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 crystalline zeolite, namely faujasite type Y with SiO2/Al2O3 mole ratio of 5 was used as raw material for preparation of isomerization catalysts. A 0.5 wt % Pt/HY-zeolite catalyst was prepared by impregnation of the decationized HY-zeolite with chloroplatinic acid. The dectionized HY-zeolite was treated with HCl, HNO3 and HI promoters using different normalities and with different concentrations of Sn, Ni and Ti promoters by impregnation method to obtain acidic and metallic promoters' catalysts, respectively. A 0.5 wt% of Pt was added to above catalysts using impregnation method. Isomerization of n-hexane was carried out at different prepared catalysts. The isomerization temperature varied from 250–325° C over weight hourly space
... Show MoreScientists have delved too much into reality and metaphor, and perhaps a topic of Arabic rhetoric has not received the attention and care of scholars as much as the topic of truth and metaphor. The metaphor opens wide horizons of expression in front of the writer so that he has several means by which he can express the one experience, so his imagination takes off depicting the intelligible as tangible, the seen as audible, and the audible as seen. That image presented by the creative writer.
The first thing to note is that the emergence of metaphor as a rhetorical term was at the hands of the Mu'tazila. Muslims differed about the issue of metaphor in the Holy Qur’an, and the beginning of the dispute was about the verses in which the
The developing countries can be distinguished by spatial disparities and by this a wide gap between urban and rural settlements were produced as well as the appearance of primate cities. The effect of spatial development as a dynamic and continuous process can be perceived in the state of population distribution inside settlements inter and intra regions as well as the hierarchy of urban settlements according to time series. The research proved that the improvement judgment of the structure of the urban system using Gene factor is not accurate because it cannot be accounted for the internal components of the system which make a contrariety between the whole judgment (country) and partial components (Provinces including Sulaimaniy
... Show Morethe political changeable is important reflection in areas of life and the designers tried to high light it in the cover of Journal promised time Journal a fertile square to show reflection of political changeable, and triad to search the current path. The first chapter organized according to axes, problem of research formulated according to question:- what are reflections of political changeable in magazine cover?
The importance of research depth of specialized approach on level of technical and stylistic as ago al ago as in: the baring of political changeable in design of journal's cover. The research moves in cognitive border from 2013 to 2017 and selection of t
... Show More
The purpose of the present study is to identify the comprehensive concept of desertion through the Holy Qur’an and to derive some educational implications related to the concept of desertion and its editing. The also aims to explain the images and forms of desertion. The researcher used the qualitative analytical method. The study concluded that the comprehensive concept of desertion was represented in moving from the country of polytheism to the country of Islam, singularity, alienation, and isolation, leaving, repelling and showing off, abandoning the wife in bed, and reciting from the Qur’an recitation, action, and arbitration, insulting, abandoning, delirium, intersection, and manipulation. The researcher has drawn many education
... Show MoreSeveral studies have indicated that more than 600 cities in the world (intermas of rapid growth and development) will generate about 60% of international economic growth between 2010 and 2025 . by 2025 , 66% of the worlds population will live in urban areas the management of cities will face challenges that accompany this increase in the population which requires preparing to face these challenges and problems and the need to provide the aim of the research to know the readiness of Baghdad city to implement the strategies of urban management throught on asmple representing the ( Advisiry group for the comprechnsive development plan for the city of Baghdad 2030 and its supporters ) in the municipality of Baghdad and the number of
... Show More
The products of composites material are very sesetive to many variables, such as manufacturing process, additive materials, …. etc. Filler or additive plays a major role to determine the formation of the properties and behavior of the composites. In this study, polyethylene terephthalate-based compounds were produced and characterized. The work is concerned to prepare samples of Polyethylene terephthalate (PET) - zinc-ferrite (ZnFe2O4) with different addition ratio as zinc-ferrite (1, 2, 5, 10, 15 and 20) wt% obtained from mixing the solution with a hot pressing method applied under optimum conditions. The densities of the composites for all samples were calculated. Through the work the diffusion of zinc-ferrite i
... Show More
(11)
(11)
Abstract:
This study deals with the influence of the industrial buyer behavior in Channels of distribution. It concentrates on one section of management levels in the company. Which is that of administrative managers The research problem is attempt to study and analysis the influence of industrial buyer behavior in channels of distribution.. The aiming at achieving a number of applicable goals depending on one major hypotheses I set a questionnaire in collecting the data and information relating to the study، which was distributed to sample of ( 30) department manager heads of section states company . In order to process the data resorted to many statistical methods such as arithmetic means the sta
... Show More
The research included the introduction to the research and its importance as knee joint is an important joint in the human body that is prone to injury. One such injury is knee roughness injury that occurs as a result of the stress of the knee joint and age. The importance of examining the need for the use of rehabilitation exercises, especially in the watercourse system, is highlighted by the fact that the aquatic environment is one of the most important factors helping to alleviate pain and rehabilitate the knee joint and thereby improve the mobility of those with knee roughness. The problem of research is that rehabilitation exercises have been developed in the watercourse system on the basis of scientific bases with a repetitive and sys
... Show MoreBackground: Dental implants are a suitable option for the replacement of some or all missing teeth. The successful insertion of a biocompatible material into living tissue with little to no evidence of rejection has revolutionized medicine and dentistry. An increase in bone response was observed with local administration of growth hormone around dental implants. Growth hormone may act as a bone stimulant in the placement of endosseous dental implants and enhances osseointegration. The aim of the study was to evaluate immunohistochemically the effect of the topical application of growth hormone on the osseointegration of cpTi implant. Materials and Methods: Eighty titanium screw implants were inserted in the tibia of the forty adult rabbits.
... Show More