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.
Background: Diabetes mellitus is a common health problem of the world. Iron may be a part of the cause of the disease and its Complications
Objectives: This study was designed to determine the relationship between the levels of iron indices and diabetes mellitus type 2. Type 2
Type of the study: Cross –sectional study.
Methods: diabetes mellitus is clinical condition characterized by hyperglycemia due to the absolute or relative deficiency of insulin. It is also followed by pathological abnormalities like impaired insulin secretion, peripheral insulin resistance, and excessive hepatic glucose production. Although type 2 diabetes mellitus i
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The issue of the Circular Economy is not a new issue to several countries, especially the developed ones. Here in Iraq it is considered newly introduced, despite the few attempts to establish projects that concern recycling most of them were doomed to fail, due to two main reasons: the first one is the financial and administrative corruption widespread in all departments of the country, the second one is the priorities of public spending. It is well known that Iraq was subjected to two major attacks, the ISIS entry attack in 2014 to Iraq. ISIS occupied about a third of Iraqi lands which resulted in a collapse in oil prices, as Iraq depends almost entirely on oil revenues in its budget which is the second attack. This made the Iraqi governme
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The aim of the research is to identify the economic and cultural role of contemporary interactive artworks from the public's point of view, with knowledge of the most important obstacles and proposals to improve the level of design and spread of interactive artworks. The descriptive approach was used, and the researcher used a questionnaire tool that was distributed to the audience for the events of Noor Al Riyadh (2021) and the size of the participating sample was (194) individuals from all spectrums of society. It was found through the results of the existence of public approval of the economic role of contemporary interactive artworks, as they contribute to supporting the national economy. It attracts the public to attend various paid
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بعد ثورة تموز عام 1958في العراق, لم يكن يسمح للقطاع الخاص بأن تكون له استثمارات كبيرة في القطاعات الاقتصادية. وذلك بسبب الإيديولوجيات التي كانت تؤطر الفكر السياسي. حيث كان النهج الاشتراكي هو الغالب في إدارة الأنشطة الاقتصادية. إذ قامت الدولة بتأميم معظم الاستثمارات الخاصة الكبيرة ،لاس
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Gender has considered and become a new trend in women's studies, as it reflects the behaviors, roles and attitudes imposed by society on its members in accordance with their biological nature,with focusing on gender rather than on concentration on women, which is closely linked to the vision that concentrates on women's problems which are not primarily according to their biological differences But rather to a greater extent to social, cultural, historical and religious barriers and Obstacles.
Therefore, the qualitative division due to the concept of "gender" is not a rigid biological division, but is relied on the broad general context through which the social division of work is done. Thus, content in the pages of Facebook with high-
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The study aims to build a model that revolves around the main question of the role of strategic agility (SA) in enhancing organizational excellence (OE). For the purpose of achieving OE and to determine the extent of interest and knowledge of managers at the Midwest Refineries Company (MRC) on the theoretical and practical implications, and on the performance foundations of these two vital variables with the aim of continuous improvement. A questionnaire was used and distributed to a random sample of 54 managers in this important energy production company. The study followed the descriptive analytical approach to answer the questions raised. The study model and dimensions were built according to reference models, most notably the mo
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Abstract
Prescribing drugs to patients to treat ailments or reducing their morbidity may not be enough, even if the drugs were all indicated and in the right dose. Clinical pharmacists play a pivotal role in conducting information and instruction to patients and conveying feedback to treating physician when appropriate, and the final goal is in the interest of the patient. Identification and classification of drug related problems and discussing them with the health care providers. Prospective, interventional, clinical study for 180 hemodialysis patients, and was designed as two phases, an observational phase to identify drug related problems and classifying them according to the latest Pharmaceutical
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With the development of modern mass media and the prevalence of use continues to both researchers and practitioners their efforts to understand how the media affect Hzha on both the individual and the institutions, society and culture as a whole, which means that the need to develop models and theories explain and predict the effects of the use of such means, therefore, the study of modern technologies of communication and information as an area of research has become mature to establish the intellectual base cohesive, but they are not mature enough, which calls for more research developments therefore become social networking sites online, (Facebook, and YouTube, and straining) known today as the new social media, which is witness
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The electrical activity of the heart and the electrocardiogram (ECG) signal are fundamentally related. In the study that has been published, the ECG signal has been examined and used for a number of applications. The monitoring of heart rate and the analysis of heart rhythm patterns, the detection and diagnosis of cardiac diseases, the identification of emotional states, and the use of biometric identification methods are a few examples of applications in the field. Several various phases may be involved in the analysis of electrocardiogram (ECG) data, depending on the type of study being done. Preprocessing, feature extraction, feature selection, feature modification, and classification are frequently included in these stages. Ever
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