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.
This research aims to know the role of strategic flexibility in achieving organizational effectiveness by studying the dimensions of strategic flexibility (capacity flexibility, resource flexibility, information flexibility, and coordination flexibility) on the dimensions of organization effectiveness (environmental adaptation, productivity and achieving goals) through an analytical study conducted in six directorates in the office of the Iraqi Ministry of Education.
The research problem was represented in the form of questions, the most prominent of which was "What is the role of strategic flexibility in achieving organization effectiveness?" The descriptive analytical approach was relied on in applying
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The aim of the research is to present and discuss the subject of the budgeting estimates and how to activate the role of the Federal board of supreme audit in examining these estimates through reference to Articles 6 and 10 of the Federal board of supreme Law, which did not restrict Federal board of supreme in Preventive control on examination process for planning which is prepared from the government units, as the result of a large amount of government units Provisions and the weakness of estimates in most of its items, which rely on personal assessment and not based on scientific and logical basis of the estimate, which leads to the emergence of a deficit is not true in the general budget and this seems clear in most Iraq
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The current study aimed to investigate the viability of biofilm formation klebsilla pneumoniae and Staphylococcus aureus. 440 urine samples were collected from patients suffering from urinary tract infection (UTI) from those who were admitted and visitors to Al-Ramadi Teaching Hospital, Al-Yarmouk Teaching Hospital, Al-Ramadi Teaching Hospital for women and children and , Teaching Laboratories in the Medical City for both genders for a period extended from 5 July, 2017 to 10 October, 2017. Samples were diagnosed by culturing them on a selective media and by biochemical testes , also, diagnosis was ensured by using VITEK-2 compact system. Results showed that K.pneumoniae isolation ratio was 17.1%(68) and S.aureus ratio was 13.1%(52). Thei
... Show MoreThis study aims at identifying the correlation between digital transformation and knowledge building in educational institutions, as well as finding the influence relationship between digital transformation and knowledge building in educational institutions and knowing the dimensions of digital transformation that have the most impact in improving the level of knowledge building, and by adopting the methodological descriptive analysis method in the Ministry of Education. Education and educational institutions in Baghdad. This research deals with digital transformation as an independent variable according to two dimensions (digital adaptability and digital readiness). Knowledge building was adopted as an approved variable using the s
... Show Moreاعداد : أسرار عبد الزهراء علي - علاء الدين - ب. جواد حسن عودة عبد الله - جامعة بغداد جامعة بغداد كلية البصرة للعلوم والتكنولوجيا - كلية الإدارة والاقتصاد. كلية الإدارة والاقتصاد المركز الديمقراطي العربي – مجلة القانون الدستوري والعلوم الإدارية : العدد التاسع شباط – فبراير 2021 المجلد 3 ،
Toxoplasmosis is the term for infection and disease in man and animal caused by a parasite called Toxoplasma gondii. The more susceptible to infect with toxoplasmosis is the Diabetic patients, due to low level of immunity response. The aim of current study is to investigate the immune status of diabetes mellitus type 2. One hundred and seventy five samples of both diabetes mellitus type 2patients and controls which had been tested by ELISA technique to detect anti-Toxoplasma Abs (IgG and IgM). The positive toxoplasmosis samples were tested to detect the level of TNF alpha and MIG. Results for all samples clarified that seronegative for IgM antibodies while 53 (53%) diabetic patients were seropositive for IgG antibodies and for toxoplasmosis
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ABSTRACT:
The study aimed to identify the impact of the role of voluntary accounting disclosure in enhancing confidence in the informational content of financial reports. Correlation - Spearman to measure the degree of correlation, as well as the method of simple linear regression analysis, and the study reached several results, including: The level of enhancing the information content in the annual financial reports of the Palestinian banks listed on the Palestine Exchange under study reached the overall average (total) (94.1%), and also Voluntary Accounting Disclosure in Enhancing Confidence in the Informational Content of the List of Change in Ownership Equity of Listed
... Show MoreThe financial market plays an important role in influencing the economic sectors, including the private industrial sector, through the provision of capital and transfer from savers to investors for the purpose of establishing or expanding projects. Therefore, the financial market is one of the important tools in stimulating the economy in general and the industrial sector in particular, Through the inclusion of industrial companies in the financial market and the introduction of industrial shares to the public, and then provide the necessary funding to stimulate the private industrial sector, Iraq is one of the oil-dependent countries on the oil sector mainly, which lacks industrial production, which is from Are the sectors that
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The research aims at clarifying the role of green human resource management practices in achieving sustainable development. The research problem is that the health sector is less concerned with environmental aspects, specifically green human resource management practices, Which are reflected on sustainable development with their economic, environmental and social dimensions as well as reducing costs, waste minimization and recycling, And the research started from two main hypotheses to explore the correlation and influence between the variables of the research by analyzing the answers of the research sample, which included (136) employees of the Al-Imamein Al-kadhemein medical city, Data and information were collected using quest
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This research aims at highlighting the strategic role of human resource development in developing competitive advantage in light of the great challenges and rapid changes witnessed in recent years in the business world. The human element is the main engine of the organization's resources, especially when it possesses the skill quality and cognitive abilities commensurate with the nature of work. Therefore, this research focuses on the importance of human resources development strategy in contemporary organizations and reviews the summary of literature and theoretical foundations related to human resources development, as well as various philosophical concepts related to the competitive advantage and to indicate the important role
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