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.
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Our research sheds light on one of the most important aspects of David Grossman's play, "Ricky's Garden, גן ריקי " which is characterized by its realistic portrayal of characters. Grossman gradually moves towards the inner awareness of his characters, expressing their emotions and thoughts through conversations and emotional conflicts, referring to their past and rooted background. Grossman transformed the main subject of his play (psychological depth) into a presentation and arrangement of all the elements of the play in a way that expresses emotional nature more powerfully by each child in the garden. This is reflected in their actions and words, making Grossman's works suitable for study and always of interest to specialized resear
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The provision of electric power is necessary for the advancement of the country's economy. It is the main engine of the economy and its various activities. It is an indicator of social welfare and it is considered as the basic pillars for achieving sustainable development (economic, social, environmental and institutional) by raising the levels of performance and meeting local needs. The problem of research was the absence of a program to audit the performance of the electricity sector contributes to ensure the application of sustainable development. The research was based on the hypothesis that the preparation of a proposed program to audit the performance of the electricity sector contributes to the achievement of The researchers sough
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Due to the developments taking place in the field of communications, informatics systems and knowledge management in the current century, and the obligations and burdens imposed on the business organization to keep pace with these developments, the traditional methods of administrative decision-making are no longer feasible, as recent trends have emerged in management that focus on the need to rely on quantitative methods such as operations research.. The latter is one of the results of World War II, which appeared for the first time in Britain to manage war operations. The first method used in this field is the linear programming method. The use of operations research has developed greatly in the past years, and the methods of analysis in
... Show MoreIt has become clear to see the role of the small and medium enterprises in the economy, and for the continuity of these projects it is necessary to supply finance from the banks, How ever the latter suffers risk of lending.
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Objective: To identify the role and importance of the clinical pharmacist in the Emergency Department on prevent
or reduced the medication error.
Methodology: We collected the medical file of 3400 patients, 1400 patient's file in (A) hospital, and 1000 patient's
file in each of (B and C) hospital, who admitted to the ED, at primary weekdays between 8 am to 2 pm, and
recorded all the intervention made by clinical pharmacist through an active search in clinical charts, with analysis
of the daily medical prescription. The potential severity of harm of the medication error judged by two reviewers,
a permanent emergency physician, and clinical pharmacist based on the National Coordinating Council (NCC) of
Medication Error
The study problem is about the role of Shaqra University in building the mental image of the Kingdom’s 2030 vision among its female students. The study aims to examine the university’s role in providing information about the Kingdom’s 2030 vision, its role in shaping the vision’s image, the university’s role in the behavioral aspect of the vision, along with studying the extent of differences in answers of the sample individuals towards the study themes attributed to the personal variables. The researcher adopted the descriptive survey method. A sample of (1399) female students was used to achieve the study objectives. The results showed that university’s role in building the mental image of the Kingdom’s 2030 vision, among
... Show MoreThe aims of the research is to know the role of strategic to manage the human resources in enhancement the process of knowledge management in the Ministry of Transportation , In addition to the effects occurred on outcomes for both the managers and practitioners .
For the purpose of achieving the objectives of the research , the researchers designed a questionnaire that included (40 Points for collecting the primary data from the sample of the research which contained (51) indiviluals. In light of that, the data was to collect and analyzed and hypotheses were tested by using the (SPSS) Program, and a number of statistical techniques was used to attain the goal of the research such as the means , Sta
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MT Abed, ALSG Irhayyim, TH Rija, International Journal of Psychosocial Rehabilitation, 2020 - Cited by 1
The article describes a study on the role of vitamin C as a protective agent for the teeth, gum, and implants using quantum chemical calculations and polarization tests. The Density Functional Theory (DFT) at 6-311G (d, p) basis set is used to estimate the ability of vitamin C to inhibit the corrosion of the abovementioned parts. The experimental study was performed in a at human body media simulator (Hank’s balanced salt solution) at a temperature of 37°C. The compound was optimized for its ground state, physical properties, and corrosion parameters. Further, HOMO, LUMO, energy gap, dipole moment, and other parameters were used to predict the inhibitor’s efficiency. Gaussian 09, UCA-FUKUI, MGL tools, DSV, and LigPlus software was used
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