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.
Proved Islamic banks in many countries where they are present, whether Muslim or non-Muslim in the wake of the global financial crisis, it is more efficient, profitable, and stable compared with the conventional banks, so went many of the worlds towards providing Islamic banking through Islamic windows to Besides financial services and products offered by the traditional, or the initiative to enter formulas Islamic finance is fully compliant with the principles and rules of Islamic law and is Brokerage basic function of conventional banks and Islamic alike ) and that means working on the mobilization of savings from surplus units and directed towards the financial units of the fiscal deficit) , which operates commercial banks
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This paper presents an analysis of selected qualitative characteristics of pellets produced from rape straw obtained from cultivations subjected to different fertilization treatments and from mixtures of straw selected for testing with crude glycerol obtained as a by-product from biodiesel production. The assessment focused on the following qualities of the obtained pellets: Moisture content, mechanical durability, heating value and main elements, that is, carbon, hydrogen, nitrogen, sulphur, chlorine and oxygen. The obtained results indicated that the different treatment regimens applied in spring rape cultivations had a significant impact on the physicochemical qualities of the straw. In terms of the heating value, traditional fer
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Abstract:
Witness the current business environment changes rapidly reflected on the performance of the facility wishing to stay , which is no longer style reaction enough to handle installations with their environment , and quickly began to lose its luster with the emergence of a message and the vision of contemporary business environment from a set of parts interacting with each other and the concept of behavioral includes all dimensions of performance, it is imperative to adopt a system installations influence variables and positive interaction through the development of strategic plans and the use of implementation and follow-up strategies to ensure the effectiveness of the method for meas
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Objectives: The research aims to demonstrate the integration between Quantum Computing (QC) and Predictive Analysis (PA) and their role in reducing costs while achieving Sustainable Development Goals (SDGs). The study addresses the inefficiencies in calculating and measuring product costs under traditional systems and examines how QC and PA can enhance cost reduction and product quality to better meet customer needs. Additionally, the research seeks to strengthen the theoretical framework with practical applications, illustrating how this integration improves a company’s competitive position while promoting social, environmental, and economic sustainability. Methods: The study employs a descriptive analytical approach, focusi
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Background: Laparoscopic cholecystectomy has many difficulties which include port Insertion, Dissectionof the Calot’s Triangle , Grasping of the Gallbladder , Wall thickness, Adhesion and extraction of theGallbladder. Aim of the Study: To predict how difficult cholecystectomy will be from assessing the patientpreoperatively which, in turn, help in decreasing the risks on the patients and preventing post-operativecomplications. Patients and Methods: A prospective study conducted in the department of General Surgeryat Al-Ramadi Teaching Hospital for the period of nine months from 15th of May 2018 till the 15th of February2019. It included 60 patients, all of them were undergone laparoscopic cholecystectomy for Gallstone. Patientswit
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This research aims at identifying the nature of addressing the Middle East issues in the talk shows in the foreign channels speaking in Arabic "France 24, a model", and identifying the extent of interest of the channel in addressing middle east issues in the talk shows, the nature of the guests and the hosts, methods of addressing the issues, and the technical features that characterize the presenter of the research sample program. This research is considered an analytical descriptive study. It depends on the analysis of the content of the series of the weekly talk show "a week from the world" on the French channel (France 24) during the period (August 1/July 31 2018).
The most important results indicated that the foreign channels sp
This study aimed to improve the microencapsulation technique using a type coating the encapsulation Layer by Layer, which provide the best protection for life Lactobacillus casei in the extrusion method and use the microencapsulation of materials of the protein concentrated by protein 80% and the coating with alginate and chitosan have the results showed the variation in the difference of the binding process encapsulation yield among the types of coating through. by studying of these the effect o stability of the bio probiotic free cell and the three types coated towards three different concentrations from bile salts 0, 0.3, 0.5 and 0.7% when the periods of time different of zero and two and three hours at incubation the recorded
... Show MoreThe aim of the research is to identify to what extent to which Malcolm Baldrige standards of total quality are applied in the after-sales services of a private sector company for electrical appliances, from the point of view of administrative leaders, in it. To achieve this aim a questionnaire has been used to measure the degree of application of Malcolm’s seven criteria for total quality, namely: (leadership, strategic planning, focus on the customer, measurement and analysis and knowledge management, focus in human resource and operation management and results of the company’s management), the research found that the company achieved a good level of the standard from the de
... Show MoreThe research aims at the possibility of measuring the technical and scale efficiency (SE) of the departments of the College of Administration and Economics at the University of Baghdad for a period lasting 8 years, from the academic year 2013-2014 to 2018-2019 using the method of Applied Data Analysis with an input and output orientation to maintain the distinguished competitive position and try to identify weaknesses in performance and address them. Nevertheless, the research problem lies in diagnosing the most acceptable specializations in the labor market and determining the reasons for students’ reluctance to enter some departments. Furthermore, the (Win4DEAp) program was used to measure technical and scale efficiency (SE) and rely on
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