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.
Five Saccharomyces cerevisiae isolated from the ability of chitinase production from the isolates were studied. Quantitative screening appeared that Saccharomyces cerevisiae S4 was the highest chitinase producer specific activity 1.9 unit/mg protein. The yeast was culture in liquid and solid state fermentation media (SSF). Different plant obstanases were used for (SSF) with the chitine, while liquid media contained chitine with the diffrented nitrogen source. The favorable condition for chitinase producers were incubated at 30 ºC at pH 6 and 1% colloidal chitine.
The dispersion relation of linear quantum ion acoustic waves is derivate according to a fluid approach that depends on the kinetic description of the systems of charged particles model. We discussed the dispersion relation by changing its parameters and graphically represented. We found through graphs that there is full agreement with previous studies on the subject of interest. That motivates us to discuss the dispersion relation of waves depending on the original basic parameters that implicitly involved in the relationship which change the relationship by one way or another, such as electron Fermi temperature and the density at equilibrium state.
Media, especially press plays an important role in fighting corruption and tackling this phenomenon, which has become widespread in our society, through its effective role in raising awareness of the seriousness of spreading of corruption of all its forms in society.
All international conventions and agreements stress the necessity of the role of media and its importance in the light of corruption. All countries also commit themselves to the necessity of guaranteeing the freedom of media and the circulation of information and preparing it as a prerequisite for activating the People’s Control Mechanism and supporting measures and means to prevent and combat financial and administrative corruption more actively and effectively.
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Self- curing is the potential of lightweight aggregate to absorption great amount of water thru mixing which prominently can moves to the paste during hydration process. Self- curing empowers a water to be distributes more evenly act out the cross section. Whereas, the external curing water is only able to penetrate several millimetres into concrete with low water cement ratio. Brick dust accumulates in the demolish site creates serious environmental contamination. This study investigates the effect of brick dust recovered from construction site on the Properties of mortar cured in three curing conditions. Mortar in this study produced using BD as cement additive with (2, 4, 6, and 8) % by weight of cement. BD was used a
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The current investigation conducted to examine the anatomical aspects of the Arum colocasia L. cultured in Iraq. The study included the anatomical characteristics of the different plant parts, including the root, stem and leaf, the results of the study on the vegetative parts were shown the important anatomical characteristics in terms of the form of the sections reviewed and vertical in them, and the study of their tissues, as well as the stomata complexities and the thickness of the epidermis, vascular bundles, pith, additionally the dimensions of mesophyll and in blade of the leaf. The research was conducted as it is one of the monocotyledon plants and because of the lack of anatomical studies on it, therefore it was studied to know the
... Show MoreBackground: Penetrating neck injuries are common problem in our country due to increasing violence, terrorist bombing and military operations.
These injuries are potentially life threating and need great attention and proper management.
Objective: The aim of this study is to focus on the importance of anatomical zonal classification of the neck in the management of penetrating injuries of the visceral compartment of the Neck.
Methods :70 patients with various injuries who were managed at causality unit and Otolaryngology department in Al-Kindy Teaching Hospital during aperiod from January 1st 2015 to October 31st 2015.
The study carried on those patient depending on proper clinical examination and their urgent management.
The issue of peace, renunciation of violence, and acceptance of the other is one of the vital issues that rose to the top of the list of priorities at the end of the last century and the beginning of the new millennium of the conscience of the Iraqi people by spreading the culture of peace. In this context, we seek during this research to identify the concept of the culture of peace and its impact on sustainable development, and to draw a set of results and suggestions to consolidate this culture in our Iraqi society as an obligation of sustainable development.