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.
Based on the theoretical review of researches and studies concerned with virtual teams in organizations, it was found that the role of virtual teams varies from case to another, and it may be positive or opposite. The purpose of the current research is to examine the role of virtual teams in the impact of cultural intelligence on the strategic excellence of Zain worldwide Group. An electronic questionnaire was designed through the (Google) and (Microsoft) forms, and distributed then on a sample of (146) participants with a high organizational level of the HRM departments within the group. The results showed that there was a positive moderator role of virtual teams in the relationship of cultural intelligence and strategic excellence
... Show MoreThe present study tackles the complex issue of the urgent need for Environmental Auditing (EA) in Iraq in the absence of laws that support environmental management and in the light of the high rates of cancerous diseases in Iraq, which coincided significantly with the increase in oil production, according to the numbers indicated in the Iraqi Ministry of Health. The study aimed to investigate the mediating role of Management Systems (MS) related to the role of EA supporting sustainability reports concerning the reduction of the negative effects of gas emissions from oil companies. We adopted the descriptive approach which relies on studying relationships through a questionnaire that was distributed to a group of workers at Doura Refinery in
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Occupies total quality management applications play a key role in the development of institutions of higher education performance and achieve its strategic objectives through the commitment of senior management and their employees to continuous improvement of the quality of performance in the various areas of work, and can be integrated knowledge management processes, which means identifying information of value and how to take advantage. The data were collected using the style of the questionnaire for the purpose of analyzing their results on a sample composed of 83 member of the administrative leadership in colleges as representing the decision-making centers in those colleges .
 
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Receipt date:6/3/2021 acceptance date:4/5/2021 Publication date:31/31/2021
This work is licensed under a Creative Commons Attribution 4.0 International License.
The research in the role of variables contact for non-state actors have become more influential in the current of contemporary events, that related with the reality of seeking services and providing all of that in favor of maintaining the social peace, and ensuring its empowerment in order to make peace and stability outcomes as a real fa
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The study aimed to identify the role of public relations management in its dimensions (mental image, media, advertising, and the public) on green human resource management practices in Jordanian private hospitals in Amman, and this study relied on the quantitative approach (descriptive and analytical) to test hypotheses. Where the questionnaire was relied upon to collect data and their number was (1771) workers, and the study population consisted of workers in the hospitals that were studied on them and their number was 10 hospitals, where 316 questionnaires were distributed, 300 questionnaires were retrieved, and 16 questionnaires were not valid for analysis. That is, 91.7% of the sample, and the study relied on proportional stratified
... Show MoreThe aims of the research is to know the role of Organisational learning in building talent management strategies in the Ministry of Science and Technology , where we see the challenges facing organizations today dictate now and in the future activation of scientific expertise to meet these challenges and the dissemination of these concepts within the priorities and data organizational culture of these organizations despite having a lot of the importance of organizational knowledge and learning applications .Despite learning and adopting some of the organizations have to enhance their competitiveness, we find a lot of organizations, including (The ministry researched) still do not realize the importance of the role of organization
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Local communities are in need of self-resources so that they can perform their multiple functions which serve the objectives of the local development, and tax revenues are considered as important sources of their funding. However, despite the efforts of the state to reform the fiscal system and to improve the management in the local administration, tax collection can increase when the state adopts a more effective policy to combat tax evasion and tax fraud. Accordingly, this research aims to shed light on the role of local tax revenues in the local development. A set of conclusions are drawn; the most important one is that Algeria, in order to achieve local development, has taken a set of reforms, which are still valid until now. The mos
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Abstract
Leadership has now become a process for applying methods and techniques that make the Organization at the top of its competitive pyramid a greater market share. Leadership has become a focus for all leaders and managers، and leaders and managers are increasingly seeking to develop their skills and leadership skills. The research started with a clear problem of specific questions to ensure that the general objective of the research is to describe the characteristics of the leader and to clarify the dimensions of empowering the workers and to highlight the role of the leader in empowering the workers. The study examines the relation between the role of the leader in
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The aims of this study to diagnose the role of the (relationship and impact) Academic driving practices dimensions (model the way, inspire a shared vision, challenge the process, enable others to act, encourage the heart ) in the activation of human capital (investment and development) for (knowledge, skills, expertise, creative and training capabilities) in a sample of university professors in Baghdad city(Baghdad University, Al Mustansiriya University, University of Technology). (367 )samples were distributed to (232 at the University of Baghdad, 97 at Al-Mustansiriya University and 38 at the University of Technology). The goals of descriptive analytical method research have been used, questionnaire has been a main tool for dat
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