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.
Using the traditional methods in teaching Islamic subject have neglected student's role and focus mainly toward teacher. Thus, the role of student in teaching process would take a negative side: following these methods cannot achieve the educational objectives of Islamic subject. Teachers who give Islamic subject do not have a full knowledge of the appropriate techniques in teaching. They lack the scientific background that qualify them for teaching. The weakness of knowledge that face Islamic teachers have arisen over different stages of education which showed their lacking in the provision of intonation and interpretation of the Quran as well as the utterance of Prophet Mohammed Hadiths. It takes time to train teachers to do a
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The research aims at achieving a set of objectives, which is to study a vital variable in the organizations which is the talent management and its impact on encouraging and empowering employees to take part in making appropriate decisions with their heads in the Iraqi Cement State Company. The problem of this research is in finding solutions to the weaknesses that face the managers in attracting talented employees and keep them in the company, and this leads to a weak capacity of the company on authorizing talented employees and giving them the needed confidence to participate in decision making process. The research sample was included (45) managers in the researched company. Th
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The current research aims to diagnose the extent of interest in knowledge sharing and its role in achieving organizational excellence at the level of the Iraqi environment Primary data through descriptive statistics (arithmetic mean, standard deviation, coefficient of variation, percentages, frequencies) and hypothesis testing using appropriate statistical methods for inferential statistical analysis (Pearson correlation coefficient, simple linear regression, multiple regression, path analysis) and checking the quality of the data from During (normal distribution, confirmatory factor analysis, structural modeling method, and exploratory factor analysis), after collecting data from (358) observations from the company’s leaders, as
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Abstract
The research aims to study the problem of high production costs and low quality and the use of total quality management tools to detect problems of the high cost of failure and low quality products, diagnosis, and developing appropriate solutions.
To achieve the goal, we studied the overall quality tools and its relationship with the costs and the possibility of improving quality through the use of these tools.
Was limited to these tools and study the relation to the reduction of costs and improving quality have been studied serially by the possibility of the reduction.
To achieve the goal, the study of the concept of total quality management
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The risk of breast cancer development is believed to be attributed to the alterations of a number of key biological components. Within this context, elevated levels of some chemokines that act as growth factors and can promote cancer development. The current study was designed to evaluate CXCL3 (a chemokine C-X-C Motif Ligand 3) and leptin (a peptide hormone synthesized by adipose tissue with cytokine activity) serum of Iraqi breast cancer patients in comparison to healthy controls. A total of 90 participants consisted of 60 patients diagnosed with breast cancer and 30 healthy women as control group were enrolled into this case-control study. Venous blood samples were collected from all participants to evaluate CXCL3 and leptin serum levels
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The purpose of research is highlighting the role of tax expenses in promoting direct foreign investment in Iraq, The main objective of the increase in the field of tax expenses is to manage the competition in the production of goods and services locally, in addition to the various qualities of the economical. As the search contributes to the idea of the role of the policy of the tax expenses in the promotion of foreign companies operating in Iraq. The analytical and transparent transparency used by adoption of cases of the relevant body of the tax body. For each image or form of tax expenses have been reliably related to the promotion of direct foreign investment, the taxpayers highlighted the annual controls, tax cuts as the sample was
... Show MoreObjectives: This study aims to broaden our knowledge of the role of eDNA in bacterial biofilms and antibiotic-resistance gene transfer among isolates. Methods: Staphylococcus aureus, E. coli, and Pseudomonas aeruginosa were isolated from different non-repeated 170 specimens. The bacterial isolates were identified using morphological and molecular methods. Different concentrations of genomic DNA were tested for their potential role in biofilms formed by study isolates employing microtiter plate assay. Ciprofloxacin resistance was identified by detecting a mutation in gyrA and parC. Results: The biofilm intensity significantly decreased (P < 0.05) concerning S. aureus isolates and insignificantly (P > 0.05) concernin
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The current research aims to verify the relationship and impact of internal control activities as an independent variable in its dimensions (efficiency, training, independence) in making administrative decisions as a responsive variable and its dimensions (identifying and diagnosing the problem, searching for alternatives, evaluating alternatives, choosing the appropriate alternative, implementing the decision, following up Decision and evaluation) in the Kirkuk Water Directorate, as well as to identify the levels of their practices, and then try to come up with a number of recommendations contribute to the strengthening of internal control activities and the process of making administrative decisions of the researched Directorat
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Background: Pseudomonas aeruginosa is a devious pathogen with the tendency to prompt many acute and serious chronic diseases. This study aims to detect novel genes (Toxins-Antitoxins II system), especially; higB and higA encoded from P. aeruginosa by PCR technique and the relation between these genes and antibiotic resistance of P. aeruginosa. Methods: This study detected 50 isolates of P. aeruginosa from distinct clinical sources. The most common origin of isolates was (44%) burn swabs, (22%) urine culture, (12%) wound swabs, (14%) sputum, and (8%) ear swabs. The bacteria were isolated using implantation MacConkey agar and blood agar, as well as biochemical tests including oxidase test, catalase test then VITEK-2 System of P. aerug
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Background: Conventional MR imaging is essential for diagnosis and evaluation of the posterior fossa tumors Objectives: To assess the value of diffusion weighted imaging and apparent diffusion coefficient in making distinction between different histological types of posterior fossa tumors.
Type of the study: Cross-sectional study.
Methods: Brain MRI and DWI assessed 19 patients (12 female and 7 male) with MRI diagnosis of posterior fossa tumors. absolute ADC values of contrast -enhancing solid tumor region and ADC ratio of solid tumor to ADC of normal -appearing deep White matter were compared with histological diagnosis postoperatively .The m
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