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 increase in military spending has become a feature of the times for many countries, including China. They have sought to increase their defence spending, not with the aim of domination and possession, but rather to protect their economic interests and to secure their foreign trade. The research aims to identify the impact of military spending by studying the nature of defence spending and its role in providing security. And stability and facilitating foreign investment in it, as well as storming the military industry, securing some humanitarian supplies, and participating in a variety of public works that can be used in the civil and military fields, and the aim of the research is to id
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The research aims to shed light on the importance of forensic accounting and its impact on the outcome of the activity of the Iraqi general insurance company by winning the lawsuits filed against the company because the forensic accountant (the judicial expert) possesses the ability to interpret and analyze the data. The research community represents the insurance companies in Iraq. Iraqi insurance, and the researchers adopted the descriptive approach in covering the theoretical aspect and the deductive approach in covering the practical side, depending on the financial statements of the Iraqi insurance company for the years of research.
One of the most important conclusions reached by the researchers was that forensic accounting
... Show MoreDuring the study the current selection seven stations in the Zab River bottom and the Tigris River took samples a month to study the signs of bacterial contamination study coliform and colon fecal Almsobhaat and Almsobhaat Bazah and the total number of bacteria and bacterial gangrene gas causing Knkeran as well as a study to isolate and diagnose some races and types of bacterial pathogens in water or intensityusing the traditional system and the system of intestinal bacteria
This study included an analysis of three stations (Al Dora, Al Za'franiya, and Arab Ejbur) chosen to study the Physiochemical and microorganism (Fungi and Bacteria) loud of the Tigris River in the southern section of Baghdad city. The result of this research shows that the highest temperature recorded in summer in Al Za'franiya was 37Co, while the lowest temperature recorded in winter in Al Dora was 9Co. and the value of pH recorded the highest in summer it was 7.9 in Arab Ejbur, and the lowest value was in winter 7.1 in Al Dora regions, While Total Organic Carbon (TOC) shows the highest values found in the summer was 6.7 Mg L-1in Al Za'franiya Samples, and the lowest values were 2.0 Mg L-1in Arab Ejbur during the winter. The more f
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In this study an illustrated key for the identification of the Iraqi species of the genus Chalcophorella Kerr. is given with information about general distribution for each species. Information is also given about period of collection, plants on which the specimens were collected. The real host plant if they are available and known are also given referring to the previous works.
The study aims to find out the effectiveness of using the Google classroom educational platform in teaching mathematics curricula from the viewpoint of teachers in the Governorate of Al Dhahirah, Sultanate of Oman. The researcher adopted the descriptive-analytical approach. To collect the needed data, a questionnaire of two dimensions was used. It includes (13) items to measure the effectiveness of using the Google classroom in teaching mathematics curricula from the teacher's point of view and includes (10) items to measure the difficulties of using the Google classroom in teaching mathematics curricula from the teachers' point of view. These tools were applied to (32) male and (31) female as the study sample. They represent mathematics
... Show MoreThe variables of quantitative and qualitative Population role in the economic development process and it was said the human center of development and population is the goal of development and its tool , and Iraq suffers from problems in the economic growth and the standard of living and development in general, and if I want him evolution and development sectors must pay for these demographic changes especially , to study and that invest Pmaasb in the interest of the man
The study of the demographic situation in Iraq and at the provincial level to track paths demographic change and its impact on the entry of Iraq to the demographic window due to the change in the age structure of the population and how to use them and invested well in
The tax system, like any other system, as a set of elements and parts that complement each other and are interrelated and interact to achieve specific goals, and is a natural reflection of the economic, social and political conditions prevailing in society, and therefore the objectives of tax policy formulated in line with the objectives of economic policy in general, which means that any change in economic policy clearly affects fiscal policy measures and fiscal policy in particular.
The problem of searching for the impact of foreign direct investment in the Iraqi tax system was focused on the study the of foreign direct investment and therole played in developing and improving the economic reality and its implicatio
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The right of the patient to know the medical risks surrounding the medical intervention is one of the most prominent rights based on the principle of "physical safety", which has undergone several stages of development until it reached the development of the patient's independence in making medical decision without relying on the doctor, The patient's prior informed consent is informed of his / her medical condition. We will study this development in accordance with the French March 4, 2002 legislation on the rights of patients in the health system, whether it was earlier and later. We will highlight the development of the patient's right to "know the medical risks surrounding medical intervention" The legislation and its comparison with th
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