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: In this study, the female reproductive system of Columba oenas was examined during the egg laying stage, focusing on its general structure and microscopic characteristics. Methods: Obsessive monitoring operations were performed, as well as different parts of the egg canal, which include infundibulum, magnum, isthmus, uterus and vagina. Result: These parts showed clear anatomical differences, each with special textile features that seem to play distinctive roles related to the growth and movement of eggs. In magnum it was found that the bulk contains clear mucous folds and many secretory glands. The isthmus had a star-shaped lumen and was lined with a false cylindrical epithelium. In the uterus, branching tube glands, ric
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The features of strategic thought transformation in Russia based on attempt confirm the Russian influenced on Region of Eastern Europe through series of common defense treaties and mutual security between USSR and another states this treaties emphasis size on direct Russian supervision on these states in addition, Russia in trusted to formation communism regimes in its vital space, Russia inherited the status of former USSR in political and economic levels.
Shortly we can see that Russia witnessed large Transformation in political strategic thought as a result of change in internal strategic environment and change of nature understanding which influenced on Russia. This
... Show MoreThis paper presents a comparison between the electroencephalogram (EEG) channels during scoliosis correction surgeries. Surgeons use many hand tools and electronic devices that directly affect the EEG channels. These noises do not affect the EEG channels uniformly. This research provides a complete system to find the least affected channel by the noise. The presented system consists of five stages: filtering, wavelet decomposing (Level 4), processing the signal bands using four different criteria (mean, energy, entropy and standard deviation), finding the useful channel according to the criteria’s value and, finally, generating a combinational signal from Channels 1 and 2. Experimentally, two channels of EEG data were recorded fro
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Background: Preeclampsia occurs in 3-5% of
pregnancies and is a major cause (12-20 %) of
maternal mortality in developed countries. It is the
leading cause of preterm birth and intra-uterine
growth restrictions (IUGR).
Objective: The study was designed to determine and
demonstrate the ultra structural changes of
endothelial cells in placenta of women suffering from
hypertensive disease.
Patients & Methods: Placental samples were
obtained from two groups of pregnant women
groups (preeclamptic and normal pregnant women).
The specimens were fixed in 2.5% gluteraldehyde
and preceded for electron microscopic examination.
Results: Placenta of women with preeclampsia has
shown marked degenerative
After the internal audit as a tool of internal control in any organization, and helps in the evaluation of all internal control activities, as a tool to ensure compliance with the plans and policies to achieve the goals of the institution as much as possible of the efficiency, effectiveness, and should have the Internal Audit full independence and is linked to senior management, and aims to get the credibility and accuracy of information and data, and keep abreast of modern developments.
The practical side includes the preparation of the questionnaire, which included a set of questions that fit the hypothesis of the research, was Tozeiha the research sample consisting of employees of the Internal Audit Department an
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The Role of Japan in the Reconstruction of Iraq
This study was done at Al-Balad City Hospital on 60 diabetic patients (25 male and 35 female). The study included Fasting Blood Sugar and fungal diagnosis (systemic and superficial fungus). The results showed that the high concentration of blood sugar belonged to the group > 70 years among the diabetic patients with high significant differences in comparison with other groups P<0.001 . The result showed that percentage of female systemic fungus infection was higher than male systemic fungus infection ( female 63% and male 24%) and vice versa about superficial fungus infection (female 37% and male 76%) . Data showed that the percentage of nail fungus infection among female diabetic patients was higher than the percentage of male diabetic p
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The tourism activity is one of the pillars on which the economy of any country is based , the importance of the tourism sector is reflected in its potential to become an effective development alternative in many countries, especially Iraq ,this has a direct impact on the national economy as an important source in attracting hard currency and eliminating unemployment. Adding the Iraqi Marshlands to the list of effects makes it contribute to diversification of sources of income and stimulating rest of the economic sectors, the potentials and qualifications possessed by Iraq in the field of tourism and monuments have a significant impact on the state budget if they were exploited optimally. The research aims at identifying the contr
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