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.
Interleukins (IL-2 and IL-4) are increased in asthmatics and were reported to induce resistance to steroid therapy in some patients who fail to get benefit from glucocorticoids when used in full dose and for long period of time. In this context, the present study was conducted on Iraqi patients to provide additional laboratory mean, beside the clinical diagnosis, for the decision whether the asthma is steroid sensitive or resistant by monitoring the level of immunoglobulins, complement proteins and interleukins among asthmatic patients (steroid sensitive or resistant) and the possible contribution of other factors like age, sex and environments in the development of steroid resistance. A total number of 55 asthmatics and 28 normal subjec
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Was conducted neutralize content Albulamedi for local isolates using Alacardan dye orange selection experience showed loss of local isolates resistant life antibiotic ampicillin, chloramphenicol
يهدف البحث إلى تشخيص أوجه القصور ونقاط الضعف في تطبيق أبعاد جودة الحياة الوظيفية ومدى تأثيرها على اتجاهات وسلوكيات الموظفين، وبالتالي علاقتها بتعزيز مقدراتهم الجوهرية. وتنبع القيمة العلمية للبحث من إبراز أهمية أبعاد جودة حياة العمل في تحسين الكفاءة الإنتاجية للعاملين في القطاع العام ورفع مستوى الأداء التنظيمي. ولأن جودة الحياة العملية تلعب دوراً مهماً في تعزيز المقدرات الأساسية للموظفين في القطاع الع
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The primitive streak and notochord and previously the anterior marginal crescent (AMC), anterior visceral endoderm (AVE) and the anterior hypoblast (AHB) are embryonic entities which identify main body axes and thus establish body plan in the early stages of embryonic development. All of the anterior pre-gastrulation differentiation structures are addressed terminology as anterior pre-gastrulation differentiation (APD). These structures are defined morphologically and are called in mouse (AVE), in rabbit (AMC) and in the pig (AHB). The anterior hypoblast cells of APD are higher and denser than at the opposite pole of the embryo. Moreover, the APD stretches variously between species and has different shapes in the mammalian embryos, for exam
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A field study aimed at identifying the degree of satisfaction of secondary school principals with regard to the role of universities and their obstacles in developing their administrative skills. It adopted the descriptive analytical approach. The research community consisted of (249) male and female principals in the schools of Baghdad (Al-Rusafa and Karkh), and the research sample was chosen by the simple random stratified method at a percentage of (40%) of the research community, and the number of the sample was (100) male and female principals. A questionnaire consisting of (40) items distributed between two domains was developed. Its validity and reliability were confirmed. The researcher used the (SPS
... Show MoreThe influence of culture on accounting systems and practices, including financial reports and accounting information through the values identified by Gray and derived from social-cultural values, and the four accounting values were derived from generally accepted accounting principles represented by (Conservatism, Uniformity, Secrecy, and Professionalism). Important and significant in maximizing financial performance, and measuring the extent of the role of these values in improving financial performance through attention to the values of accounting culture, this research
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The research sought to demonstrate the effectiveness of monetary policy in banking stability by measuring the impact of monetary policy in the composite index of banking stability in Iraq for the period 2010/2017, as the stability of the financial system is one of the main objectives that the Central Bank is keen to achieve along with other objectives to ensure the performance Effective for all economic units, this is what prompted the central banks to give more attention in ensuring the safety, durability and stability of their financial systems, and the increasing interest by the Central Bank of Iraq in the subject of financial stability stems from its responsibility in ensuring a sound and stable financial system. Maintain it and mini
... Show MoreThe objective of this research is to develop a method for applying financial derivatives in the local environment to reduce the risk of foreign exchange rate fluctuations to enhance quality of accounting profits through Financial reporting to local units In accordance with international financial reporting standards, To accomplish this objective was selected a sample of Iraqi units exposed to the risk of fluctuations in foreign currency rates, As the research found:
- many companies and banks in the local environment a lot of losses due to fluctuations in foreign currency exchange rates.
- that financial derivatives in the Iraqi environment represent
The developing countries, like our country Iraq suffer from deep comprehensive structural crisis, manifestations and a clear imbalance between the demand and the supply sides. The overall imbalance in the external balance. As a consequence, this caused the accumulation of foreign debts or failure in the implementation of economic development programs. The countries which are forced to resort to the International Monitoring Funds, and the World Bank for assistance and to express an opinion on policies that include restrictions controls that belong to the monetary, and fiscal side group, imposed on the economies crisis, as a condition for returning to normal which called reform programs. The organize of the events of radical changes in the
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