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 reaction of [Benzoyl hydrazine] with [Diphenyl mono oxime] and Glacial acetic acid was carried out in methanol gave a new tridentate ligand [Benzoic acid (2- hydroxyimino- 1, 2-diphyneylethylidene) - hydrazide]. This ligand was reacted with some metal ions (Fe(II), Co(II), Ni(II), and Cu(II)) in methanol with (1:1) metal : ligand ratio to give a series of new complexes of the general formula [M(L)Cl2.H2O], where M= Fe(11), Co(11), Ni(11) and Cu(11) . All compounds were characterized by spectroscopic methods (I.R, UV-Vis), elemental microanalysis (C.H.N), atomic absorption, magnetic susceptibility, and conductivity measurements. From the obtained data the proposed molecular structures were suggested for the complexes of Fe (II), Co (II)
... Show MoreThe reaction of [Benzoyl hydrazine] with [Diphenyl mono oxime] and Glacial acetic acid was carried out in methanol gave a new tridentate ligand [Benzoic acid (2-hydroxyimino- 1, 2-diphyneylethylidene) - hydrazide]. This ligand was reacted with some metal ions (Fe(II), Co(II), Ni(II), and Cu(II)) in methanol with (1:1) metal : ligand ratio to give a series of new complexes of the general formula [M(L)Cl2.H2O], where M= Fe(11), Co(11), Ni(11) and Cu(11). All compounds were characterized by spectroscopic methods (I.R, UV-Vis), elemental microanalysis (C.H.N), atomic absorption, magnetic susceptibility, and conductivity measurements. From the obtained data the proposed molecular structures were suggested for the complexes of Fe
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These deposits take many forms like current acc, deposits in order to growth and serve national economy Various in varicose perspectives .
The problem of this paper its concern with un applied the mathematical models that used in profitability analysis of current acc , and deposits in view of risk, profit efficiency and financial leverage for this reason the paper discussion use the cumulate mathematical model to solve these problem, that content three variables that be used to measuring profitability by consequent replacement method by stable base and by moving base for 2007 – 2009 applied the data collect from Iraq middle east bank. &nbs
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Background: Oral SCC is a complex malignancy where environmental factors, viral infections and genetic alterations most likely interact, and thus give rise to the malignant condition. The HSP70 play a direct role in apoptosis inhibition by aligning the improved integrity of a cell’s proteins with the improved chances of that particular cell’s survival.P21 gene produces p21 protein which is a potent cyclin-dependent kinase inhibitor that plays a significant role in carcinogenesis. The aims of the study were to evaluate and compare the immun-histochemical expression of the HSP70 and cell cycle protein p21in NOM, OED, and OSCC. Correlate both marker expressions with each other. Materials and methods: Forty six formalin-fixed, par
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Objectives: To determine the effectiveness of the instructional program on patients’ knowledge about home safety while receiving anti-cancer treatment at Al- Karama Teaching Hospital in Al-Kut City.
Methodology: A quasi-experimental design is conducted through the application of a pre-test and post-test approach for the study and control groups from February 5th, 2020 to April 25th, 2020. A non–probability (purposive) sample of (50) patients treated at the Blood Disease and Oncology Center is selected and divided into two groups. Each group contains (25) patients as control and study groups. An instrument is constructed that is comprised of two parts; t
... Show MoreSYNTHESIS, CHARACTERIZATION, STRUCTURAL, THERMAL, POM STUDIES, ANTIMICROBIAL AND DNA CLEAVAGE ACTIVITY OF A NEW SCHIFF BASE-AZO LIGAND AND ITS COMPLEXATION WITH SELECTED METAL IONS
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3D‐printed scaffolds loaded with healing directed agents could be employed for better treatment outcome in regenerative dentistry. The aim of this study was to fabricate and characterize simple 3D‐printed poly lactic acid (PLA) scaffolds coated with nanoHydroxyapatite (nHA), Naringin (NAR), or their combination, and testing their morphological, chemical, mechanical, antibacterial, biocompatible and bioactive properties. Methodology: Two variants pore sizes, 300 and 700 μm, of 3D‐printed PLA disc scaffolds measuring (10 × 1 mm) were fabricated. These scaffolds were dip‐coated with nHA, NAR, or both (nHA/NAR). Field emission scanning electron microscopy (FeSEM), energy‐dispersive X‐ray spectroscopy (EDX), Fourier transfo
... Show MoreNew Schiff base and their Mn(II),Co(II),Ni(II), Cu(II) and Hg(II) complexes formed by the condensation of O-phathaldehyde and ethylene diamine (2:1) to give ligand (L1) in the first step ,then the ligand (L1) with 2- aminophenol (1:2) to give ligand (L2) were prepared by classic addition through microwave method . These compounds (Ligands and complexes) have been diagnosed electronic spectra, FT-IR,1H-&13C-NMR (only ligand), magnetic susceptibility, elemental microanalysis and molar conductance measurements. Analytical values displayed that all the complexes appeared (metal: ligand) (1:1) ratio with the six chelation. All the compounds appear a high activity versus four types of bacteria such as; (Escherichia coli), (Sta
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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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A total of 200 clinical samples included Burns and Wounds infections were collected from Baghdad Governorate. Results showed that rate all isolates of P. mirabilis was 31(15.5%) and rate of Burns infections was 14 (45%) and rate of wounds infection 17 (55%). Where was diagnostic based on conventional biochemical tests and confirmed by the Vitek-2 Compact system and the specific primer of the16SrRNA gene, the ability of bacterial isolates to biofilm formation to be studied. It's considered an important virulence factor in Incidence of diseases and play important role in increasing resistance to antibiotic of encased bacteria, by two methods Congo Red Agar method and Microtiter Plate method. The Congo Red Agar method showed that most isolates
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