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 problem of medical waste over the past tow decades has emerged as one of the most important issues.
Which have negative effects on health and the environment ,and as a result specialists looked into the field.
Public health and research issues . This phenomenon in all its dimensions and efforts made For their containment through the development of health and environmental controls for the disposal of such wastes.
In a safe manner starting form the source of these wastes and the various health organizations are finished The final treatment ,and this is why the producers of hazardous medical waste. &nb
... Show More
This research is an initial attempt to explore the reality of reform and its concept in Islam, and to describe the presence of educational practices in the Arab-Islamic heritage. The importance of this research lies in addressing a number of important issues related to the contemporary Islamic reform system. The research showed the need for authentic educational reform values that draw their reference from the origins of Islam. The research also emphasized the analysis of the reality of education in the Muslim world and the identification of its problems and the search for solutions through a quick and comprehensive look at the diverse contributions of Muslim thinkers to Islamic educational reform thought, and their active role in addressin
... Show MoreThis research aims to study and reveal the influence of Bauhaus principles in contemporary graphic design. The researcher determined the objective/spatial/temporal limit: Study of the Bauhaus influence in the design of the graphic poster in Germany in 2020. The theoretical framework in the first section dealt with (the emergence and factors of the emergence of the Bauhaus school and its characteristics), while the second topic dealt with (the intellectual, functional and aesthetic data of the Bauhaus School), after which the indicators that resulted from the theoretical framework were produced.
He mentioned four previous studies, one of them was discussed in detail. In the third chapter he defined the methodology, society, and sam
... Show More
Abstract
The current research aims to identify the psychological security of students in the kindergarten department and identify if there is a significant difference between stage one and stage four students. To do this, the researcher adopted the psychological research scale of (Al-mohamdawi, 2007) that consisted of (30) items. It was administered to (120) female students chosen randomly from the kindergarten department in the college of education for women for the academic year (2029-2021). The results revealed that students in the kindergarten department have psychological security. There is a significant difference between stage one and four students in favor of stage four students.
Objective: This study aims to analyze the role of the People's Republic of China in the 1955 Bandung Conference and assess its contributions to international cooperation and peace. It specifically examines how China's participation aligns with the United Nations Sustainable Development Goals (SDGs), particularly Goal 16. Theoretical Framework: The research is grounded in a structuralist approach to international relations, focusing on the agency of developing nations in shaping a post-colonial global order. It considers concepts such as peaceful coexistence, national sovereignty, and South-South cooperation. Method: A historical-analytical method is employed, tracing China’s diplomatic trajectory from the 1954 Colombo and Bo
... Show More
If we go beyond the technical aspects of the Web 2.0, and we focus specifically on its interactive characteristics, we may say it represents not only a fundamental shift in the structure of the press institutions and its practices but also a shift in the relationships that existed, previously, between the press and the audience. Web 2.0 has enabled the newspapers to renovate their representations and practices of the profession and opens to the new horizons either in terms of readership or advertising revenues. Parallel to that it also has empowered the user to transcend the passivity he has always been confined in and has become a more active participant in the creation and generation of media contents even though this practice is somew
... Show More
Theatrical art, from (Plato) to (Heidegger), passing through (Husserl) and (Husserl) has propagated the parallel relations between the overlapping formal patterns in the world of hypotheses crowded with diaspora and scattering, leading to the manifestations of implicit meaning in the intellectual and aesthetic discourse, through the deconstructive pattern that restructures The aesthetic image according to the aesthetic data to be employed, so the effectiveness of the deconstructive system had an important role in authorizing the Ghanaian logic and continuity on which the Western meta meaning was based, and the artistic scene was subjected to it in line with literature and art to be able to pay attention to the achievement and clarify it
... Show More
(1)
The aim of the research is try to answer the questions about the importance of the participation of scientists in the scientific researcher Google Scholar for the professor and the university, and the extent of participation of Iraqi universities, and the rank of the University of Qadisiyah, and the number of participants and teachers of this engine, The research came out with several conclusions, the most important of which is that (21%) of university professors are involved in the google engine and most of the participants did not carry their full research through the site