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.
Accurate description of thermodynamic, structural, and electronic properties for bulk and surfaces of ceria (CeO2) necessitates the inclusion of the Hubbard parameter (U) in the density functional theory (DFT) calculations to precisely account for the strongly correlated 4f electrons. Such treatment is a daunting task when attempting to draw a potential energy surface for CeO2-catalyzed reaction. This is due to the inconsistent change in thermo-kinetics parameters of the reaction in reference to the variation in the U values. As an illustrative example, we investigate herein the discrepancy in activation and reaction energies for steps underlying the partial and full hydrogenation of acetylene over the CeO2(111) surface. Overall, we find th
... Show MoreThe present study was conducted to determine histopathological changes caused by chronic effect of Nitrofurantoin(NFT) in The albino mice Testes. The Study included 40 mice were divided on the five groups: the first group taken distilled water and become control group . the remaining group which are exposure with NFT drug in concentration (100-150-200-250) mg / kg, respectively, Doses were given orally for a period (month and two months). The results of histopathological changes included occurrence of congestion in the blood vessel and degeneration of spermatogonia and aggregation of spermatids in the lumen of semineferous tubules and inhibition of spermatogensis process and decrease of sperm inside the lumen
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The present study reports the effect of temperature and liquid hourly space velocity (LHSV) on the cumene cracking reaction rate and selectivity by using a laboratory continuous flow unit with fixed bed reactor operating at atmospheric pressure. The prepared HX zeolite was made from Iraqi kaolin with good crystallinity .The activity and selectivity of prepared HX-zeolite was compared with standard HY zeolite and HX zeolite catalysts in the temperature range of 673-823K and LHSV of 0.7-2.5 h-1 . It was found that the cumene conversion increases with increasing temperature and decreasing LHSV at 823K and LHSV of 0.7 h-1 the conversions 65.32, 42.88 and 59.42 mol% for HY, HX and prepared HX catalysts respectively and at LHSV of 2.5 h-1 and th
... Show MoreBrainstorming is one of the fundamental and necessary concepts for practicing the auditing profession, as auditing standards encouraged the implementation of brainstorming sessions to reach reasonable assurance about the validity of the evidence and information obtained by the auditor to detect fraud, as the implementation of brainstorming sessions and the practice of professional suspicion during the audit process lead to increase the quality of auditing and thus raise the financial community's confidence in the auditing profession again after it was exposed to several crises that led to the financial community losing confidence in the auditing profession.
The research aims to explain the effect of brain
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The aim of this study is to develop the science textbook for the 1st intermediate grade by analyzing it according to life skills. Its core areas were mental skills, environmental skills, and health skills. The analysis tool was used after verifying its validity and stability in analyzing the science textbook for the 1st intermediate grade, and the results of the study resulted in the inclusion of mental skills on a high percentage of repetitions, while we find that this percentage is low in the inclusion of environmental and health skills. The study recommended the importance of achieving balance and justice in including skills in the science textbook for the 1st intermediate grade, by emphasizing the environmental and health skills by incr
... Show MoreThin films of ZnSxSe1-x with different sulfide content(x)
(0, 0.02, 0.04, 0.06, 0.8, and 0.1), thickness (t) (0.3, 0.5, and 0.7 μm) and annealing temperature (Ta) (R.T 373 and 423K) were fabricated by thermal evaporating under vacuum of 10-5 Toor on glass substrate. The results show that the increasing of sulfide content (x)and annealing temperature lead to decrease the d.c conductivity σDC of and concentration of charge carriers (nH) but increases the activation energy (Ea1,Ea2), while the increasing of t increases σDC and nH but decrease (Ea1,Ea2). The results were explained in different terms
Education specialists have differed about determining the best ways to detect the
talented. Since the appearance of the mental and psychological measurement movement, some
scholars adopted intelligence ratios as a criterion to identify the talented and others went to
rely on the degree of academic achievement. Each of these two methods has its own flaws and
mistakes and a large number of talented children were victims of these two methods.
Therefore the need to use other scales for the purpose of detection of talented children
appeared because they provide valuable information which may not be obtained easily
through objective tests and these scales are derived from consecutive studies of gifted andtalented children
Thin films of the blended solution of (NiPc/C60) on glass substrates were prepared by spin-coated method for three different ratios (100/1, 100/10 and 100/100). The effects of annealing temperature and C60 concentration on the optical properties of the samples were studied using the UV-Vis absorption spectroscopy and FTIR spectra. The optical absorption spectrum consists of two main bands, Q and B band, with maxima at about (602-632) nm and (700-730) nm for Q1 and Q2 respectively, and (340-375) nm for B band. The optical energy gap were determined from optical absorption spectra, The variation of optical energy gap with annealing temperature was nonsystematic and this may be due to the improvement in crystal structure for thin films. Whi
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This study focuses on evaluating the suitability of three interpolation methods in terms of their accuracy at climate data for some provinces of south of Iraq. Two data sets of maximum and minimum temperature in February 2008 from nine meteorological stations located in the south of Iraq using three interpolation methods. ArcGIS is used to produce the spatially distributed temperature data by using IDW, ordinary kriging, and spline. Four statistical methods are applied to analyze the results obtained from three interpolation methods. These methods are RMSE, RMSE as a percentage of the mean, Model efficiency (E) and Bias, which showed that the ordinary krigingis the best for this data from other methods by the results that have b
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In this paper, we establish the conditions of the occurrence of the local bifurcations, such as saddle node, transcritical and pitchfork, of all equilibrium points of an eco-epidemiological model consisting of a prey-predator model with SI (susceptible-infected) epidemic diseases in prey population only and a refuge-stage structure in the predators. It is observed that there is a transcritical bifurcation near the axial and free predator equilibrium points, near disease-free equilibrium point is a saddle-node bifurcation and near positive (coexistence) equilibrium point is a saddle-node bifurcation, a transcritical bifurcation and a pitchfork bifurcation. Further investigations for Hopf bifurcation near coexistence equilibrium point
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