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.
Terrorism is a global phenomenon that engulfs most regions of the world to varying degrees. Media outlets are aware of the many incidents of violence and terrorism that have increased in recent times. The differences between the size of the phenomenon in different societies are the causes and severity of the phenomenon. On the role of local satellite channels in shaping the knowledge and trends of the Iraqi public towards the events of terrorism, in light of the assumptions of reliance on the media. The importance of this study is that it assesses the role of local satellite channels in the formation of knowledge and trends The study seeks to know the extent of exposure of the Iraqi public to local satellite channels, and to reveal the e
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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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BACKGROUND: Acute coronary syndrome (ACS) is the clinical manifestation of acutely diminished coronary arterial blood supply. The rate of increase of intraventricular pressure during isovolumetric contraction (left ventricular dP/dt) represents the rate of change of pressure during ejection. OBJECTIVE: The aim of this study is to evaluate the usefulness of the rate of increase of intraventricular pressure during isovolumetric contraction (dP/dt) in assessment of left ventricular function in patients with acute coronary syndrome and its relation to certain clinical and echocardiographic features. PATIENTS AND METHODS: The study is a cross sectional study including 50 patients with an established diagnosis of acute coronary syndrome. The
... Show MoreThis study aimed to provide a conceptual model for the use and benefits of the e-Government as related to administrative fraud and financial corruption. The study also looked into their concepts, forms, dimensions and types and the role of e-Government on fraud reduction, corruption in administration and finance and its impact on the government performance. From the result, it is revealed that there is need for electronic government for implementation in order to curb the rate of fraud and administrative and financial corruption and improve the quality of service provision for better performance
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Represents a supervisory and oversight role of the Central Bank towards finding a sober banking sector, as the procedures , regulations and laws that the Central Bank insists on its implementation with the utmost precision, and that was to protect depositors and shareholders' class basis rights, but it is in the interest of the bank in the end, as it seeks to improve the performance of commercial banks and vaccinated against falling into the blunders, they also contribute to building a sober and stable banking sector and security contributes to the welfare and employment optimization of economic resources, and treatment of research (and the presence of banks decline in financial performance, according to financial performance indic
... Show MoreIntroduction: In recent decades, the endovascular treatment of cerebral arteriovenous malformations (AVMs) has advanced. However, it still carries risks of unanticipated complications. Coil migration is a reported complication of aneurysmal coiling procedures. Herein, we report a case of early intraprocedural coil migration during pressure cooker technique embolization of right thalamic AVM, discussing the management and potential explanations. The literature showed no report of coil migration after the pressure cooker technique in the form of coil-augmented Onyx injection technique (CAIT). Case description: An otherwise healthy 26-year-old female suddenly developed a severe headache with no loss of consciousness. Computed tomograp
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لقد تسبب انتشار الإرهاب في العالم وكذلك الحروب الأهلية والصراعات في أوائل القرن الحادي والعشرين في جميع أنحاء العالم في الكثير من الأضرار وخلفت ضحايا جسيمة. أدت الهجمات الإرهابية على النساء، مثل اختطاف بوكو حرام لأكثر من 270 تلميذة في نيجيريا وتقارير عن انتشار الاغتصاب والاعتداء الجنسي في المناطق التي مزقتها الحرب، إلى إنتاج العديد من العروض المسرحية في الولايات المتحدة التي تصور خواص الجناة وكذلك الضحا
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