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 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
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Context has occupied a distinguished place as far as the understanding of the texts and deducting the rules from them or analyzing them. The context was considered as one of the important presumptions as far arriving at the desired meanings is concerned. The word is worthless and the meaning is not known unless we know the context in which it came. The context in its two types the lingual and non-lingual types. It is the best for knowing the intended meaning of the Quranic verses to know the real meaning.
History matching is a significant stage in reservoir modeling for evaluating past reservoir performance and predicting future behavior. This paper is primarily focused on the calibration of the dynamic reservoir model for the Meshrif formation, which is the main reservoir in the Garraf oilfield. A full-field reservoir model with 110 producing wells is constructed using a comprehensive dataset that includes geological, pressure-volume-temperature (PVT), and rock property information. The resulting 3D geologic model provides detailed information on water saturation, permeability, porosity, and net thickness to gross thickness for each grid cell, and forms the basis for constructing the dynamic reservoir model. The dynamic reservoir mo
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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
The Collapse of the Dreams in Ayad Akhtar’s Disgraced (2012) is a study that examines the theme of shattered dreams within the context of the play. Focusing on the protagonist Amir Kapoor, a successful Pakistani-American lawyer, and his journey from assimilation to self-discovery. This study explores the consequences of denying one's cultural heritage and the disintegration of personal aspirations. Through a close analysis of Amir's interactions with his wife, friends, and colleagues. This research investigates the underlying factors that contribute to the collapse of dreams and the unraveling of identity. By employing literary analysis and cultural criticism, the research sheds light on the complexities of cultural assimilation, racial i
... Show MoreThis Study is Concerned with (the debate of democracy in the modern islamic political thought ) which discovers the attitudes and this trend of thought so-called democracy . Therefore this study is divided into three sections : the first section is concerned with the democracy in extremist Islamic speech, the second section tackles appropriation of democracy in moderate Islamic speech , while the third section is concerned with the democracy in Aistighrabi Islamic speech . Finally the conclusion sums up the findings of the study
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
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The research aims:
1- To know the intemperance use of the internet by the University's students.
2- To know the differences with a statistical indication in the intemperance use of the internet after the gender's inconstant ( Males-females).
3- To know the differences with a statistical indication in the intemperance use of the internet after the Major's inconstant ( scientific- humanistic)
This current research restricts a sample of the university students for both sexes.
Theoretical frame:
The research viewed several theories that explains intemperance use of the internet & the results.
Research measures :
1- Research has been adapted the scale ( Internet use) which was prepared by the Moroccan researcher (
Lorraine Hansberry’s A Raisin in the Sun (1959) appeared at the beginning of renewed political activity on the part of the blacks; it is a pamphlet about the dream of recognition of black people and the confusion of purposes and means to reach such recognition. It embodies ideas that have been uncommon on the Broadway stage in any period. Situations such as a black family moving into an all-white neighborhood were not familiar before this time; they were just beginning to emerge. In depicting this so realistically, Hansberry depends more on her personal experience as an African American embittered by social prejudices and discrimination.