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.
This study explores the role of nanomaterials in the performance of asphalt binders and mixtures. Two commonly available nanomaterials, i.e., nanosilica (NS) and nanoalumina (NA), were used at contents of 0%, 2%, 4%, 6%, and 8% by weight of asphalt binder. A set of experiments was carried out at the binder level to investigate properties such as penetration, softening point, aging-related mass loss, nanomaterial dispersion (storage stability), and workability (rotational viscosity). In addition, the suitability of NS and NS was also assessed through the testing of nanomodified asphalt mixtures, which focused on Marshall properties, the resilient modulus, moisture susceptibility, permanent deformation, and fatigue resistance. The findings in
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Abstract
In light of the great technological development and the emergence of globalization has increased global competition, where it became competitive exercise pressure on all sectors. In light of this companies mast enviorment depend on the means that keeps them on the competitive position through access to information about competitors in order to help them to draw a strategy that will achieve a competitive edge either through excellence or reduce the costs of their products and this means intelligence competitive and reverse engineering that help to gain information on competitors analyze and put of the decision-maker From this point formed the idea of research in the statement of the role of
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Developing countries have depended since long time on the developed countries to increase the levels of development and improving rates of growth direction to the best way where taking this dependence many shapes influenced by the evolution form of international relations and this dependence shows how the great deficiencies in sources of local financing, which called developing countries to increase their reliance on external funding sources, represented in the form of grants, subsidies, loans and foreign investment, pursuing States in that the application of economic reform policies in pursuit of faster economic growth and restructure its economy and achieve economic stability. In the early eighties of the last
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This research investigates the engagement of the Iraqi audience with ethnographic programs and their impact on knowledge enhancement and intellectual perspectives. A questionnaire consisting of closed-ended questions was designed and administered to a purposive sample of 400 participants who exclusively follow ethnographic programs and documentary channels. The data were transcribed and subjected to statistical analysis using the SPSS software to ensure reliability and test hypotheses. The findings revealed that Al Jazeera Documentary Channel had the highest viewership percentage among respondents for ethnographic programs, while DW (Deutsche Welle) had the lowest viewership percentage. This suggests that Al Jazee
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This study dealt with the basics of financial inclusion in terms of concept, importance and objectives, The empowerment of women financially and bank,and then the relationship between financial inclusion and women, and determine the requirements of inclusion Financial resources for women. The analytical descriptive method was used for data, which included reviewing and analyzing information And data in economic and financial literature. The study: reached a number of conclusions, the most important of which are Financial inclusion contributes to women's financial and banking support, as there is a positive relationship between financial institutions Banking and women's access to financial and banking services, thus playing a role i
... Show MoreIn the years recently city planning projects have been confirmed sustainable high concentration on planning streets and pedestrian paths being the most prominent component of the urban structure in the city and these me and diverse departments link the city’s sectors and serve as a space for economic, service, and social activities. On the other hand, pedestrian traffic is an essential component of the various means of transportation within the city. Suffer cities in the Middle East and Arab cities in particular are neglecting pedestrian paths in the vital urban environment. Vehicle control mechanisms on roads, and changing the uses of pedestrian paths as result of encroaching on the sidewalks designated for pedestrians. Which leads to a
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The arise of Islam as a multidimensional changing phenomenon with its own revolutionary and comprehensive character was inherent with a lot of alterations in social aspects , and this is explicit particularly in the scope of urban life and town planning . Essentially, Islamic style of life has its own urban identity. The urbanization process in Islam has been developed across two integrated sides, the first one concerned on ideational and theoretical aspects , while the other associated with practice .Many urban centers emerged during the Islamic era since the erection of Basrah , the first Islamic town in the middle of the 7th. centaury. Some contemporary urban concepts , both environmental and social could be noticed in Islamic
... Show MoreIt is not long time since globalization has started along with knowledge economy and, communication media and technical information control on the world. As a result serious events appeared like failure in businesses, financial corruption and shortage of administration and control.
In spite of the great efforts held by international organizations and foundations to find organizational frames that adopt independence, que
... Show MoreABSTRACT The importance and objectives of the study were an attempt to understand the methodology of disseminating radical thought and the reasons of social acceptability that make young people embrace this thought. It also sheds light on the impact of this phenomenon on the regional role of Egypt and examines the strategic means and standards that the Egyptian state focuses on in immunization and prevention of extremism.