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.
Three hundred and fifty five patients with hepatitis were investigated in this study all cases gave negative result with HBs Ag , IgM-anti HCV , IgM-anti HEV, IgM-anti HDV and anti-HIV tests . The frequency of IgM-anti HAV was 113 and the percentage was 32 % in all ages but when these patients divided into five groups dependent on ages. The highest percentage of IgM-anti HAV was (45%) in age <10 and the percentage declined with age increase till to 9% in age >41 year.
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Cadmium sulphide CdS films with 200 nm have been prepared by thermal evaporation technique on glass substrate at substrate room temperature under vacuum of 10-5mbar.In this paper, the effect of Dielectric Barrier Discharge plasma on the optical properties of the CdS film. The prepared films were exposed to different time intervals (0, 3, 5, 8) min. For every sample, the Absorption A, absorption coefficient α , energy gap Eg ,extinction coefficient K and dielectric constant ε were studied. It is found that the energy gap were decreased with exposure time, and absorption , Absorption coefficient, refractive index, extinction coefficient, dielectric constant increased with time of exposure to the plasma. Our study conside
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The researcher, in this academic research, seeks to highlight the role of the semantic production in the dramatic act and to know the extent of its work and importance, because drama is an act and the dramatic work is a group of acts. The dramatic meaning and act are two inseparable concepts that cannot be divided, because each dramatic act is a container of meanings through connotations, signs and symbols. The production of the connotations in the dramatic act is considered one of the important issues in the content language of communication between the sender and recipient in order to get to the intended meaning. These sign connotations engage the spectator in the codifying activity and get him immersed in the events. The research pres
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BACKGROUND: Mental health problems are reflected and linked to human behavior in many aspects. Medical students are susceptible to a wide variety of events that compromise their mental well-being, social life as well as their academic achievements. AIM: This study aimed to find the impact of social support on medical students’ behavior in Iraq via assessing their depression, anxiety, and stress status. METHODS: A cross-sectional online survey-based study targeted all medical students in Iraq. The employed questionnaires covered mental health status of participants by evaluating their perceptions of depression, anxiety, and stress using. Data were analyzed using the Statistical Analysis System. RESULTS: The study revealed a signifi
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The current research aims at transforming the concept of implication from the rhetoric into the industrial design in order to have a new term (the design implication) in which the industrial designer takes all or part of another's design to imply his design in it and acknowledge that, and if he did not do so, it would be (design theft) parallel to the literary plagiarism.
In order to show the potentials of the industrial design in the production of new formulations of the industrial products forms, as the design is the carrier of language that addresses the recipients, it is possible to use the implication as a the tool of literature in the design and as a design strategy as it is one of the concepts that takes its course in e
In the last few years, there have been a lot of changes in the economy, society, and the environment. This has led to much competition between companies, directly and indirectly affecting production and marketing processes. Most companies are trying to cut production and manufacturing costs by using modern cost techniques such as product life cycle costing and Continuous Improvement (Kaizen) technology, in the method of measuring production costs or service costs, and the need for internal control to keep an eye on how these technologies are being used and how well they work. And to find out the effect of internal control on the implementation of costing techniques in Iraqi companies, 64 questionnaires were given to people who work in the i
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The design studies, especially in their contemporary stages, have not been isolated from the subjects that underpin advanced ideas in the field of technical treatments that enrich and improve the social life of users through those technological innovations that have enhanced and changed life styles, Especially in the field of general institutional techniques, including cinemas, as the ideal places for people and visitors to this space, which can contribute to the promotion of cultural, social and technical aspects within this millennium. DONC as reflected on the positive communication and communication between the intellectual and cognitive develop individuals, including cultural and technical side of the individual. The first chapter co
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Background: The microhardness of a composite resin is a vital parameter that is used to determine its clinical behavior. Measuring the microhardness of a composite resin has been used as an indirect method to assess its degree of conversion and extent of polymerization. The purpose of this in vitro study was to evaluate the effect of three curing distances (0, 2, and 4 mm) on the microhardness of the top and bottom surfaces of three types of flowable bulk-fill composite resins (smart dentin replacement, Opus bulk fill flow, and Tetric N). Material and method: Sixty-three specimens from the three types of composite resins (n=21) were fabricated using Teflon mold with a 4mm depth and a 5 mm internal diameter and cured for 20 seconds. For e
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The Arabic grammatical theory is characterized by the characteristics that distinguish it from other languages. It is based on the following equation: In its entirety a homogeneous linguistic system that blends with the social nature of the Arab, his beliefs, and his culture.
This means that this theory was born naturally, after the labor of maintaining an integrated inheritance, starting with its legal text (the Koran), and ends with its features of multiple attributes.
Saber was carrying the founding crucible of that theory, which takes over from his teacher, Hebron, to be built on what it has reached. It is redundant to point to his location and the status of his book.
So came to my research tagged: (c
Three scolopacids out of 150 are found infected with Haemoproteus scolopaci Galli-
Valerio 1929 and H. tringae n. sp. A detailed description of the new taxon is presented along
with a comparison of the diagnostic measurements between the two species.