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.
Small and Medium Enterprises (SMEs) in Iraq have experienced low performance due to the limited usage of accounting information systems (AIS) and the inability to exploit knowledge of management capabilities (KMC). These deficiencies have led to competitive pressures in the marketplace that have adversely affected their sales and production. This study investigates the role of AIS in terms of operation support, knowledge support, regulatory support, and the role of KMC, including knowledge acquisition, knowledge transfer, and knowledge utilized to enhance organizational performance in Iraqi SMEs. The target population was managers and owners in SMEs using AIS in Iraq’s cities. A non-probability purposive sampling technique was use
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The main purpose of the research is to demonstrate the importance of the insurance sector in the economy through its role in providing security for all economic sectors and thus stimulating the gross domestic product and reducing dependence on the output of the oil sector, which may expose the Iraqi economy to several problems and imbalances, I have found that there is a great weakness in the role of the insurance sector in Iraq at the level of government, companies and individuals, and the reason for this is the lack of policies supporting the insurance sector and the lack of work in the strategy of economic diversity and the decrease of security awareness by individuals so became Developing the sector to ensure the urgent need
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Deconstructionism opened the door wide to multiple readings and restore the reader his authority that he lost in the modernism, thus became more able to decipher the plastic discourse through reconstruction according to what he wants or what the plastic discourse gives him of possibilities beyond consumerism and thus the author has been canceled. The problem of the current research is limited to the following question: does deconstructionism in postmodern arts have a role in teaching the artistic tasting for the learner? The aim of the current research is to reveal the deconstruction work mechanisms in postmodern arts and their role in teaching the artistic tasting for the learner. As for the theoretical framework, the first section focu
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Besides the role of state institutions that come in the forefront of their priorities and obligations to provide security and development of the economy and reduce the unemployment rate and the reduction of inflation and improving education, health and others, the Community Partnership At frames what has become known as the institutions of society civil-with the state does not eliminate the role, but rather complements its role ; it is the role of civil society partner and an extension of the role of the state in the face of challenges and crises, but it may be sometimes a race role in addressing social, political and economic issues of the role played by the state, not complementary.
The highlighting the specificity of the relationsh
This research aims to shed light on the necessity of establishing an information security management system through which banking security risks are managed in the light of the ISO (IEC 27001) standard, through which bank departments seek to demonstrate the management of their security systems and their controls in accordance with the specifications of the standard to obtain an internationally recognized security certificate And the need for senior management in banks to an independent person with scientific and practical qualification and who has accredited certificates in the field of information technology for the purpose of helping them to verify the level of compatibility between the policies and procedures applied and the p
... Show MoreThe research aims present to highlight the importance of creating construction Organizational appropriate to achieve strategic success and reduce many of the negative effects experienced by organizations has been developing his questionnaire especially so was distributed to a sample of workers in the Asia-cellular as sample included (60) responsive 0 and can embody intellectual dilemma following questions (What are the dimensions of the organizational infrastructure, and what are the justifications for carrying out the reform and development cleared the organizational structure to make it more flexible) to contribute to the achievement of the strategic requirements for success of the organization surveyed.
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Polycystic ovary syndrome (PCOS) is the most endocrine problem in women of regenerative age. PCOS women typically belong to an age and sex group which is at higher risk for severe coronavirus disease (COVID-19). COVID-19 targets cells through angiotensin-converting enzyme 2 (ACE2) receptor presents on cells in veins, lungs, heart, digestion tracts, and kidneys. Renin-Angiotensin System (RAS) over activity has likewise been described in metabolic disorders; type 2 diabetes mellitus (T2DM), and conditions shared by women with polycystic ovary condition. The point of this study is to know the job of renin and ACE2 in PCOS and coronavirus and its relationship with hormones and other metabolic parameters related. The study groups consist of 1
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Cultivation of the green seaweed Enteromorpha compressa was performed under natural laboratory spring environmental conditions of temperature, light intensity and photoperiod to study the salinity tolerance of this intertidal green macroalga. Cultivation was carried out under artificial seawater (ASW) of different concentrations (18, 35, 53 and 106 g/l sea salt) compared to the control using natural seawater (NSW). Growth rate and pigment content of the cultivated alga were recorded at regular intervals during the experimental duration. Antioxidant activity of the crude ethanolic extract and its fractions (petroleum ether, chloroform, ethyl acetate and acetone) was performed against DPPH radical scavenging assay and compared to
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