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 research aims to identify Determination talent management dimensions of (attracting talent, developing talent, directing talent, performance management talent, retain talent) in the entrepreneurial performance of the organization dimensions of (advance planning, efficiency, effectiveness), so search occupies the extreme importance of being treated important and recent issue of the performance Entrepreneuria, management talent, aware of the importance of the subject and expected results of the company surveyed, was an analysis of data obtained through field visits in addition to the questionnaire and interviews, highlights were the results that have been reached to take the sample into account all the management requirements knack of att
... Show MoreReceipt date: 2/2/2021 accepted date: 4/6/2021 Publication date: 12/31/2021
This work is licensed under a Creative Commons Attribution 4.0 International License.
The approval of the federal general budget in Iraq is one of the most important competencies of the legislative authority , Being one of the important financial and monetary policy instruments on which the state depends for its economic growth , Hence, the obstruction of the approval of the federal b
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The research aims to identify the concept of green taxes and their role in reducing environmental pollution through the poll of Abnh of taxpayers and employees of the General Authority for taxes totaling 200 individual .autam adoption of the resolution as a tool head for the collection of data and information from the sample and analyzed their responses using a statistical program (spss - 10), and calculating the percentages and the arithmetic mean, standard deviation and research found to a number of conclusions, notably the lack of legislation with the challenges and the difficulty of the existence of a measure or a standard lack of planning for the application of environmental taxes that the state taxation application between the Gene
... Show MoreObjective: The aim of the present study is to assess the practices of nurses towards standard precautions at Azady
Teaching Hospital in the City of Kirkuk.
Methodology: A descriptive study, which uses the assessment approach and it was conducted on nurses from January
18th, 2009 to September 30th, 2009, using non-probability sampling a purposive sample of (37) subject (male and
female nurses) who worked at surgical wards in Azady Teaching Hospital in Kirkuk city was selected. Two study
instruments were utilized for proper data collection [questionnaire and observational checklist]; a questionnaire was
developed for the purpose of the study. It was comprised of two parts which included the nurses' demographic
characte
The present study was set to demonstrate the prevalence of toxoplasmosis infection and its effects on patients with systemic lupus erythematosus (SLE) through determining their serum levels of anti-dsDNA and IL-18 antibodies. For this purpose, the sera from 132 SLE and/or toxoplasmosis patients and 30 healthy women, were collected. The study sample was divided into four groups of SLE, toxoplasmosis, SLE coinfected with toxoplasmosis, and healthy control. Anti-Toxoplasma IgG antibodies were examined for all the samples using ELISA kit. The results showed a high mean level of anti-Toxoplasma IgG among SLE patients coinfected with toxoplasmosis (104.8792±12.31585pg/ml) in comparison to that in toxoplasmosis patients (91.1705±12.577
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Abstract
We can see the phenomena of small and medium-sized enterprises, by important and a new subject contemporary, thro related between important concept that develop and add. This research focused on the important concept of small and medium-sized enterprises, in public and privet sectors. small and medium-sized enterprises discrimination by large filer ratio in the especially at the first years when they started because of the limited managerial skills, financial recourses and marketing problems. On it they will creative new procedures. this research treatment the core issues about wakens local and international enterprises, so threat. the goals of this research are extended malty dimension concept o
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Non-thermal atmospheric pressure plasma has emerged as a
new promising tool in medicine and biology. In this work, A DBD
system was built as a source of atmospheric pressure non-thermal
Plasma suitable for clinical and biological applications. E. coli and
staphylococcus spp bacteria were exposed to the DBD plasma for a
period of time as inactivation (sterilization) process. A series of
experiments were achieved under different operating conditions. The
results showed that the inactivation, of the two kinds of bacteria, was
affected (increasing or decreasing) according to operation conditions
because they affects, as expected, the produced plasma properties
according to those conditions.
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This research sheds light on how press advertising affects consumer behavior and draws attention to it by identifying the factors that influence the intellectual perception process or attention to it. The aim of the research was to identify the factors that help achieve the objectives of the press announcement. The aim of the research was to identify the factors that help to achieve the objectives of the press announcement. The research problem was identified in four questions that were answered through a questionnaire distributed to a sample of students of College of Mass Communication, University of Baghdad. Do newspaper advertisements meet the readers’ need to search for the req |
Objective(s): The study aims to identify the role of sociodemographic factors in predicting the level of psychological hardiness of nurses.
Methodology: A descriptive correlational study conducted in the Medical City hospitals in the city of Baghdad during the period from November 1, 2022 to May 1, 2023 on a sample of 156 male and female nurses. The validity of the quest
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