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.
Diabetes mellitus type 2 [DMT2] is a disturbance of metabolism and complex diseases influenced by environmental, genetic agents, and linked with inflammation, happens when the pancreas either does not use the insulin as it should or the body does not make enough insulin, lead to insulin resistance [IR] alongside with gradual loss of ß-cell secretory ability. The aim of this study was to investigate the role of soluble L-selectin (sL-selectin) in diabetes mellitus type 2 patients in Iraqi Arabs patient. Study includes seventy six Iraqi Arabs patients (male and female) having newly diagnosed type 2 diabetes mellitus (T2DM), with Fifty three Iraqi Arabs healthy subjects matched in age, sex and ethnic group. Patients and healthy subjec
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In globalization, the world became open area to competition for the attractive of investment, and the abilities of each country to win the confidence of investors depend upon the preparation to optimize circumstances. The competitiveness is an essential means of expanding the capacity of developed to coexist in an international environment characterized by globalization. While competition describes the market structure, the behavior of investors and business, competitiveness is interested in the evaluation of business performance or countries and compare them in the conditions of competition available in these markets. Regarding Malaysia, which is depend on FDI-Export- Led Growth strategy, it has taking on diffe
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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
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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
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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
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With the spread of globalization, the need for translators and scholars has grown, as translation is the only process that helps bridge linguistic gaps. Following the emergence of artificial intelligence (AI), a strong competitor has arisen to the translators, sweeping through all scientific and professional fields, including translation sector, with a set of tools that aid in the translation process. The current study aims to investigate the capability of AI tools in translating texts rich in cultural variety from one language to another, specifically focusing on English-Arabic translations, through qualitative analysis to uncover cultural elements in the target language and determine the ability of AI tools to preserve, lose, or alter the
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After 2003, Iraq witnessed new challenges represented by the predominance of sectarian discourses, hatred and extremism at the expense of moderate political discourse and the predominance of sub-affiliations and external agendas at the expense of national affiliation, which led to the creation of an unsafe or stable environment dominated by the character of violence and terrorism. Moderate discourse would work to fuse sub-affiliations into one melting pot in which it would be the first loyalty to the homeland and not to the tribe, party or sect... Etc., and this in turn will contribute to promoting peaceful coexistence between the various other sub-affiliations within the framework of one community construction
Because of the new political stage that Iraq is living in, which called on researchers to choose the subject of political marketing and increase its effectiveness through strategic intuition. The problem of research was reflected in the following question: How can strategic intuition be used to achieve efficiency in marketing marketing to achieve voter acceptance and achieve political success later on? ).
The research derives its importance from the fact that it is related to the developments in the concepts and areas of marketing in various fields, and it has a role in identifying the gain of new markets, where it is specialized to provide a political product and identify the mechanism of marketing the p
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Publications are generally considered an effective visual artistic means that addresses the recipient (the audience), with the functional, aesthetic and expressive dimensions they carry that contribute to spreading a diverse cultural awareness, especially those publications that are concerned with their media, promotional and organizational performance, as well as specific cultural events at specific times, in pursuit Access to renewable and elaborate designs to achieve the functional and aesthetic purpose, as the completed design and construction process is subject to many variations, whether this diversity is intellectual or technical, internal or external, and all of them may overlap to obtain a comprehensive system of artistic format
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