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.
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
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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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
... Show MoreThe 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
... Show Moreالزكاة 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
... Show MoreThe study aims to examine the problem of forced displacement and its social and economic problems in light of the Syrian crisis. Such an aim helps to know the difficulties and challenges facing the children of displaced families in learning, and the reasons for their lack of enrolment. It also clarifies whether there are significant statistical differences at among the attitudes of the children of the displaced families towards education regarding the following variables: (the work of the head of the family, the economic level of the family, and the work of the children). The study has adopted the descriptive-analytical approach; a questionnaire was adopted as a tool to collect information. The study was applied to a sample o
... Show Morestudy aims to examine education and the challenges of globalization in light of Corona pandemic. The examination involves surveying a randomly selected sample from the University of Baghdad’s professors, particularly from the colleges of Education for Women, Arts, and Sciences. The purpose of this examination is to learn about the dimensions of globalization, its effects on the educational process, and the importance of distance education during the spread of Corona virus quarantine. To achieve this, the researcher followed a descriptive and analytical approach by applying a questionnaire to a sample of 70 teachers who were randomly selected electronically. Results have shown that 78.6% emphasized the contribution of globalization duri
... Show MoreBackground: Laparoscopic cholecystectomy (LC) has become the standard treatment for symptomatic cholelithiasis. Bile duct injury and accidental gallbladder perforation with spillage of bile and stone are common complications of LC. This study was carried out to assess the early complications of gallbladder perforation during LC, and identify the risk factor of that perforation.
Objectives: to evaluate the early complications which may occur after the perforation of the gallbladder during laparoscopic cholecystectomy and to determine the risk factors which are associated with the perforation of the gall bladder.
Subjects and methods: A prospective comparative study o
... Show MoreThe current study aimed to investigate the viability of biofilm formation klebsilla pneumoniae and Staphylococcus aureus. 440 urine samples were collected from patients suffering from urinary tract infection (UTI) from those who were admitted and visitors to Al-Ramadi Teaching Hospital, Al-Yarmouk Teaching Hospital, Al-Ramadi Teaching Hospital for women and children and , Teaching Laboratories in the Medical City for both genders for a period extended from 5 July, 2017 to 10 October, 2017. Samples were diagnosed by culturing them on a selective media and by biochemical testes , also, diagnosis was ensured by using VITEK-2 compact system. Results showed that K.pneumoniae isolation ratio was 17.1%(68) and S.aureus ratio was 13.1%(52). Thei
... Show MoreThis paper depends on sheding some litgt on the characteristics of political
relations between the arab and the Persian during the reign of sassane kings.
"Ardashir the first, shahbour the first, shahbour the second, Bahram the fifth; kisra
Anushrwan and kisrah abruis"
And who rulled the Persian before the Islamic conquest and were adopted in this studym
as a model. It was possible to get some information from invaluable refereces in order to
arrive at a clear image as regards the nature of these relations. These relations were
differently political according to the circumstances of ruling, interests and the personality
of those kings.