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.
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Abstract:
The underlying objective of the international standard No. (6) to assist in accounting applications for the extractive industries, taking into consideration the goals and objectives contained in the sixteenth of the private International Accounting Standards criterion accounting for land, machinery and equipment, as well as Standard No. axes (38) relating to intangible assets, and in order to create a vision of a comprehensive development needs oil in order to exact evaluation of policies related to the particular needs and draw a comprehensive frameworks with respect to treatment of expenditures and revenues in the oil production industry, is also interested in Standard No. (6) within the primary objectiv
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This research sought to detect the level of organizational culture prevailing in the Integrity Commission as well as the level of the organizational citizenship behavior of staff of the Commission and the impact of organizational culture in these behaviors. To achieve the objectives of the research and test the validity of hypotheses have been used questionnaire derived from measurements ready modern researchers foreigners have been adapted to suit the Iraqi environment, have been distributed (189) questionnaire on the number of employees from the Integrity Commission, which represented the research sample where the research community has a number is (1365) employees in the Baghdad was the use of a number of statistical met
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International relations scholars have increasingly debated the evolving landscape of actors that challenge the traditional state-centric world order. A key element of this transformation is the rise of sub-state actors, which engages in alternative diplomacy parallel to the state, transcending traditional state-centric frameworks. This paper explores the significant shifts in international actorness over the late 20th century, focusing on the emergence and implications of sub-state diplomacy, or "paradiplomacy." First, the study introduces sub-state actors and their role in challenging the dominant state-centric discourse. It then examines the dynamic evolution of paradiplomacy, highlighting how sub-states have expanded their global
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Background : Gastroesophageal reflux disease (GERD) is one of chronic gastrointestinal diseases in which patient may be asymptomatic or was complained from heartburn and regurgitation or pulmonary symptoms. Aim of the study : Examine the serum level of sHLA-G in GERD patients and can be used as a biomarker for early detection of GERD disease. Materials and methods : The design of the study was a case- control prospective enrolled forty patients consulted Gastroenterology Unit- Al-Kindy Teaching Hospital, were diagnosed as GERD by their physician, and compared to second forty control healthy group form January-2023 to May-2024. Serum used for quantitative assessment of soluble HLA-G (sHLA-G) using a sandwich enzyme-linked immunosorbent a
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After the information revolution that occurred in the Western world, and the developments in all fields, especially in the field of education and e-learning, from an integrated system based on the effective employment of information and communication technology in the teaching and learning processes through an environment rich in computer and Internet applications, the community and the learner were able to access information sources and learning at any time and place, in a way that achieves mutual interaction between the elements of the system and the surrounding environment. After the occurrence of the phenomenon of Covid 19, it led to a major interruption in all educational systems that had never happened before, and the disrupt
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The researcher seeks to know the extent of applying the concept of design by Iraqi electronic press sites to provide media product with the acceptance of their browsers and ensure their repeated visits to such sites in the framework of the guiding rules for laser browsing. The researcher uses analytical study on a sample of six Iraqi electronic newspaper sites to identify the general features of their design and the methods of distribution of the structural elements of the pages. The researcher also conducts a field study on a sample of the surfers of electronic newspaper sites to see the extent of their evaluation to their design and the degree of their satisfaction.
Disabled people are among the most important groups that need attention, care, and financial and moral care. They cannot fulfill the requirement of life normally without care from a person to meet their special needs. The disability is either mental or physical. The Iraqi government has paid attention to this category by adopting a law for this category, represented by Law No. (38) for the year (2013), which keeps their rights and duties in Iraqi society by establishing institution of persons with disabilities and special needs of the Ministry of Labor and Social Affairs to create a modern society politically, socially, culturally or economically. In view of the importance of this group in society, the media reinforces the communit
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