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 issue of Palestinian prisoners inside the prisons of the Israeli occupation is considered
a humanitarian issue par excellence، as it affects every Palestinian family as a
result of the absence of a husband، wife or son.
Almost no Palestinian house is vacant without one or more prisoners، and even women،
children and the elderly are not spared from these arrests.
The problem of the study was to identify the role of public relations in the Ministry
of Detainees and Ex-Prisoners Affairs in educating the Palestinian public about the
issue of prisoners، the nature of this role and the means used to bring support and
solidarity with this important and sensitive issue through the applied study on the
employee
(1)
Abstract
This study identified the developing of a range of students' geography learning skills and the change in their attitudes toward fieldwork as a consequence of leaning experiences that occurred within a field trip. The sample of the study consisted of (27) students within a special topic course enrolled in Geography Department at Umm Al-Qura University in Saudi Arabia in semester 2, 2018. A range of students' geography learning skills were measured by the skills questionnaire that consisted of 12 geography skills after completing field work. Changes in students' at
... Show MoreThe field of graphic design has witnessed a unique, unique form transformed in its construction and installation and superior to systems through its creation of foundational data for design ideas with functional aesthetics and utilitarianism and effective and moving formulation in light of modern trends and what globalization has brought about in terms of openness to the outside world and the processes of communication and communication with the international community through graphic design. Based on the above, this study marked (Aesthetics of the Design Idea and its Communication Role in the Graphic Outcome) comes to clarify the topic through three chapters, including the first chapter, which was devoted to the research methodology, th
... Show More
The developing countries, like our country Iraq suffer from deep comprehensive structural crisis, manifestations and a clear imbalance between the demand and the supply sides. The overall imbalance in the external balance. As a consequence, this caused the accumulation of foreign debts or failure in the implementation of economic development programs. The countries which are forced to resort to the International Monitoring Funds, and the World Bank for assistance and to express an opinion on policies that include restrictions controls that belong to the monetary, and fiscal side group, imposed on the economies crisis, as a condition for returning to normal which called reform programs. The organize of the events of radical changes in the
... Show MoreThe process of transformation from the central economy to a free economy requires restructuring the economy according to a new economic philosophy that relies on activating the role of private economic activity in which private and medium-sized institutions occupy an essential axis for their active role in the economies of all countries, especially those countries that have directed towards the market mechanism and sector leadership. The special process of economic development and the role that commercial banks can play in advancing the financing of these projects by establishing specialized business incubators for financing.
What encouraged countries to pay attention to these institutions is the ease of
... Show More
The current study is based on previous findings, where corporate governance (CG) significantly increased corporate social responsibility (CSR) to enhance transparency while reducing the tendency of corporate management to engage in earnings management (EM). A sample of 11 Iraqi banks listed on the Iraq Stock Exchange from 2010 to 2020 was selected. The CG was included in the board size and board independence apart from the variables of Chief Executive Officer (CEOs) gender, majority shareholder ownership, foreign ownership, and institutional ownership. The CSR included the wage growth rate, bank contribution growth rate for social security, training programmes, subsidies, environmental protection, and bank compliance with the law. Specifica
... Show More
(10)
(6)
This study aims to identify the amount of the effect of the ability to learn the individuals within the organization on the accumulation of intellectual capital and the role it plays in improving the performance of the organization, and to achieve that, the researcher designed a questionnaire to collect data and information from the surveyed respondents and analyzed using SPSS software, the study concluded after testing hypotheses to have a direct impact between the capacity for organizational learning and the accumulation of intellectual capital, which in turn affects the accumulation of intellectual capital as a positive and direct impact on the performance of the organization, al
... Show More