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: 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
This 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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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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Leishmania parasites reproduce wherever there are cells of the mononuclear phagocyte system, almost in macrophages. These are most copious in the liver and spleen;therefore, infection leads to an expansion of both of them. This study determined the burden of visceral leishmaniasis (VL) infection on liver and spleen. A total of 20 mice were infected peritoneally with 2x107promastigotes of Leishmania donovani / ml and other 12 mice left without infection as a healthy control. The weight of whole body, liver and spleen were measured and the histological development using hematoxylin and eosin stains were determined after 15, 30, 45-and 60-days post infection. The results represent that the mean weights of liver and spleen were increased in inf
... Show MoreThe genus Hafnia, a member of the family Enterobacteriaceae, consists of Gram negative bacteria that are occasionally implicated in both intestinal and extraintestinal infections in human. This genus contains only a single species (Hafnia alvei). Methods The above bacterium was identified from 250 bacterial strains which were isolated from 220 urine samples of patients with urinary tract infection. Results One H. alvei strain was isolated from an elderly patient, and identified by conventional biochemical tests and API20E system at the first time in Iraq. Antimicrobial susceptibility test showed that this strain is sensitive to Cefotaxime, Ciprofluxacine, Chloramphenicol, Doxycycline and Trimethoprim-sulfamethaxzole, while it is resistant t
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Administrative procedures in various organizations produce numerous crucial records and data. These
records and data are also used in other processes like customer relationship management and accounting
operations.It is incredibly challenging to use and extract valuable and meaningful information from these data
and records because they are frequently enormous and continuously growing in size and complexity.Data
mining is the act of sorting through large data sets to find patterns and relationships that might aid in the data
analysis process of resolving business issues. Using data mining techniques, enterprises can forecast future
trends and make better business decisions.The Apriori algorithm has bee
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