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 investment environment is the incubator for all types of domestic and foreign investments, so if their determinants are encouraging, they increase the levels of investment flows and vice versa, as there is a relationship between the nature of the investment environment and the level of investment flows, and the determinants of the investment environment are numerous and the most important of which are security and political stability, and economic and financial factors that include relative stability In the exchange rate and inflation rates, the availability of banks and their development, transparency and integrity in administrative dealings and the lack of prevalence of administrative and financial corruption, and the clari
... Show MoreThe current research aims to know the complementary use of the paper book and the digital book by defining the paper book and the digital book and knowing the methods and methods of obtaining each of them and indicating the extent of their use and for what purpose and knowing the difficulties that researchers face in using each of them and which is better using the paper book or the digital book in preparing research Studies and for no reason. The research relied on the descriptive approach and the questionnaire as a tool for data collection, and it was distributed to professors and students of Iraqi universities. The research sample reached (219) individuals and reached a set of results, the most important of which are: Preference for the
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Abstract This research deals with the definition of the concept of nodal purposes, And what is related to it, from its aim and importance, And for the purposes of the importance of Streptococcus In trying to understand the nodal truths For different minds, Especially with those who object to the introduction of belief in purposes studies, This research has two requirements: The first requirement: the concept and the aim of contractual purposes,It consists of two branches, The first is in the concept of nodal purposes, And it dealt with the definitions in terms of language and terminology And what we see is proportional to what aim |
Knowing the nature of the relationship in federal systems lies in studying the political, social, economic and cultural forces, for their role in laying the foundations and the federal system. No matter how important the pillars of that system are, and through this research, we will learn how the political elites were able to crystallize this unique system, until it became one of the political systems that some countries seek to copy and apply its experience.
The first section of this research discussed the manner of the research from many sides like the problem it faces, importance of it , its targets ,boundaries, the way to collect and get information's and its assumption.
When the second chapter discussed the press – manufacturing and the development ,importance and types of newspapers, also its merits and weaknesses.
The third chapter talked about the scientific side and how to choose an assumption for the research . as it talked also about the apparent honest and stability tests that help in analyzing the research until getting results and so the right assumption for the research will be chosen.
And finally, the fourth chapter put highlight on the be
... Show MoreThis research includes the principles of the democracy، and to which extent it can contribute in establishing these principles. Democracy is not only to hold parliamentary or presidential elections but also the result of these elections wills it lead to the emergence of an integrated regime that can actually expresses the citizen's rights and to which extent those citizens can contribute in that regime and control it. Since 2005، when the first elections took place in Iraq after the US occupation of Iraq 2003، Iraqi people are looking to a rule that represented them and achieve their interests after getting rid of the totalitarian regimes and establishing an institutional regime that work by democratic means in order to achieve the so
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Ifosfamide (IFO), an alkylating chemotherapy agent, is known for its association with neurotoxicity and encephalopathy. This trial was designed to evaluate the protective action of daidzein (DZN) against IFO-induced neurotoxicity in male rats by determining the difference in certain inflammatory and apoptotic markers in the brain tissue of rats. Twenty-eight Wistar rats, weighing 120-150 g, were divided into four groups of seven rats: Group 1 (Control) received no treatment; Group 2 was orally administered DZN (100 mg/kg/day) for seven days; Group 3 received a single intraperitoneal (IP) dose of IFO (500 mg/kg); Group 4 received oral DZN (100 mg/kg/day) for one week prior to a single IP dose of IFO on the seventh day. Twenty-four hours post
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The experiment was carried out in the wooden canopy in the green garden of Biology Department , College of Education for Pure Science – Ibn AL –Haitham, Baghdad University, during the growing season of 2012- 2013 , to study the influence of foliar application of three concentrations of zinc (0,50,75)mg. L ¯¹ with four concentrations of boron (0, 25, 50, 75) mg. L¯¹ and their interactions on some growth parameters of vegetative part of chickpea plant. The experiment was designed according to Randomized Completely Block Design(RCBD)with three replications, results indicated that:- 1- Foliar application of zinc and boron caused a significant increase in the averaye of dry weight for t
... Show MoreThe main purpose of this research aims to measure the role of banking strategies marketing in achieving competitive advantage within a sample of Iraqi private banks, and in order to achieve this purpose, the researcher depend on number of sober research approaches which consisted of descriptive, analytical and practical methodologies, to strengthen concepts addressed by the research, size of the sample was (56) individuals which makes up the senior leadership represented (Chairman and members of the Board of Directors, Commissioners and their assistants and department heads) while the primary tool for research (questionnaire), which has been designed based on a number of solemn scientific metrics, after adapted these metrics commen
... Show MoreThe high bounce activity according to the fosbery way is regarded as of the difficult sports concerning its way of training and perfection due to hard technique of its performance on one hand and because it depends on the player’s ability to overcome body weight resistance against the gravity. In addition to the strong ability to control the body posture when leaving the land and flying over the barrier. This activity needs to high plosion power at the moment of bouncing and this plosion depends on the period of bouncing, so the two researchers aimed to use a mechanical bouncing platform and an electronic one through several training by one foot and both feet in different directions and positions in order to reduce the time of bouncing an
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