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.
Lead toxicity elicits neurological damage which is a well-known disorder that has been considered to be a major cause for multiple condition such as behavioral defect; mental retardation; and nerve insufficient activity.
This research is designed to estimate potential protective effect of vinpocetine on neurotoxicity stimulated by lead acetate in rats.
Eighteen adult rats of both sexes were randomly enrolled into three groups. Each group includes 6 rats as followings: Group I- Rats were given 0.3ml normal saline solution orally; then intraperitoneal injection of 100μl of the normal saline was given 1h later; this group was considered as control. Group II- Rats were given an intraperitoneal injection of 20mg/kg lead acetate
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Background: Any child with Down's syndrome does not develop in the same manner as normal child. Therefore, the child should not be viewed as being like everyone else. Developmental enamel defects in primary teeth have been found at least twice as frequently in disabled children as in control children. Down's syndrome consumed protein more than the recommended daily allowance compared to other disabled groups. Therefore, the aim of this study was to investigate developmental defects of enamel and their relations to nutrient intake among Down's syndrome children in comparison to normal children. Materials and Methods: A sample consisted of fifty institutionalized Down's syndrome children (study group) and 50 normal children (control group)
... Show MoreA novel series of mixed-ligand complexes of the type, [ML 1 (L 2 ) 3 ]Cl x [M = Cr(III), Fe(III), Co(II),Ni(II), Cu(II), Cd(II) and Hg(II), n = 2, 3], was synthesized using Schiffbase (HL 1 ) as main ligand, nicotinamide (L 2 ) as secondary ligand, and the corresponding metal ions in 1:3:1 molar ratio. The main ligand, HL 1 was prepared by the interaction of ampicillin drug and 4-chlorobenzophenone. The synthesized mixed ligand complexes were characterized by elemental analysis, UV-Vis, FT-IR, 1 H-NMR, 13 C-NMR and TG/DTG studies. In the mixed-ligand complexes, the Schiffbase ligand, HL 1 showed coordination to the central metal ion in tridentate manner via azomethine nitrogen, β-lactam ring oxygen and deprotonated carboxylic oxy- gen atom
... Show MoreIn addition to their high quantities of active chemicals, medicinal plants are well-known for their pharmacological qualities, which include immunological modulation. T Consequently, this study aimed to examine the effects of Avena sativa and Glycyrrhiza glabra leaf extracts on immunological responses as measured by blood cytokine and liver enzyme levels. The phytochemical analysis of Avena sativa crude leaf extracts revealed the presence of alkaloids,flavonoids, tannins, phenolic compounds, and saponins but the absence of resins and violet oils. On the other hand, violet oils, flavonoids, tannins, saponins, and glycosides were detected in significant concentration in Glycyrrhiza glabra ethanolic extract, although resins and phenolic compou
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To determine the relationship between herpes simplex virus 1, 2 and neurological disorders, sixty samples from patients with neurological diseases were collected (40 patients with Multiple sclerosis and 20 patients with Parkinson’s disease) all of whom attended both the Neurological science Hospital as well as the Neuropathology consultation Department in Baghdad Hospital In Iraq. The samples were collected in the time frame between November 2017 and April 2018. The ages of the patients that were investigated were between (17-76) years and compared to a control group consisting of 25 samples collected from apparently healthy individuals. All the studied groups were subjected to the measurement of anti-HSV 1, 2 IgG antibodies by the means
... Show MoreBackground: This study aimed to determine the value of Beta angle for a sample of Iraqi adults with class I skeletal and dental relations and to verify the existence of sexual dimorphism and to find out the relation between this angle and other craniofacial measurements. Materials and Methods: Sixty dental students (23 males and 37 females) with an age ranged between 20-31 years old and having class I skeletal and dental relations were chosen for this study. Each student was subjected to clinical examination and digital true lateral cephalometric radiograph. The radiographs were analyzed using AutoCAD 2007 computer program to measure the angular and linear variables. Descriptive statistics were obtained for the measurements for both genders
... Show MoreBackground: The long term survival of dental implants is evaluated by the amount of crestal bone loss around the implants. Some initial loss of bone around dental implants is generally expected. There is reason to believe that reflecting a mucoperiosteal flap promotes crestal bone loss in the initial phase after an implant has been inserted. The surgical placement of a dental implant fixture is constantly changing and in recent years, there has been some interest in developing techniques that minimize the invasive nature of the procedure, with flapless implant surgery being advocated. The purpose of this study was to compare the radiographic level of the peri- implant bone after implant placement between traditional flapped surgery and f
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Aromatic Schiff-bases are known to have antibacterial activity, but most of these compounds are sparingly soluble in water. The present work describes the synthesis of new Schiff-bases derived from branched aminosugars. Treatment of 3-Amino-3-Cyano-3-Deoxy-1,2:5,6-Di-O-Isopropylene-α-D-Allofuranose (1) with the aldehydes (2) under reflux in methanol afforded the Schiff-bases (3) in good yields. The new Schiff-bases were in accord with their NMR, IR spectral data and elemental analysis.
n this research, some thermophysical properties of ethylene glycol with water (H2O) and two solvent mixtures dimethylformamide/ water (DMF + H2O) were studied. The densities (ρ) and viscosities (η) of ethylene glycol in water and a mixed solvent dimethylformamide (DMF + H2O) were determined at 298.15 K, t and a range of concentrations from 0.1 to1.0 molar. The ρ and η values were subsequently used to calculate the thermodynamics of mixing including the apparent molar volume (ϕv), partial molar volume (ϕvo) at infinite dilution. The solute-solute interaction is presented by Sv results from the equation ∅_v=ϕ_v^o+S_v √m. The values of viscosity (B) coefficients and Falkenhagen coefficient(A) of the Jone-Dole equation and Gibbs free
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