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 shows the importance of orientation towards the formulation of the green strategy and its effect in determining the behavior of the green municipal institution in Babel governorate. The research highlighted the formulation of the green strategy as an important variable, especially today, the trend towards protecting the environment and minimizing the damage resulting from the delivery of services, and through it also the type of green behavior or performance adopted by the municipal institution and the emergence of the need for a strategy that is not harmful to the environment. The research took the sample intentionally comprehensive size of 222 personnel of municipal institutions and some formations concerned with t
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The skill of management educational activities gradually grow with the experience, but they differ from personal skill educator to another, because each style nanny personally and the way to work. There educator and active movement and vitality that look like happiness and clear during the implementation of the activity, and the other runs educational activities quietly, efficiently and without emotion and clear (dry, 2001: p. 274). And the stage of childhood is one of the most important stages that are based upon the future life as a whole because the man also confirmed by the School of analysis psychological is the son of his childhood and the best example to us what the Holy Prophet Muhammad (peace be upon him): (Every child i
... Show MoreHypothyroidism is a frequent disorder in the general population, especially among women, is defined as adeficiency of thyroid activity that results from insufficient production or action of thyroid hormones leading to a totaldecrease of metabolic. Human leukocyte antigen is the most polymorphic genetic system in man. Genes of this regioninfluence susceptibility to certain diseases.Objectives: The purpose of the present study is to investigate the role of HLA-DRB1 genotyping in hypothyroidpatients with and without periodontitis. Sixty hypothyroid patients 30 of patients were with periodontitis and 30without periodontitis compare with 30 healthy subjects as control enrolled in this study. DNA was extracted fromblood samples, then HLA- genotyp
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Background: The materials and techniques of orthodontic bonding systems remain a pivotal concern in orthodontic research. This issue is further complicated by orthodontists' preferences. To assess the effect of knowledge and practice on the attitudes of orthodontists towards bonding materials and techniques. Methods: A cross-sectional, questionnaire-based study was conducted using Google Forms. The questionnaire comprised 17 multiple-choice questions that targeted orthodontists' awareness, knowledge, and attitude towards bonding materials. It was distributed via email or social networking platforms to specialist Iraqi orthodontists. Results: A total of 176 participants responded with nearly equal representation between the sexes. Th
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Occupies total quality management applications play a key role in the development of institutions of higher education performance and achieve its strategic objectives through the commitment of senior management and their employees to continuous improvement of the quality of performance in the various areas of work, and can be integrated knowledge management processes, which means identifying information of value and how to take advantage. The data were collected using the style of the questionnaire for the purpose of analyzing their results on a sample composed of 83 member of the administrative leadership in colleges as representing the decision-making centers in those colleges .
 
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The aims of this study to diagnose the role of the (relationship and impact) Academic driving practices dimensions (model the way, inspire a shared vision, challenge the process, enable others to act, encourage the heart ) in the activation of human capital (investment and development) for (knowledge, skills, expertise, creative and training capabilities) in a sample of university professors in Baghdad city(Baghdad University, Al Mustansiriya University, University of Technology). (367 )samples were distributed to (232 at the University of Baghdad, 97 at Al-Mustansiriya University and 38 at the University of Technology). The goals of descriptive analytical method research have been used, questionnaire has been a main tool for dat
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Abstract
Leadership has now become a process for applying methods and techniques that make the Organization at the top of its competitive pyramid a greater market share. Leadership has become a focus for all leaders and managers، and leaders and managers are increasingly seeking to develop their skills and leadership skills. The research started with a clear problem of specific questions to ensure that the general objective of the research is to describe the characteristics of the leader and to clarify the dimensions of empowering the workers and to highlight the role of the leader in empowering the workers. The study examines the relation between the role of the leader in
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