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.
In the present work the nuclear structure of even-even
Ba(A=130-136, Z=56) isotopes was studied using (IBM-1). The reduced matrix element of magnetic dipole moment (11 II f(Ml) II/,) and the magnetic dipole transitions probability B(M 1) were calculated
for one and two bodies of even-even Ba(A=lJ0-136, Z=56). A good
agreement had been found of present with available experimental data.
A total number of 33 isolates of Pseudomoans aeruginosa were collected from different clinical samples, such as: burn, wound and urine from patients attending Al-Yarmouk teaching hospital and some private clinical laboratories in Baghdad city through the period from October to December 2016. On the other hand, 21 isolates of P. aeruginosa were collected from 38 different food samples; such as: vegetables and fruits, from different local markets in Baghdad city during the period from November to December 2016. All isolates were identified by using different bacteriological and biochemical assays and confirmed by Vitek-2 identification system. The antimicrobial susceptibility test for clinical and food isolates towards 17 antimicrobial a
... Show MoreThe special core analysis tests were accomplished on a set of core plugs for Mishrif Formation (mA, mB1, and mB2cde/mC units) in West Qurna/1 oilfield, southern Iraq. Oil relative permeability (Kro) data and the Corey-type fit of the data as functions of the brine saturation at the core outlet face for individual samples in the water-oil imbibition process to estimate relative permeability measurements by the centrifuge method were utilized. Identical correlations for oil and water relative permeabilities were extracted by steady-state and unsteady-state methods. For the mA samples, the gas-water capillary pressure curves were within a narrow range (almost identical) indicating that mA is a homogeneous unit. Kro curves for thr
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In the present study, a novel ligand (L) made of 2-hydroxynaphthaldehyde and 3-hydrazone-1,3-dihydro-indole-2-one(3-[(3-hydroxynaphthalen-2-yl-ethylidene)-hydrazono]-1,3-dihydro-indol-2-one). The ligand was characterized by FTIR, UV-vis, mass, 1H-NMR, 13C-NMR, and CHN elemental analysis. New complexes of this ligand were created by treating methanol and a drop of DMF solution of the produced ligand with the hydrated metal salts of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) in a molar ratio of 2:1 (L:M). As a result, complexes have been emerged and identified FTIR, UV-vis, C.H.N., chloride-containing, molar conductance, magnetic susceptibility, and atomic absorption. The characterization result for each complex indicated complexes wi
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Anew Schiff base (NaHL) has been prepared from the reaction between the salt of amino acid glycine with 2-hydroxy naphthaldehyde. By tridentate Schiff base of (ONO), donors were characterized by using U.V and spectrophotometer techniques. Complexes of Co(II) Ni(II) Cu(II) and Zn(II) ion with the ligand have been prepared, these complexes were identified by infrared, electronic spectral data, elemental analysis, magnetic moments, and molar conductivity measurements. It is concluded from the elemental analysis that all the complexes have (1:2) [metal:ligand] molar ratios, octahedral, with the exception to Zn(II) complex which have (1:1)[metal:ligand] molar ratio.
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A field experiment was carried out in the fields of the Field Crops Department - Faculty of Agricultural Engineering Sciences. The study included five inbred lines (ZM43W (ZE), ZM60, ZM49W3E, ZM19, CDCN5), given numbers 1, 2, 3, 4 and 5) to study the hybrid vigor and both general and special combing ability (GCA, SCA) of the half diallel mating method, for the spring and fall seasons (2016). The genetic analysis shows that all crosses gave a positive hybrid vigor for grain yield per unit area at the two population densities. the highest value is 116.20% for cross (3´5 )at low density, and 89.22% for cross( 1´4 )at high density. The hybrid vigor for all crosses is positive at two densities for dry matter yield, crop growth rate an
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Objective(s): To assess mothers’ knowledge about their children with sickle cell anemia and non-Pharmacological approaches to pain management and found some relationship between mothers knowledge and their demographic data of age, level of education, and occupation.
Methodology: A descriptive design used in the present study established was for a period from September 19th, 2020 to March 30th, 2021. The study was conducted on a non-probability (purposive) sample of (30) mother their children with sickle cell anemia was chosen. The data were analyzed through the application of descriptive and inferential statistical approaches which are applied by using SPSS version 22.0.
Results: The findings of the study indicated that moderate
A new mixed ligand complexes were prepared by reaction of quinoline -2-carboxylic acid (L1) and 4,4?dimethyl-2,2?-bipyridyl (L2) with V(IV),Cr(III), Rh(III), Cd(II) and Pt(IV) ions. These complexes were isolated and characterized by (FT-IR) and (UV-Vis) spectroscopy, elemental analysis, flame atomic absorption technique, thermogravimetric analysis, in addition to magnetic susceptibility and conductivity measurements. Most complexes were mononuclear and with octahedral geometry, except Cd (II) with tetrahedral geometry, and V (IV) with square pyramidal geometry. A theoretical treatment of the ligands and the prepared complexes in gas phase was done using two programs Hyperchem.8 and Gaussian program (GaussView Currently Available Versions (
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Focusing of Gaussian laser beam through nonlinear media can induce spatial self- phase modulation which forms a far field intensity pattern of concentric rings. The nonlinear refractive index change of material depends on the number of pattern rings. In this paper, a formation of tunable nonlinear refractive index change of hybrid functionalized carbon nanotubes/silver nanoparticles acetone suspensions (F-MWCNTs/Ag-NPs) at weight mixing ratio of 1:3 and volume fraction of 6x10-6 , 9x10-6 , and 18x10-6 using laser beam at wavelength of 473nm was investigated experimentally. The results showed that tunable nonlinear refractive indices were obtained and increasing of incident laser power density led to increase the nonlinear refractive inde
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