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.
Objective of the research This study aimed to manufacture an innovative device that enables the player to walk after the operation and improves functional efficiency through improvement in the range of motion as well as improvement in the size of the muscles working on the knee joint Imposing research There are statistically significant differences between the pre and posttests of the experimental and control groups, there are Statistically significant differences between the post-tests between the experimental group and the control group in favor of the experimental group of the research sample. The researchers used the experimental approach by designing the control and experimental groups with a test (pre-post) for the suitabili
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Municipal solid waste is one of the most important environmental problems in the world and is an important source of environmental pollution and contributes significantly to the pollution of the basic environmental elements of soil, water and air. The management of municipal waste in general is a process of monitoring, collection, treatment or recycling if possible or disposal of waste. This term is used for waste produced by some human activities. States provide this process to mitigate the negative effects of waste on the environment, health and appearance of the city. It is possible to find solutions to the problem of solid waste and make it an important source of income and contribute to securing employment oppor
... Show MoreThe field study of this paper focused on the motives for lawyers to use the website
of the Supreme Judicial Council, and the gratifications achieved as a result of its use.
This study sought to achieve a number of goals, including:
1. Monitoring the patterns of lawyers’ use of the website of the Supreme Judicial Council.
2. Determining the forms that lawyers use to interact on the website of the Supreme
Judicial Council.
This study is a descriptive in kind as the researcher relied on the ‘survey method’ in
its study of the external audience (lawyers) using the questionnaire and scale toolThe questionnaire was distributed among a deliberately chosen sample, consisting of
(160) lawyers who used the website of
In this paper, compared eight methods for generating the initial value and the impact of these methods to estimate the parameter of a autoregressive model, as was the use of three of the most popular methods to estimate the model and the most commonly used by researchers MLL method, Barg method and the least squares method and that using the method of simulation model first order autoregressive through the design of a number of simulation experiments and the different sizes of the samples.
Abstract
This research is aimed at indicating the impact of business process reengineering on corporate performance in the Office of the Inspector General of the Ministry of Higher Education and Scientific Research of the Iraqi study has identified a problem in a number of the most important questions - what the impact of the Business Process Reengineering at the corporate office performance indicators respondent? What are the actual results of the analysis of paths Administrative Process Engineering and Corporate Performance respondent in the office? In order to achieve the goal of the research and answer the questions of the problem, the study applied to a sample of
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Abstract
The logistic regression model is one of the nonlinear models that aims at obtaining highly efficient capabilities, It also the researcher an idea of the effect of the explanatory variable on the binary response variable. &nb
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This study focuses for improving the increase the solubility of fiber cellulose in sodium hydroxide solution in concentrations ranging from (4- 12%), from one point of view and from other point of view in (sodium hydroxide and urea) solution concentration (6% NaOH + 4% urea), under low temperature (- 15, - 20 Co) , depending on the principle of reducing the degree of polymerization for fiber cellulose, which is represented in our tests cotton linter who its represent (Whatman filter paper, Grade 1), some samples subjected to chemical pretreatment as simulation the method of decomposition of cellulosic materials by white or brown fungi that grow on trees, this method involves the use of
... Show MoreThis research has been devoted to the objective and important issue which is the legal protection of the printing form of the newspaper in the Iraqi press.
As this issue constitutes the integrated unit of the printing format in addition to achieving legal protection for the illustrative image used in the press. Such matter, on both level the integrated unit of the printing format and the legal protection, is out of reach of study due to the comprehension of the subject is concerned.
Although there is a justification for dealing with both of them together as the explanatory image is one of the foundations on which the printing format of the newspaper is built. This case generates, at least, the same legal subject that appe
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