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.
No country in the world has an ancient heritage of its own. It represents the product of the civilizations left behind by previous eras. It represents the development of urban life and its capital of the interest of its people in the field of construction and reconstruction. The urban heritage and its associated arts may seem to be a material heritage at first glance, but it is not free from the spiritual side. Therefore, the nations in different parts of the earth cherish it and care for it with all due diligence, because it mixes with its history, memories and emotions.
This research discusses the use of local environment materials in the production of urban fabric constituents. I
The issue of the prisoners' rights and the way of dealing with them is not just a minor or
primary issue according to the contemporary attitudes to deal with criminals, but it is a fatal
issue that goes with the development of life and comprehension of human rights. As the
criminal is considered as a human-being who can be reformed and qualified, according to the
aims of the contemporary social service the prisoner is regarded as an idle human source who
can be reformed, treated and qualified so as to make him participate to improve his family and
society in the end.
This study aims at reconstructing the prisons bases when applying the laws of the lowest
level of treatment through the research of oppositions, atti
The affliction is a remaining year and not a past incident, and the most evil people are the prophets - peace and blessings be upon them - and the most severe is the Imam of the Prophets Muhammad - may God bless him and grant him peace - because they are exposed to harm from their people because of their call to a religion that violates the religion of parents and grandparents, the religion of injustice and injustice And polytheism and disbelief, and therefore the Qur'an had attitudes towards the entertainment of the people of affliction in general and our beloved - peace be upon him - in particular, this research came about the entertainment of the Qur’an for the Prophet - may God bless him and grant him peace - and many areas of ente
... Show More8-hydroxyguanosine (8-OHdG) is considered as an indicator of the oxidative stress. Pro inflammatory cytokines are critical parts of the pathophysiological processes to which treatment can be applied. The aim of this study was to evaluate 8-OHdG and pro inflammatory cytokines concentration in colon carcinoma patients. Blood samples were taken before treatment from 50 incident cases with colon cancer (stage III) admitted for health examination at the Nanakali Hospital in Erbil city with 45 healthy samples of controls with age range between 38-69 years for both groups. All studied parameters were estimated by ELISA. Participants at this study were 95 Participants ranged in age from 38 to 69 years, 50 Participants had been newly diagnosed wi
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phenomenon in the Arab women's contemporary literature, but it is rare in Iraqi women's
literature and falls short to the level of the phenomenon until now. Perhaps this is one of the
main reasons that caused the reluctance of researchers to study it, and this is probably the first
academic research in this field.
This research followed the discourse of Autobiography of women in Iraq, depending on the
two factors of charter and reference of the elements of Philippe Lejeune’s definition of the
genre of Autobiography, without focusing on narrative method, so it handled notes,
memories, diaries and biography of the other and counted all under the genre of the
Biography.
It came in three sections, the first follo
The aim of the research is the knowing of the academic Scientific Journals of the colleges of University of Baghdad , through searching in the University of Baghdad website and the websites of colleges and thus studying the presentation of these journals in those website , and this is done by surfing the main pages of the websites for the colleges included in the research , and by analyzing the research made a menu for all the academic Scientific Journals for all institutes of the University of Baghdad , which simplifies the way for the researchers to publish these researches in the specific journals for their specialties .
This research is concerned with studying the representations of the event in the drawings of the ancient civilizations of the world, and the research consists of two axes, the axis of the theoretical framework, which included (the research problem, its aim, its limits, and the definition of its terminology).
The research aims to reveal how the event pattern was formulated by the artist on the surface of his visual achievement, and the limits of the search were spatial in the ancient civilizations of Iraq, Egypt, Greece and Rome, but the limits of the temporal research could not be determined because they were before birth, and objectively:
representations of the event in the civilizations of the ancient world This axis also in
The research aims at shedding light on the impact of the organizational commitment on the performance of the Iraqi insurance company as a service company that provides many services to customers both internal (individuals working) or external, Whenever the company was able to adopt new concepts to increase the understanding and knowledge of how their attention to individuals working and to provide an appropriate working environment, and to clarify the objectives and strategies for them, and create a sense of their importance, as reflected on job performance in attracting new customers, and build long-term relationships with them . In order to achieve this, the research relied on the questionnaire as a main tool for collecting data and in
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This research after financial ratios in the detection of fraud to the financial statements published which enables specialists from the work of their studies and their conclusions to obtain the information they seek on the activities of the entity. Has provided researchers what these relics They then field study to test the validity and sincerity of the findings of the suggestions that have been upheld the need to study all financial ratios extracted in general, organized and used in decision-making processes necessary administrative.And that the financial management attention more financial analysis and extraction of financial ratios and compare them with industry standards taken from historical norms
The acceptance sampling plans for generalized exponential distribution, when life time experiment is truncated at a pre-determined time are provided in this article. The two parameters (α, λ), (Scale parameters and Shape parameters) are estimated by LSE, WLSE and the Best Estimator’s for various samples sizes are used to find the ratio of true mean time to a pre-determined, and are used to find the smallest possible sample size required to ensure the producer’s risks, with a pre-fixed probability (1 - P*). The result of estimations and of sampling plans is provided in tables.
Key words: Generalized Exponential Distribution, Acceptance Sampling Plan, and Consumer’s and Producer Risks
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