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.
Prostate cancer is the commonest male cancer and the second leading cause of cancer-related death in men. Over many decades, prostate cancer detection represented a continuous challenge to urologists. Although all urologists and pathologists agree that tissue diagnosis is essential especially before commencing active surgical or radiation treatment, the best way to obtain the biopsy was always the big hurdle. The heterogenicity of the tumor pathology is very well seen in its radiological appearance. Ultrasound has been proven to be of limited sensitivity and specificity in detecting prostate cancer. However, it was the only available targeting technique for years and was used to guide biopsy needle passed transrectally or transperineally
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Background: Lumbar disc degeneration (LDD) is a common musculoskeletal disorder that frequently causes low back pain (LBP). In addition to the discomfort of lower back pain, it can accompany pain in one or both legs. The lumbar spine and sacrum, consisting of five vertebrae and one bone, determine the spine's balance. Microelements are essential in bone metabolism and are associated with the prevention of osteoporosis and the alleviation of musculoskeletal pain. Objectives: To examine the correlation between lumbar spinal surgery and the concentrations of microelements, namely zinc and copper. Methods: A case-control study was conducted in Ghazi Al-Hariri Hospital in Baghdad, Iraq, during the period from October 2023 to January 2024
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As long as the place in which a person lives has a meaning and temporal dimensions , memory is the main axis of these dimensions , today , city centers and old historical sectors of cities are abandoned , and began to turn into slums , the contradiction between old and historical sectors led cities to lose their identity while people lost their sense of belongingness to the old sectors where their ancestors used to live . The old city of Hilla used to have social , historical and cultural role on determining the identity . The study problem can be summarized as the ( lack of studies regarding the impact of historical memory related to Hilla old city on social and cultural mobility ) , the study hypothesis claims that the social , histori
... Show MoreThe Developing economies of countries have witnessed essential changes to words the development of tourism industry in the 21st century . in addition to adopting same of policies and strategies to grow up with the tourism sector to make it one of the important economic sector to compete the tourist cal developments in the wear .
As for the tourism sector in Iraq ,it's still afresh one , has many of elements which can be in vested ,needs a wide strategies of tourist cal in statutes and variety completive services and change of success for the locale and forgin investor ,the essential aim after this research is to prompt the national economic through the tourism industry and making concisen
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The role of university in awareness of Social and Cultural Human Rights to Students
still at the beginnings . the irritable secure of Iraqi environment is the most challenges that
cease any work that may raise the human rights in university . in spite of obstacles the same
society of university like conferences and meetings that related to this subject . as well as the
luck of professional teachers.
This study raises a group of important questions, perhaps the most :
The contribution of university in educates their students of the social and cultural human
rights? What are the most challenges that facing these students? Does the university
responsible of this luck of understanding these human rights?
This Study
based on the importance of public relations in companies, I will discussed the issue of public relations and its role in marketing national products, given what these companies represent of great importance in terms of providing products and services to large segments of Iraqi society, which necessitated the need to search and investigate the role and importance of activities that Provides public relations in Iraqi companies in all categories( public, private and mixed).
the study tables and theirinterpretations, results and recommendations, and the studyreachedseveralresults, including the positive and the negative, the positive including the success in marketing the products by the number of companies in the Fairswhere the level of
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The study aims to indicate the role of strategic financial accounting in the service investors to take appropriate decisions in the future, Through what is provided by the strategic accounting, the future of information and data that enable the investor to make future investment decisions appropriate، If no longer traditional financial accounting putting meet all existing and prospective investors Requirements، That reliance on historical data and information already signed and neglected aspect of future, From this point it was to highlight the role of strategic financial accounting to contribute in this area.
Introduction: In recent decades, the endovascular treatment of cerebral arteriovenous malformations (AVMs) has advanced. However, it still carries risks of unanticipated complications. Coil migration is a reported complication of aneurysmal coiling procedures. Herein, we report a case of early intraprocedural coil migration during pressure cooker technique embolization of right thalamic AVM, discussing the management and potential explanations. The literature showed no report of coil migration after the pressure cooker technique in the form of coil-augmented Onyx injection technique (CAIT). Case description: An otherwise healthy 26-year-old female suddenly developed a severe headache with no loss of consciousness. Computed tomograp
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Often there is no well drilling without problems. The solution lies in managing and evaluating these problems and developing strategies to manage and scale them. Non-productive time (NPT) is one of the main causes of delayed drilling operations. Many events or possibilities can lead to a halt in drilling operations or a marginal decrease in the advancement of drilling, this is called (NPT). Reducing NPT has an important impact on the total expenditure, time and cost are considered one of the most important success factors in the oil industry. In other words, steps must be taken to investigate and eliminate loss of time, that is, unproductive time in the drilling rig in order to save time and cost and reduce wasted time. The data of
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The goal of this study is to build an application that can be used in difficult cases and sudden circumstances during the pandemic and post-disaster state, which can be the development of digital risk management and mitigating the difficult impact of the epidemic through the improvement of IT and IoT that can be fine by finding initial solutions and make the world like a digital city that could be managed by the network. We provide this study to gain an overview of reasons for delayed and exceeded costs in a select of thirty Iraqi case projects by controlling the time and cost. The drivers of delay have been investigated in multiple countries/contexts. however, there is little country data available under the conditions that have ch
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