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 aims to show the correlation between inflation rates and the volume of private sector deposits in Jordan on one hand, and Amman Stock Exchange index for the period of 1999-2017. The study used the “Vector Auto Regression” model. Different types of tests are used such as: The “Johansen Co integration” test of joint integration, “Granger causality” test, the “Analysis of Variance Decomposition”, and “Impulse response Function” test.
The results showed there is a positive-one-way causal effect from Amman Stock Exchange index to inflation. Also, a one-way causal effect that comes from Amman Stock Exchange index to the size of private sec
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The research gained its importance from the importance of technical reserves in the insurance activity and its impact on the result of the activity of insurance companies and their financial position and thus reflected on the insurance prices as the technical reserves are one of the most important and most valuable budget items usually, as well as that the insurance activity has a role in maintaining economic development where some countries develop laws and instructions for the formation of those reserves binding application to insurance companies and the fact that the financial statements in general are of interest to shareholders, banks, the General Tax Authority and other beneficiaries In the insurance activity as policyholders and t
... Show MoreObjectives: This Paper is an attempt to evaluate the services provided by the private hospitals
and to identify the strength and weakness in
their performance The results can be utilized in stating conclusion and recommendations to improve
and activate the role of private medical sector in society .
Methodology: A questionnaire has be designed for this purpose and distributed to ( 132 ) beneficiaries
mostly from Baghdad private hospitals .
Results: The paper has come out with many important results . Among These are the following :
* these who benefit from services provided by private hospitals believe that the good performance of
such hospital is not due to the medical services alone but also to scientific aspect
The research aims to determine what a photograph intends to convey as a visual text. Photographs are not captured randomly, especially those of politicians. Each photograph carries a message, even if interpretations of that message vary from person to person. The research adopts a methodology based on semiotic analysis, applying Laurent Gervero's model to analyze a photograph of the Iraqi Prime Minister Mustafa Al-Kadhimi's visit to Fallujah on the anniversary of the victory over ISIS. The photographs in question constitute a visual language built upon a sequence of iconic symbols and signs. These elements coalesce to give rise to an image centered around a particular theme, one designed to convey a precise messag
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This study aims at identifying the reality of alternative assessment for teachers of the first cycle of the basic education in the Sultanate of Oman with respect to the degree of teachers' use of alternative assessment strategies, level of self-efficacy for alternative assessment strategies, and attitude towards alternative assessment, and their relationship with other variables. To achieve the aims of the study, a descriptive research approach was utilized. A 5-point self-rated questionnaire was developed. It consists of three sections: Actual use of alternative assessment strategies (21 items), self-efficacy for alternative assessment strategies (21 items), and attitude towards alternative assessment (27 items). The psychometric proper
... Show MoreThe purpose of this paper is to recognize the impact of database levels on fields of banking service (provision of remittance services and transfer of funds, save financial deposits, provision of personal loans services) in some of Iraqi banks using one-way multivariate analysis of variance. The paper population consisted of (120) employees, then a random stratified sample of (104) employees was taken. A questionnaire paper consists of (24) items were designed in order to analyze by one-Way multivariate analysis of variance (MANOVA) using SPSS.One of the main findings of the current paper is that there is an impact of database on fields of banking service in Iraqi banks (Al Rafidain and Al Rasheed).
This study includes applying chemical tests on cow, sheep and chicken bones including both hallow and flat. The results of chemical tests on bones mentioned the moisture percentage which was between 4.95-7.32 %, and it was noticed the difference in protein percentage among different kinds of bones, The highest protien percentage was 39.62 % in hallow chicken bones and the lowest was in hallow sheep bones 20.31%, at the same time, the highest Ash percentage was in hallow sheep bones48.11% , whereas the highest percentage of fat was in hallow cow bones 30%. The chemical and physical tests were conducted for extracted fat from hallow and flat bones for cows, sheeps and chicken. It was found that peroxide values (PV), and free fatty acids (F
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The research deals with the statement of the importance of unanimous in Islamic Sharia in terms of being the third source of Islamic legislation after the Holy Qur’an and the Sunnah of the Prophet, and the extent of interest of the scholars of interpretation in it, and those who took great interest in mentioning what was agreed upon in every site that necessitated mentioning its issues within, or mentioning an event that has encountered an unanimous, and in various sciences, to extract and extrapolate Sharia rules when these rules are lost in the texts, because it is based on them and derived from them. Among these distinguished scholars is Muhammad bin Jarir al-Tabari. Besides, the research discusses in
... Show MoreA chemical study was carried out to evaluate the efficiency of the liver enzyme concertation and uric acid level and its antagonists in the serum of the professors exposed to chemicals in the laboratories of the University of Samarra and their comparison with the healthy people. The research included 25 samples of the exposed professors and 20 samples as a group of officers.
The results of the current study showed a significant increase in the level of AST, ALT in the serum of professors exposed to chemicals compared to healthy people. The results showed no significant increase in
... Show MoreEmpirical and statistical methodologies have been established to acquire accurate permeability identification and reservoir characterization, based on the rock type and reservoir performance. The identification of rock facies is usually done by either using core analysis to visually interpret lithofacies or indirectly based on well-log data. The use of well-log data for traditional facies prediction is characterized by uncertainties and can be time-consuming, particularly when working with large datasets. Thus, Machine Learning can be used to predict patterns more efficiently when applied to large data. Taking into account the electrofacies distribution, this work was conducted to predict permeability for the four wells, FH1, FH2, F
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