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.
Abstract
The Holy Quran is the greatest motivator for the mind to keep pace with life. The doctrine of faith is a requirement of logic and wisdom, and it cannot be reached by the hand of superstition. The Qur’an destroyed the principle of superstition in the verses of the creation of the universe. The principle of inactivity of the Qur’an is a false accusation that collision with the texts of the Qur’an. The secret of scientific development is to harness the laws of nature, benefit from them, and walk according to its requirements, on which the manifestations of civilization and the Qur’an are based
... Show MorePremature failure in asphalt concrete pavement has been the main concern for pavement construction companies and engineers in recent years because of the large rise in traffic volume and loads and the temperature extremes in the summer and winter. The use of modifiers in asphalt concrete mixtures has attracted much attention to increase the performance and lifespan of pavements. As nanotechnology developed, several researchers concentrated on how these materials can help increase pavement serviceability by minimizing rutting and moisture damage. This study evaluates the Hydrated Lime (HL) effect by two methods (wet and dry hydrated lime) on the durability of the warm mix asphalt. The first method, HL, has been supplemented to the as
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The introduction to the research included a presentation of some physical characteristics and their importance in sports, including the speed of kinesthetic response response and the extent of its usefulness and importance, especially for soccer goalkeepers, as it is the most important element that goalkeepers must have, and it is also the main key to the excellence and development of all physical and kinesthetic response qualities and skills of a goalkeeper. Football. The speed of kinesthetic response response and reaction is one of the requirements of the game of football, as well as all other sports and even in general professional life. Its importance is highlighted for the football goalkeeper, so he must master it perfectly to perform
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Man was closely associated with nature in its various forms, as it represented the incubator for him in all areas of his life, so writers often made it a material for their literature and a fertile ground for their productions, so it appeared in its various forms and man’s need for it, its good and its bad in literature throughout history, and the Arabs are like Other nations, since the pre-Islamic era, nature was an important outlet and a refuge for poets in the production and creativity of literature and to this day, and when we talk about a poet from the Fatimid state, we find that nature - especially spring and its flowers - in that period took its take from literature and represented a phenomenon for many Among the
... Show MoreThe effect of the concentration of the colloidal nanomaterial on their optical limiting behavior is reported in this paper. The colloids of sliver nanoparticles in deionized water were chemically prepared for the two concentrations (31 ppm and 11ppm). Two cw lasers (473 nm Blue DPSS laser and 532 nm Nd:YAG laser) are used to compare the optical limiting performance for the samples. UV–visible spectrophotometer, transmission electron microscope (TEM) and Fourier Transformation Infrared Spectrometer (FTIR) were used to obtain the characteristics of the sample. The nonlinear refractive index was calculated to be in the order of 10-9 cm2/W. The results demonstrate that the observed limiting response is significant for 532nm. In addition, t
... Show MoreThe main goal of this work is to put a simple model of the spectral energy distribution of binary stars called WW Cha. This model is built up on the extracted data from various telescopes and archives for the target WW Cha stars and then analyzing them using a python environment. The result of the fitting proposes that there are two protoplanetary disks around the WW Cha star, with different physical properties for each disk, such as the size of the inner disk being 10 AU, while the size of the outer disk being 300 AU. The shape of the outer disk is a flaring disk not a flat disk according to the value of the power law for the surface density (1.5). The emission in the disk is caused by small amorphous olivine grains rangin
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The present study deals with the relationship of noise pollution to the mental health of university students, through the researcher field study with the use of descriptive Correlative approach to investigate this relationship. Noise is one of the elements of environmental pollution that people often expose to in their environment. The problem of noise has been exacerbated now because of cultural and technological progress in crowded cities. As a result, the researchers studied noise as an environmental stimulus that affects the mental health of the human being.The researchers, through their current research try to study a very serious problem, which is the problem of noise pollution on the health side of university students as a
... Show MoreIn this research, non-thermal plasma system of argon gas is designed to work at normal atmospheric pressure and suitable for work in medical and biotechnological applications. This technique is applied in the treatment of the Staphylococcus epidermidis bacteria and show the role of the flow rate of Argon gas on the killing rate of bacteria, and it obtained a 100 % killing rate during the time of 5 minutes at the flow Argon gas of 5 liters/ min.
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Herpes labialis is an infection caused by the herpes simplex virus, characterized by an eruption of small and usually painful blisters on the skin of the lips, mouth, gums, or the skin around the mouth. Although there is no successful treatment available, the local use of compounds with effective anti-inflammatory and cytoprotective effects may be of value in this respect. This project was designed to evaluate clinically the local use of silymarin, a group of flavonoids with powerful antioxidant, anti-inflammatory and cytoprotective activity, in the treatment of herpes simplex ulcer. Fifty three patients with herpes labialis ulcers (HLU) were enrolled in this randomized, single blinded, placebo controlled clinical study, and they were al
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