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.
شهدت العالم منذ نهايات القرن الماضي وبدايات القرن الواحد والعشرين تطورات دراماتيكية على صعيد الادبيات التنموية ، اذ تحولت التنمية من المفهوم التقليدي الذي اهتم بالنمو الاقتصادي الى رؤية جديدة هي رؤية التنمية البشرية ومن ثم الى التنمية المستدامة التي اعطت للتنمية البعد الانساني وجعلت من مشكلات واحتياجات البشر منطلق لها لتحويل الفرد والمجتمع الى مرحلة جديدة تضمن له العيش الكريم وتحقق معه
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When the Italian fascist party leaded & access to the top of regime, it took Benito
Mussolini as a post of Italian prime minister on 1922, that lead to rise the voices which need
to find colonies of Italy, like other colonial countries, especially that of its colonies in Libya,
Eritrea and Somalia were not achieved its ambitions, was to be the occupation of Ethiopia to
revive her dreams to exert control over the Red sea and the Mediterranean and the
establishment of a vast empire satisfy colonial ambitions.
the Italian invasion of Ethiopia gained particularly important, what led to the
disruption of the balance of political forces is not at the level of local powers in the region,
but at the level of the exten
Described the Arabic language being of genius sets by top models of eloquence , rhetoric and clarity of sounds and developments Moreover , it is an important element of our existence and our identity and our survival . That my methods and best in teaching Arabic language what has pursued the easiest ways to learning and teaching and helped learners to be aware of the function linguistic information , and they need it and its impact on their lives , and contributed to unleashing the potential of activism and led them to make the effort to apply them in the form of examples and uses of new life , as well as fits are the capabilities and tendencies of different learners , so the goal of current research into the importance of the curriculum
... Show MoreBackground: the coronavirus leads to upper respiratory tract-associated manifestations like nasal congestion, sore throat, and smell disorder
Objectives: To reveal the impact of COVID-19 pandemic on otolaryngology symptoms using our daily medical practice.
Subject and Methods: A cross-sectional study that was carried on in the isolation wards at Al-Kindy and Al-Nu’man Teaching Hospitals during three months from the 1st of Jun. till the end of Aug. 2020. It included 1270 patients who were diagnosed with COVID-19 infection seen in the ENT consultation clinic and admitted to the isolation wards.
Results: Otolaryngological manifestations were shown
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Agricultural development occupies an important position in the economies of developing countries, and its role is greater for the Arab countries. The first task is to provide food security for all the population through sustainable development, which includes the investment of available natural resources and employment opportunities for the rural population, As well as the provision of raw materials for agricultural processing in order to increase agricultural exports to reduce the balance of payments deficit. Sustainable development is linked to increased production and improvement, as well as to food security. On the one hand, it has to cope with the increase in population and if it is possible to achieve a surplus allocated for export, a
... Show MoreThe aim of the research to measure the correlation relationship between modern manufacturing systems and process design and measure the effect by adopting the regression; the research consists of two main variables, which are modern manufacturing systems and process design; it was applied in the production lines of the General Company for Construction Industries, There is a sample of managers, engineers, technicians, administrators, and some workers were selected to fill the special questionnaire with (70) forms which distributed and (65) were approved suitable for use, For data analysis the correlation coefficient was adopted to measure the relationship and regression analysis to find out the effect, Using (SPSS), So the first h
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A Forensic Accounting is represent science that deals with the application of knowledge in the areas of accounting, finance, tax and audit for the analysis, investigation, inquiry, inspection and testing issues in the civil law and criminal law in an attempt to reach the truth through which enable the Forensic Accountant to provide his Expert opinion , forensic accounting plays a major role by providing a range of important services in the field of investigation for fraud and litigation support, As one of the most important legal and accounting functions is to investigate allegations of alleged by the related parties, especially those allegations related to the existence of fraud, since the goal of judicial accountant will depend
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There is substantial data supporting the importance of both endogenous and exogenous estrogen in maintaining reproductive health and preventing chronic disease, androgens in women's health are rarely discussed. This is one of the first researches to investigate correlates of blood testosterone concentrations in women with osteopenia, in anticipation of the growing interest in the role of androgens in women's health. A 65 volunteer women were enrolled in the current study, they were divided into two groups, 35 postmenopausal women with osteopenia were in the first group, and the second group contained 30 postmenopausal women without osteopenia as a control. Blood samples were collected from all participants and analyzed for testosterone l
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Results: it was found that labelled cells participated in the formation of myotubes, which formed mature muscle fibers, and possibly new satellite cells. The results of this experiment may eventually revolutionized therapeutic procedures for some form of muscle diseases
Sustainability is a concept embodied in traditional architecture around the world since ancient times through spontaneous experimental compatibility with the environment and efficient exploitation of the natural resources of the environment according to a rapid development of trial and error over the years . Architecture was the basic means that man devised to protect him from the harsh conditions of the external environment by exploiting natural energy sources such as the sun, wind, and soil capabilitie, Many of the principles of sustainability overlapped with the social organization and human behavior of the community as it was reflected in the urban production at the level of standards of city planning and urban agglomerations as well
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