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 design of components subjected to contact stress as local compressive stress is important in engineering application especially in ball and socket Joining. Two kinds of contact stress are introduced in the ball and socket joint, the first is from normal contact while the other is from sliding contact. Although joining two long links (drive shaft in steering cars) will cause the effect of flexural and tensional buckling stress in hollow columns through the ball and socket ends on the failure condition of the joining mechanism. In this paper the consideration of the combined effect of buckling Load and contact stress on the ball and socket joints have been taken, epically on the stress distribution in the contact area. Different
... Show MoreThe aim of this research is to construct a cognitive behavior program based on the theory of Meichenbaum in reducing the emotional sensitivity among Intermediate school students. To achieve the aims of the research, two hypotheses were formulated and the experimental design with equal groups was chosen. The population of research and its sample are determined. The test of negative emotional sensitivity, which is constructed by the researcher, was adopted. The test contains (20) items proved validity and reliability as a reliable test by presenting it to a group of arbitrators and experts in education and psychology. An educational program is constructed based on the theory of Meichenbaum. The test was applied to a sample of (60) second i
... Show MoreThis research aims to study the target costing and value chain with their complimentary relationship in reducing product costs, meeting the needs of customer, and achieving strategic competitive advantage for manufacturing corporations in response to face international competition, technological development and continuous changing expectations of customers. No doubt, the target costing and value chain both currently occupy a great deal of the attention of managers and accountants at the manufacturing corporations due to the significance to insure their continuity, growth and development. This significance has been the main motive to examine the role of target costing and value chain in a sample of public corporations of the
... Show MoreThe research studied and analyzed the hybrid parallel-series systems of asymmetrical components by applying different experiments of simulations used to estimate the reliability function of those systems through the use of the maximum likelihood method as well as the Bayes standard method via both symmetrical and asymmetrical loss functions following Rayleigh distribution and Informative Prior distribution. The simulation experiments included different sizes of samples and default parameters which were then compared with one another depending on Square Error averages. Following that was the application of Bayes standard method by the Entropy Loss function that proved successful throughout the experimental side in finding the reliability fun
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Abstract
This research aims to analyze the reality of the production process in an assembly line Cars (RUNNA) in the public company for the automotive industry / Alexandria through the use of some Lean production tools, and data were collected through permanence in the company to identify the problems of the line in order to find appropriate to adopt some Lean production tools solutions, and results showed the presence of Lead time in some stations, which is reflected on the customer's waiting time to get the car, as well as some of the problems existing in the car produced such as high temperature of the car, as the company does not take into account customer preferences,
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This Paper aims to plan the production of the electrical distribution converter (400 KV/11) for one month at Diyala Public Company and with more than one goal for the decision-maker in a fuzzy environment. The fuzzy demand was forecasting using the fuzzy time series model. The fuzzy lead time for raw materials involved in the production of the electrical distribution converter (400 KV/11) was addressed using the fuzzy inference matrix through the application of the matrix in Matlab, and since the decision-maker has more than one goal, so a mathematical model of goal programming was create, which aims to achieve two goals, the first is to reduce the total production costs of the electrical distribution converter (400 KV/11) and th
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On Saturday, May 13, 2023, a glorious day was engraved in the history of Al-Kindy College Medical Journal as it is the day of indexing the journal in the Scopus Database Journals. The journal has paced a strenuous journey to make that achievement.
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The exchange rate is of great importance at the global and local levels alike, as this importance increases with the increasing rates of development of economic relations between countries of the world due to openness and integration into the global economy, expressed by the expansion of the volume of trade and financial relations between countries. The Central Bank of Iraq has set the need to stabilize this price as a goal to reduce inflation rates and reduce them to the internationally accepted rates by using the foreign currency sale window to achieve a balance between the forces of supply and demand for foreign currency and to preserve the value of the Iraqi dinar. The research concluded that the central bank was It has a maj
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The most important issue that 21-century in knowledge organization try successfully to face and solve is the determination of the ways and the processes through which they can measure and assess the intellectual capital (IC). In spite of the importance of the human capital in the knowledge organization, The accounting as an information systems, does not give a great deal of consideration to the human capital, and does not treat investment in it as an original factor, but it shows it on the base of salaries and payrolls that is appears in the financial statements as a revenue expenditure. As a result of that the financial statement are not a true expression of the actual status and then some of the decisions taken under the present circum
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