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.
Abstract:
The tax is one of the elements of the general revenues of the state and contributes to covering its expenses. Taxes are imposed in most countries of the world. The tax proceeds depend on a set of factors that contribute either positively or negatively to the tax share by increasing or decreasing it. Therefore, the research aims to demonstrate the role of the tax examiner's procedures in achieving the validity of the taxable base and its reflection on the tax proceeds, as well as reviewing the tax examiner's procedures related to the tax return process. Examination and tax audit of the financial statements, as well as presenting the financial statements to an independent and i
... Show MoreObjective: This study aimed to evaluate the effectiveness of the Benson Relaxation Technique (BRT) in reducing pain during femoral artery sheath removal after percutaneous coronary intervention (PCI). Methods and Materials: A randomized controlled trial was conducted at three cardiac centers in Iraq. A total of 58 patients undergoing therapeutic PCI were randomly assigned into two groups: intervention (n=27) and control (n=31). The intervention group received BRT for 10 minutes before and after sheath removal. Pain was assessed using the Visual Analogue Scale (VAS) immediately after the procedure. Demographic data and clinical variables were collected. Data were analyzed using SPSS v26 and non-parametric tests (Mann-Whitney U, Krus
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في البداية اود الاشارة الى ان فهم حقيقة الازمة هو ذو جانب فني يتعلق بالجينات الوراثية لنظام يملك في احيناته قدرة عالية على تفريخ المشتقات. هذا النظام الذي يزداد عقما وتدميرا يزداد قدرة على خلق النقود الائتمانية/المشتقات، وكلما اقتربنا اكثر من فهم هذا الجانب كلما اسقطت في ايدينا تلك التوصيفات الاكاديمية الجاهزة في نقص الرقابة والاشراف، تركيز المخاطر،....الخ التي تناولتها الكتابات الشائعة في معظم طروحات
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Abstract
This study was to demonstrate the role-use planning scientific methods is disabled and little used in the planning and follow-up construction of vital projects in the province of Baghdad, including network planning methods, in order to find the optimal time to finish the project in light of the resources available and the budget set for it, in the current research has been used the most prominent network planning methods and two stylistic (CPM / PERT), was the application of the critical path method on standard-design school project (traditional) to draw Action Network according to confirmed times for the activities of the project and account his Crashing time , It was Pert technique applied to the project hemato
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Community pharmacists faced more complex challenges in meeting patients’ medication needs during the pandemic than previously reported in the literature. Objectives To explore the perception and abilities of community pharmacists in managing patients’ needs in terms of medication dispensing during the pandemic, and to examine its effect on improving the patients’ situations. Materials and Methods A cross-sectional study design, validated by 30 experts, was conducted using an electronic survey (Google Form) to assess the effect of the dispensing practice of Iraqi community pharmacists on the patient’s clinical outcomes during the pandemic. The survey was distributed on professional pharmacist’s social media platforms from December
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Background: Study looking into cardiovascular disorders (CVD) medicines or analgesics cost-saving activities during dispensing process is lacking.
Aim: To determine differences in factors and costs associated with refused CVD medicines or analgesics during dispensing process
Method: This study was approved by Medical Research and Ethics Committee (MREC) (Registration number: NMRR-20-177-53153(IIR)). Participants receiving CVD medicines or analgesics during dispensing process were recruited via convenience sampling technique between February and March 2020 at the Specialist Pharmacy Department of Jerantut Hospital, Malaysia. Refusal to medications and its reasons were asked based on the questionnaire developed by the resea
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The study titled “The role of the social media sites of Iraqi satellite channels in prioritizing the public” is a field study for the public of Dhi Qar.
The emergence of the social networking sites we are currently experiencing has undergone radical and important changes in the role of the mass media in light of the growth and rapid spread of modern technologies Or the so-called new media، which led the media organizations to create satellite channels on the social networks، which led to bypass the traditional lines between the public and media institutions with the public gain the possibility of The purpose of the research is to determine the habits and patterns of public use of the social media sites of the Iraqi satellite cha
Background: Lung cancer is a common disease for patients over the age of 50 years, especially males due to smoking habits. This study aimed to compare the modulation complexity score (MCS) for the advanced treatment planning techniques which the intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Materials and Methods: Thirty patients who had non-small lung cancerous tumors on their left side participated in this study. The range ages were 68 to 98 years, the heights were between 151 and 182cm and they having weights from 46 to 79 kg. For Each patient will create two plans dial using two different techniques, which will be Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy
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The success of any institution must be based on means to protect its resources and assets from the waste, loss, misuse and the availability of accurate and reliable data by accounting reports to increase its operational efficiency, namely, that the internal control system is considered as a safety valve for top management in any economic unit. The problem is represented by the need for an efficient system, so to ensure its success, there must exist external parties which monitor and evaluate the performance because of its importance by following clear criteria. So, the research problem came to address performance evaluation indicators which are set by the Federal Board of Supreme Audit (FBSA) and identify the extent of its contribution t
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