, the results were analyzed statistically and several results were reached, the most important of which is that there is an interest among the public in following traffic programs at a rate of one to two hours to receive information through traffic programs and to identify and apply gener
... Show MoreInvestment drives the wheel of the development of different developed and developing countries. Sudan is a model for a developing country facing a lot of difficulties in the field of both local and foreign investment. The present study was focused on the problem of poor diversification and efficiency of both local and foreign investment in Sudan. Also, it clarified the important role of administrative supervision to strengthen the efficiency of investment, taking the experience of the Sudan as a model. The researchers used the well-known descriptive and analytical tools (questionnaire, interview, observation) to complete this study. A well designed questionnaire was used. It included all questions that could cover all aspects of
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