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.
Biosignal analysis is one of the most important topics that researchers have tried to develop during the last century to understand numerous human diseases. Electroencephalograms (EEGs) are one of the techniques which provides an electrical representation of biosignals that reflect changes in the activity of the human brain. Monitoring the levels of anesthesia is a very important subject, which has been proposed to avoid both patient awareness caused by inadequate dosage of anesthetic drugs and excessive use of anesthesia during surgery. This article reviews the bases of these techniques and their development within the last decades and provides a synopsis of the relevant methodologies and algorithms that are used to analyze EEG sig
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The subject of improving the performance of services provided by government institutions of the important topics at the present time because of their direct contact at the service of citizens and the increased importance of these units as a result of the diversity of activities performed by the so governments of the countries and their people made sure to pay attention to the good use of those allocated to those sectors of resources and spending in the service prescribed and manage the highest level of efficiency and effectiveness and monitor the proper management of the money used in those sectors and evaluate their performance through the Supreme Audit Institutions so that they can play their role oversight and contribute to th
... Show MoreThe study aims to identify the degree of Tabuk University practices to raise the intellectual awareness of students through scientific research, as well as to identify the degree of Tabuk University practicing to raise the intellectual awareness through the educational process (faculty member – activities). The study also seeks to identify the degree of Tabuk University practicing to raise the intellectual awareness of students through community service and university media. The study is descriptive in nature that employed the questionnaire as a tool in collecting data. Total of (540) students were chosen randomly from different colleges at universities of Tabuk to form the study sample. The results showed that faculty member has pract
... Show MoreAfter diagnostic tests on ten isolates of S. marcescence, were made an examination of sensitivity to various antibiotics and checking the ability to produce β-lactamase of all isolates. The outer membrane protein quantity was determined in μg/cm3 for all isolates. The results showed that S. marcescence have antibiotic multiresistant and all isolates had the ability to produce β-lactamase and its resistance may arise from more than two mechanisms like overproduction of antibiotic inactivation enzymes and the decrease of permeability by outer membrane protein.
The construction of development is required to develop various economic sectors with the necessity to meet the various requirement of both individuals and institutions , or through the import process , which must be commensurate with the needs of the market and the economy and development. But in fact , we find that the process of import in Iraq after 2003 took a turn dangerous excesses on limits of philosophy and objectives of the import , which is reflected at the level of national production as well as the policy of dumping and given and the lack of matching a lot of goods and materials imported for Standards and Measures of quality and stands behind it causes many of them exposure to the market and weak sectors with an overlap betwee
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The construction of development is required to develop various economic sectors with the necessity to meet the various requirement of both individuals and institutions , or through the import process , which must be commensurate with the needs of the market and the economy and development. But in fact , we found that the process of import in Iraq after 2003 took a turn dangerous excesses on limits of philosophy and objectives of the import , which reflected the level of national production as well as the policy of dumping and given to the lack of matching a lot of goods and materials imported for Standards and Measures of quality and stands behind it causes many of them exposure to the market and weak sectors with an o
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Constitutional Review of 1992 and 1996 and the role of the Party of Progress and Socialism
The parasite E.histolytica was first isolated from a stool sample, and then cultivated and maintained in vitro using Locke-egg medium (LEM) and Liver infusion agar medium (LIAM) . Then, the effect of some types of erythrocytes (human and sheep), on the growth and activity of the parasite in the two culture media was investigated. The parasite was able to ingest and lysis erythrocytes of human and sheep that were supplemented to the culture media and such manipulation was able to augment the reproduction rate of the cultivated E. histolytica, however, such consequence was media- and concentration-dependent. The reproduction rate was significantly increased (66.0, 57.5 and 58.6%, respectively) in LEM medium containing human erythrocytes ty
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The development in the presentation and presentation of the service in order to distinguish them from the same, was one of the most important reasons to choose the current issue to upgrade the level of service, especially in the Iraqi restaurant sector, which has become today of the important sectors successful. The problem of research was to try to answer a range of questions: to what extent are Iraqi restaurants interested in physical service factors? Do Iraqi restaurants apply physical factors in a way that leads to customer satisfaction? Are Iraqi restaurants interested in the satisfaction of their customers? The objective of the current research is to try to determine the extent to which the
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This paper focuses on the concept of cognition and its clarification in the light of Islamic epistemology. Knowledge passes through two essential parts: conception and assent. Conception explains simple knowledge, while assent explains knowledge involving a judgment. The paper proceeded with the identification of the problem of relationship blurring between cognition and knowledge. The external and inner senses have explained the relationship between the stages of knowledge and cognition. The external senses receive stimuli and form primary conceptions. These conceptions transfer to the first part of the inner senses, which is common sense; it collects the sensations and transmits them to pictorial power. Secondary conceptions are f
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