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 research aimed to explore the recall habits and developing the right recall habits at middle school students. A sample of (40) students were chosen intentionally from middle school students in two schools (almntzr- zany aleabdyn) with an average of (20) students from each school. They were evenly distributed in two experimental and control groups. To achieve the aims of the research, a scale was designed to measure the recall habits, and a preparation of an educational program to develop recall habits.
To process data statistically, the researcher used several statistical methods such as Pearson correlation coefficient, chi-square, T-test for one sample, T-test for two independent samples, Wilcoxon test, Mann-Whitney test, ET
... Show MoreThe research in Islamic history is considered a title for the glory of the nation and a mirror for the intellectual and mental maturity of the men of the Islamic state who played an important role in saving humanity from darkness to light and from ignorance to knowledge and to show their position in building the Islamic state, and to highlight the importance of their conquests of neighboring cities and the expansion of Islam, and for this reason they appear The importance of writing on the topic (The Battle of Dumat al-Jandal and its impact on the era of the Prophethood and the Rightly Guided Caliphate). The reason for choosing this topic was to show the status of Dumat al-Jandal and its importance in the Islamic state and its great role
... Show MoreThe current research aims to analyze the mathematics book for the first intermediate grade according to the dimensions of mathematical power by answering the following question: What is the percentage of the availability of the dimensions of mathematical power included in the content of the mathematics textbook for first-grade students, average, in its first, and second parts for the academic year 2020-2021, approved by the Iraqi Ministry of Education / General Directorate of Curricula? The research community was determined by middle school mathematics books, and middle school students for middle ,and high school day schools affiliated to the Directorate of Education in Dhi Qar, and by the intentional test, the research sample was s
... Show MoreBackground: Breast cancer is the most frequently diagnosed malignancy and the second leading cause of mortality among women in Iraq forming 23% of cancer related deaths. The low survival from the disease is a direct consequence to the advanced stages at diagnoses. Aim: To document the composite stage of breast cancer among Iraqi patients at the time of diagnosis; correlating the observed findings with other clinical and pathological parameters at presentation. Patients and Methods: A retrospective study enrolling the clinical and pathological characteristics of 603 Iraqi female patients diagnosed with breast cancer. The composite stage of breast cancer was determined according to UICC TNM Classification System of Breast Cancer and the Ameri
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The current research aims to identify the " impact of strategic warheads numbered ( NHT) in the collection average second grade students in the article of history). " To achieve this, I assumed the researcher that there is no different between the statistically significant the average score for the collection of experimental group who teaches the Arab Islamic history on and a strategic warheads numbered and the average score for the collection of the control group who were studying the same article according to the classic method ( traditional) . The study sample consisted of 64 students from the second grade average in the secondary warka bin nawfal in the general Directorate for education first karkh in Baghdad for the annual cources 2
... Show MoreThe research deals with the problems of improvisation in two basic subjects and applied a samples and conclusion. The first topic focuses on the concept of improvisation and spontaneity and clarifies the confusion between them. The second topic deals with the foundations and principles on which the actor is based in his artistic preparation for the purpose of developing his improvisational abilities.
The research focuses on clarifying the dimensions of improvisational techniques and its multiplicity in the modern theater. It analyzes the method of improvisation and its use in the construction and composition of the theatrical performance. It deals with two important experiments, such as the experience of the Russian directo
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The current study, which extended from February 2020 to June 2021 at the University of Thi- Qar\ College of Education for Pure Sciences, aimed to follow the changes in external morphological features at different Embryonic Developmental stages in pregnant mice treated with different doses of Rapamycin (Rapa). Use In this study, 32 pregnant mice were divided randomly into four groups, each of which had eight pregnant mice. Each group received different dose of Rapa via intraperitoneally injection at different gestation days until the end of the specified periods, whereas the control group received a DMSO. Mice were administered under the same circumstances and dosages were determined based on body weight, as specified in pharmaceutical const
... Show MoreThe research aims to study the marketing costs in its various items, which are important costs as it specializes in tunnels on the marketing side through which the company's services are introduced to ensure that these services reach as many segments of society as possible, which serves the company's objectives and expand its business and increase its market share. As well as the definition of profitability and its relation to marketing costs in the portfolios of the national insurance company. The research hypothesis was formulated to study and analyze the relationship and impact between the marketing costs and profitability of the research sample company. The research sample was determined by the National General Insurance Comp
... Show MoreThe objective of this study is to determine the sources of growth of the cement industry in Iraq for the period 1990-2014 and to indicate the nature of the technological progress used in it. To achieve this objective we have built an econometric model, by adapting the production function constant elasticity for substitution, using multiple regression, and enforcement, SPSS program, and using the ordinary least squares method (OLS). The results showed that quantitative factors (labour and capital) are the main sources of growth the cement industry in Iraq, and the qualitative factors (technological progress) did not contribute effectively to achieve this growth. And that the production techniques adopted in the cement industry in
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The objective of the research is to identify the effect of the five-finger strategy on the holistic thinking of chemistry students in the second intermediate grade, where the sample consisted of 60 female students in a second classfrom one of the intermediate schools in Baghdad city, divided into two groups: control and experimental. The experimental design was based on the partial control; the scientific course was defined in the third and fourth chapters of the science book of the second intermediate grade.The two research tools were prepared: the attainment test with the scientific course and the holistic thinking scale paragraph (36) of multiple-choice pre- and posttest. The results showed a statistically significant difference between
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