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 study focuses on how tax administrations in Iraq use Artificial Intelligence (AI) techniques to monitor tax evasion for individuals and companies to achieve Tax Compliance (TC). AI was measured through four dimensions: Advanced Data Analytics Techniques (ADAT), Explainable AI (EAI), Machine learning (ML), and Robotic Process Automation (RPA). At the same time, TC was measured through registration, accounting, and tax payment stages. We relied on the questionnaire form to measure the variables. A sample of employees in the General Tax Authority in Iraq was selected, and a questionnaire was distributed to 132 people. The results indicated that the dimensions of AI affect achieving TC at all stages. This study provides evidence of using A
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The problem of the paper focused on the role of the learning organization in the crisis management strategy, and the extent of the actual interest in both the learning organization and the crisis management and aimed at diagnosing and analyzing that and surrounding questions. The Statistical Package for the Social Sciences (SPSS) program was used to calculate the results and the correlation coefficient between the two main variables. The methodology was descriptive and analytical. The case study was followed by a questionnaire that was distributed to a sample of 31 teachers. The paper adopted a seven-dimensional model of systemic thinking that encourages questioning, empowerment, provision of advanced technologies, and strategic lea
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Cutaneous leishmaniasis (CL) is a widespread, yet often overlooked, parasitic disease caused by the Leishmania protozoan, which is prevalent in numerous countries, including Iraq. This condition is marked by the appearance of skin lesions on various exposed areas of the body. In most old-world regions, sodium stibogluconate (SSG) is the classical widely used drug to treat CL. The progression of skin ulceration is controlled by different inflammatory modulators including cytokines and enzymes. In this study, the possible role of the enzyme Matrix metalloproteinase9 (MMP-9) and its inhibitor Metallopeptidase inhibitor-1 (TIMP-1) as immunological markers was evaluated in CL patients suffering from cutaneous leishmaniasis before and aft
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Abstract As the United Nations approaches its 70th anniversary, the world is going through the most severe accumulation of serious international security failures in recent memory, challenging the UN Security Council’s ability to address them effectively. Over the past four years, crises in Libya, Syria and Ukraine have precipitated a worrisome erosion of great power relations that has complicated Security Council decision making on a number of trouble spots. Its inability to devise consensus responses to the escalating civil war in Syria has been particularly troubling, resulting in the regional spill over into Iraq and the emergence of Islamic State as a new threat to peace in the region and beyond. Meanwhile, the UN’s often under
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The research deals with the important and modern two subjects, strategic leadership which have six demotions and knowledge management
(four demotions') . the gools & the research is to know the relation & the effect them in the oil ministry (project department) , the sample was (50) persons who works in the department the questionnaire was the tool of data gathering .
The research divided to four parties, the first to the theotical review of the research variables, the second to the research methrology, the third to analysis and discoed the empirical results the last to the conclusions and recommendations .
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The current research aims at testing test the relationship and the impact of strategic leadership (strategic vision, Core competencies , human capital, organizational culture and Ethical practices) in the talent management (to attract talent, performance management talent, developing talent and retain talent) among managers in the Ministry of Science and Technology Iraq, and figuring out a number of recommendations to the ministry to help achieve its desired objectives, and to clarify the relationship between the variables to find the main and secondary aim of the research two major hypotheses have been formed which split into ten sub-hypotheses. Collecting data on a form questionnaire has been relied on as an essenti
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Background A prospective clinical study was
performed to compare the efficacy of the use of lowmolecular-
weight heparin group (enoxparin group)
with control group in the prevention of deep-vein
thrombosis after total knee arthroplasty.
Aim of the study: to assess the prevalence of DVT
after total knee arthroplasty and evaluate the
importance of the use of low molecular weight
heparin in the prevention of this DVT.
Methods Thirty-three patients undergoing total
knee arthroplasty were randomly divided into two
groups. One group consisted of 12 patients who
received no prophylaxis with an anticoagulant (the
control group), other group consisted of 21 patients
who received the low-molecular-weight h
The present study aims to illuminate the assessment of the Turkish elite of the role of the Turkish media in forming the attitudes of public opinion vis a vis the attempted military coup of 15 July 2016. The authors utilized the survey method of a nominal sample of 315 individuals, equally distributed among the three foremost categories of the Turkish elite, namely: the political academic, and media elite. The foremost findings of the study are that the orientation of the coverage of the Turkish media of the events of the attempt military coup of 15 July, based on the perception and assessment of the Turkish elite, was positive to a high degree; it refuted the news and the inciting information given to foreign media revealed the bloodine
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Banks are considered the main basis of financial sector ,so they must be submitted to sound and strict regulatory system and so as to ensure their operations and according to instructions and regulations , in order to maintain the integrity of the banking sector and financial sector in general .One of the importance regulatory tools that are adopted by the Iraqi Central Bank to control over the banks an financial and periodic statements that are provided by the banks in accordance with planned schedules .The financial statements of the banks must reflect clearly and accurately financial situation and the result of their activities during the period in which they represent to achiveing its purposes.So it has the goal of Search is statemen
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This research aims to identify the effective role of self-managed teams in the quality of service performance in the directorate of Ramadi municipality. The problematic nature of our research involves this main question of the effective role of self-managed teams in the Municipality of Ramadi in improving the services of performance quality to the beneficiaries from the Directorate service. The importance of this study lies in the role played by the work teams in the organizations that excel in their field, the attendant of the changes in the leadership, administrative roles of the institutions, and teams leaders, will be achieved by the self-managed teams in improving the quality of the service provided by the institution to whi
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