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.
This research discusses the developmental role of the social worker in providing care for children at risk. The research is desicriptive in nature include both the theoretical and field aspects. The theoretical aspect focuses on the characteristics and requirements of these children and what forms and implications are exposed to them by society, what is the developmental role of the social worker in the rehabilitation of this group. As for the field aspect, the study sample took a (40) social workers who working in Aiwa institutions inside Baghdad. A questionnaire of (14) questions was used as tool to collect the needed data.
Characteristic of money laundering phenomenon is a compound and complex nature like the style of regular crimes . These operations are planned and excuted with those who have high quality experiences to hide the evidences of their deeds so They ask the help of financials ,economicals and legists to plan for money laundering. Banks are important and suitable places for illegal circulation of money because of the different types of accounts , rapidity and overlap which emphasis of its main duty to dislocate illegal money which comes from illegal sources without adding legal characteristic to it . Here we should explain the important role of banks in striving the phenomenon –Bank should try to show and analyze inward proced
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Housing finance is considered to be an important and basic element in housing market, so it’s very important to aid individuals and particular institutions to built or buy new housing units.Inadequate finance system for housing is capable of supporting families to fulfill their needs and helping them to buy and built houses represented a big gap between the need to housing units and available stock. The most important finance institutions in Iraq nowa days are the Real Estate Bank and Housing Fund.Althoughthe role played byeach ofthese institutions, but thattheir roleis stilllimited in thehousing financeat the level ofindividuals orinstitutions. the adoption of the real estate Bank and housing fund to the amount allocated by th
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The research aims to study the role of e-government in enhancing institutional performance. The dimensions of e-government are: (support and commitment of senior management, technical structures, organization and human resources, knowledge and information, work procedures, attention to citizens' satisfaction, and client parties),while the dimensions of institutional performance are: (Service improvement, innovation, efficiency and effectiveness).
The research used electronic questionnaire as a main tool for data collection, The questionnaire included all the employees in the e-government project in Department of Government Coordinate and Citizen Affairs at the General Secretariat of the C
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This study was carried out to measure the percentage of heavy metals pollution in the water of the Diyala river and to measure the percentage of contamination of these elements in the leafy vegetables grown on both sides of the Diyala river, which are irrigated by the contaminated river water (celery, radish, lepidium, green onions, beta vulgaris subsp, and malva). Laboratory analysis was achieved to measure the ratio of heavy element contamination (Pb, Fe, Ni, Cd, Zn and Cr) using flame atomic absorption spectrophotometer during the summer months of July and August for the year 2017. The study showed that the elements of zinc, chromium, nickel and cadmium were high concentrations and exceeded. The maximum concentration of these
... Show MoreObjectives: the study aims to findout the effectiveness of educational program concerning infection control guideline on nurses, and to find out the relationship between effectiveness of program and types of hospital unit, age, level of education, and years of experience of nurses. Methodology: A quasi-experimental design study was carried out in Baghdad teaching hospital in the wards, for the period of December, 20th 2013 to September, 30th of July 2014, The study samples is composed of (60) nurses who have been actually working in the medical ward, blood disease, psychiatric ward, and neurological war
An increasing trend to use probiotic and study their effects on the pathogens has been conductor where they are defined as live micro-organisms that give a health benefit to the host when ingested in sufficient quantities, including the yeast Saccharomyces boulardii In addition research show that a magnetic field (MF) has a biological effect. This study aims to investigate the effects of magnetic field on the inhibitory action of Saccharomyces boulardii against bacteria isolated from urinary tract infection, Study the sensitivity of bacterial isolates to antibiotics after diagnosis by microscopic, Cultural and biochemical examinations as well as Api20 E examinations were used gram negative bacteria , Most isolates were resistant to an
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The present work aimed to examine the nature and degree of the cross-correlations among three different ionospheric indices: these are Optimum Working Frequency (OWF), Highest Probable Frequency (HPF), and Best Usable Frequency (BUF). VOCAP and ASASPS models were adopted to determine the datasets of the selected ionospheric indices. The determination was made for different transceiver stations that provide certain HF connection links during the minimum and maximum years of solar cycle 24, 2009 and 2014, respectively. Matlab program was implemented to produce the geodesic parameters for the selected transceiver stations. The determination was made for different path lengths (500, 1000, 1500, and 2000) Km and bearings (0o, 45
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In this research, a study of the behavior and correlation between sunspot number (SSN) and solar flux (F10.7) have been suggested. The annual time of the years (2008-2017) of solar cycle 24 has been adopted to make the investigation in order to get the mutual correlation between (SSN) and (F10.7). The test results of the annual correlation between SSN & F10.7 is simple and can be represented by a linear regression equation. The results of the conducted study showed that there was a good fit between SSN and F10.7 values that have been generated using the suggested mutual correlation equation and the observed data.
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Background: Reliable detection the etiological agent of amoebic dysentery and extra-intestinal amoebiasis have Public health importance specially in asymptomatic human and animals, Since the acquisition of pet dogs in the recent period has become widespread in our city. Aim: To give correct perception of infection rate in asymptomatic individuals (human and domestic dogs) for the first aspect and about detection and diagnosis of the pathogenic species of Entamoeba histolytica from another morphologically similar and commensal one using the molecular technique in stool samples of asymptomatic individuals the second aspect. Methods: During the study period from the beginning of September 2020 to the end of February 2021, a total of 95 stool s
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