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 study aimed to investigate the role of Dectin-1 and Card-9 in pathogenicity of inflammatory bowel disease (IBD). This investigations involved 150 blood samples for IBD patients which divided in to two groups (50 for crohns disease CD (G2) and 50 for ulcerative colitis UC (G3)). All a apparently (male and female) attended to) Al-Kindy hospital) in Baghdad city, department of Gastroenterology. and all of thin were diagnosis by consulters medical staff and pathologists with age range 15-65years average 40 years. in addition to 50 blood samples were collected from apparently healthy individuals as control group (G1). 10 ml were withdrawn from all participants, 5ml for the immunological study which carried by ELISA technique and 5 ml used fo
... Show MoreThe aim of this study is to assess nurse's knowledge and role in the management of thalassemic patients in the Sulaimania Thalassemia Centre. Methodology: This study utilized a qualitative approach to explore nurses’ knowledge about thalassemia through semi structured group interviews. Questionnaire was synthesized through a comprehensive review of literature. Results: The results show that nurses in Kurdistan region of Iraq have a limited role in terms of decision making and there is lack of nursing documentation other than that of recording abnormal events, and a lack of knowledge about and engageme
Recently, Malaysia has been recognized as one of the most popular destinations for Foreign Direct Investment (FDI) in Southeast Asia. But how do these FDI inflows affect Malaysia economy? This paper aims to identify the role of FDI inflows in Malaysia economic growth through a proposed endogenous growth model. Annual data covers from 1975 to 2010. Unit root test and Johansen Co-integration test are adopted to respectively verify the time series data is stable and the linear combination of the variables is stationary. Hierarchical Multiple Regressions (HMR) Analysis is then conducted to find out the momentum of the Malaysia economic growth including FDI inflows. The results show that the FDI inflows together with the human capital deve
... Show MoreHypothyroidism is a frequent disorder in the general population, especially among women, is defined as adeficiency of thyroid activity that results from insufficient production or action of thyroid hormones leading to a totaldecrease of metabolic. Human leukocyte antigen is the most polymorphic genetic system in man. Genes of this regioninfluence susceptibility to certain diseases.Objectives: The purpose of the present study is to investigate the role of HLA-DRB1 genotyping in hypothyroidpatients with and without periodontitis. Sixty hypothyroid patients 30 of patients were with periodontitis and 30without periodontitis compare with 30 healthy subjects as control enrolled in this study. DNA was extracted fromblood samples, then HLA- genotyp
... Show MoreThe research shows the importance of orientation towards the formulation of the green strategy and its effect in determining the behavior of the green municipal institution in Babel governorate. The research highlighted the formulation of the green strategy as an important variable, especially today, the trend towards protecting the environment and minimizing the damage resulting from the delivery of services, and through it also the type of green behavior or performance adopted by the municipal institution and the emergence of the need for a strategy that is not harmful to the environment. The research took the sample intentionally comprehensive size of 222 personnel of municipal institutions and some formations concerned with t
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This work aimed to produce PVA and PVA/Ag nanofibers ultra-high sensitivity photodetector by electrospinning. The electrospinning process was used to successfully prepare PVA nanofibers and a PVA-Ag nanofiber composite. FE-SEM, XRD, UV, I-V characterizations are used to study the morphological, structural, optical, and electrical properties of the material. In contrast, the PVA-Ag nanofiber composite film displayed a cubic structure with favored orientation (200) that indicated the presence of Ag NPs in the PVA-Ag nanofibers film. While the optical energy gap for PVA was 3.96 eV, it was only 2.14 eV for PVA-Ag nanofibers composite film, making this composite sensitive to visible light, particularly green light at 550 nm with a 65% photosens
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The skill of management educational activities gradually grow with the experience, but they differ from personal skill educator to another, because each style nanny personally and the way to work. There educator and active movement and vitality that look like happiness and clear during the implementation of the activity, and the other runs educational activities quietly, efficiently and without emotion and clear (dry, 2001: p. 274). And the stage of childhood is one of the most important stages that are based upon the future life as a whole because the man also confirmed by the School of analysis psychological is the son of his childhood and the best example to us what the Holy Prophet Muhammad (peace be upon him): (Every child i
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