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.
Abstract
Magnetic abrasive finishing (MAF) is one of the advanced finishing processes, which produces a high level of surface quality and is primarily controlled by a magnetic field. This paper study the effect of the magnetic abrasive finishing system on the material removal rate (MRR) and surface roughness (Ra) in terms of magnetic abrasive finishing system for eight of input parameters, and three levels according to Taguchi array (L27) and using the regression model to analysis the output (results). These parameters are the (Poles geometry angle, Gap between the two magnetic poles, Grain size powder, Doze of the ferromagnetic abrasive powder, DC current, Workpiece velocity, Magnetic poles velocity, and Finishi
... Show MoreIn light of the increasing interest in Child-rearing in nurseries and kindergartens and the most important experiences gained by the child at this stage that form the basis for the subsequent stages of her/his physical mental and social growth.
The significance of the research concentrates the need to asses the affecting variables on the child growth to create opportunities for her/him to have intact rearing.
The research also aims to classify these variables at each age level and highlight its moral role.
The problem of the research is the lack of clarity of different variables impact of the child growth in different age levels in nurseries and kindergart
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Education in it s different levels becomes development in any country. There fore, nations pay great attention to educational systems, because they perceive that preparing human resources is essential to the development of these nations.
The present study deals with the a academic frames which formulate education in each educational system such as educational philosophy , educational aims , educational strategies by which the academic frames are carried out, which is limited to curriculum, teacher preparations, school activities, in addition to guidance and counseling.
This study reaches some conclusion which are derived from the description of the academic and practical frames some suggestion are made for the mechanism which facil
Background: Laser is a novel physical therapy technique used to treat various conditions, including wound healing, inhibition of bacterial growth, and postoperative wounds. High-power pulsed alexandrite laser therapy is one of the most prevalent forms of laser therapy, which is a noninvasive method for treating various pathological conditions, thereby enhancing functional capacities and quality of life. It is a modern medical and physiotherapeutic technology. Generally, the Alexandrite laser emits infrared light with a wavelength of 755 nm, allowing it to propagate and penetrate tissues. Objective: This study focused on the application of a high-power pulsed alexandrite laser in vitro to evaluate the effect of a pulsed alexandrite l
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Urban planning task and the control of constructional planning and urban management for cities considers the main tasks that the government takes care off. The paper discusses the concept of power from historical view of ancient Islamic cities to discover the strategies of urban management that the Islamic city adopt and to employ it in contemporary cities ,the more problems that modern cities suffer from which appears through poorness of urban context ,belongs to the loss of balance exists between the different faces of power that takes the tasks of urban management .therefore enhancement of urban environment is being through re-back that balance in administrative structures that make the cities go ahead . So the attention has b
... Show MoreThe degree of the woman’s satisfaction on clothing depends, to a large extent, on the body measurements. If clothing is very wide, it shows her enormous and if it is too tight it may draw attention to the defects of the body. It may also lead to the compatibility or incompatibility of clothing with fashion. Whatever the quality of the garment in terms of sewing and design, the costume which is not suitable for body size may affect the physical style negatively and may give the wearer an improper look. Clothing was carried out without measurements and did not use models (templates). The method of preparation affected the overall appearance because it often did not fit the shape of the body completely. Therefore, people thought in many w
... Show MoreDiscussed the research variables are important, privatization options and strategic analysis of the external environment, and that the purpose of the research is the trade-off between privatization options and choose the most appropriate alternative in proportion to the external environment, the research aims to determine the privatization the most appropriate option for companies and public contracting, showing the importance of the study provide the privatization of public companies as a strategy can all its way public sector organizations from the transfer of work practices or private sector organizations and mechanisms to it as contributing to improving the level of skills Develop the current and future level of performance,
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International trade in services is becoming increasingly important as it is an economic activity that deals with invisible trade, which has become increasingly important in the balance of international trade. The establishment of the WTO is a starting point in international trade relations. It is responsible for all aspects of international trade, , And in view of the continued increase in international trade in services, the need for more internationally recognized rules has become more urgent, especially as it has been increasingly proven that the traditional framework of public services is inadequate to operate some of the most dynamic and innovative sectors of the economy. (GATS) to be the regulatory framework for this sector
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Geodiversity is the variety within abiotic natural elements that include: rocks, minerals, landforms, soil types, and water resources. Recently ecologists and naturalists recognized that there is close relationship between geodiversity and ecosystems. Huwaiza marsh is located south eastern Iraq within Lower Mesopotamian plain. The main rock bed units which crop out north east of the studied area comprises many types of rocks: conglomerate, sandstone, mudstone, siltstone and claystone belong to Bai Hassan, Mukdadiya and Injana Formations. The general elevation of the area ranges around 5 meters (a. s. l.) near the marsh and increase northeast to more than 100 meters (a. s. l.) and the Land forms are: cuesta, oxbow lakes
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