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.
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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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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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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: 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 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
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.
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
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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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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