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 reality of small and medium enterprises analysis reflects weaknesses plaguing these enterprises and strengths that are characterized by, and thus the formulation of appropriate solutions to the obstacles faced by these enterprises to enhance its contribution to the achievement of economic and social development. Iraqi small and medium enterprises suffer from several obstacles stand in front of development and support their competitiveness, the finance one of the main obstacles which impede growth and development of these enterprises, noting the banking system in Iraq reluctance to lend to small and medium-sized enterprises, as a result of the high cost of lending these enterprises compared to large projects, as well as
... Show More
The current research aims to identify the impact of ambidextrous leadership behaviors on organizational energy in Al-Faris Company. The descriptive analytical method was used as a research approach. Adept leadership includes two dimensions (open leadership behaviors and closed leadership behaviors), and organizational energy includes three dimensions (emotional energy, physical energy, and cognitive energy ). The research sample included all the administrative leaders (General Manager, Associate General manager, Department Manager, Division Official ) in AL-Faris Company / the Iraqi Ministry of Industry. The researcher distributed (74) valid questionna
... Show More
Based on previous research results that recognized the role of paternalistic leadership in promoting a positive work climate, this study explored the impact of a toxic work environment on the mental health and well-being of employees. We used the quantitative methodology to collect and analyze data. A sample of 108 participants from Iraqi internet service provider (ISPs) companies represented the purposive study sample. We targeted employees who experienced the COVID-19 pandemic. All data was collected through an electronic questionnaire (Google and Microsoft Forms). The research model was tested using structural equation modeling (SEM). The results showed a negative effect of the toxic workplace on the mental health of employees. T
... Show More
(3)
Most of the literature on the management and application terkzat waved the last period on large organizations was the negligence of knowledge management in small organizations where research aims to find out knowleddge management, small projects In oxygen Ahli plant in Iraq, and the fact the role of knowledge management in small projects from the standpoint of employees in order to achieve this used production method results. The results showed that knowledge management has a role in the high level of productivity during the years 2010-2013. The results showed that knowledge management has a role in the high level of productivity during the years 2
... Show More
Adolescence important and sensitive stage in social terms, being a stage where learns teenager bear social responsibilities and composition of their ideas about family life, as well as it is the stage where the teenager looking to himself for an important place in the community to become independent socially people, so it highlights the role of Social Work to do better effort and I believe him in order to prepare for the adolescent stage of adolescence and help him overcome the problems so that makes it adapts to the society in which he lives
Head nurses are vital in understanding and encouraging knowledge sharing among their followers. However, few empirical studies have highlighted their contribution to knowledge-sharing behaviour in Online Health Communities (OHCs). In addition, scant literature has examined the moderating role of knowledge self-efficacy in this regard.
This study examines the moderating role of self-efficacy between the association of four selected individual factors of head nurses (i.e., Trust, Reciprocity, Reputation, and Ability to Share) and their knowledge-sharing behaviour in OHCs in Jordan.
<
(7)
(7)
The aim of the present study was to demonstrate the possible role of statins on the inflammatory biomarkers in patients with periodontal disease (PD) This cross-sectional study involved 74 patients with PD and/or dyslipidemia divided into Group A: 34 patients with PD (nonstatins users); Group B: 40 patients with PD (statins users); and Group C: 30 healthy controls. Total cholesterol (TC), triglyceride (TG) and high-density lipoprotein, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and malondialdehyde (MDA) were measured . Blood pressure prolife and indices of PD were evaluated in each group. Statistical analysis was conducted by using SPSS version 20.0.
(10)
(8)
Researching performance audits according to the dimensions of financial sustainability in light of the scarcity of resources and economic and social transformations in the business environment is of utmost importance in the non-profit non-governmental organizations in achieving the goals and correct the path and address deviations, and help them in improving the outputs of processes and associated procedures and capacity The research was based on the hypothesis that the existence of a performance audit program in accordance with the dimensions of financial sustainability leads to the measurement of the commitment of the Olympic Committee. National Iraqi indicators of financial sustainability of the dimension of revenue in order to improv
... Show MoreThe agricultural activity has a great significance in the all four dimensions of sustainable development. Firstly, the economic dimension which it contributes with the GDP, as well as, it is considered as an important source to attract the investment. Secondly, the environmental dimension which also contributes with conserving of the biodiversity, combating the desertification, and increasing the farmlands. Thirdly, for its role in the social dimension to achieve the food security, to eradicate the poverty, and providing jobs. Fourthly, toward the institutional dimension as well it is considered as a source that allows all people to participate effectively, and to exchange of the local and universal experiences and perspectives. For conf
... Show More