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 study of the concepts of "democracy" and "human rights" and their impact on development, has taken a prominent place in the context of general political and cultural concerns, or in specialized studies even though researchers and scholars do not agree on defining the concepts: Democracy, Human Rights, Development or deriving a global definition hindering them, and that because of the importance of this topic, which proceeds from a number of considerations standing in the forefront, of which:
First: What the world witnesses today in the first decade of this century of consecration of the unipolar theory, trying to give its concepts and perceptions through the law ((excessive force)) to the power of international
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الاستثمار الاجنبي المباشر في العراق ودوره في تحقيق التنمية الاقتصادية
This study aimed to clarify the importance of ecological taxation in achieving sustainable development, by analyzing a set of economic measures such as taxes, taxes levied by the legislation in the field of ecology, to fight against pollution. And we tried to evaluate this initiative in Algeria. The results of the study showed that economic measures of ecological taxation contribute to achieving sustainable development, and Although Algeria has adopted a series of ecological tax mechanisms, it is far from keeping pace with developments in this area.
Abstract\
Dealing economic units at the present time with an industrial environment characterized by competitiveness and the pace of change and its strength as a result of this changing environment shall be on those who made it to adopt strategies that allow them to confront these variables and work in order to meet the market requirements of quality and price appropriate products to suit and the demand for those products and conditions to maintain
its competitive position and its development.
As a result, it became the subject of competitiveness in recent years and enjoys widespread attention at the global level. And in order to keep up
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The study of the historical figures is one of the important in modern history since it is main focus is to show the political , economic or social product of a specific person throughout his life . Therefore , the subject of my research is “ Hussein AL-Husseiny and his politilcal role in Lebanon1968-1992. The research focused on high highting his role in Lebanon within the parliament and the ministry , he has help for the duration of the study. It also dealt with his national attitudes which he lived toward most of crucial issues in Lebanon
QA Sarhan, University of Anbar Sport and Physical Education Sciences, 2019
Acting on the Holy Qur’an by contemplating its meanings, stopping at its commands and prohibitions, and everything in it that guides us to truth and mercy. The Holy Qur’an includes it for various purposes in one verse, and there is no doubt that this is part of the perfection of this great book, and one of the sciences of the fundamentalists is the indication of the context, and it is a great science of high rank, and it is one of the most important things that lead to the correct understanding of the miraculous and decisive book of God Almighty, and one of the best meanings of the Qur’an It was not from the context of the verses, and from here it can be said that the indication of the context is one of the origins of deriving lega
... Show MoreBackground: Dorsal plication on each side of the penis at the 2 and 10-o’clock positions had been a mainstay for correction of ventral penile curvature. However, because only the 12-o’clock position proved to be a nerve-free zone, dorsal plication at the 12-o’clock position can be advocated.
Objectives: To evaluate tunica albuginea plication with and without neurovascular bundle mobilization in patients with ventral penile curvature. Type of the study: A prospective study.
Methods: A 34 patients with a mean age of (4.8 ± 0.54) years, Who still
Increased interest in the subject of the image because of its great and growing link to the life of the individual and society and its impact on the overall political, economic and cultural conditions. This interest is no longer confined to the images of people or institutions, but has become beyond that to the images of countries and peoples and the impact on bilateral relations between them,
However, we find that the image of the Iraqi abroad remained vague and has not been scientifically recognized and the most that we can generalize are the features of the image of Arabs and Muslims abroad; and assume that the image of the Iraqi applies to them as the Iraqi is in the end an Arab or Muslim.
Based on this, the research
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The aim of this research to show the role of some enzymes in pathological mechanism of rheumatoid arthritis (RA) disease. Sixty patients with RA and matched number of apparently healthy volunteers were included in the study. Spectrophotometric methods were used to determine Peroxy nitrite (ONOO), Nitric oxide (NO), Nitric oxide synthase activity (NOS) cycloxygenase-2 activity (COX-2), glutathione peroxidase (GPX) activity and superoxide dismutase (SOD) activity in serum of both groups. Colorimetric assay kits were used to determine Iron. Rheumatoid factor (RF) was determined using Imuno-Latex kit. ONOO, NO levels, and NOS activity were significantly higher in the patients compared to the control group. Conversely, Iron level, SOD
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