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 economical units in the world face great and rapid challenges in all aspects, a matter that requires facing these challenges throughout continuous improving and developing in their performance to keep their competitive position "place".
The Benchmarking Technique is one of the modern managerial tools that are proved to be successful in application throughout making continuous comparisons between products or services and the best – performance levels the compete with it . This is achieved to develop its performance and give it the competitive criterion with which it faces its competitors.
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A polycrystalline CdTe film has been prepared by thermal evaporation technique on glass substrate at substrate temperature 423 K with 1.0 m thicknesses. The film was heated at various annealing temperature under vacuum (Ta =473, 523 and K). Some of physical properties of prepared films such as structural and optical properties were investigated. The patterns of X-ray diffraction analysis showed that the structure of CdTe powder and all films were polycrystalline and consist of a mixture of cubic and hexagonal phases and preferred orientation at (111) direction.
The optical measurements showed that un annealed and annealed CdTe films had direct energy gap (Eg). The Eg increased with increasing Ta. The refractive index and the real p
الزكاة فريضة من فرائض الإسلام وعبادة من العبادات التي اقرها الشرع الإسلامي هذه الفريضة المالية التعبدية بالإضافة الى دورها المعنوي الذي يهدف الى إرساء قواعد العدالة الاجتماعية والقضاء على مشكلة الفقر في المجتمع الاسلامي وكما ينص عليها الدين الإسلامي فان لها ابعادها ووظائفها الكثيرة التي تخدم اليات العمل الاقتصادي في مجتمع يعمل وفق نظام اقتصادي أسلامي .
ان انفاق الاموال المتحصلة من فريض
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This research is aiming to find the effective role of the personality characteristics of the Leader in business organization entrepreneurship by studying the effect of the special dimensions of personality characteristics (neuroticism, extraversion, openness, Agreeableness, and conscientiousness) on business organizations entrepreneurship dimensions representing in the two main dimensions (entrepreneurship direction and strategic entrepreneurship) across field study was conducted in thirteen private colleges in Baghdad.
The problem of the research relies in asking the question, is there an effect for Leader personality characteristics on business organizations entrepreneurship. and statistical methods hav
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The present study is concerned with the concept of ethics academically. It aims to investigate the major problems that contemporary Iraqi society suffers from; on top of which is the problem of sectarian and religious intolerance. Such a problem has a major role in the emergence of extremism and terrorism. It further destabilizes the security and stability of the country, exposing, as a result, the lives of citizens to the danger of genocide, disintegrating the social structure, stopping the wheel of development, rampant corruption, and deteriorating the political, social, moral and economic situation. Here comes the role of social work as governmental institutions and civil society organizations in curbing this reprehensible phenomenon
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The aim of the current study was to investigate the impact of workplace stress on employee engagement within Iraqi universities through the mediator role of leadership style. Work-related stress and non-work-related stress were identified as representing workplace stress. Employee engagement has been measured through three types: social engagement, affective engagement, and intellectual engagement. Two types of leadership styles have been tested: directive and participative leadership. the structural equation Modeling was used to test the study model. A sample of 245 employees in Iraqi universities, including university professors, was targeted. Only 214 respondents participated in the survey. The results showed that non-work-relate
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This study aims mainly to identify the role of the use of blockchain technology in improving the quality of digital financial reports, answering questions and testing the hypothesis of the study, the researchers relied on the descriptive analytical approach, and to obtain the necessary data a questionnaire was distributed after evaluation to the study community.
The results of the study have shown that the use of blockchain technology helps to provide a high degree of reliability in digital financial reports published to banks over the Internet, ensure the speed of completion and completion, and maintain the privacy and confidentiality of the information contained in the digital financial reports of banks
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The aim of the research is to highlight the role of electronic human resources management practices in the sustainability of knowledge capital as one of its success factors, as well as the diagnosis and interpretation of the relationship between research variables and their dimensions. The research problem is that the University of Babil implements some electronic human resources management practices not in a complete way, The level of its application and the problems it faces, as well as the extent to which these practices reflect the knowledge capital and sustainability in the university, and highlights the importance of research as it is concerned with the electronic aspects and achieve the competitive advant
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Many countries are very important in their interest not only in diversifying foreign reserves, but in determining and planning their volume in accordance with the goals set, namely facing potential external shocks, as the research aims to determine the extent of the strength of foreign reserves in the possession of the Central Bank in relation to every influential variable in the Iraqi economy. , in order to determine the minimum level of reserves that requires reconsideration of the exchange rate, as the research adopted the inductive analytical method in analyzing real (Quantitative data) for the research variables in the years of study, as the research adopted a set of analytical indicators approved by the International Moneta
... Show MoreLaryngoscopy and tracheal intubation are considered the most invasive stimuli in anesthesia. They provoked cardiovascular responses that include hypertension, tachycardia and dysrhythmias. Various pharmacological approaches have been used to blunt or attenuate such pressor responses. The present study was designed to evaluate the effect of medazolom, lignocaine and propranolol as a valuable adjuvant to fentanyl in attenuating hemodynamic responses to endotracheal intubation in normotensive patients. Thirty two patient with physical status I or II according to the score of American Society of Anesthesiologist (ASA), scheduled for elective surgery under standard general anesthesia, were randomly allocated into four groups (8 patients in ea
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