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 aims to find out "the effectiveness of the self-questioning strategy in the achievement of students Phase III institutes of teacher preparation and decision-making in chemistry." The researcher follows approach quasi-experimental with a post-test, and the sample consisted of (27) from " Teachers Training Institute-AL-Byaa "in Directorate of Education Baghdad Karkh / 2 students divided into two unequal groups: experimental its number (14) students studied using reciprocal teaching strategy and control its number (13) students have studied in the usual way.The two groups were equivalent extraneous variables.
The researcher was prepare achievement test consist of 40 items was the adoption of a measure of decision-makin
... Show MoreEveryone agrees on the importance of internal music, as it is the greatest pillar in poetry music. Because it differs in internal music, and we seek in this research to shed light on the internal music in the book The Young Branches of Ibn Saeed Al-Andalusi, in terms of the poets' choice of words and styles that make up the internal music
This study is concerned with organizational learning and its impact on total quality management in the education sector. Organizational learning is a process that provides the educational sector with the ability to adapt and respond rapidly to developments and changes in a better way according to its main dimensions (Mental Models, Personal Mastery, Team Learning, Shared Vision, System Thinking) by adopting the philosophy of Total Quality Management (TQM) in accordance with its basic dimensions (leadership, customer satisfaction, participation of workers, continuous improvement, training and education). The main purpose of this study is to know (the impact of the Senge model of organizational learni
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This research aims to identify the effectiveness of counseling by using the technique of self-talkin developing the habits of mind among middle school students by testing important hypotheses, and choosing the experimental design for the two groups (experimental - control). The classification of "Costa & Kallick" was adopted to measure the habits of the mind, and the scale consisted of (64) items, and after confirming the psychometric properties of the scale, the researcher applied it to the research sample (487) students from middle school students. One of the students who got the lowest marks after answering the scale. purpose of applying the experiment. He divided them into two groups, one of them is experimental (10) students, as
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Is a high degree of economic freedom an important part in the development of the economies of developing countries in the last decade of the twentieth century and the beginning of the twentieth century and the atheist. This is because a test subject (deltoid analysis of the relationship between the degree of economic freedom and foreign trade of selected developing countries for the period
( 1990 -2005) to determine the degree of economic freedom in foreign trade promotion in Singapore and Turkey. The research recommends a number of recommendations, the most important is the responsibility of the Ministry of Planning in Iraq that is providing the necessary data for the Fraser Institute, the aim of increasing cooperation
Research includes three axes, the first is the average estimate time of achievement (day) to work oversight, to five supervisory departments in the Office of Financial Supervision Federal and then choose the three control outputs and at the level of each of the five departments above, and after analyzing the data statistically back to us that the distribution of the times of achievement It is the exponential distribution (Exponential Distribution) a parameter (q), and the distribution of normal (Normal Distribution) with two parameters (μ, σ2), and introduced four methods of parameter estimation (q) as well as four modalities parameter to estimate (
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The study consisted in the development and use of a practical method to detect and
monitor, analyze and produce maps of changes in land use and land cover in the district of
Mahmudiya in Baghdad during the period 1990-2007 using the applications of remote sensing
techniques and with the assisstant of geographic information systems (GIS),as a valuable
contribution to land degradation studies.
This study is based maiuly on the processing on two subsets of landsat5 TM images picked up
in August 1990 and 2007 respectively in order to facilitate comparision and were thengeometrically and radiometrcally calibrated ,to used for digital classification purposes using
maximum liklihoods classification or six spectral bands of
This study is concerned with organizational learning and its impact on total quality management in the education sector. Organizational learning is a process that provides the educational sector with the ability to adapt and respond rapidly to developments and changes in a better way according to its main dimensions (Mental Models, Personal Mastery, Team Learning, Shared Vision, System Thinking) by adopting the philosophy of Total Quality Management (TQM) in accordance with its basic dimensions (leadership, customer satisfaction, participation of workers, continuous improvement, training and education). The main purpose of this study is to know (the impact of the Senge model of organizational learni
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Abstract
The current research aims to identify the effectiveness of concept maps in the academic achievement of the art of elegance and fashion for third vocational students. The current research is a quasi-experimental one. The research sample consisted of (74) female students in Al-Saydiyah secondary school for girls, they were divided into two groups: the experimental group and the control group. The following hypothesis was developed: There are no statistically significant differences at the level (0.05) between the average scores of the students who studied the subject using concept maps and the average scores of the students who studied the subject in the traditional method in the post-achievement test. The
... Show MoreThe relationship between music and plastic arts can be viewed as an interdependent relationship, as they both develop imagination, focus and sensory perception, as well as the presence of some artistic concepts that music shares with the art of drawing, on this basis the rationale for this research aimed at identifying (the influence of music) was dealt with On the artistic output (drawing) of students of the Department of Art Education - College of Fine Arts) In the first chapter the problem of research, importance, terminology, boundaries and goal was addressed, and in the second chapter the researcher dealt with in the first topic the relationship between music and painting, and in the second topic the use of music in education. As fo
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