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.
: Cervical malignancy positioned as the fourth most prevalent disease among women around the world. HPVs especially HPV16 are the causative agent of cervical cancer, responsible of about 5% of all human cancers worldwide. Some researchers found that the fibronectin is repressed by the papillomavirus (HPV) type 16 E7 oncoprotein in both HPV-positive nontumorigenic and tumorigenic cell lines, while others found that the HPV oncoprotein increase the levels of fibronectin. The aim is to study the effect of HPV infection on Fibronectin expression and their correlation onthe development of Cervicalcancinoma. The current retrospective study enrolled paraffinized blocks of two groups. The research included 30 cervical carcinomatous tissues as well
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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
... Show MoreThis 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 MoreThe 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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Abstract
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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Objectives: 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
The need for an intellectual understanding of the context from many aspects' dictates understanding the ways through which the graphic designer walks in simulating the intent of the design process and elevating it to levels of communicative perception that leads to communicating the idea to the recipient, and it is thus a need closely related to the context, if it is historical. Culturally or socially, and between the mechanisms of selecting and operating the elements and units of the graphic and design achievement. On this basis, the role of context in graphic design can be studied.
The research included four chapters, the first chapter of the research problem and the need for it, and the aim of the research was (discovering the
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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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ABSTRACT
The research aims to clarify the role of electronic marketing and what it can achieve in promoting the products of the national industry in Iraq. Marketing channel depends on modern communication and information technology that industrial and metal companies can use in promoting and selling their products along with traditional marketing outlets. To achieve the objectives of the research, a questionnaire was used, which consists of three axes, the first includes the personal data of the sample (gender, age, educational attainment, place of residence, marital status, income level), while the second axis includes various questions about the products of the national industry. Third axis includes que
... Show Moreلم تعد ظاهرة غسل الأموال ظاهرةً محلیة أو إقلیمیة، فكل دولة معرضة لهذه الظاهرة لانتأثیراتها تستهدف الإنسان أینما كان باستهدافها الأوضاع الاقتصادیة والمالیة والاجتماعیة وحتىالأخلاقیة، سواء على المستوى الوطني أم على المستوي الدولي، فضلاً عن استغلال الاندماج الحاصلفي أسواق المال الدولیة والتطور التقني في الأنظمة المالیة لنقل الأموال المراد غسلها وتحریكها إلى إيمكان في العالم، وهو ما