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.
|
Social networking sites have become very popular since the beginning of the current decade and have become linked to our daily life. We follow the news, Analyses and opinions on the one issue in a way that attracts millions of users and the number grows every secon On Twitter, one of the most important social networking sites, all social groups rushed from the president to the last citizen to open accounts when they found themselves forced to do so . During the recent Gulf crisis, Twitter was buzzing with Twitter, which achieved the largest circulation globally. Instead of serving the issue and directing it to serve the Arab interest, most of the publications were on th |
(1)
Nowadays, the use of natural bio-products in pharmaceuticals is gaining popularity as safe alternatives to chemicals and synthetic drugs. Algal products are offering a pure, healthy and sustainable choice for pharmaceutical applications. Algae are photosynthetic microorganisms that can survive in different environmental conditions. Algae have many outstanding properties that make them excellent candidate for use in therapeutics. Algae grow in fresh and marine waters and produce in their cells a wide range of biologically active chemical compounds. These bioactive compounds are offering a great source of highly economic bio-products. The prese
... Show More
(3)
The research problem was to identify the impact of monetary policies on economic growth in the oil and non-oil countries. The researcher chose the Republic of Iraq as an example for the oil countries and the Arab Republic of Egypt as an example for the non-oil countries to hold a comparison on the impact of monetary policies.
The research found that the monetary policies and their tools in the Iraqi economy affect the rate of GDP growth by 73%, which shows the strong impact of monetary policies on the economic growth in the Iraqi economy as an example of an oil state. GDP growth rate of 61%, indicating the impact of monetary policies on economic growth in the
Insects have a vital role in solid waste composting process. Insects are detritus feeders that enhance changing the physical and chemical properties of decomposed materials during composting processes. This behavior makes insects excellent organisms in recycling of organic matter. The present study assesses the success of insects’ population in relation with the degradation of solid waste. The study was carried out in the glass house facility of the College of Science, Salahaddin University in Erbil City, Kurdistan region of Iraq, using household organic waste. During composting process, three stages of lifecycle of insects were observed and recorded. The total number of insects reached to 1268 indiv
... Show More
(3)
(3)
In This study a comparison between Proteus mirabilis DNA and Candida albicans DNA in Arthritis. Fourteen Proteus isolates (11.6%) were collected from 120 specimens collected from midstream urine of patients of both sex and different ages attending different hospitals in Baghdad. Antibiotic sensitivity assay showed that All Proteus mirabilis recovered from UTI developed multidrug resistance and variable degree of resistance. Histopathological changes in model treated with Proteus mirabilis DNA revealed congestion, inflammatory cells infiltration, oedema, hemorrhagic exudates as well as necrotic cells. Furthermore, articular joints damage has been noticed with articular tissue in ligament and lining epithelium. In addition, an aggregation
... Show More
(1)
(1)
The survival of dried spores of A.flavus, Penicillia Spp., and Cladosporia Spp.inoculated into multivitamins and folic acid tablets were examined at different compression pressures.Survival of fungal spores decreased with increasing compression pressure. The level of survival at particular pressures was shown to depend on the size of the contaminating fungal spores.The lethal effect of tabletting was attributed to shearing forces upon the contaminating spores generated by interparticulate movement. This hypothesis was supported by the dependence of survival upon spore size.
Key words: Fungal spores, microbial contamination.
The covid-19 global pandemic has influenced the day-to-day lives of people across the world. One consequence of this has been significant distortion to the subjective speed at which people feel like time is passing. To date, temporal distortions during covid-19 have mainly been studied in Europe. The current study therefore sought to explore experiences of the passage of time in Iraq. An online questionnaire was used to explore the passage of time during the day, week and the 11 months since the first period of covid-19 restrictions were imposed in Iraq. The questionnaire also measured affective and demographic factors, and task-load. The results showed that distortions to the passage of time were widespread in Iraq. Participants co
... Show More
(9)
(9)
This paper aims to early study of detection and diagnosis of kidney tumors and kidney stones using Computed Tomography Scanning CT scan images by digital image processing. Computerized Axial Tomography (CAT) is a special medical imaging technique that provides images with 3D, including much information about the body's construction consisting of bones and organs. A C.T scan uses X-rays to create cross-sectional images of the body and gives the doctor a full explanation of the diagnosis of the situation through the examination. It has been used in five cases of kidney images, including healthy, stones, tumors (cancer), cystic and renal fibrosis. The masking procedure is used to separate the required C.T. images
... Show More
After the fall of the Soviet Union, a number of Eastern Bloc countries and Soviet republics have witnessed political transition. However, Turkmenistan, as one of the former Soviet republics, succeeded to preserve the authoritarian nature of the former Soviet regime. This study seeks to answer a number of research questions, the most prominent of which are: How were the political elite in Turkmenistan able to preserve the legacy of the Soviet policy based on centralization of power and individual rule?. The study reaches a set of conclusions, the most important of which are:
1-The roots of the tyranny in Turkmenistan are du to internal and external structural factors. The most important of which are: the former Soviet policies of m
... Show More