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
This study aims to identify the level of emotional intelligence among principals of basic education schools in Al-Dakhiliya Governorate. The descriptive approach was used. A questionnaire of two parts was utilized; its second part included (27) items divided into five dimensions related to emotional intelligence. The study sample consisted of (337) teachers representing 52% of the study sample were randomly selected. The study result showed that level of the emotional intelligence is high and the motivation dimension is the highest. There were no statistical differences at the level (α≤ 0.05) due to the impact of (the social type, the educational qualification, and the years of experience) in all the
... Show MoreThe studying trying to determine the role of Strategic Intelligence on the Process of Green Manufacturing of Sample of Mineral water factories at Dahuk city. The study submit a theoretical frame of Strategic Intelligence and Green Manufacturing, a supposed sample, had been set to reverye the nature of the relations and effect in the study Varity, the study depend on group of the main and branch concurring with the relations and effect between the Strategic Intelligence and Green Manufacturing to answer the following questions about research to problems:
What are the relationships and effects between stra
... Show More
(2)
This research focus on studying 3 types of Bakhour in the markets of Baghdad city and assessing their impact on the quality of life for asthmatic whom used Bakhour at their houses through investigating particles physical properties, also estimating the levels of heavy metals (Cd, Cu, Mn, Pb and Zn), Particulate Matter PM2.5, PM10, Total Volatile Organic Compounds (TVOC) and formaldehyde (HCHO). The quality of life for asthmatic patients whom use Bakhour was assessing by Mini Asthma Quality of Life Questionnaire. The results indicated that shapes of Bakhour particles were irregular or spherical. Burning process generated the higher percent of PM ˂1μm. Type 2 Bakhour showed the highest percent of <1μm which was 73%.The amount of
... Show More
(1)
Achieving goals effectively reflects the success of the institution. However, unless this indicator is coupled with efficiency when achieving goals, the institution will be equal in its achievements, and distinction will remain unachieved. Perhaps the role of the teaching staff in pushing the institution or college towards brilliance focuses on their ability to motivate people on the one hand and their interest in achieving brilliance for the institution. On the other hand, the importance of the research lies in the institution’s reaching a prominent position through the brilliance and creativity of teaching and achieving competition between institutions that make it more brilliance. The study seeks to achieve the goal of the real
... Show More
Hegel's book entitled"The science of Beauty" is a serious attempt to establish a foundationfor this science. Hegel decided from the beginning, that his research is limited to artistic beauty more than natural beauty. He regards artistic beauty above the natural beauty as the former is the product of the soul.
Everything that comes from the soul is superior to what is found in nature and the worst idea that penetrates human's thoughtbetter than any product of the nature. Man turned to art as a means of his awareness of his superior soul and his interests. All nations poured their highest outputs of their perceptions in the product of art.
... Show MoreThe subject of multi- ethnics is one of the most important subjects in the study of political
geography, as multi- ethnics and its consequent problems are global geopolitical phenomena
that started early and reached its peak with the beginning of the twentieth century, because of
major changes in the political landscape that resulted by wars and led to the collapse of many
empires and major powers, a matter which led to put new political maps according to certain
considerations of the colonial powers, especially in Africa and Asia. All these things led to
the most serious challenges based on ethnic and sectarian conflict and led to the development
of geopolitical problems. Among the examples what most countries in th
In this paper we will study some of the properties of an operator by looking at the associated S-act of this operator, and conversely. We look at some operators, like one to one operators, onto operators. On the other hand, we look at some act theoretic concepts, like faithful acts, finitely generated acts, singular acts, separated acts, torsion free acts and noetherian acts. We try to determine what properties of T make the associated S-act has any of these properties.
Abstract
Toady technology Nano since it launched human Alivia third interest and anticipation unusual and that by the decision-makers in the world's governments and its institutions and research departments productivity, especially after the US Congress enact a law (the National Initiative for Tknlojba nanotechnology in the United States of America) and the allocation of large sums of money To support this initiative, the research aims to shed light on the concept of technology nanotechnology, which is technology atheist and the twentieth century, and reflect its economic importance and in order to reach the objectives of the research has been the division of research into several axes has been allocated
... Show More