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 mix promotion important to any organization in general, has been selected promotional mix tools in this research to identify the role in maximizing the Organization of sales growth business, which included the research problem several fundamental questions about the role of each promotional tool of advertising, public relations and personal selling and sales promotion direct marketing within the promotional mix in the promotion of business sales organization. The research aims to provide theoretical and field organizations surveyed about the role played by the mix promo in sales growth, and importance of research on the identification of more than promotional tools impact on sales gr
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The present study aimed to evaluate sera TGF- ?1 concentration in patients with urinary bladder carcinoma (UBC). All malignant of them was transitional cell carcinoma (TCC) type , patients with urinary bladder disorders (UBD ) and healthy control , and to study the correlation between sera TGF-?1 levels and tumor stages and grades in UBC patients . A direct ELISA test was used to quantify the seraTGF-?1 concentrations in sera of 58 patients with urinary bladder carcinoma UBC of different grades (G) and stages (T) all malignant of them was transitional cell carcinoma (TCC) type , 15 from patients with UBD and 15 healthy subjects . Sera levels of TGF-?1 were elevated in patients with UBC and UBD compared to healthy (P ? 0
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Abstract
The study aims to identify the levels of core competencies dimensions and types of organizational flexibility in the investigated organization, as well as to determine the nature of the relationship and the impact of core competencies dimensions with the process of organizational flexibility. Thus, a number of research questions were presented to express the research problem as follows:
- What is the level of the investigated individuals' awareness to core competencies and organizational flexibility across their dimensions and types in the investigated organization?
- To what extent are core competencies and organizational flexibility available in the Organiz
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. Therefore, it is critical for researchers to understand molecular biology in greater depth. In several diseases including cancer, abnormal miRNA expression has been linked to apoptosis, proliferation, differentiation, and metastasis. Many miRNAs have been studied in relation to cancer, including miR-122, miR-223, and others. Hepatitis B and C viruses are the most important global risk factors for HCC. This study is intended to test whether serum miRNAs serve as a potential biomarker for both HCC and viral infections HBV and C. The expression of miRNA in 64 serum samples was analyzed by RT-qPCR. Compared to healthy volunteers, HCC patients' sera expre
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Background: Bone is essentially a highly vascular, living, constantly changing mineralized connective tissue. It is remarkable for its hardness, resilience and regenerative capacity, as well as its characteristic growth mechanisms. This study aimed to: 1. To evaluate the effect of bone morphogenetic protein7 (BMP7) on bone healing in artificially created intrabony defect in rabbits upper diastema, histologically. 2. To study the immunohistochemical expression of TGF-β3 and IGF-1R as bone formation markers in experimental and control groups during bone healing. Material and method: Forty male rabbits, was used in this study, 8 rabbits for each healing interval (3 days, 1,2 ,4 and 6 weeks). In each rabbit two bone holes were created on th
... Show MoreObjectives: The study aimed to clarify the role of Al-Sayyid Al-Ajall and his family in the service of the Mongol Empire. They worked to develop its administrative and military institutions, benefiting from their extensive experience in administration, politics, economics, and urban affairs. Due to their capabilities, they received the patronage of Genghis Khan and subsequent generations, earning the confidence of the ruling Mongol authority. As a result, they were granted significant powers within the state. Methods: The study relied on the analytical method to analyze historical texts, compare them with others, and discuss them accurately. Results: The study yielded several results, including the minister's keen interes
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Artificial neural networks usage, as a developed technique, increased in many fields such as Auditing business. Contemporary auditor should cope with the challenges of the technology evolution in the business environment by using computerized techniques such as Artificial neural networks, This research is the first work made in the field of modern techniques of the artificial neural networks in the field of auditing; it is made by using thesample of neural networks as a sample of the artificial multi-layer Back Propagation neural networks in the field of detecting fundamental mistakes of the financial statements when making auditing. The research objectives at offering a methodology for the application of theartificial neural networks wi
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Iraq is Suffering nowadays from the criminal triad represented by the fiscal and administrative corruption, money laundering and terrorism, which are intertwined in a very related relations, as each of them support the other . Since the over growth has been one of its characteristics leaving behind a very dangerous negative effects whether it was social , economic or even political impacts . As a result , this trial is now represents a high risk that threatens the present and the future of Iraq . On the political , economic and social level , it is well to mention that the poor direct investment , the increasing rates of poverty , unemployment , inflation as well as the smuggling of goreign currency an
... Show MoreBackground: Folic acid (vitamin B9) is one of the important vitamins that are necessary for growth and development of the embryo and preventing the occurrence of congenital malformations which are one of the important health problems in the developing countries and the world as it has a direct effect on the affected babies, their families and the community. It affects an estimated 3% of newborns worldwide.Periconceptional supplementation with folic acid (before conception and during the first 12 weeks of pregnancy) was found to decrease many important types of these anomalies. Objectives: The aim of this study is to assess knowledge, attitude and practice of periconceptional use of folic acid in pregnant women who are attending antenatal
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