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:The effects of contraception on Trichomonas vaginalis have important implications for women who suffer from infections associated with disruptions in the vaginal ecology, such as bacterial vaginitis and urinary tract infections.
Objective: To find the association of the common types of contraceptions with the Trichomonasvaginalis infection in women admitted to the Al-BatoolTeaching Hospital for Maternity and Children in Baqubah city.
Type of study: Cross-sectional study
Methods: This study consist of 75 women with contraception use and71 apparently healthy non contraception user women admitted to outpatient in Al
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Since June 2020, an explosion in number of new COVID-19 patients has been reported in Iraq with a steady increment in new daily reported cases over the next 3 months. The limited number of PCR kits in the country and the increment in the number of new COVID-19 cases makes the role of CT scan examinations rising and becoming essential in aiding the health institutions in diagnosing and isolating infected patients and those in close contacts. This study will review the spectrum of CT pulmonary changes due to COVID-19 infection and estimate the CT severity score index and its relation to age, sex, and PCR test results
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The adsorption process of 5-Fluorouracil (5FU) drugs on Aluminum nitride nanotubes surface (AlNNTs) have been evaluated through density functional theory (DFT). The DFT results show that the interaction of AlNNTs with the F atoms of 5FU drugs is strong due to the fact that the amount of adsorption energy was about − 29.65 kcal.mol−1. Conversely, the interaction of the 5FU through O atoms with the AlNNTs was weaker due to the lower value of adsorption energy. Also, based on the values of Gibbs free energy, the 5FU adsorption on the surfaces of AlNNTs was spontaneous. In addition, based on natural bond orbital (NBO) analysis, the direction of charge transfer was from fluorine’s σ orbitals of the drug to nitrogen’s and aluminum’s n*
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Checkpoint inhibitors are a type of immune therapy used to treat different types of cancers. These drugs block different checkpoint proteins, for example, CTLA-4, PD-1, and PD-L1 inhibitors.
They block proteins that stop the immune system from attacking the cancer cells. Checkpoints are also described as a type of monoclonal antibody that antagonizes binding between B7 to CTLA-4 and PD-L1 to PD-1.
Immune checkpoint inhibitors are used to treat BARCA mutated triple-negative breast cancer (TNBCS) in patients who do not respond to chemotherapy, and also in the treatment of highly mutated and solid tumors such as brain tumors, liver, and pancreatic cancers.
Immune checkpoint inhibitors exhibit an effect on solid tumo
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The Experiment was carried out to determine the level vibration transfer in three axes Horizontal X, Lateral Y and Vertical Z direction to seat driver tractor, Vector sum of vibration and Daily Vibration Exposure (8 hours) in seat driver tractor, and vibration in steering wheel tractor, Heart Rate, Systolic and Diastolic blood pressure and temperature were measure to all Drivers before and after used Chisel plow in operation tillage. Statistical analysis system was used, Split-Split Plot Design under Randomized Complete Block Design, Three factors were used in this experiment included Two types of Soil Moist and Dry soil which represented main plot, Three Velocity Tractor was second factor included 1.6,3.5 and 5.4 km/hr and Three Drivers Tr
... Show MoreEconomic analysis plays a pivotal role in managerial decision-making processes. This analysis is predicated on deeply understanding economic forces and market factors influencing corporate strategies and decisions. This paper delves into the role of economic data analysis in managing small and medium-sized enterprises (SMEs) to make strategic decisions and enhance performance. The study underscores the significance of this approach and its impact on corporate outcomes. The research analyzes annual reports from three companies: Al-Mahfaza for Mobile and Internet Financial Payment and Settlement Services Company Limited, Al-Arab for Electronic Payment Company, and Iraq Electronic Gateway for Financial Services Company. The paper concl
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Marketing Intelligence is one of the important methods of collecting information about competitors ' products and changes in customers ' tastes and needs that contribute to determining the policies to be followed in product development.
The problem of research, which seeks to be answered by the extent to which the companies in question have the appropriate and effective mechanisms to develop their products, and the nature of the relationship between the components of marketing intelligence and new product development policies. The importance of research is determined by the importance of obtaining important and necessary information to make the appropriate decision on the development of the new product an
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A cross-sectional study was conducted on 80 type 2 diabetic patients aged 20-60 years in Baghdad and 20 non diabetic persons as controls. Laboratory assessment of glucose related parameters; Fasting blood sugar (FBS), Glycated hemoglobin (HbA1c), Insulin and Insulin resistance (IR), renal function test; Blood urea, serum creatinine, Calcium (Ca) and Phosphorus (P), Calcium regulating hormones; Parathyroid hormone (PTH), calcitonin and vitamin D, cytokines, Adiponectin and Tumor necrosis factor (TNF-α) and comparison these parameters between patients and controls. The results: a high significant (p˂0.01) increase in FBG level in the patients (211.34 ± 11.20 mg/dl) as compared with control (85.89 ± 3.07 mg/dl). A high significant (p˂0.01
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