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.
Abstract
The main question raised in this paper is: Is it possible to translate the ‘genre’
of Quran? And if this ‘genre’ is Quran specific, a ‘genre’ of its own, i.e. a unique one,
how can the Quranic text be translated from Arabic into English or any other
language? This question has been raising a lot of controversy among translation
theorists, linguists, philosophers and scholars of Islam and specialists in the sciences
of Arabic language let alone Quran exegetes. Scholars of the Arabic language and
scholars of Islam have argued that because of the genre of Quran is the genre of (ijaz),
translatability can never be possible. Equivalence, thus, cannot be achieved especially
if we know that so far
يهدف البحث الى صياغة استراتيجية اعلامية لمواجهة اعلام التنظيمات الارهابية
This day, we see the Significant role that social media platforms play, it plays a vital role in shaping the Social, political, and economic awareness of individuals. The Iraqi Society, which is experiencing rapid cultural and social transformations, is considered a fertile ground for social media and its influences, whether negative or positive. Research and studies indicate that the negative use of social media will lead to weaking of the sense of belonging and citizenship among members of Iraqi society. This, in turn, threatens moral and educational values, increases feelings of family estrangement, and leads to social isolation. On the contrary, if social is used correctly, it can significantly contribute to enhancing educational values
... Show MoreOxidative stress plays a crucial role in the pathogenesis of peripheral artery disease (PAD). This study aimed to investigate the effect of clopidogrel on oxidative stress in PAD patients. Seventy subjects were divided into three groups: PAD patients before treatment (B-PAD), PAD patients after treatment with clopidogrel (A-PAD), and healthy controls. Serum levels of superoxide dismutase (SOD), copper (Cu), zinc (Zn), manganese (Mn), and oxidized protein were measured. SOD activities were also determined. The results showed that SOD activities, and SOD specific activities were significantly decreased in PAD patients compared to healthy individuals. After treatment with clopidogrel, SOD activities, and SOD specific activities were continuous
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Conflict, peace, and sports have a long history as practical realities, and their correlation has become an important subject of study in the last decades of the twentieth century. Sport has infiltrated peace and conflict studies as a tool for resolving conflict and building peace, but opinions have differed between those who say it is a positive tool and others who see it as negative. The Gulf Cup is one of the champions that have never been studied, and in-depth research about it has not been done. This tournament has affected the relations between the states involved. The politics cast its shadow on the Gulf Cup. The paper aims to shed light on how political events in the region have consistently affected the Gulf Cup and how politics in
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Actinomycetes are free, spore-forming, high (G+C) ratio (>55%) saprophytic microorganisms that are widely distributed in most soils, colonize plants, and are prevalent in water. This is frequently accompanied by the production of filament airborne mycelium. Actinomycetes are well-known microcolonies for creating antibiotics and other critical bioactive components that are beneficial to humans. Approximately 70% to 80% of commercially available medications and antiviral active compounds have been synthesized so far. Secondary metabolites produced by microbes have the potential to be used in a variety of sectors, including antimicrobial agents, enzyme technology, pigment manufacture, antitumor agents against cancer cells, and toxin pr
... Show Moreتسعى المحاسبة الى مسايرة القفزات الهائلة والمتسارعة في تطور العلوم الصرفة والتطبيقية والتقدم التكنولوجي، والتي ادت على ظهور مفاهيم جديدة الغت مسلمات وبديهيات كانت سائدة لمدة طويلة، فعلى سبيل المثال: كان مخزون المواد الاولية والبضاعة التامة في المؤسسات الصناعية او التجارية يشكل العمود الفقري لها بتكاليفه ومشاكله، حتى اذا ما جاء نظام (JIT) الغى بتطبيقاته هذه المفاهيم واعتمد م
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This review delves deep into the intricate relationship between urban planning and flood risk management, tracing its historical trajectory and the evolution of methodologies over time. Traditionally, urban centers prioritized defensive measures, like dikes and levees, with an emphasis on immediate solutions over long-term resilience. These practices, though effective in the short term, often overlooked broader environmental implications and the necessity for holistic planning. However, as urban areas burgeoned and climate change introduced new challenges, there has been a marked shift in approach. Modern urban planning now emphasizes integrated blue-green infrastructure, aiming to harmonize human habitation with water cycles. Resil
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Abstract:
The research aims to monitor the image of the man in the group (The Cart and the Rain) by the storyteller (Badiaa Amin); With the aim of highlighting an aspect of feminist writing, especially with regard to the relationship of women to men, and determining the form adopted by the storyteller in drawing the features of men.
The research used the descriptive-analytical method in the space of its textual formation, which aims to stand on the text and deconstruct its narrative significance. To provide a comprehensive picture of it.
Three images of the man appeared in the group's stories, represented by (the authoritarian, the negative, and the positive), and the image of the authoritarian ma
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