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 aim of the current study was to investigate the impact of workplace stress on employee engagement within Iraqi universities through the mediator role of leadership style. Work-related stress and non-work-related stress were identified as representing workplace stress. Employee engagement has been measured through three types: social engagement, affective engagement, and intellectual engagement. Two types of leadership styles have been tested: directive and participative leadership. the structural equation Modeling was used to test the study model. A sample of 245 employees in Iraqi universities, including university professors, was targeted. Only 214 respondents participated in the survey. The results showed that non-work-relate
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This research is aiming to find the effective role of the personality characteristics of the Leader in business organization entrepreneurship by studying the effect of the special dimensions of personality characteristics (neuroticism, extraversion, openness, Agreeableness, and conscientiousness) on business organizations entrepreneurship dimensions representing in the two main dimensions (entrepreneurship direction and strategic entrepreneurship) across field study was conducted in thirteen private colleges in Baghdad.
The problem of the research relies in asking the question, is there an effect for Leader personality characteristics on business organizations entrepreneurship. and statistical methods hav
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A polycrystalline CdTe film has been prepared by thermal evaporation technique on glass substrate at substrate temperature 423 K with 1.0 m thicknesses. The film was heated at various annealing temperature under vacuum (Ta =473, 523 and K). Some of physical properties of prepared films such as structural and optical properties were investigated. The patterns of X-ray diffraction analysis showed that the structure of CdTe powder and all films were polycrystalline and consist of a mixture of cubic and hexagonal phases and preferred orientation at (111) direction.
The optical measurements showed that un annealed and annealed CdTe films had direct energy gap (Eg). The Eg increased with increasing Ta. The refractive index and the real p
الزكاة فريضة من فرائض الإسلام وعبادة من العبادات التي اقرها الشرع الإسلامي هذه الفريضة المالية التعبدية بالإضافة الى دورها المعنوي الذي يهدف الى إرساء قواعد العدالة الاجتماعية والقضاء على مشكلة الفقر في المجتمع الاسلامي وكما ينص عليها الدين الإسلامي فان لها ابعادها ووظائفها الكثيرة التي تخدم اليات العمل الاقتصادي في مجتمع يعمل وفق نظام اقتصادي أسلامي .
ان انفاق الاموال المتحصلة من فريض
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Many countries are very important in their interest not only in diversifying foreign reserves, but in determining and planning their volume in accordance with the goals set, namely facing potential external shocks, as the research aims to determine the extent of the strength of foreign reserves in the possession of the Central Bank in relation to every influential variable in the Iraqi economy. , in order to determine the minimum level of reserves that requires reconsideration of the exchange rate, as the research adopted the inductive analytical method in analyzing real (Quantitative data) for the research variables in the years of study, as the research adopted a set of analytical indicators approved by the International Moneta
... Show MoreThe research aims at a statement Internal Debt options during shocks and the impact of this borrowing in the volume of the foreign reserve, using induction and deduction with available data analysis. During the period (2004-2013) did not require the use of borrowing across (financial institutions, discounted transfers, bonds); it was only sufficient by transfer with commercial banks that can finance of temporary budget deficits: rose and decline of volume of foreign reserve according to the changes of oil prices and the volume of purchases and sales of the Central Bank of Iraq. Central Bank of Iraq (CBI) has significantly contributed to Internal Debt through bond and discounted transfers in the secondary market; thus, funding the
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This paper depends on sheding some litgt on the characteristics of political
relations between the arab and the Persian during the reign of sassane kings.
"Ardashir the first, shahbour the first, shahbour the second, Bahram the fifth; kisra
Anushrwan and kisrah abruis"
And who rulled the Persian before the Islamic conquest and were adopted in this studym
as a model. It was possible to get some information from invaluable refereces in order to
arrive at a clear image as regards the nature of these relations. These relations were
differently political according to the circumstances of ruling, interests and the personality
of those kings.
This study concluded detection of Toxoplasma gondii in milk, immunologically by using Elisa and nested PCR)nPCR (based on B1 gene, also to investigate the effect of toxoplasmosis, parity, breed and flock on some milk composition in the Iraqi local and Shami goats in the middle of Iraq. A total of 80 milk samples of the lactating goats were collected. Results of this study showed the prevalence of Toxoplasmosis was 21.25% and 28.75% by Elisa and nPCR respectively without significant differences. The sensitivity of Elisa was a low (30.43%) whereas the specificity was a high (82.45%). The degree of agreement estimated by Kappa coefficient revealed a slight agreement (0.14) between two methods. The results indicated that goats infected
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The basis of the personality of each individual lies in the early years of his or her life. If the personality of the child has been well organized and if the motives have been fully expressed and effectively directed, the child will have a strong will, happy self-confidence and a strong personality. If there is a failure In the early years, the individual will be unable to meet his responsibilities in life and may be the victim of many psychological disorders. The family is a learning process through which children acquire the customs, traditions, attitudes and values prevailing in their social environment. (Pre-and-after) play and its relationship to parenting methods of (democratic-bullying-overprotection- and neglect), which wi
... Show MoreBackground: One common undesirable side effect of orthodontic treatment with fixed appliances is the development of incipient caries lesions around brackets, particularly in patients with poor oral hygiene. Different methods have been used to prevent demineralization; the recent effort to improve the resistance against the demineralization is by the application of lasers. Materials and method: Thirty human premolars extracted for orthodontic purposes were used to test the effect of two energy level of ER-YAG laser on enamel resistance to demineralization. The brackets were bonded on the teeth and all the labial surface excluding 2 mm area gingival to the brackets were painted with acid resistance varnish. Three groups were generated. The fi
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