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.
Infection with Trichomonas vaginalis and its relation to some diseases have lately had much attention. The objective of this study was to assess the infection rate of T. vaginalis and its relation to pelvic inflammatory diseases, infertility, and vaginosis. The study also assessed some demographic, clinical, and immunological parameters in women infected with T. vaginalis. The study included 160 non-pregnant married women who attended some private clinics and public hospitals in Baghdad from October 2020 to February 2021. All participants had symptoms of vaginal discharge only or vaginal discharge with lower abdominal pain. The participants were divided into an infertility group (n = 61) and fertility group (n = 99). The participant
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Objective(s): The study aims Finding relationship between UTI and demographic variable include: child's age, child's gender, if males are circumcised or not, child's order in his family, father's level of education, mother's level of education, place of residence and family socioeconomic status. Methodology: A descriptive study was conducted on students of primary schools for both sexes, for the period from 19th. February 2014 through to 4th March 2014. A selected sample from two steps the first stage is to choose a school by a stratified- cluster sample, getting schools that have been selected (12) sch
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Abstract
This research aims to the relationship and the effect of concurrent engineering dimensions analyze (product design, process design, and supply chain design) on the dimensions of strategic performance (efficiency, and effectiveness) The research was conducted in public Zora Electrical Industries Company, on a sample of departments and officials, engineers, managers and people in the company amounted to (45) . A questionnaire was used for the purpose of data collection which has been adopted, with the use of statistical methods via computerized system (spss) for processing data , identifying them and testing the research hypotheses. The research
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The research aims to determine the principles of total quality management (commitment of senior management, product planning, customer satisfaction, process improvement) and its role in promoting employee loyalty through a sample survey of the opinions of managers in public redemption Company. Which amounted to (45) individuals adoption of the questionnaire as a tool head in collecting data and information and their responses were analyzed using several statistical methods, which included (arithmetic mean, standard deviation, correlation coefficient, and the coefficient of simple regression) depending on the program (spss). The research found a group of the most important conclusions from the presence
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The Agricultural Policy is one of the most important tools adopted by the state to guide its economic and social activities through the delivery of suitable agricultural commodities to the consumer and in return to deliver agricultural inputs to the agricultural producers at the lowest possible cost to contribute in achieving a profit that helps the agricultural product to continue in the production process with the same efficiency and ambition. So as to help increase the contribution of the agricultural sector to GDP and achieve the best picture of sustainable agricultural development.
The research aimed at identifying the reality of agricultural policies and their role in achieving sustaina
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The banks mobilize savings and channel them to the economy, whether commercial or Islamic banks and thus both contribute to increasing financial depth, the objective of this paper is to measure the contribution of the Islamic banks in increase financial depth in Iraq, and compared the role played by private commercial banks in contributing to increasing financial depth in Iraq. The paper has been applying the most used indicators of financial depth that used widely in the literatures, especially those applicable with the Iraqi economy.
The paper found via using the Autoregressive Distributed Lag Model (ARDL) that Islamic banks did not contribute to increasing financial depth in Iraq, as well as for the p
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The acute phase response is a major pathophysiologic phenomenon that accompanies inflammation whether acute or chronic. Complement (C3 and C4) and C - reactive protein (CRP) are positive acute phase proteins (+ ve APPs ). Their production takes place in hepatocyte and the blood concentration of these parameters are increased in osteoarthritis (OA). Chloroquine (CQ) is a diprotic weak base traditionally used to treat malaria. Recently the phosphate salt of CQ is used to decrease this type of (+ve APPs) . In this study, patients who suffered from knee osteoarthritis (KOA) are treated with oral dosage form of chloroquine phosphate (CQP) for one month, twice daily. Our results demonstrate that CQP improves the patient status by decreas
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