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.
Banks are considered the main basis of financial sector ,so they must be submitted to sound and strict regulatory system and so as to ensure their operations and according to instructions and regulations , in order to maintain the integrity of the banking sector and financial sector in general .One of the importance regulatory tools that are adopted by the Iraqi Central Bank to control over the banks an financial and periodic statements that are provided by the banks in accordance with planned schedules .The financial statements of the banks must reflect clearly and accurately financial situation and the result of their activities during the period in which they represent to achiveing its purposes.So it has the goal of Search is statemen
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Background A prospective clinical study was
performed to compare the efficacy of the use of lowmolecular-
weight heparin group (enoxparin group)
with control group in the prevention of deep-vein
thrombosis after total knee arthroplasty.
Aim of the study: to assess the prevalence of DVT
after total knee arthroplasty and evaluate the
importance of the use of low molecular weight
heparin in the prevention of this DVT.
Methods Thirty-three patients undergoing total
knee arthroplasty were randomly divided into two
groups. One group consisted of 12 patients who
received no prophylaxis with an anticoagulant (the
control group), other group consisted of 21 patients
who received the low-molecular-weight h
Abstract As the United Nations approaches its 70th anniversary, the world is going through the most severe accumulation of serious international security failures in recent memory, challenging the UN Security Council’s ability to address them effectively. Over the past four years, crises in Libya, Syria and Ukraine have precipitated a worrisome erosion of great power relations that has complicated Security Council decision making on a number of trouble spots. Its inability to devise consensus responses to the escalating civil war in Syria has been particularly troubling, resulting in the regional spill over into Iraq and the emergence of Islamic State as a new threat to peace in the region and beyond. Meanwhile, the UN’s often under
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The present study aims to illuminate the assessment of the Turkish elite of the role of the Turkish media in forming the attitudes of public opinion vis a vis the attempted military coup of 15 July 2016. The authors utilized the survey method of a nominal sample of 315 individuals, equally distributed among the three foremost categories of the Turkish elite, namely: the political academic, and media elite. The foremost findings of the study are that the orientation of the coverage of the Turkish media of the events of the attempt military coup of 15 July, based on the perception and assessment of the Turkish elite, was positive to a high degree; it refuted the news and the inciting information given to foreign media revealed the bloodine
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Cutaneous leishmaniasis (CL) is a widespread, yet often overlooked, parasitic disease caused by the Leishmania protozoan, which is prevalent in numerous countries, including Iraq. This condition is marked by the appearance of skin lesions on various exposed areas of the body. In most old-world regions, sodium stibogluconate (SSG) is the classical widely used drug to treat CL. The progression of skin ulceration is controlled by different inflammatory modulators including cytokines and enzymes. In this study, the possible role of the enzyme Matrix metalloproteinase9 (MMP-9) and its inhibitor Metallopeptidase inhibitor-1 (TIMP-1) as immunological markers was evaluated in CL patients suffering from cutaneous leishmaniasis before and aft
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The importance of the study lies in highlighting the role of smartwatches as a modern tool for analyzing training load based on functional indicators, such as heart rate and calorie consumption. This allows coaches to monitor individual players’ responses during different training periods, helping to improve physical performance efficiency and reduce the risk of overload-induced fatigue. The study aimed to analyze calorie consumption at different heart rate levels between the special preparation and competition periods for youth football players, with the goal of determining the effect of physiological adaptation on energy efficiency. To achieve this objective, the researcher adopted the descriptive method due to its suitability f
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Background: During Ramadan, Muslims fast throughout daylight hours. There is a direct link between fasting and increasing incidence of infections. Antibiotic usage for treatment of infections should be based on accurate diagnosis, with the correct dose and dosing regimen for the shortest period to avoid bacterial resistance. This study aimed to evaluate the practices of physicians in prescribing suitable antibiotics for fasting patients and the compliance of the patients in using such antibiotics at regular intervals. Materials and methods: An observational study was carried out during the middle 10 days of Ramadan 2014 in two pharmacies at Baghdad. A total of 34 prescriptions (Rx) for adults who suffered from infections were examined. For
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The main source of water supply in Iraq is the surface water, especially Tigris and Euphrates Rivers and their tributaries. In the recent years there was a great drop in the water levels of Tigris River within Baghdad City which had affected the operation of twelve water supply projects located on the banks of Tigris River in Baghdad City, due to significant climate changes, and the expansion of hydraulic construction (dams) and implementation of new irrigation projects in Turkey, these factors have greatly reduced the water flowrates of river by about 46%. In the present study the flow characteristics of Tigris River within Baghdad City was studied, the reach involved was about 49km in which it represents the urban zone
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This work aims to provide a statistical analysis of metal removal during the Magnetic Abrasive Finishing process (MAF) and find out the mathematical model which describes the relationship between the process parameters and metal removal, also estimate the impact of the parameters on metal removal. In this study, the single point incremental forming was used to form the truncated cone made of low carbon steel (1008-AISI) based on the Z-level tool path. Then the finishing was accomplished using a magnetic abrasive process based on the Box-Behnken design of the experiment using Minitab 17 software was used to finish the surface of the formed truncated cone. The influences of different parameters (feed rate, machining step s
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