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 current study aimed the syntheses and characterizations of Gold nanoparticles (Au NPs) using a laser ablation Q-switched Nd: YAG laser with a wave-length of 355 nm at a variety of laser pulse energies (E) and deposited on porous silicon (PS). Optical emission spectrometer was used to diagnosed medium air to study gold plasma characteristics and prepared Au nanoparticles. The laser pulse energy influence has been studied on the plasma characteristics in air. The data showed the emergence of the ionic (Au II) spectral emission lines in the gold plasma emission spectrum. XRD has been utilized to examine structural characteristics. Moreover, AFM results 37.2 nm as the mean value of the diameter that is coordinated in a shape similar to the
... Show MoreKE Sharquie, AA Al-Nuaimy, WJ Kadhum, Saudi medical journal, 2006 - Cited by 3
This study estimated seven heavy metals (Fe, Cu, Zn, Pb, Ni, Cd, Cr) in water (dissolved and particulate phase), sediments and some aquatic organisms including two species from aquatic plants (Ceratophyllum demersum&Phragmites australis); one species of clam (Psedontopeses euphratics) and two species from fish (Oreochromis aureus& Leuciscus vorax)in four sites within Mashroo AL- Musayyib channel project/ branch of Euphrates river, Babylon , medial of Iraq . This aims to show the concentration of these elements, their fate and the mechanisms of their transmission through the food chain in this lotic aquatic system ; also in addition to examining some physicochemical properties of ri
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Dapagliflozin is a novel sodium-glucose cotransporter type 2 inhibitor. This work aims to develop a new
validated sensitive RP-HPLC coupled with a mass detector method for the determination of dapagliflozin, its
alpha isomer, and starting material in the presence of dapagliflozin major degradation products and an internal
standard (empagliflozin). The separation was achieved on BDS Hypersil column (length of 250mm, internal
diameter of 4.6 mm and 5-μm particle size) at a temperature of 35℃. Water and acetonitrile were used as
mobile phase A and B by gradient mode at a flow rate of 1 mL/min. A wavelength of 224nm was selected to
perform detection using a photo diode array detector. The method met the
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Photodynamic Action (PDA) by using appropriate wavelength of irradiation conjugated with porphyrin derivatives is a powerful mechanism of tumor destruction. Hematoporphyrin derivative has been shown to selectively localize in neoplastic cells and then cause destruction of them by generation of singlet oxygen when activated by low power He-Ne laser. Light which used in this study has been emitting from this laser has a wavelength equal to 632.8 nm (red light). Doses of laser had been varied from 3.6 J/cm2 to 14.4 J/cm2 . The beam of laser adjusted with a modified tissue culture plate. Cell lines had exposed to Hematoporphyrin D (HpD) for 24 hours before Laser exposure, their concentrations were varied from 5 µg/ml to 80 µg/ml. Resu
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Background: diabetic mellitus is one of the serious systemic diseases that may cause general systemic changes, which may be reflected in the oral cavity. The aims of this study were to assess the severity of dental caries, Mutans Streptococci and Lactobacilli in addition to flow rate and pH among uncontrolled and controlled diabetic groups in comparison with non-diabetic control group. Materials and Methods: Study groups consisted of 25 uncontrolled diabetic patients (HbA1c > 7), 25 controlled diabetic patients (HbA1c ? 7), in addition to 25 non-diabetic healthy looking individuals. Their age was (18-22) years from both genders. The diagnosis and recording of dental caries was according to severity of dental caries lesion through the applic
... Show MoreThe study aimed at identifying youth and sport forums from planning and leadership point of view and their relation with organizational culture. The researchers used the descriptive method on (140) worker in Baghdad youth and sport forums. A scale was designed for measuring planning and leadership in youth and sport forums as well as designing a scale for measuring organizational culture. After the application of the main experiment, the results showed that both youth and sport forum administration scale and organizational culture scale are appropriate to the study community. Finally the researchers recommended using these scales by workers in youth and sport forums and involving administration mangers in periodical training courses
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Traumatic radial nerve injury in humeral shaft fracture is the most common traumatic nerve injury in long-bone fracture, with overall prevalence 2-18%, ranging from traction to complete transection. Spontaneous recovery may reach 88%. The aim of the study is to assess the sensitivity & specificity of the ultrasound to detect the radial nerve injury and to see if this can be used as a diagnostic test. This is a prospective study on 17 adult patients with a closed fracture of the humeral shaft, dividing into two groups, the first group of 7 patients had signs and symptoms of radial nerve palsy at presentation and the second group of 10 patients had intact radial nerve function was considered as a control group. All these patients had at leas
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