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 aimed at identifying the factors that affecting in the recruitment of a teaching staff for the Massive Open Online Courses (MOOCs) in university teaching at the University of Khartoum. The descriptive method was followed. The questionnaire was used as a tool for data collection,, which was distributed directly to a sample of (181) respondent of the teaching staff members of the senate at University of Khartoum from those who were attend at the senate meeting No. (409) which was held on 22 August 2016 Of (272). The researcher followed for the distribution the chance method, where each questionnaire was distributed to each of a teaching staff from different faculties at the University of Khartoum, according to his willingness
... Show MoreThe aim of the research is to identify the reality of administrative motivation for the deans of the faculties of physical education and sports sciences at the universities of Baghdad and Al-Mustansiriya from the point of download of the faculty members. The number of the exploratory sample was (7) faculty members, they were taken in a random way, while the rest of the sample number was (150) faculty members who considered the application sample for the scale, and the two researchers also adopted a questionnaire for the scale and it is applied to the Iraqi environment. phrase, which are phrases that are interrelated with the administrative leadership motivation in the faculties of physical education and sports sciences. The researchers did
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Experienced economic environmentRadical changes at the end of the last century and the beginning of the present century, resulting in new concepts and expectations in all aspects of economic, political, social and even behavioral.Each of these concepts is the result of rapid developments in the intangible space. Competition is no longer limited to the mere possession of tangible material resources, but because of its link to knowledge and technology content and to the comprehensive quality standards and efficient and effective policies of States. With the increasing pace of growth and interdependence among the global economies, this resulted in the birth of a new economic system led by technological development and financial liberalizati
... Show MoreThe study aimed at identifying the mental capacity of the research sample and classifying them for the purposes of the study, preparing the scale of cognitive control of the subject of teaching methods of sports education, preparing educational units by establishing the question network for the subject of the teaching methods of sports education, and adopting the experimental method by experimental design workers (2×2) for the two groups The limits of the research community are represented by third-stage students of the Department of Physical Education and Sports Science in the morning study of the College of Knowledge, the Community University, which continues in the regular working hours of the year (2019-2020) adult Their number
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(2)
This research aims to identify the role of external environment factors on the quality of educational services, from the academic point of view, where the distribution of a questionnaire to a random sample of (100) university professors, and then analyzing a model, and test the validity of this model using structural modeling (SEM) (Structural Equation Modeling).
And then test the relationships between variables using the software of Statistical Package for Social Sciences (SPSS V.18), the research found a number of conclusions, the most important conclusion is: the external environment factors has significant impact on the quality of educational services.
The study aimed to identify the effect of Total Quality Management on enhancing competitiveness through the opinions of employees of the front- rows of customer service in local Palestinian banks, the researcher adopted an analytical descriptive method through developing a special questionnaire to accomplish the study’s objectives and answer its questions. The study involved all the Palestinian local banks, with their scattered branches in West Bank. The study sample consisted of 3470 executive employees for banking services out of 4753 employees, in the rate of 73%, and the study sample reached (485) employees who were randomly selected working in the front -rows to provide services in the local Palestinian banks during the ye
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Abstract
The use of electronic valves is commonly available. yet, the most
common is the techniques of communications as prod casting transmitter that
are used by these valves in addition to their use in communication tools as far
distance telephone, electronic measuring techniques , and others.
In this study, an attempt is endeavored for improving the efficiency of the
vacuum micro- valves(GI-19b) through activating their internal surfaces by the
use of ionic pumping which is used for treating valves which are out of order
(because of sedimentation some materials and oxide on its poles). The
existence of these materials and oxide increase the sum of current leakage
moving in between. The use of ionic pumpin
The research aimed to prepare a measure of the importance of enlightenment, academic education, and applied skills for third-stage female students, including teaching methods from their point of view/College of Education and Sports Sciences/University of Baghdad/Al-Jadriyah. The researchers used descriptive description in the comprehensive research procedures, an appropriate methodology in achieving the research objectives, sufficient for interpretations, how important is the academic teacher’s knowledge of teaching methods for student learning, what are the roles that the learners have acquired from the academic teacher. The scale of importance and horror consists of 15 items. The research population includes female students of t
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The research aims to demonstrate the impact of tax techniques on the quality of services provided to income taxpayers by studying the correlational and influencing relationships between the exploited variable (tax techniques) and the dependent variable (the quality of services provided to income taxpayers), and in line with the research objectives, the main hypothesis of the research was formulated (there is a relationship Significance between tax techniques and the quality of services provided to income taxpayers) a number of sub-hypotheses emerged from this hypothesis that were stated in the research methodology, and a number of conclusions were reached, the most important of which were (through the use of the correlation coeff
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