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 role and procedures for accountability in the spending units significant impact in enhancing the results of the budget it is found by studying and comparing the results of the implementation of the budget for the research sample for a period of two years to repeat the same deviations and irregularities of Guanyin, regulations and instructions that have occurred in implementation results and two consecutive Kaltjaoz customizations and low rates of implementation and the lack of exchange of allocations Finance despite the presence budget note that such remarks are always indicate in regulatory reports, but these observations repeated Bostmr in the results of the implementation of the budget. Which clearly reflects the absence of the ro
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تشهد بیئة الأعمال المعاصرة جملة من التغیرات والتطورات التكنولوجیة وتزایداً في حدةالمنافسة، وأتساع الفجوة بین العاملین والإدارة ، وقدرة الإدارة على التمییز بین الموظفین، والمشاركة فيإتخاذ القرارات، الامر الذي یلقي على عاتق شركة التأمین إجراء التغییر التنظیمي لتحقیق تطور فيالخدمات التأمینیة التي تقدمها للجمهور من تنوع التغطیات التأمینیة )الوثائق( والسرعة في تسویةالتعویضات وغیرها من الانشطة التي تمارسه
... Show MoreSustainable development is launched through the interaction between the economy and natural resources and preserving them from exhaustion as well as the efficient management of natural and social resources and includes a diversified economic condition and thus is the focus of attention to the development of economic structures, which is intended to improve the level of human well-being by increasing its share in the necessary goods and services and their relationship With economic growth, which is the most important driver of economic transformation, because it reflects the ability of society and increasing its productive capabilities and investing in the optimal way Although the Iraqi economy is considered one of the diversified
... Show MoreThis research seeks to explore the impact of notifications on enhancing user engagement with websites, primarily through user subscriptions and their interaction with notifications on these websites. The significance of this study lies in its implications for crafting compelling headlines that capture users' attention, streamline their access to journalistic content, and align with the objectives and editorial policies of news websites. It sheds light on the factors influencing users' preferences for specific notifications and their engagement with content based on their individual interests, motivations, and the satisfaction derived from such interactions.
The researcher has reached several key findings, inc
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The research aims at a statement Internal Debt options during shocks and the impact of this borrowing in the volume of the foreign reserve, using induction and deduction with available data analysis. During the period (2004-2013) did not require the use of borrowing across (financial institutions, discounted transfers, bonds); it was only sufficient by transfer with commercial banks that can finance of temporary budget deficits: rose and decline of volume of foreign reserve according to the changes of oil prices and the volume of purchases and sales of the Central Bank of Iraq. Central Bank of Iraq (CBI) has significantly contributed to Internal Debt through bond and discounted transfers in the secondary market; thus, funding the
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Background: The Covid-19 pandemic changed the world; its most important achievement for education was changing the approach from traditional to virtual education. The present study aimed to investigate the role of virtual education networks on mental health of students including personality, beliefs, scientific, and cultural dimensions, in selected countries.Methods: This was an exploratory and applied study. According to the phenomenology strategy, theoretical saturation occurred after 24 semi-structured and targeted qualitative interviews with teachers from Iran, Iraq, Syria and Lebanon, in 2023. Quantitative data was collected through a researcher-made online questionnaire with 423 participants. Teachers with at least a Bachelor’s degr
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The study investigates the possibility of utilizing public interactive sculptures to enhance physical activity in Saudi Arabia. The paper uses a descriptive-analytical methodology to identify the characteristics of interactive sculptures promoting physical activity in public areas as follows: The size and space of the work area are appropriate to the type of physical activity that is achieved, and the importance of the work site in the city and its relation to the surrounding space, identifying participants at the same time and their relationship to ensure safe interaction, as well as the relationship between the esthetic and intellectual concept of working in the community. The study concludes that three technical proposals were present
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The research aims to demonstrate the impact of internal audit in Iraqi economic units on enhancing social performance reports, through the statistical models used, as a survey list (for the independent variant) of the search, which contains five axes of each axis, contains a set of The questions were prepared on the basis of the standards issued by the Institute of Internal Auditors (IIA) and were distributed to a sample of internal auditors, as for (for the approved variable) the researcher obtained numerical data represented by the financial statements of the research sample and used statistical models such as model (Kolmakrov-Smirnov) is a good match (goodness of fit) which assumes that the data is distributed naturally as wel
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