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 absence of ecological perception in the local urbanization resulted in the lack of a clear conception of achieving sustainability in its simplest form in the urban reality and in the city of Baghdad in particular. The research assumes the possibility of achieving urban sustainability in Iraqi cities by applying the cities for the most effective methods to implemented ecological solutions and introducing appropriate urban planning tools and improve the living environment. The research focuses on the ability to define some aspects to achieve a sustainable local urban identity from global experiences. This was performed by proposing a scheduled theoretical framework, through which the features of sustainability can be extrapolated from the
... Show MoreMy research deals with the positions that the Prophet (PBUH) distressed. And condolences to those who lost her father and other problems and calamities that impede the life of women, has been given to the Lord of men, and good qualities, to strike the nation's finest proverbs in ensuring lost and lost of women and children, to be shown to us humanity in its finest form, and the best analyzed, and I hope God help And guidance and Rashad
Purpose – determine the impact of the promotional mix in achieving competitive advantage in industrial organizations.
Problem- indicated a clear deficiency in employing the dimensions of the marketing mix in ensuring a competitive advantage for the researched organization.
Design/methodology/approach – Al-Dora Refinery was selected as a field of application. The sample was chosen by an intentional sample of (143) individuals in the Human Resources departments. The questionnaire was adopted as a data acquisition tool that was prepared based on a set of ready-made standards after being subjected to a number of v
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Leaching scheduling techniques are one of the suggested solutions for water scarcity problems .The aim of the study is to show the possibility of using leaching scheduling, when applying the irrigation scheduling program for a certain irrigation project, which was prepare by Water Resources Engineering –University of Baghdad with some modifications to generalized it and it make applicable to various climatic zone and different soil types.
The objectives of this research is to build a system that concerns the prediction of the leaching scheduling (depth and date of leaching water), illustrating the main problems (soil salinity, save the amount of leaching requirement, and to maintain crops growth).The other objective is to compare be
The research aims to study the impact of the dimensions of fun in the workplace in achieving internal marketing And knowing the type of relationships That link the dimensions of fun in the workplace With each other, None of the researchers mentioned (to the researcher's knowledge) the link between fun in the workplace and internal marketing From this point of view the main objective is determined, which is to study the effect of fun in the workplace in internal marketing, The research was conducted at Al Salam Public Company for Communications and Information Technology The research community was represented by (308) employees of the aforementioned company , Where a random sample was selected tha
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Abstract: Stars whose initial masses are between (0.89 - 8.0) M☉ go through an Asymptotic Giant Branch (AGB) phase at the end of their life. Which have been evolved from the main sequence phase through Asymptotic Giant Branch (AGB). The calculations were done by adopted Synthetic Model showed the following results: 1- Mass loss on the AGB phase consists of two phases for period (P <500) days and for (P>500) days; 2- the mass loss rate exponentially increases with the pulsation periods; 3- The expansion velocity VAGB for our stars are calculated according to the three assumptions; 4- the terminal velocity depends on several factors likes metallicity and luminosity. The calculations indicated that a super wind phase (S.W) developed on the A
... Show MoreThe current study aims to identify the effect of guided visualization strategy in developing the visual perception among kindergarteners. The experimental design was used; pre-post test. A total of (32) boy and girl ranging 5 to 6 years old were selected from al-Rabeea’ kindergarten, directorate of al-karkh 2 / Baghdad. The sample divided into equal two group (16) boy and girl of each one. al-Talaqany’s (2016) visual perception skills test among kindergarteners was adopted to collect the required data. The collected data had processed based on (gender, pre-post test, and age). To achieve the objectives of the study; the researcher set up series of sessions that addressed the guided visualization strategy among kindergarteners compose
... Show MoreThe logistic regression model is one of the oldest and most common of the regression models, and it is known as one of the statistical methods used to describe and estimate the relationship between a dependent random variable and explanatory random variables. Several methods are used to estimate this model, including the bootstrap method, which is one of the estimation methods that depend on the principle of sampling with return, and is represented by a sample reshaping that includes (n) of the elements drawn by randomly returning from (N) from the original data, It is a computational method used to determine the measure of accuracy to estimate the statistics, and for this reason, this method was used to find more accurate estimates. The ma
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The research aims to determine the mix of production optimization in the case of several conflicting objectives to be achieved at the same time, therefore, discussions dealt with the concept of programming goals and entrances to be resolved and dealt with the general formula for the programming model the goals and finally determine the mix of production optimization using a programming model targets to the default case.