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 research aims to measure the impact of knowledge management processes individually and in total in the innovative marketing.
We depart search of a problem expressed in a number of intellectual and practical questions, the application of this research in the General Company for Vegetable Oil Industry, represented composed a sample of (63) (Director General and Deputy Director General and Director of the Department and the Division) in the company researched, it has been designed measuring instrument to collect the necessary data either statistical means they are the percentage and the arithmetic mean and standard deviation and coefficient of variation and the coefficient of simple correlation and model
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The Egyptian labor movement is the oldest trade union movement in the Arab region. Beside, the labor movement in any society is, in fact, only a reflection of the extent of awareness of that class in that society. Such a comparison is based on the degree of social growth the working class has reached. Moreover, the Egyptian working class was characterized by modernity in its inception compared to other social forces and classes. In addition, its development is linked to the level of industrial development of the country. The peasants and craftsmen were the mainstay of production in the Egyptian society over several centuries. The labor union movement also represents the human aspect of the labor force when it encounters and interacts wit
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The research sheds light on an important religious sect that played a fundamental role in the structure of the Iraqi society in general and the Baghdadi society in particular, in which the Jews in general and the Jewish women in particular played an active role in the culture and heritage of Baghdadi society. The educational, cultural and artistic activity of Jewish literacy is a model for study.
The aim of the research to measure the correlation relationship between modern manufacturing systems and process design and measure the effect by adopting the regression; the research consists of two main variables, which are modern manufacturing systems and process design; it was applied in the production lines of the General Company for Construction Industries, There is a sample of managers, engineers, technicians, administrators, and some workers were selected to fill the special questionnaire with (70) forms which distributed and (65) were approved suitable for use, For data analysis the correlation coefficient was adopted to measure the relationship and regression analysis to find out the effect, Using (SPSS), So the first h
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The contemporary role of administrative accounting Renewal or threat
Link failure refers to the failure between two connections/nodes in a perfectly working simulation scenario at a particular instance. Transport layer routing protocols form an important basis of setting up a simulation, with Transmission Control Protocol and User Datagram Protocol being the primary of them. The research makes use of Network Simulator v2.35 to conduct different simulation experiments for link failure and provide validation results. In this paper, both protocols, TCP and UDP are compared based on the throughput of packets delivered from one node to the other constrained to the condition that for a certain interval of time the link fails and the simulation time remains the same for either of the protocols. Overall,
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Dust storms are typical in arid and semi-arid regions such as the Middle East; the frequency and severity of dust storms have grown dramatically in Iraq in recent years. This paper identifies the dust storm sources in Iraq using remotely sensed data from Meteosat-spinning enhanced visible and infrared imager (SEVIRI) bands. Extracted combined satellite images and simulated frontal dust storm trajectories, using the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model, are used to identify the most influential sources in the Middle East and Iraq. Out of 132 dust storms in Iraq during 2020–2023, the most frequent occurred in the spring and summer. A dust source frequency percentage map (DSFPM) is generated using ArcGIS so
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Abstract:
Rabi’a tribe lived on the land of Euphrates since the first century of the
Christ. Then that land becomes her homeland. The Persians tried many times
to drive her away from that land, but with out result.
In the course of time Rabi’a become more knowledgeable of Persia.
This tribe proved her love and sanctification to the land of Euphrates, in the
battle of Dhyqar.
Rabi’a converted to Islam quickly and helped the Muslims to conquer
Iraq with a big number of fighters in many battles like al- Qadisyyah. That
influenced the anger of Mudriat Arab tribes who were their old enemies.
Mudriat tribes did their efforts to reduce the importance of Rabi’a because of
some its branches were among of t
The research aims to show the effect of some short-term debt instruments (central treasury transfers, cash credit granted to the government by commercial banks) on the production of the wheat crop in Iraq, through its effect on money supply during the period (1990-2018), As the study includes two models according to the statistical program (Eviews9), the first model included measuring the effect of short-term debt instruments on money supply, and the second measuring the extent of the money supply's impact on Wheat crop production, as the results of the standard analysis showed that the short-term debt instruments used in the model were Significant effect on wheat crop production indirectly through its effect on money supply, As
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