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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Economic units can benefit from the cleaner production strategy, which aims to reduce the environmental impact of economic activities while improving efficiency and profitability. Accordingly, the aim of the research was to clarify the knowledge foundations of cleaner production costs and to indicate their role in reducing the costs of poor quality (the costs of failure). A set of conclusions has been reached, the most important of which is that cleaner production has achieved a reduction in the costs of external failure, represented by the costs of guarantee, by an amount of 12,339,000 dinars. Contributes to reducing the costs of failure, and based on the conclusions, a set of recommendations were presented, the most important of w
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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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Sustainable 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 Moreتشهد 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
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Biosignal analysis is one of the most important topics that researchers have tried to develop during the last century to understand numerous human diseases. Electroencephalograms (EEGs) are one of the techniques which provides an electrical representation of biosignals that reflect changes in the activity of the human brain. Monitoring the levels of anesthesia is a very important subject, which has been proposed to avoid both patient awareness caused by inadequate dosage of anesthetic drugs and excessive use of anesthesia during surgery. This article reviews the bases of these techniques and their development within the last decades and provides a synopsis of the relevant methodologies and algorithms that are used to analyze EEG sig
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This 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
The Ilkhanid Mongols (651-756 AH / 1253-1355 AD) were interested in urbanization and construction in keeping with civilized countries and to have an architectural imprint that competed with the neighboring nations. The Ilkhan Öljeitü Muḥammad Khudābandeh (703-716 AH / 1303-1316 AD), known for his love of building and construction, wanted to have a capital that would immortalize his name and history, so he ordered its construction to compete with contemporary cities, and he summoned workers and engineers from all over the world to contribute to its construction. The city has several educational and service institutions such as schools, ribats, khanqas, mosques, hospitals, markets, and baths, as well as a mausoleum for him, which
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