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.
Background: Diabetes mellitus type 2 has been known for many years as the most common endocrine metabolic disorder that affect the oral cavity and cause many oral diseases including candidiasis. In this study, the incidence of Candida spp. in the saliva of controlled and uncontrolled diabetic patients were determined and compared with non diabetic group. Material and method: The sample consists of 200 subjects: 100 diabetic patients [57 (28.5%) uncontrolled diabetes, 43 (21.5%) controlled diabetes] and 100 (50%) non diabetic groups. Saliva samples was obtained from the subjects and cultured on selective media using appropriate microbiological method to observe the presence of Candida spp. Results: The results revealed a significant associat
... Show MoreThe study aimed to investigate the effect of using the intructional computer individually or through the cooperative groups on the achievement of the ninth grade students in mathematics compared to the traditional method. The experimental method adapted three groups out of three schools were chosen, two groups of the students where applied the computer method. The comtrol group used the simple random method, and it used the diagnostic test as tool for the study.The result showed that there is a statistically significant difference between the mean scores of the experimental groups and the control group on the post-test for the two experimental groups.
Atmospheric residue fluid catalytic cracking was selected as a probe reaction to test the catalytic performance of modified NaY zeolites and prepared NaY zeolites. Modified NaY zeolites have been synthesized by simple ion exchange methods. Three samples of modified zeolite Y have been obtained by replacing the sodium ions in the original sample with lanthanum and the weight percent added are 0.28, 0.53, and 1.02 respectively. The effects of addition of lanthanum to zeolite Y in different weight percent on the cracking catalysts were investigated using an experimental laboratory plant scale of fluidized bed reactor.
The experiments have been performed with weight hourly space velocity (WHSV) range of 6 to 24 h
... Show MoreThis research studies the rheological properties ( plastic viscosity, yield point and apparent viscosity) of Non-Newtonian fluids under the effect of temperature using different chemical additives, such as (xanthan gum (xc-polymer), carboxyl methyl cellulose ( High and low viscosity ) ,polyacrylamide, polyvinyl alcohol, starch, Quebracho and Chrome Lignosulfonate). The samples were prepared by mixing 22.5g of bentonite with 350 ml of water and adding the additives in four different concentrations (3, 6, 9, 13) g by using Hamilton Beach mixer. The rheological properties of prepared samples were measured by using Fan viscometer model 8-speeds. All the samples were subjected to Bingham plastic model. The temperature range studi
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The place and environment in which the artist lives is considered one of the influences and drivers active in him, thus determining his style and artistic direction later, and in our research we have dealt with the effect of place and environment in the drawings of Nuri al-Rawi and the extent of their reflection on the general, so the research came within two frameworks: The first is the methodological framework that represents We have the problem of the research, its importance, its goal and the limits of research in it in addition to defining terms. As for the theoretical framework, the study dealt with two topics, the first of which included the topic (Nuri the narrator, the environment and the place) dealing with the role and effect
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Background:The demand for esthetic orthodontic appliances is increasing so that the esthetic orthodontic archwires were introduced. This in vitro study was designed to evaluate the surface roughness offiber-reinforced polymer composite (FRPC) archwires compared to coated nickel-titanium (NiTi) archwires immersed in artificial saliva. Materials and Methods:Three types of esthetic orthodontic archwires were used: FRPC (Dentaurum), Teflon coated NiTi (Dentaurum) and epoxy coated NiTi (Orthotechnology). They were round (0.018 inch) in cross section and cut into pieces of 15 mm in length.Forty pieces from each type were divided into four groups; one group was left at a dry condition and the other three groups were immersed in artificial saliva (
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Unmanned aerial vehicles (UAVs) can provide valuable spatial information products for many projects across a wide range of applications. One of the major challenges in this discipline is the quality of positioning accuracy of the resulting mapping products in professional photogrammetric projects. This is especially true when using low-cost UAV systems equipped with GNSS receivers for navigation. In this study, the influence of UAV flight direction and camera orientation on positioning accuracy in an urban area on the west bank of the Euphrates river in Iraq was investigated. Positioning accuracy was tested in this study with different flight directions and camera orientation settings using a UAV autopilot app (Pix4Dcapture software
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Low grade crude palm oil (LGCPO) presents as an attractive option as feedstock for biodiesel production due to its low cost and non-competition with food resources. Typically, LGCPO contains high contents of free fatty acids (FFA), rendering it impossible in direct trans-esterification processes due to the saponification reaction. Esterification is the typical pre-treatment process to reduce the FFA content and to produce fatty acid methyl ester (FAME). The pre-treatment of LGCPO using two different acid catalysts, such as titanium oxysulphate sulphuric acid complex hydrate (TiOSH) and 5-sulfosalicylic acid dihydrate (5-SOCAH) was investigated for the first time in this study. The optimum conditions for the homogenous catalyst (5-SOCAH) wer
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The research aims to determine optimal urban planning and design indicators of the urban clusters form in hot arid zones through studying of three urban areas in Baghdad, analyzing their urban indicators which include floor area ratio (FAR), urban clusters height, building density or land coverage, green areas, paved areas, shading ratio and how they affect urban temperature. The research reached the conclusion that air outdoor temperature on urban areas affected primarily by shadows casted on the ground, the effect of shaded area equals (5) times the effect of paved areas and (3.7) times the effect of green areas, this means that increasing urban clusters height in hot arid zones could minimize air outdoor temperature, building
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The examination of gills of the common carp Cyprinus carpio revealed the presence of two species of the family Trichodinidae belonging to the genus Dipartiella (Raabe, 1959) Stein, 1961 namely D. indiana Saha and Bandyopadhyay, 2017 and D. kazubski Mitra and Bandyopadhyay, 2009 for the first time in Iraq from Al-Graiat location on the Tigris River at Baghdad city. This also represents the first record of the genus Dipartiella from fishes of Iraq. The descriptions and measurements of these two parasite species as well as their illustrations were given.