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 present work aimed to make a comparative investigation between three different ionospheric models: IRI-2020, ASAPS and VOACAP. The purpose of the comparative study is to investigate the compatibility of predicting the Maximum Usable Frequency parameter (MUF) over mid-latitude region during the severe geomagnetic storm on 17 March 2015. Three stations distributed in the mid-latitudes were selected for study; these are (Athens (23.50o E, 38.00o N), Jeju (124.53o E, 33.6o N) and Pt. Arguello (239.50o W, 34.80o N). The daily MUF outcomes were calculated using the tested models for the three adopted sites, for a span of five-day (the day of the event and two days preceding and following the event day). The calculated datasets were co
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The purpose of this research shed light on the analysis of the relationship between training needs and organizational commitment and the role of a variable contract psychological, and start search of a dilemma thought provoking fundamental questions revolve around the search was the answer to all those questions of tricks theoretical framework to the variables of research first and test models of the relationship and impact secondly During six hypotheses major, The objective of the research the impact of the factors that affect training needs in organizational commitment center the psychological contract, and applied research on a sample of 100 individuals working in the engineering department and maintenance at the D
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The article describes a study on the role of vitamin C as a protective agent for the teeth, gum, and implants using quantum chemical calculations and polarization tests. The Density Functional Theory (DFT) at 6-311G (d, p) basis set is used to estimate the ability of vitamin C to inhibit the corrosion of the abovementioned parts. The experimental study was performed in a at human body media simulator (Hank’s balanced salt solution) at a temperature of 37°C. The compound was optimized for its ground state, physical properties, and corrosion parameters. Further, HOMO, LUMO, energy gap, dipole moment, and other parameters were used to predict the inhibitor’s efficiency. Gaussian 09, UCA-FUKUI, MGL tools, DSV, and LigPlus software was used
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MT Abed, ALSG Irhayyim, TH Rija, International Journal of Psychosocial Rehabilitation, 2020 - Cited by 1
The aim of the research is to diagnose the methods of enhancing the value of citizenship in children through the interactive life process in educational institutions; the descriptive approach was used to achieve the objective by identifying social theories that corresponded to the national value or the theoretical principles of citizenship education. The study focused on educational activities and their role in establishing values, national educational philosophy in interactive activities, as well as the presentation of previous studies on the subject of citizenship, and maps of each of the strategies of active learning, skills in the process of interactive life in the field of education, Institutions that have the responsibility to prom
... Show MoreShmuel Yosef Agnon, a well-known Jewish writer, wrote many literary works, including poetry, story, etc. In the field of story, this writer used two areas: the first: a simple exterior, and the second: an inner full of secrets and mysteries. This area is common when Agnon is affected by his symbolic method of purpose. In his productions, we find the political and historical significance embodied in his characters, where there is almost no story without it.
Agnon and all his productions gave the character a large area, Agnon’s characters often play the center and cornerstone in those productions, where the author dealt deeply and stated the fines details of the external and internal of that ch
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Background: Vasospasm occurs commonly in the intracranial arteries as a complication of subarachnoid haemorrhage. On the other hand, extracranial Internal carotid artery (ICA) vasospasm is scarce, and it may occur due to mechanical manipulation during cerebral angiography. We report a case of cervical carotid artery vasospasm during diagnostic cerebral angiography, which caused anterior cerebral artery territory hypoperfusion, to discuss potential risk factors. Case description: For a 22-year-old female with a ten-year history of epilepsy on multiple drugs, brain magnetic resonance imaging (MRI) showed frontal periventricular developmental venous anomaly. Diagnostic catheter cerebral angiography was used to better identify the vas
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The internal observing system is considered a cornerstone for the high management in all the systems. It aims at defending the things for waste and increasing efficient and application the rules and regulations and constrictions. To easier for the high management activity in the internal observing system which in presented and practiced and to what extent can depend on it. Thus it goes to evaluate the internal observing system periodically to check the weak points in that system so as the find out the mistake, in the construction of the system or mistake, by indication of the workers. The importance of this study is represented in the need of increasing the coactivity in the internal observing system so as to be in touch with the new tre
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This research set to indicate the role of the opportunity cost in the overall economic development (human and social development) by selecting the most appropriate alternative for the growth of the country in exchange for sacrificing profit limits to achieve this growth and development of the country, especially in the present circumstances of the country and after studying the reality of the economic case for him, as the problem lies with don't selecting the best alternative that enhances the gross domestic product, which extends to promote overall economic development and revive the industrial and agricultural sectors, productivity is more like Impotent, versus sacrifice alternative consumption may bring more financially lucrative than
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