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.
Toxoplasmosis is an infection caused by Toxoplasma gondii that leads to abortion or hydrocephalus during pregnancy.One hundered and twenty two aborted women were selected for this study. Serum samples were collected form Al-Kadhmia and Kamal Al-Samari Hospitals,and laboratories around Baghdad, and tested for specific IgG and IgM anti-toxoplasma antibodies to confirm toxoplasmosis in those women by using ELISA test.The result recorded that 51(41.8%) women had antibodies against Toxoplasma gondii, 25(59.5%) women were positive for IgG, and 17(40.5%) women were positive forIgM, while 9(17.6%)women were positive for both.
تشكل التغيرات الحاصلة في اسعار النفط تحديا" حقيقيا" لاستمرار عملية النمو في العراق, وامام الحكومة فرصة كبيرة لإيجاد حلول ناجعة لمشكلة تزايد عجز الموازنة العامة من خلال اللجوء الى اصدار ادوات الدين العام الداخلي والخارجي, وهذا يتطلب بناء استراتيجية لإقامة وتطوير سوق السندات الحكومية في العراق, لتتمكن الحكومة من خلاله توفير مصادر تمويل اضافية, تسهم في تمويل الانفاق الاستثماري الحكومي ودعم النمو ودعم
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New developments imposed different patterns of interactions between major international powers and Iran during 2018, ranging to varying degrees between cooperation and tension, the most important of which is the new measures taken by the United States to withdraw from the nuclear agreement and impose new US sanctions on Iran, which in turn insisted on not responding to pressure to which they are exposed to make changes in their policies and to negotiate again about the main contentious files, especially the nuclear program and ballistic missiles, and the roles they play for crisis countries, especially supporting some armed organizations in Syria, Lebanon, Iraq and Yemen. These differences have put the international forces before difficult
... Show MoreThe compliance is considered
This study aimed to deduce the net atrioventricular compliance which is affected the trans mitral blood flow.
This study focuses on study group of 25 patients (15 males
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This study is concerned with the comparison of the results of some tests of passing and dribbling of the basketball of tow different years between teams of chosen young players in Baghdad. Calculative methods were used namely (Arithmetic mean, Value digression and T.test for incompatible specimens). After careful calculative treatments, it has been that there were abstract or no abstract differences in the find results of chestpass, highdribble and cross-over dribble. The clubs were: (Al-Khark, Air defence, Police and Al-Adamiyah) each one separate from the other for the year (2000-2001). After all that many findings were reached such as the lack of objective valuation (periodical tests) between one sport season and the other. In the light
... Show MoreWhen the Italian fascist party leaded & access to the top of regime, it took Benito
Mussolini as a post of Italian prime minister on 1922, that lead to rise the voices which need
to find colonies of Italy, like other colonial countries, especially that of its colonies in Libya,
Eritrea and Somalia were not achieved its ambitions, was to be the occupation of Ethiopia to
revive her dreams to exert control over the Red sea and the Mediterranean and the
establishment of a vast empire satisfy colonial ambitions.
the Italian invasion of Ethiopia gained particularly important, what led to the
disruption of the balance of political forces is not at the level of local powers in the region,
but at the level of the exten
شهدت العالم منذ نهايات القرن الماضي وبدايات القرن الواحد والعشرين تطورات دراماتيكية على صعيد الادبيات التنموية ، اذ تحولت التنمية من المفهوم التقليدي الذي اهتم بالنمو الاقتصادي الى رؤية جديدة هي رؤية التنمية البشرية ومن ثم الى التنمية المستدامة التي اعطت للتنمية البعد الانساني وجعلت من مشكلات واحتياجات البشر منطلق لها لتحويل الفرد والمجتمع الى مرحلة جديدة تضمن له العيش الكريم وتحقق معه
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Described the Arabic language being of genius sets by top models of eloquence , rhetoric and clarity of sounds and developments Moreover , it is an important element of our existence and our identity and our survival . That my methods and best in teaching Arabic language what has pursued the easiest ways to learning and teaching and helped learners to be aware of the function linguistic information , and they need it and its impact on their lives , and contributed to unleashing the potential of activism and led them to make the effort to apply them in the form of examples and uses of new life , as well as fits are the capabilities and tendencies of different learners , so the goal of current research into the importance of the curriculum
... Show MoreEndometriosis is an estrogen dependent inflammatory disorder plays a pivotal role in the reproductive system of the females which regarded as one of the most important gynecological disorders due to it is a key cause of infertility for women and also it has a remarkable impact on the women's life quality. Indeed, environmental pollution have an extremely importance in the etiology of endometriosis. Hence, the present article submits an abbreviated literature review to the biochemical role of environmental pollutants in the etiology and development of endometriosis. Anyway, this review article represented the major environmental pollutants: the organic pollutants of air, heavy metals, gaseous pollutants and the particulate matter. Th
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