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 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
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Abstract
The objective of the research is to identify the role of innovative leadership in achieving the dimensions of administrative empowerment in the company for the public of food industries. The various variables have shown the importance of innovative leadership to achieve the dimensions of administrative empowerment in both international and local companies. Administrative Empowerment "In order to answer this question, a virtual model was developed to reflect the relationship and impact between innovative leadership and administrative empowerment. The research was based on the analytical descriptive approach. the research community, The company represented the general company for food industries, retrie
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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
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Oral swab samples were collected from 120 children (ages between one month- 10 years) who were infected with oral thrush and 30 healthy children. The percentages of isolated yeasts and Bacteria were 66.6% and 96.6% respectively. The dominate yeast and bacteria were Candida albicans and Staphylococcus aureus with of 78.7% and 34.4% respectively. Results revealed that the highest percent of infection with oral thrush disease was 32.5% in children within the age of 1-2 months.
Objectives: To highlight the knowledge of Al-Kindy medical students regarding varicella infection and to assess their knowledge and attitude toward its prevention. Methodology: This descriptive cross-sectional study enrolled academic year 2020/2021 students at Al-Kindy College of Medicine from first to final year. We used an online questionnaire by Google forms to collect data, which were analyzed with SPSS 26. Results: A total of 208 students participated with 126 in the preclinical and 82 in the clinical grades. Generally, most clinical students were more aware about epidemiology, clinical manifestations, and complications of varicella infection than the preclinical students. Conclusion: Educational stage is a significant variab
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Giardia lamblia is the worldwide most common intestinal protozoan parasite. It was indicated that Giardia is the most important agent that causes acute and chronic diarrhea in infants, young children and travelers. The aim was to detect the influence of host HLA alleles on the susceptibility to infection with G. lamblia in a sample of Iraqi patients. A total of (40) patients with giardiasis aged (14-39) years were registered. All of them were symptomatic and (40) healthy individuals matched age and sexes were included as controls. All patients were prepared to stool examination to detect G. lamblia and eliminated other pathogens, as well as human leukocyte antigen (HLA) class II alleles (DRB1) typing. The most common detected alleles in pat
... Show MoreExperiments were carried out at the College of Veterinary Medicine, University of Baghdad, during the period from October 26th 2023 to December 20th 2023, to study the effect of pasteurizing treatments of shell table egg using traditional Microwave oven on its quality characteristics during Zero, 1, 2, 4 and 8 weeks of refrigerator storage. A total of 120 fresh table eggs (White shell eggs) were collected from 20000 Luhman layer hens flock at Al-Amir project commercial farm, Al-Musaib city. These eggs were divided into 4 treatment of microwave pasteurization treatments which were Zero, 10, 20, and 30 sec. Results revealed that the numbers of total bacteria and total coliform on the surface of table egg shells is affected by pasteuri
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An experiments were carried out at the College of Veterinary Medicine, University of Baghdad, during the period from October 26th 2023 to December 20th 2023, to study the effect of pasteurizing treatments of shell table egg using traditional Microwave oven on its quality characteristics during Zero, 1, 2, 4 and 8 weeks of refrigerator storage. A total of 120 fresh table eggs (White shell eggs) were collected from 20000 Luhman layer hens flock at Al-Amir project commercial farm, Al-Musaib city. These eggs were divided into 4 treatment of microwave pasteurization treatments which were Zero, 10, 20, and 30 sec. Results revealed that significant differences (P<0.05) for the internal characteristics of the egg after storage for 2, 4
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The auditor has a role in allocating joint costs in the gas industry, and the auditor's procedures are considered as systematic critical examination, analysis and evaluation of everything related to costs in general and joint costs in the gas industry in particular, with the aim of controlling the joint costs of gas industry products, and knowing the share of the cost of each product from the total industry costs Gas products reflect the reality of the company's performance by discovering weaknesses, defects and any errors, to ensure increased effectiveness and efficiency of the parties concerned with auditing them and imposing control and control over the company's resources, as well as
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