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.
Wrong behavioral deviations among youth witnessed an obvious growing, some of these deviations are, robbery, drug and internet addiction, and smoking. Additionally, intellectual extremism and the disrespect of the traditions and genuine customs, In light of this issue, the research aims to shed light on the educational and preventative role of the woman in protecting and immunizing children from the wrong behavioral deviations. The woman has a significant and influential role in the society in general and in her family, in particular to the responsibility lies on her. The research shed light on the manifestations of behavioral deviation in children and the mechanisms of prevention and treatment. The research concluded with a set of recom
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Abstract
The aim of the research is to clarify the requirements of the qualification of the external auditor in Iraq and the extent of their impact on the quality of the professional performance of the audit process. The research was based on analyzing the results of the questionnaire prepared for the impact of qualifications on the quality of professional performance. The researcher has reached a number of conclusions, the most important of which is that a highly qualified and unethical auditor has a greater negative impact on the quality of professional performance than those with low qualifications. The most important recommendations of the research were the need to pay
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Increased the need to promote the profession of auditing, and improving the performance of the audit process, which comes through the effective implementation of its tasks, where the auditor collects the necessary data about the nature of client activity, and any other information it deems necessary to carry out the planning and development of the strategy for how to determine the procedures for implementing the audit process and the scope and timing for evidence clues in order to form an opinion technician neutral about the fairness of the financial statements, as required by the standards of the field work of the planning and supervision of the internal control and evidence to prove, but the failure of the auditor whether in th
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The objective of this study is to enable the role of modern and advanced computerized information systems. The model or mechanism should be developed by collecting the necessary information about the taxpayers and the sources of the taxpayers' income, on the basis of which the accuracy of the inventory process will be adopted. In addition to studies related to computerized information systems and showing their importance to the tax institution. To achieve the objectives of the study and to answer its questions, the researcher relied on collecting data and information on the subject on the literature and previous studies The secondary sources, which also formed the theoretical framework of the study, were obtained either as a practical fr
... Show MoreNew 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 Moreتشكل 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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The imperative of achieving financial stability has transcended national boundaries, necessitating heightened attention from both researchers and policymakers. Consequently, this article delves into an examination of the impact of government debt and public debt on financial development within the context of Iraq. The study employs monetary policy, interest rate, inflation, and population growth as control variables to prognosticate financial development. Utilizing data extracted from the World Development Indicators (WDI) spanning the period from 1995 to 2022, the study employs the dynamic autoregressive distributed lag (DARDL) approach to scrutinize the associations under investigation. The findings underscore a negative association betwe
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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 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