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 present study aimed to investigate the effect of re-operations engineering business in continuous improvement, as the rapid development of service activities generally private and the great diversity in the goals of its operations and programs of the university and the service has led to the increasing importance of re-operations engineering business as well as continuous improvement so began to study the relationship between the re engineering and continuous improvement of university service, and applied study on a sample of professors from the faculties of administration, economics and law. Find and reach to several conclusions, notably that the preparation of the teaching staff training sessions on how to use modern teaching
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Gastro oesophageal reflux disease is due to involuntary gastric contents reflux into the esophagus from stomach, causing heartburn and acid regurgitation symptoms. Genetic and environmental factors are important factors in the causation of disease. Human Leukocyte antigens considered as an excellent marker for population genetics analysis and disease association. This study aimed to investigate the association between HLA-DRB1-DQB1 haplotype that inherited in linkage and its association with gastro oesophageal reflux disease (GERD). Patients and healthy controls were prospectively recruited from gastrocolonoscope unit at Al-Kindy Teaching Hospital (Baghdad-Iraq) between January and July 2016. Forty Iraqi Arab Muslims patients with a history
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The present paper investigates the role of fear and predator dependent refuge in the prey-predator system. The system describes the interaction between prey and a stage structure of predator that incorporates Holling II functional response. The predator splits into two compartments immature (juvenile) and mature (adult). The mature predators can hunt and reproduce but this capability is not found in the immature predators, the immature depend on their parents. The growth rate of prey decreases due to the existence of mature predators. The existence, uniqueness, and boundedness of the solution of the system are investigated. Three equilibrium points of the system are determined. The local stability of the system is studied. The global stabil
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The first chapter includes introduce the research and the problem of the research that there are negligence of some educational institutions and schools management , some parents and supervisors .Also there are some educators who believes that school activities are obstacles means to learning and prevent pupils from studying and understanding the subjects. That may due to social , psychological and educational reasons
The purposes of the researches come from the reports of supervision visits which indicate a lot of difficulties faced by pupils and teachers related to education activities and its influence on in education and the necessity of indentify these difficulties and remedy them
... Show MoreCorruption, in all its categories and forms, is regarded as the nowadays virus which has greatly spread in most institutes and society, a matter that cause a great waste of resources.
According to the reports of international transparency Institute, Iraq is regarded as one of the greatest countries in corruption.
Regardless of the reasons and forms of corruption, the retreat in work – values and ethics are the main reasons behind that.
Being the main source of providing qualified staff "educators" for the working market, the high education institutes face great challenges in standing against corruption inside and outside
... Show MoreThe research aims to determine the principles of total quality management (commitment of senior management, product planning, customer satisfaction, process improvement) and its role in promoting employee loyalty through a sample survey of the opinions of managers in public redemption Company. Which amounted to (45) individuals adoption of the questionnaire as a tool head in collecting data and information and their responses were analyzed using several statistical methods, which included (arithmetic mean, standard deviation, correlation coefficient, and the coefficient of simple regression) depending on the program (spss). The research found a group of the most important conclusions from the presence
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