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 study aimed to clarify the meanings learned and inferred from reading books، letters and messages in Surat Al-Qur’an. The inductive method، the analytical method، and the deductive method، One of the most prominent results of the research: that the multiplicity of Qur’anic readings produces a variety and expansion in the meaning that has a clear impact on the interpretation by clarifying the meaning of the verse.
Abstract
It is clear to everyone how important it is to implement transactions electronically, as it facilitates the provision of services to beneficiaries, whether individuals or institutions, to achieve many benefits that are not exclusive to the beneficiary or the applicant, but extends to the governmental and international bodies. And the number of users has reached millions since its emergence in 1995, because the concepts of electronic transactions have great advantages for the economy in general and the banking sector in particular, so cooperation in various fields with the aim of becoming an information society has become paramount, It allows customers to pay money to any company they want t
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The present study discusses the names of the Day of Resurrection in Uri Rubin’s translations of the Holy Qur’an. To identify the translation difficulties and complications and to find out the Hebrew equivalence, the study, through the application of a comparative analytical approach, aims at analyzing the linguistic structures of Day of Resurrection names cited in the Holy Qur’an. Heavenly religions are rich with distinct and unique terms that distinguish and reflect their specificity of other religions; something requires a great accuracy in the translation of such terminology. By investigating selected examples of the names of the Day of Resurrection in Arabic and Hebrew, the present study sheds light on the morphological and semant
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Abstract
The term public budget defects became nowadays a chronic, economical phenomenon, almost all the countries weather advanced or development country suffered from it, despite the different visions to economic schools of a thought to accept or reject the deficit in public budget but the prevailed opinion that is needed to rule the role of the state by reducing the public spending which led to continuous deficits in public budget and the consequent upon increase in government borrowing, increase taxes on income and wealth, thus weakening the in contrive for private investment which contributed to the increase of in flationary stagnation, it became a duty to state covered by the lack of financial sources
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This study was designed to investigate the effect of aqueous extract of ginger Zingiber officinale Roscoe on the histology of corpus luteum and the concentration of the hormones progesterone and estrogen during the first trimester of pregnancy (0 - 7) days from fertilization. 30 pregnant mice were divided into five experimental groups: control group (administrated with distilled water), and four groups treated at doses (284, 568, 1136,1420 mg / kg), orally administrated , daily with (0.1 ml). Microscopic examination results have shown histopathological changes in corpus luteum included: Pyknosis in some nuclei of granulosa cells, Karyorrhexis, Karyolysis in some granulosa cells, and necrosis in corpus luteum, with additional significant dec
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The aim of the research is to diagnose the nature of the relationship between the dimensions of organizational immunity with its dimensions represented by (organizational memory, organizational DNA, organizational learning) in enhancing the strategic capabilities of the company with its dimensions represented by (marketing capabilities, administrative capabilities, technological capabilities, creative capabilities), and the degree of arrangement of those dimensions According to priority, as well as revealing the differences in the respondents’ response to the two variables according to the personal and functional variables, and the importance of the expected results, the researchers adopted the questionnaire as a tool for collecting da
... Show MoreThis research highlights the light on the general framework of accounting discloser in the Islamic banks, and show the types and the concepts of Cost Efficiency, In this present study, the sample included Fourteen Islamic banks, where the data was collected from the annual financial reports. Accordingly, the study in order to achieve the aims and access to the results based on the analytical method and the descriptive analysis, and conducted a Simple & Multiple Linear Regression analysis, in order to test hypotheses of the research by using of statistical analysis software (SPSS). The research has arrived to many results such as: the commitment of Islamic banks working in the Kingdome of Bahrain (Wholesale) to the requirements of the
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The subject of the evolution of fire insurance of the hottest topics accidents, because it falls within the commercial insurance, as its importance is reflected for being a security source and contentment of the insured person and so it is worth pointing out the importance of fire insurance in enterprises and organizations of all kinds, because of the guarantee of its assets from meridian as well as protection from the effects of the fire therefore ensure continuity in the performance of their activities
Abstract: The aim of the research identify the effect of using the five-finger strategy in learning a movement chain on the balance beam apparatus for students in the third stage in the College of Physical Education and Sports Science, as well as to identify which groups (experimental and controlling) are better in learning the kinematic chain on the balance beam device, has been used The experimental approach is to design the experimental and control groups with pre-and post-test. The research sample was represented by third-graders, as the third division (j) was chosen by lot to represent the experimental group, and a division Third (i) to represent the control group, after which (10) students from each division were tested by lot to repr
... Show MoreIn this paper, the effect of changes in bank deposits on the money supply in Iraq was studied by estimating the error correction model (ECM) for monthly time series data for the period (2010-2015) . The Philips Perron was used to test the stationarity and also we used Engle and Granger to test the cointegration . we used cubic spline and local polynomial estimator to estimate regression function .The result show that local polynomial was better than cubic spline with the first level of cointegration.