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.
Urinary 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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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 MoreThe 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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: 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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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 MoreTime crosses one of the most important principles that are agreed upon in contracts, because the temporal dimension has a significant impact on all contract provisions and is not limited to a certain group of them. French and Arab legal jurists alike called for this dimension to be given special attention. That is the term of the contract term; To try to limit the temporal elements, clarify their provisions and distinguish between them, but in the Arab world it did not receive the same attention that it received in the West.
This research is a modest contribution to Put the finishing touches on therole of managerial leaders represented by static companies belonging to theministry of transport and communication/ [iraq] . the research has adopted thedescriptive. Analytical methodology and field study technique, using thequestionnaire as a tool for data collection [58] forms Nar, been distributed tothe research sample. The sample has been deliberately selected {generalmanager, as assistant general manager and heads of department}. Thequestionnaires and the main hypotheses of represented by the existence ofsignificant correlation and impact between successful managerial leadershipand crisis management using the software {SPSS}, were analyzed. Resultswere identic
... Show MoreThe 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 is an initial attempt to explore the reality of education and its concept in Islam, and to describe the presence of educational practices in the Arab-Islamic heritage. The importance of this research lies in addressing a set of important issues related to the contemporary Islamic educational system. The research revealed the extent of the need for authentic educational values that draw their reference from the origins of Islam, and it emphasized the analysis of the reality of education in the Islamic world and the identification of its problems and the finding of solutions through a quick and comprehensive look at the diverse contributions of Muslimthinkers to Islamic educational thought, and their active ro
... 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