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 research aims to know the effect of investment risks measured by the beta coefficient on the efficiency of stock pricing measured by the pricing error. The research was applied in the banks listed in the Iraq market for the period (2017-2020). That affects the value of the shares of the companies listed in it and the risks associated with it, as the risks are a dynamic process that changes over time depending on the variables that affect the general development of the economy, so these fluctuations should be taken into account to achieve maximizing returns and reducing risks and what is reflected in stock prices in the Iraqi markets Securities, through which the following question was asked: How does investment risk affect the efficienc
... Show MoreAt atmospheric pressure and at a frequency of 9.1 kHz, a constructed magnetically stabilized tornado gliding arc discharge (MSGAD) system was utilized in this study to generate a non-thermal plasma with an alternating voltage source from 2,4,6,8 to 10 kV. Argon gas was used to generate the arc plasma with an adjustable flow rate using a flow meter regulator to stabilize the gas flow rate to 2 L/min. A gliding plasma discharge is achieved by a magnetic field for the purpose of a planned investigation. The influence of the magnetically stabilized tornado gliding arc discharge parameters such as magnetic field and applied voltage on microscopic tornado plasma parameters was studied. The electron temperature1was measured using a Boltzmann plot
... Show More
(2)
(2)
Abstract:
The research aims to define the theoretical framework for corporate governance and its mechanisms and shed light on corporate governance in Iraq as well as the theoretical framework for the quality of financial reports and their relationship and the role of corporate governance in activating them. A commercial bank as a sample for the research, and a survey list was prepared to show the extent to which the research sample banks are committed to applying internal governance mechanisms. imposed on them by the local environment, which leads to improving the quality of financial reports for these banks.
Recently, some of Iraq's newly constructed asphalt concrete pavements showed premature failures with significant negative impacts on roadway safety and the economy. Using Nano hydrated lime (NHL) in pavement construction could be one of the possible steps to improve pavement durability. This article discusses how NHL affects the durability of hot mix asphalt. NHL was added in two methods to the asphalt concrete mixture for the wearing course. The first is the dry method, i.e., on the aggregate, whereas the second is the wet addition method, i.e., to the bitumen. The percentages were tried for each additional method; 1, 2, and 3% by weight of aggregate for the dry method and 0.5, 1, and 1.5% by weight of asphalt concrete for the wet
... Show More
(1)
Thin films were prepared from poly Berrol way Ketrrukemaaih pole of platinum concentrations both Albaarol and salt in the electrolytic Alastontrel using positive effort of 7 volts on the pole and the electrical wiring of the membrane record
This work has been done with using of epoxy resin mixed with Granite powder were weighted by percent volume (5,10,15, and 20)%and then mixed with epoxy polymer to compose polymer composite. Hand lay-up technique is used in fabrication of the composite samples. Hardness test was carried out for the proper samples in both normal condition and after immersion in HCL (1 M and 2 M) solutions for periods ranging up to 10 weeks. After comparing the results between the polymer and their composite, the hardness increased with increasing Granite weight percent, it was found that Hardness were greater for the composites before immersion compared with their values after immersion.
Our research which is under the name "Polarization and Communication mechanism in the formation of green industrial products " The problem of the research focuses in identifying what is polarization and its function mechanisms , by displaying the inventive and creative cases of the designer in how to exploit the industrial products and its recycling process to attract the user and recipient by asserting on the values of beauty of the appearance of the industrial product with the attraction Of the user and the recipient with the new function of that product and how its different from the function achieved by the old product , with consideration of nature and its preservation . The results of the research were as following : The designer e
... Show More
In the field of residential community planning, one of the appropriate places to study the mutual influences between man and the environment, away from the influences, concepts and mechanisms of contemporary planning theories are isolated environments in rural areas, and the marshlands in Iraq represent one of these models. These areas still retain the planning patterns of residential communities for thousands of years. This research attempts to conduct a descriptive study of traditional settlement patterns, which relied on the capabilities of the surrounding areas to provide planning and architectural solutions based on the environmental factor. Establishing such a clear framework for these impacts can help in any future interventi
... Show More
(2)
The research aims to delve into the nature of international financial reporting standards and the unified accounting system adopted in the Iraqi environment and financial ratios in the theoretical side. In the practical aspect, the results of some financial ratios of Basrah Gas Company were compared with the adoption of the financial statements prepared on the basis of the consolidated accounting system with the prepared financial statements Based on the International Financial Reporting Standards (IFRS). The research has reached a number of conclusions, including a difference in the accounting rules and practices between IFRS and the consolidated accounting system in force in Iraq. The adoption of IFRS has led to a decrease in profitabi
... Show More