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.
The unresolved COVID‐19 pandemic considerably impacts the health services in Iraq and worldwide. Consecutive waves of mutated virus increased virus spread and further constrained health systems. Although molecular identification of the virus by polymerase chain reaction is the only recommended method in diagnosing COVID‐19 infection, radiological, biochemical, and hematological studies are substantially important in risk stratification, patient follow‐up, and outcome prediction.
This narrative review summarized the hematological changes including the blood indices, coagulative indicator
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The role of the climate in the development of the performance of the administrative bodies of sports clubs
Amino and fatty acids in the liver tissue of Uromastyx aegyptius microlepis during the periods of hibernation (December) and activity (May) were estimate by a high performance liquid chromatography, liver of a lizard during the activity and hibernation seasons, contained 18 amino acids, which include, 10 essential amino acids and 8 non-essential amino acids, and the liver in the male lizard contained five fatty acids during each season, the concentration rates of all the amino acids during the activity season were higher than their counterparts during the hibernation season, the total concentrations of essential and non-essential amino acids during the activity season were 19434.8 µg/ml, which was greater than the total concentrations leve
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Dust storms are typical in arid and semi-arid regions such as the Middle East; the frequency and severity of dust storms have grown dramatically in Iraq in recent years. This paper identifies the dust storm sources in Iraq using remotely sensed data from Meteosat-spinning enhanced visible and infrared imager (SEVIRI) bands. Extracted combined satellite images and simulated frontal dust storm trajectories, using the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model, are used to identify the most influential sources in the Middle East and Iraq. Out of 132 dust storms in Iraq during 2020–2023, the most frequent occurred in the spring and summer. A dust source frequency percentage map (DSFPM) is generated using ArcGIS so
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this study was perform to defined the effect of fungus Metarhiziumanisopliae Sorokin with concentrations 5x101, 5x103 and 5x105 spore/ ml and Actelic insecticide with concentration 0.001% in in rate of germinate treated string bean seeds also study effect of packed bags in two different type: jute and polypropylene bags which treated with fungal suspension pervious mention and insecticide in rate infested the string bean seeds packed in it.Results of the study showed the following: Lower rate of weight loss of cowpea seeds appear in poly propylene bags 4.41, 5.95% after six months of treatment with 5x 105 spore/ ml and Actelic insecticide respectively compared with 15.08% to control treatment. The fungal concentrations and insecticide not
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Background: EBV infection in tissue micro-environment is challenged by the precisely regulated survivaland apoptosis mechanisms. Abnormal bcl-2 proto-oncogene expression in colonic carcinomas allowsaccumulation and propagation of these genetically altered cells.Objective: To analyze the relevant concordance of BCL-2 gene , EBNA1 s and LMP-1-EBV expression inissues from a group of Iraqi patients with colonic adenocarcinomas.Patients and Methods: One hundred (100) tissue biopsies, belonged to (40) patients with colorectalcancers, (40) patients with benign colon tumors, and (20) apparently normal colorectal control tissues,were enrolled in this study. The detection of EBNA1 s and LMP-1-EBV as well as BCL-2 was done byimmunohistochemist
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The region is defined by the spatial dimension, which consists of a set of stabilizers (towns and villages). The concept of the territory requires conditions on the nature of functional relations and the mutual influence of the regions within the region. Any territory must be based on the interdependence and interaction between the mother city and its surrounding countryside and cities, and when the interdependence is strong and the interaction is clear, it helps to define the territory. The regions are divided on different bases. There are geographically or national homogeneous regions, and there are cultural regions that want to preserve their culture in terms of language or religion. There are administrative regions to manage
... Show MoreThe research aims to show the effect of some short-term debt instruments (central treasury transfers, cash credit granted to the government by commercial banks) on the production of the wheat crop in Iraq, through its effect on money supply during the period (1990-2018), As the study includes two models according to the statistical program (Eviews9), the first model included measuring the effect of short-term debt instruments on money supply, and the second measuring the extent of the money supply's impact on Wheat crop production, as the results of the standard analysis showed that the short-term debt instruments used in the model were Significant effect on wheat crop production indirectly through its effect on money supply, As
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