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.
A developed model has been put for the hypothesis of capturing moons in explaining the origin of Jupiter moons, and study the change of the orbital properties of these satellites as well as the distance from the planet. Jupiter moons were divided into two types according to their physical and orbital properties, they are the moons , which are formed from the same material as the planet, so it was named the original moons ,while the moons that have been captured from the surrounding space was renamed exotic moons . And the moons of exotic origin asteroid belt and the Kuiper belt in the region which is behind Neptune, the origin of each clique of moons is an asteroid fragmented after colliding previously with another body and
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Because of the experience of the mixture problem of high correlation and the existence of linear MultiCollinearity between the explanatory variables, because of the constraint of the unit and the interactions between them in the model, which increases the existence of links between the explanatory variables and this is illustrated by the variance inflation vector (VIF), L-Pseudo component to reduce the bond between the components of the mixture.
To estimate the parameters of the mixture model, we used in our research the use of methods that increase bias and reduce variance, such as the Ridge Regression Method and the Least Absolute Shrinkage and Selection Operator (LASSO) method a
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This research discusses the subject of identity in the urban environment as it attempts to answer a number of questions that come with the concept of identity. The first of these questions: What is identity? Can a definition or conceptual framework be developed for identity? What about individual, collective, cultural, ethnic, political and regional identity? Is there a definition of identity in the urban environment in particular? If there is a definition of identity, what about social mobility responsible for social change? How can we see identity through this kinetics? Can we assume that identity in the urban environment has a variable structure or is of variable shape with a more stable structure? Can we determine the spatial-tempora
... Show MoreThis paper is illustrates the sufficient conditions of the uniformly asymptotically stable and the bounded of the zero solution of fifth order nonlinear differential equation with a variable delay τ(t)
The research entitled "the attitudes of Iraqi People towards the Logic Propaganda for Terrorist Organization such as Daash Regulation, as-Qaida, and Jabhat al-Nasra". It is a field study on the professors and the students of the College of Mass Media at Baghdad University in 2014.
After the global war on terrorism declared on September 11, 2011, the researcher finds it is important to study such subject as it threats the unity and sovereignty of Iraq especially after th
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The Marshlands cover an area of about 24% of the land area of Iraq, which gives it special importance to the country with its resources, resources and human capabilities, and because the conditions of this region are different from other areas environmentally and living necessitates subject to certain design principles achieve sustainable environmental integration to maintain them from For future generations, the idea of research is crystallized by the interest of environmental organizations and urban designers in planning and establishing special laws to exploit the region environmentally, economically and tourism, especially after the current focus of the country's economic revival. T tourism and begin the development
... Show MoreThe aim of study is to identify the histological changes in ovaries of the albino mice exposed to silver nanoparticles. Sixty adult females were collected and exposures by 4000 p.p.m. and 50-150 nm in size, Females were divided into 3treated groups. The concentration dosage was (1, 1.5 and 2) p.p.m. of silver nanoparticles for 7, 14 and 21 days as exposure periods as well as control group which treated by normal saline. Treated groups appeared different histopathological changes, it is depending on the concentration of silver nanoparticles and the period of exposure. These changes were included congestion in the blood vessels, hemorrhage, hyaline degeneration, fatty degeneration, pyknosis, necrosis as well as fusion of cells in follicula
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The main objective and primary concern to every investor not only to achieve a greater return on his or her investments, but also to create the largest possible value of these investments the, researchers and those interested in the field of investment and financial analysis try to develop standards for performance valuation is guided through the  
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Photonic Crystal Fiber Fabry–Perot Interferometers (FPI) based on Surface Plasmon Resonance (SPR) was investigated in this paper in order to detect changes in photonic crystal fiber sensitivity with increasing temperature. FPI is composed of a PCF (ESM-12) solid core spliced with a single-mode fiber (SMF) on one side and a 40nm thick gold Nano film on the other. In order to obtain the SPR curve, the end of PCF can be spliced with the side of SMF before covering the gold film on the PCF. SPR results are included in the suggested sensor, based on the conclusions of the investigations. Resolution (R) is 0.0871, Signal-to-Noise Ratio (SNR) is 0.1867, a figure of merit (FOM) is 0.0069, and sensitivity (S) is 1.1481 . This sensor proposed is s
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