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 effect of adding different volume of coumarin dye (5, 15, 25 and 35) ml on optical properties of Poly (Methyl Meth Acrylate) was studied. Films of pure PMMA and PMMA with different volume of coumarin dye (5, 15, 25 and 35) ml were prepared using the casting technique. Transmission and absorption of the films were measured by using UV-VIS spectrometer technique type (100 Conc), in order to assess the type of transmission which was found an indirect transition. An optical energy gap of pure PMMA is (4.95e v) and after adding coumarin with volume (25, 35) ml, the energy gap for PMMA decrease by (0.05) compere to pure PMMA films and addition energy gap appear equal to (4.1 e v). It was found that the absorption coefficient, extinction coeff
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The purpose of this study is to assess the level of computer literacy of the students at AlQuds open university in Tulkarm Branch. The study investigates the effects of the variables of gender, specialization, academic level, owning a personal computer, internet communication, and own an email account on the level of computer literacy. A test of computer literacy was constructed by the researchers consisting of (37) multiple choice items with a reliability rate (0.85). The study population consisted of (4100) students, while the sample contained (352) students. The study revealed that the level of computer literacy of the students at AlQuds Open University in Tulkarm Branch was (66.2 %) which is educationally acceptable. It also
... Show MoreSome research reports that cognitive grammar (CG) theory has good contributions to teaching English as a foreign language. In this research, the researchers seek to apply this theory and its principles when teaching the simple present tense to Iraqi students who face difficulties in differentiating between the multiple usages of this tense. To achieve this objective, the researchers have conducted an experimental study on a group of 60 Iraqi students in the University of Baghdad, College of Education for Women. Langacker’s (2003) theory has been adopted in the analysis of the cognitive relations to understand the common and different connections of these usages of the simple present. The study has concluded that the cognitive grammar t
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The irony pushes us to inquire about what is in the text of contradiction, irony, suspense, and other acts of paradox, as well as a departure from what is logical, or familiar, that attracts the attention of the addressee, and this is what drives us to introspect the text and interrogate it in order to get to know the intended product of the text or its real or metaphorical intent. On the other hand, the irony is more in the literary text than in the scientific texts. Therefore, critics add the word literature to it in their definition.
As it is represented by the paradox, we will seek to study the paradox of the title and the problematic that it may pose as the beginning of the text, and i
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The nuclear structure included the matter, proton and neutron densities of the ground state, the nuclear root-mean-square (rms) radii and elastic form factors of one neutron 23O and 24F halo nuclei have been studied by the two body model of within the harmonic oscillator (HO) and Woods-Saxon (WS) radial wave functions. The calculated results show that the two body model within the HO and WS radial wave functions succeed in reproducing neutron halo in these exotic nuclei. Moreover, the Glauber model at high energy has been used to calculated the rms radii and reaction cross section of these nuclei.
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Crude oil still affects many countries because it is one of the essential fuel sources. It makes life more manageable in modern communities and cannot be overstated because it is easy to use and find. However, the pollution caused by its use in industries such as mining, transportation, and the oil and gas business, especially soil pollution, cannot be ignored. Soil pollution is an issue in most communities because it influences people and ecology. Accidental infusions and spills of ore oils are prevalent occurrences leading to the entire or fractional exchange of the soil pore fluid by oil-contaminated soils that have affected the geotechnical engineering properties. The liquid limitations for polluted soil grades silty loam and sa
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Crude oil still affects many countries because it is one of the essential fuel sources. It makes life more manageable in modern communities and cannot be overstated because it is easy to use and find. However, the pollution caused by its use in industries such as mining, transportation, and the oil and gas business, especially soil pollution, cannot be ignored. Soil pollution is an issue in most communities because it influences people and ecology. Accidental infusions and spills of ore oils are prevalent occurrences leading to the entire or fractional exchange of the soil pore fluid by oil-contaminated soils that have affected the geotechnical engineering properties. The liquid limitations for polluted soil grades silty loam and sa
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Fear, harvesting, hunting cooperation, and antipredator behavior are all important subjects in ecology. As a result, a modified Leslie-Gower prey-predator model containing these biological aspects is mathematically constructed, when the predation processes are described using the Beddington-DeAngelis type of functional response. The solution's positivity and boundedness are studied. The qualitative characteristics of the model are explored, including stability, persistence, and bifurcation analysis. To verify the gained theoretical findings and comprehend the consequences of modifying the system's parameters on their dynamical behavior, a detailed numerical investigation is carried out using MATLAB and Mathematica. It is discovered that the
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In this study, geopolymer mortar was designed in various experimental combinations employing 1% micro steel fibers and was subjected to different temperatures, according to the prior works of other researchers. The geopolymer mortar was developed using a variety of sustainable material proportions (fly ash and slag) to examine the influence of fibers on its strength. The fly ash weight percentage was 50%, 60%, and 70% by slag weight to study its effect on the geopolymer mortar's properties. The optimal ratio produced the most significant results when mixed at a 50:50 ratio of fly ash and slag with 1% micro steel fibers at curing temperature 240oC for 4 hours through two days. The compressive strength of the geopolymer mortar increas
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The global rise in temperature and the desert climatic conditions prevalent in Middle Eastern countries have exacerbated rutting distress in heavily trafficked highways. Conventional asphalt binders with a high-temperature performance grade (PG 70) have proven inadequate under such extreme conditions, necessitating the development of modified binders with enhanced high-temperature performance. While polymer modification using styrene-butadiene-styrene (SBS), an elastomeric polymer, and ethylene-vinyl acetate (EVA), a plastomeric polymer, has been widely studied, limited research provides a direct comparison of their effectiveness at both the binder and mixture levels under extremely high-temperature conditions. This study addresses this gap
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