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 aim of the research is to:. Preparation and implementation of special educational units using multimedia to learn the skill of scrolling from below. 2 to recognize the impact of the use of multimedia in learning the skill of scrolling from below. 3 to identify the differences between the tests after the two groups research in learning the skill of passing from the bottom volleyball. The research represented the students of the first stage and the sample of the research was drawn randomly and the number of (50) students were divided into two experimental and control groups and each group (25) students were used standardized tests and conducting pre-tests and the implementation of the main exp
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What is meant by objectives: the purpose, secrets, judgment, and interests that the legislator set for each of its rulings is a doctrine and a law.
Faith is belief with certainty in God Almighty, and what is required of him in his divinity, lordship, names and attributes, belief in his angels, books, messengers, the Last Day and destiny, both good and bad.
And the purposes of faith are the wisdom and secrets contained in the Islamic faith and which achieve human well-being and happiness in the immediate and the future. And that the purposes of belief and faith are the essence of religion, rather it constitutes a basic pillar on which the basis of the intentional consideration as a whole, because the structure of worship i
... Show MoreThe adoption of many mathematical concepts contributes to the construction of models of sports and the population can be interpreted to explain the movement and growth of the population lead to proper planning to manage the requirements of the population and meet their needs of providing education or providing medical services, health and others. In this study, the number of births in the Governorate of Basrah for the period (1998-2050) is estimated to be based on the assumption that the population of the visually impaired is a stable society. If the rate of growth is (0.0492), some demographic indicators are important for maintaining the average age of women at pregnancy (27.817). Each woman will give birth (3.74) female birth d
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The current study included details of the anatomical characteristics of vegetative parts including the root, stem, leaf in cultivated Iraq for the species Brassciaaleraceacabbage, where the study dealt with the stomatal index and the rate of both the length and width of the stomatal complex and the thickness of the periderm, the tissue, cortex, vascular cylinder and pith. The parts were taken and measured after the plant was treated with brassinolide and the treated species with brassinolide and non-treated were measured and the study showed that there was a clear variation in the properties above.
The aim of this study is to explain methods to be followed for the recovery Alsnav Hor, who represents the northwest portion of the Hammar Marsh in the province of Dhi Qar, after the drought in which that happened in 2008. The study included description of the region before the drought, the description of its natural and human environments, the economic events and activities, then the study included drought throughout the region, the environmental impacts caused by drought, its impact on social reality, economic and healthy for its environment, and then reached to the problems of social and economic in the region, depending on the Field studies and documented in the specialized government departments, information analysis for the
... Show MoreThis study was conducted to investigate the relationship between corticosterone hormone in the blood of local Iraqi white chicken mothers and the sexual ratio of the hatching chicks. A field experiment located at the Poultry Research Station, Livestock Department, Agricultural Research Department, Ministry of Agriculture for the period from 16 of September 2018 to 25 of December 2018. One hundred and forty birds of Iraqi local chicken mothers (100 females+ 40 males) at the age of 28 weeks were provided from the poultry research station. The birds were raised in individual cages and distributed sequentially to the cages after the numbering of the females. Data were recorded in three periods, each period was of 28 days, and then the general a
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The interactive websites are the interaction between the product and the user, and interactive design is based on the user interface for communication and how the interface responds to the user and how to help him to achieve his goals and enjoy the use of the interface. The interactive design is based on the design of interactive programs, i.e., programs that directly interact with the user, taking into account the different culture of the audience, the age group and many other factors. An example for the use of the user interface: Web designs, smartphone application designs and it even includes computer operating systems and electronic game interface. The interaction is the communication between the source and the receiver. The we
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This study aims to investigate the academic leaders’ perceptions towards the degree of availability of the dimensions of organizational immunity systems at the University of Tabuk, as well as to reveal the statistically significant differences between the average responses of the study sample members about the degree of availability of these dimensions at their university due to the variables of (gender, leadership position, and college specialization). To achieve the objectives of the study, a descriptive survey method was used. The study population consisted of (200) male and female leaders who were academic leaders at the University of Tabuk. A questionnaire was used as a tool for collecting data, which its validity and reliability
... Show MoreThe selective information broadcasting service is one of the important services in libraries and information centers, as it is the link between the source and the beneficiary and between related sources, as it links similar sources through keywords and then sends them to beneficiaries, which contributes to reducing the time and effort spent by beneficiaries in obtaining sources or information. Therefore, the application of this service is an important matter and gives a positive indicator in the progress of the library towards the integration of its services. From this standpoint, this research came to answer some questions, including: 1. What are the outlets for beneficiaries (the research community) in obtaining information sources? 2. Wh
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The aim of the research is to identify the effect of using the self-questioning strategy on the achievement of fourth-grade students in science and the development of their reflective thinking in physics in the city of Baghdad. The research sample was divided into two groups: an experimental group of (20) students and a control group of (20) students. The researchers developed two tools: a test of (40) multiple-choice questions. The second tool is a test to measure the reflective thinking skills of fourth-grade students. It consists of (25) multiple-choice questions distributed on skills as follow: reflection and observation, detection of inaccuracies, reaching conclusions, giving clear explanations, an
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