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.
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Field experiment conducted to measure vibrations on three axes longitudinal X, lateral Y and vertical Z on steering wheel, platform tractor and vertical vibration in seat tractor and seat effective amplitude transmissibility (SEAT) factor during operation tillage in silt clay loam soil with depth 18 cm in Baghdad. Split – split plot design under randomized complete block design with three replications least significant design 5 % used. Three factor were used in this experiment included two types of plows included chisel and disc plows which represented main plot, three tires inflation pressure was second factor included 1.1 ,1.8 and 2.7 bar, and three forward speeds of the tillage was third factor included 2.35 , 4.25 and 6.50 km/hr. Resu
... Show MoreABSTRACT University college libraries are one of the most important information institutions for all researchers during their research and study life, they seeks to provide information sources such as; books, periodicals, theses, databases, Inquiry service and answering questions services in various disciplines to achieve its goals. In 2020, college libraries of all types stepped up to meet the needs of their users' as they responded to the impacts of COVID-19, also extended necessary lifelines to community members facing job losses, healthcare crises, and remote work and learning during an unprecedented and uncertain time. The research aim to identifying the services provided to the postgraduate students users at University of Baghdad coll
... Show MoreZubair Formation is one of the richest petroleum systems in Southern Iraq. This formation is composed mainly of sandstones interbedded with shale sequences, with minor streaks of limestone and siltstone. Borehole collapse is one of the most critical challenges that continuously appear in drilling and production operations. Problems associated with borehole collapse, such as tight hole while tripping, stuck pipe and logging tools, hole enlargement, poor log quality, and poor primary cement jobs, are the cause of the majority of the nonproductive time (NPT) in the Zubair reservoir developments. Several studies released models predicting the onset of borehole collapse and the amount of enlargement of the wellbore cross-section. However, assump
... Show MoreThis research aims to underscore the significance of women's emotional intelligence in enhancing the effectiveness of the Board of Directors, a crucial component of internal governance, particularly during crises. Despite strides made in recent decades in appointing women to senior roles in government, business, and education, challenges persist in improving women's leadership opportunities, especially in developing countries. The study utilizes statistical methods, including Pearson's correlation, to analyze the relationships between variables within a sample of banks listed on the Iraqi securities market, comparing periods before and during the COVID-19 pandemic (2019 and 2020). The goal is to measure the impact of female emotiona
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Role of Christian Wives in Elijahian Policy
Review Article Immunomodulatory Role of Cytokines in Periodontal Disease Batool Hassan Al-Ghurabi*, Maha Adel Mahmood, Zainab A. Aldhaher, Sahar Hashim Al-Hindawi Adv. life sci., vol. 11,...
The study conducted to investigate the association between Helicobacter pylori infection and eye diseases (Glaucoma, Cataract, CSR and Uveitis). One hundred and four patients with multiple eye disorders (10-80) years were observed from 10/9 to 18/11/2020 and compared to thirty-one healthy people (19 female and 12 male). Both participants were tested for anti-H. pylori IgA, and IgG antibodies using ELISA. There were non –significant differences (P≥0.05) in the concentration of anti-H. pylori IgA Abs in sera of patients with Glaucoma, CSR, and Uveitis compared to the control group, but there was a significant difference (P≤0.05) in the concentration of H. pylori IgA Abs in sera of patients with Cataract compared to the control group and
... Show MoreThe dubbing process for the Foreign Dramas by the Kurdish language became a serious phenomenon in the Kurdish satellite TV, especially in the past few years. It attracted a wide audience, especially young adolescents. And prepared by some breakthrough hostile to Kurdish culture and value coordinated by others remedy for the structural gaps and lapses have, as a result of climate which is brought into existence globalization and secretions variety dimensional, saturated value and cognitive effects bearing a strong identity of its elements. From here, the problem of this research is the ambiguity of their role in a series of developmental processes Kurdish awareness of young people and the extent of the impact that caused it.
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