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 phenomenon of delayed marriage triggered the intention of most researchers and specialists to reveal the social factors associated with the spread of this phenomenon in order to identify the characteristics of that phenomenon and the social factors resulting from it. Thus, the current research aims to identify the social factors most related to the delay in marriage age among working-women at the University of Baghdad, represented by family factors, economic factors-professional, psychological factors – subjective, and environmental factors. The researcher also aims to identify the differences in social factors associated with late marriage age for working women at the University of Baghdad in terms of the type of profession (teach
... Show MoreThe research aims to explain the role of cloud computing technology in facilitating the application of international financial reporting standards in Iraqi banks, by preparing a checklist that included a set of paragraphs to measure the level of application of IFRSs. In those banks and then the need to use cloud computing technology, and the researchers reached a set of conclusions, including, that cloud computing technology has a role in facilitating the application of international financial reporting standards in the banks, the research sample, because of the ease it provides in preparing and saving accounting information and the possibility of accessing it in any time and from any place where the Internet service is available. T
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Recently, environmental noise has arisen from various sources, such as those from exhaust mufflers of combustion engines found in cars, trucks, or power generators, which produce significant noise during their operation. Controlling the radiated noise from these mufflers is a major factor in improving acoustic comfort and minimizing the impact on the surrounding communities. Numerous research has been presented for this reason by modification of the internal structure of the exhaust muffler. The main objective of this work is to reduce the noise level emitted from exhaust mufflers. This can be achieved by adjusting structure parameters to attenuate the surrounding environment's radiated noise. Analysis of pressure-wave propagation h
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research aim :
- The research aimed to investigate the effect of two treatment
methods in the gaining of fourth grade students in geography
object.
- Research hypothesis
there are no statistically significant differences at the level of ( 0.05 )
in the average level of achievement in geography between the first
experimental group ( strengthening lessons ) and the second group
( re- teaching )
no individual differences statically significant at the level of ( 0.05 )
in the average level achievement in geography object of the second
experimental group ( re- teaching ) and the first experimental group
( strengthening lesson )
the research sample : the researcher selected randomly Baghdad
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(6)
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One of the most important phenomenon that occurs in sheet metal forming processes is the spring-back, which causes several geometrical alterations in the parts. The accurate prediction of springback after bending unloading is the key to the tool design, operation control, and precision estimate concerning the part geometry. This study investigated experimentally the effect of pretension in three rolling direction (0, 90, 45 degree) on the springback behavior of the yellow brass, sheet under V shape bending die. The pre-tension ranges from five different levels starting of 11% to 55% from the total strain in each rolling direction by regular increase of 11 %, then bent on a V-die 90 degree for the springback estimate. From experiment the
... Show MoreThis study unveils the ideologies of women empowerment encoded in the Mona Lisa Smile movie (2003). It reveals how the stereotypical image of women born only to be wives and do the duties of upbringing and housework is challenged. Katherine Ann Watson (Julia Roberts), the main character in the movie, wants to make a difference in the next generation of women. She rejects the imposed traditional ideologies. Linguistically, she opposes conventional thinking and seeks to persuade her students that life is about more than getting married. The primary focus of this study is to examine and clarify how the characters’ linguistic choices convey their ideologies concerning the notion of women empowerment. To do this, the researchers apply
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Thermal conductivity measurement was done for specimens of Polystyrene/ titanium dioxide, Polycarbonate/ titanium dioxide and Polymethylmetha acrylate/ titanium dioxide composites for weight ratio of 1.9/ 0.1 and 1.8/ 0.2 wt% for different thickness of the samples. The experimental results show that the thermal conductivity is increased with the increasing of thickness of layers and with the weight ratio of TiO2