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.
This research sheds light on the use of metal in the manufacture of jewelry, which is represented by ornamental tools in the period between the third and second millennium BC, in addition to the most important molds used in their manufacture. Man has been interested in metals since early ages, and was able to make tools that he uses in his daily life, especially jewelry. And the Syrian people got acquainted with the types of minerals, their characteristics, and how to deal with them. Minerals played an effective and prominent role in the economy of ancient Syria. Trade with those countries and secure their roads.
Marriage outside the court is a manifestation of the oppression that women are subjected to in Iraq its seriousness comes out of the consequences that it leads to The. It overlooks the age of the girl and her marriage in younger age or coerced to marry as it leads to neglecting the affordability of marital relationship as long as the marriage does not have any legal or material consequences. The present study aims to detect Characteristics of both wives, husbands and families Who agree to marry her daughters outside the court. And the reasons that lead them to marry outside the courts. It also aims to provide information on the circumstances of marriage and reasons for refusing to ratify it in court. The study was based on the sample soc
... Show MoreVocational education is the basis of contemporary educational movement that aims at satisfying human needs. Societies can develop their human resources via setting programs for the working class as an aspect of the comprehensive national development. Vocational education is the main source of technical cadres the Iraqi labor market requires of the vocational preparatory schools to provide after three years of schooling.
The vocational schools of the governorate of Basra have a number of problems that lead to the lack of proficiency of their graduates. This study is an attempt to identify these problems or obstacles
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Abstract
Suffering the human because of pressure normal life of exposure to several types of heart disease as a result of due to different factors. Therefore, and in order to find out the case of a death whether or not, are to be modeled using binary logistic regression model
In this research used, one of the most important models of nonlinear regression models extensive use in the modeling of applications statistical, in terms of heart disease which is the binary logistic regression model. and then estimating the parameters of this model using the statistical estimation methods, another problem will be appears in estimating its parameters, as well as when the numbe
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She noted most of the results of research conducted on the use of computers and the Internet in the areas of administrative, economic, agricultural and educational to a significant improvement in learning outcomes of these groups in the development of mechanisms of action, has increased rates of computer use and applications in various spheres of life at very fast pace so that the computer and the Internet is a vital part of any activity, whether administrative or research or the media, hence it can be said that the use of computers and the Internet in the management of public relations activities in any organization can accelerate the pace of echo positive goals and purposes of public relations, this study comes to looking at us
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تعد المحاسبة بشكل عام علماً لكنها ليست من العلوم الصرفة وإنما من العلوم الإجتماعية مما يتطلب للتعامل مع المواضيع المحاسبية الأخذ بنظر الاعتبار الأشخاص المعنيين بالموضوع سواء كانوا المعدين للمخرجات المحاسبية أي المحاسبين، أو الاطراف ذوي المصالح المعنيين والمستفيدين من هذه المخرجات أي المستخدمين، ويعد المحاسب جزءاً من العملية الاجرائية نفسها وبهذا يكون دوره مزدوجاً يجمع بين كونه القائم بالبحث والقي
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Objective: To identify the effect of the cube model on visual-spatial intelligence and learning the skill of spikinging in volleyball for female students, The researchers used the experimental method by designing two equivalent groups with pre- and post-measurements. Research methodology: The main research sample of (30) female students was selected from the research community represented by second-stage students in the College of Physical Education and Sports Sciences - University of Baghdad for the academic year (2024-2025). The sample was divided equally into two control and experimental groups. The researchers conducted the sample homogenization process and the equivalence process between the two groups in the variables of visua
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Factory is trotting home favorite of of Aeidid of Iraqi families since he Amta imparted to the taste of the housewife on the method of processing and preparation and the possibility of using some of the ingredients to raise the nutritional value of meat, sesame and other, but how keep Bz'zajh this product Atne storage
Autorías: Muayad Kadhim Raheem, Lina Fouad Jawad. Localización: Opción: Revista de Ciencias Humanas y Sociales. Nº. 21, 2019. Artículo de Revista en Dialnet.
Technological and digital development has allowed the emergence of many methods of producing semantics on social media sites within semiotic and propagandistic frameworks. This is what made the image appear in different molds and shapes, especially as it is the first material for visual perception.
This made the Israeli propaganda discourse use it as an important tool to manage the content of suggestive messages with semiological connotations. By doing so, such tool uses social networking sites as an appropriate environment to achieve those goals, which are related to cases of manipulating emotions and minds. It, moreover, changes convictions, attitudes, trends and behaviors according to what the propaganda planner wants.
Many Isra