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.
Background: Implant stability is considered one of the most important factors affecting healing and successful osseointegration of dental implants. The aims of the study were to measure the implant stability quotient (ISQ) values during the healing period and to determine the factors that affect implant stability. Materials and methods: Thirty patients enrolled in the study (17 female, 13 male). They received 44 Implantium® Dental Implants located as the following: 22 implants in maxillary jaw, 22 implants in mandibular jaw from them 17 implants in anterior segment and 27 in posterior segment. The bone density determined using interactive CT scan and classified according to the Misch bone density classification (29 implants in (D3), 15 i
... Show MoreAbstract
The research aims to identify the strategic leadership and its role in activating the Organisational Performance, which is an analytical study of the views of the heads of scientific departments at General Authority of groundwater researcher's quest focused towards building a theoretical framework suitable for strategic leadership and performance Organisational and itُs dimensions.To achieve the aims of the research is designed to identify the researcher included (35) items to collect the raw data from the research sample consisting of 33 of the heads of departments. Data was collected by questionnaire, field visits, interviews and some official documents to complete the search data. It has also been used a numb
... Show More
(1)
The organizational integration forms a necessity according to McKinsey model, especially for service organizations. In the context of various service sector developments, importance adoption of compact mechanisms by these organizations to upgrade their services has increased and senior management must be more aware of environmental, competitive and developmental requirements. It gets more important when it shows in an organization seeking at excellence of making services within its policies and strategies. Subject organizational integration dimensions (strategy, structure, systems, style, staff, shared values, and skills) are effective components in directing behaviors of employees and organization. This motivated both researcher
... Show More
This current research deals with the "The role of organizational change in the achievement of strategic success" Who are getting increased attention to being one of the important topics and relatively new, And which have a significant impact on the future of the organization So there is a need for this research, which aims to identify the role of organizational change across dimensions (technology, organizational structure, human resources, organizational culture) in the strategic success through its components (a specific strategy, effective implementation, innovation, customer satisfaction)، And that by two main hypotheses, branched about eight hypothes
... Show More
(2)
(54)
(35)
The aim of this study is to investigate the relationship between microRNA 378 and BMP15 gene expression levels in blood samples collected from 50 healthy fertile females as controls and 50 hyperprolactinemia infertile females by quantitative real-time polymerase chain reaction (RT-qPCR). Specific primers were designed for this purpose based on the sequences of microRNA 378 and BMP15 retrieved from NCBI and designed by primer 3 software. The result assessing the expression level of BMP15 in hyperprolactinemia (HPL) was 0.220, while the control group's fold change value was 1.000. The HPL group showed downregulation in the expression of the BMP15 gene. While the fold expression values of the miRNA378 gene in the hyperprolactinemia
... Show More
Formed leadership skills and organizational trust Based on intellectual that underpinned the current research, as represented leadership skills variable interpretative represented in organizational trust-response variable.
The research aims to test the relationship and the impact of leadership skills dimensions in organizational trust dimensions for the purpose of achieving its objectives were formulated hypotheses main relate to test the effect and the relationship between the variables of research for the purpose of testing those hypotheses applied research on a sample of heads of departments and officials of the people at the center of the Ministry of Higher Education and Scientific Research, where th
... Show More
(1)
Gender and culture are among the factors that influence the process of understanding and interpreting different types of communication, especially images. The current study, which is a part of a master’s thesis, aims at investigating the role of gender and culture in interpreting and understanding the caricatures that deal with women’s issues in Arab societies. To this end, the researchers adopted Barthes’ (1957) concepts of denotation and connotation in his theory of mythologies in addition to Langacker’s (1987) theory of (Domains). The research concludes that the female subjects have better cognitive abilities in investing the signs within the selected caricatures. The other factor the study reached to is that the respondents
... Show More
حزب العمال الكردستاني ودوره في تطوير القضية الكردية في تركيا من 1991-2013