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 intervention in the military institute represents a great role in the Nigerian
political life since 1960. There are many reasons behind this domination. The First is that
many African militants participated in liberating their countries from colonization. The
second is that they tried to stay in power as long as they could stay through the rule of one
party.
There fore, they depend on the process of political and economic reform to get rid of
military rule that dominated the Nigerian Political life to be a civilian state
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.
Babesiosis is a tick-borne disease caused by Babesia microti. We present a case of false positive HIV in the setting of confirmed babesiosis infection. An understanding that patients with babesiosis can have a false positive HIV test result is important in management decisions.
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The research aims to develop alternatives to transportation at the entrance to the Educational City (University of Baghdad) during the morning and evening peaks, which result from of the traffic congestion at the entrances to the educational city (the University of Baghdad), and affects the emotional, functional, and social performance of the whole city, and leads to hotbeds of confluence and congestion at the entrances in the morning and evening peaks. This movement was measured on the ground for pedestrians and vehicles. Some criteria were adopted to determine the density of road length to the area and density of roads for the number of users and the rate of the area served by roads. The research reviews the experiences of some
... Show MoreUrinary tract infection is a bacterial infection that often affects the bladder and thus the urinary system. E. coli is one of the leading uropathogenic bacteria that cause urinary tract infections. Uropathogenic E. coli is highly effective and successful in causing urinary tract infections through biofilm formation and urothelial cell invasion mechanisms. Other organisms that cause urinary tract infections include members of the Enterobacteriaceae family, streptococci and staphylococci species and perch. In addition, K.penumoniae is another important gram-negative bacterium that causes urinary tract infections. With the PCR technique, unseen bacterial species can be detected using standard clinical microbiology methods. In this study, the
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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 MoreThe research tackles the nature of relationship between the Orthodox Church and the state in the Russian Federation. At the beginning of the nineties of the last century, the church had been performed a different role in its relationship with the state, and it had an effect over the internal and foreign policies for the Russian Federation. In political history of Russia, the church’s existence became an evident too much in comparing with the previous historical period, starting with the educational and political system, whether through a symbolic participating roles as what happened in the inauguration ceremony to take over responsibility of the head of state or taking actual roles such as influencing on the process of holding elections d
... Show More: 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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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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This research attempts to evaluate the role of the information system by highlighting its importance in providing date and information to the tax administration the process of tax accounting for those who are subject to income tax whether they are individuals or companies where the effective information system provides accurate and reliable information in a timely manner.
At the theoretical part of the research, the research approaches the problem of the research represented in that whether the information system, applied in the General Commission for Taxes, is capable of achieving its role in reducing the phenomenon of tax evasion. The existence of a set of things which in the Commission may lead to increase tax evasion by taxpa
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