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.
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This study presents the results of atmospheric particulates sampling using high volume air sampler for selected places at Al Tuwaitha nuclear site. The collected samples were analyzed for gross alpha /beta radioactivity using Ludlum model 3030 and measurement particles activity in Al Tuwaitha nuclear site and the surrounding areas for the period from 28/12/2016 to 13/4/2017.The measurement of activity concentrations ranged from (0.42±0.03 to 4.18±0.13) Bq/m3 for alpha particles and from(0.93±0.06 to 9.21±0.26) Bq/m3for beta particles. The activity concentration of nuclides inversely proportional with air temperature and wind speed while humidity is directly proportional with it. Highest value of activity concentration has been found at(
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In subterranean coal seam gas (CSG) reservoirs, massive amounts of small-sized coal fines are released during the production and development stages, especially during hydraulic fracturing stimulation. These coal fines inevitably cause mechanical pump failure and permeability damage due to aggregation and subsequent pore-throat blockage. This aggregation behavior is thus of key importance in CSG production and needs to be minimized. Consequently, such coal fines dispersions need to be stabilized, which can be achieved by the formulation of improved fracturing fluids. Here, we thus systematically investigated the effectiveness of two additives (ethanol, 0.5 wt % and SDBS, 0.001 and 0.01 wt %) on dispersion stability for a wide range of condit
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The primary objective of this study is to monitor and collect data from the main
tributaries of Smaquli stream during rainfall storm events, which can be used to
establish relationship between suspended sediment concentration and discharge. The
Smaquli catchment is divided into two sub-catchments namely Sarwchawa and
Krosh with areas of 80.64 and 34.82 km2 respectively. Jali dam is built at watershed
outlet. Rainfall, stream discharge, and suspended sediment concentration are
monitored during ten rainfall storms in the water years (2012-2013) and (2013-
2014). Analysis of the data from the two sampling sites, shows two different
responses of suspended sediment concentrations. The Krosh sub-catchment reacts
rapi
Objectives: This study explored knowledge, attitude, and practice of infection control by dental students at College of Dentistry/ University of Baghdad, Iraq. Material and Methods: Three hundred dental students participated in this study. A self administrated questionnaire with 21 close ended questions related to use of personal protective equipments, infection control awareness, vaccination status, percutaneous exposures, and attitude towards treatment of patients with hepatitis B (HBV)/ or human immunodeficiency virus (HIV) was distributed to dental students. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 21. Fisher exact and Chi-square test were used with significance level set to 0.05. Results: The
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The study conducted to investigate the association between Helicobacter pylori infection and eye diseases (Glaucoma, Cataract, CSR and Uveitis). One hundred and four patients with multiple eye disorders (10-80) years were observed from 10/9 to 18/11/2020 and compared to thirty-one healthy people (19 female and 12 male). Both participants were tested for anti-H. pylori IgA, and IgG antibodies using ELISA. There were non –significant differences (P≥0.05) in the concentration of anti-H. pylori IgA Abs in sera of patients with Glaucoma, CSR, and Uveitis compared to the control group, but there was a significant difference (P≤0.05) in the concentration of H. pylori IgA Abs in sera of patients with Cataract compared to the control group and
... Show MoreRole of Christian Wives in Elijahian Policy
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Review Article Immunomodulatory Role of Cytokines in Periodontal Disease Batool Hassan Al-Ghurabi*, Maha Adel Mahmood, Zainab A. Aldhaher, Sahar Hashim Al-Hindawi Adv. life sci., vol. 11,...
Abstract:
The research aims to improve the insurance service through the marketing commission as a tool that enables the insurance companies to achieve a competitive advantage. The researcher, by observing the challenges faced by insurance companies, insurance agents and brokers, raised the main question of the research: Is there an effect of the marketing commission on the competitive advantage of insurance companies? The data was obtained through the financial statements and annual reports of the research sample companies (the National General Insurance Company, the Iraqi General Insurance Company, Al-Hamra Private
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