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.
This study depicts the removal of Manganese ions (Mn2+) from simulated wastewater by combined electrocoagulation/ electroflotation technologies. The effects of initial Mn concentration, current density (C.D.), electrolysis time, and different mesh numbers of stainless steel screen electrodes were investigated in a batch cell by adopting Taguchi experimental design to explore the optimum conditions for maximum removal efficiency of Mn. The results of multiple regression and signal to noise ratio (S/N) showed that the optimum conditions were Mn initial concentration of 100 ppm, C.D. of 4 mA/cm2, time of 120 min, and mesh no. of 30 (wire/inch). Also, the relative significance of each factor was attained by the analysis of variance (ANO
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2-benzamide benzothiazole complexes of Pd(II) , Pt(IV) and Au(III) ions were prepared by microwave assisted radiation. The ligand and the complexes were isolated and characterized in solid state by using FT-IR, UV-Vis spectroscopy, flame atomic absorption, elemental analysis CHNS , magnetic susceptibility measurements , melting points and conductivity measurements. The nature of complexes in liquid state was studied by following the molar ratio method which gave results approximately identical to those obtained from isolated solid state; also, stability constant of the prepared complexes were studied and found that they were stable in molar ratio 1:1.The complexes have a sequar planner geometry except Pt(IV) complex has octahedral .
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The [2-hydroxy -1,2-diphynel-ethanone oxime] was reacted with 1,2- dichloroethan to give the new ligand [H2L].this ligand was reacted with some metal ions (Co(II),Ni(II),Cu(II),Zn(II) and Cd(II) in methanol as a solvent to give a series of new (1:1)complexes of the general formula [ M(HL)]Cl ,( where : M= Co(II),Ni(II),Cu(II),Zn(II) and Cd(II)) are isolated All compounds have been characterized by spectroscopic methods [ I.R , U.V -Vis ] atomic absorption . Chloride content along with conductivity measurements. From the above data the proposed molecular structure for (Co, Cu, Ni, Zn and Cd) complexes adopting a tetrahedral structure.
The N-[(2,3-dioxoindolin-1-yl)-N-methylbenzamide] was prepared by the reaction of acetanilide with isatin then in presence of added paraformaldehyde, the prepared ligand was identified by microelemental analysis, FT.IR and UV-Vis spectroscopic techniques. Treatment of the prepared ligand with the following selected metal ions (CoII, NiII, CuII and ZnII) in aqueous ethanol with a 1:2 M:L ratio, yielded a series of complexes of the general formula [M(L)2Cl2]. The prepared complexes were characterized using flame atomic absorption, (C.H.N) analysis, FT.IR and UV-Vis spectroscopic methods as well as magnetic susceptibility and conductivity measurements. Chloride ion content was also evaluated by (Mohr method). From the obtained data the octahed
... Show MoreThe adsorption behavior of Bismarck brown (BB) dye from aqueous solutions onto graphene oxide GO and graphene oxide-g-poly (n-butyl methacrylate-co-methacrylic acid) GO-g-pBCM as adsorbents was investigated. The prepared GO and GO-g-pBCM were characterized by Fourier transform infrared spectroscopy FTIR, which confirmed the compositions of the prepared adsorbents. Adsorption of BB dye onto GO and GO-g-pBCM was explored in a series of batch experiments under various conditions. The data were examined utilizing Langmuir and Freundlich isotherms. The Langmuir isotherm was seen as increasingly reasonable from the experimental information of dye on formulating adsorbents. Kinetic investigations showed that the experimental data were fitted ve
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In this work, electrochemical process was presented to polymerized eugenol on Gr.2 and Gr.5 titanium alloys before and after treated by Micro Arc Oxidation (MAO), where Gr.2 is commercial pure titanium and Gr.5 is Ti-6Al-4V dental alloys. The deposited layers were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The adhesion strength of polymeric thin-film was estimation by using pull-off adhesion test and the result was the adhesion strength of PE was (1.23 MPa) on Gr.2 before MAO and increase to (1.98 MPa) on Gr.2 after MAO treatment. The corrosion behavior of Gr.2 and Gr.5 alloy in artificial saliva environment at
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This paper investigates the performance evaluation of two state feedback controllers, Pole Placement (PP) and Linear Quadratic Regulator (LQR). The two controllers are designed for a Mass-Spring-Damper (MSD) system found in numerous applications to stabilize the MSD system performance and minimize the position tracking error of the system output. The state space model of the MSD system is first developed. Then, two meta-heuristic optimizations, Simulated Annealing (SA) optimization and Ant Colony (AC) optimization are utilized to optimize feedback gains matrix K of the PP and the weighting matrices Q and R of the LQR to make the MSD system reach stabilization and reduce the oscillation of the response. The Matlab softwar
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It is found that hypersensitive teeth have a larger number and wider patent tubules than those of non-sensitive teeth. Objective: The aim of this study is to compare between the effects of diode laser at different power densities, with and without sodium fluoride on the sealing of exposed dentinal tubules and dentin permeability. Materials and methods: 118 teeth were used. Samples were divided into three major groups. The first consisted of 100 teeth used for permeability test. The second consisted of 16 teeth for measuring external surface temperature elevation while irradiation. The third, in turn, consisted of one pair of teeth observed under SEM for dentine surface morphology analysis. Results: For dentin permeability measurement, th
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