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 research includes studying melodic and rhythmic properties, In the audio format for Iraqi musicians. The audio form is one of the important methodological forms in Arab music in general and Iraqi music in particular. It showcases its characteristics, features, internal form, and how important it is in Iraqi music.
Addressed ((the systematic framework)) presenting the research problem and the need for it. Its importance, purpose and limitations of its research, which included music ((Khaled Muhammad Ali)) as a human limit to reveal its characteristics in the composition of the audio form. And define the terms included in the research. And included ((theoretical framework)) on three topics .. The first: composing. The second
Phoenix dactylifera l. pinnae (the green leaves of dates palm) were used as natural reinforcing (strengthening) fibers to improve the mechanical properties of polyester as a matrix material, the fibers of the green leaves of dates palm were used in two lengths, 10 and 20mm with five rates of 0, 2.5, 5, 10, and 20% , where the reinforcing with the leaves fibers increases the hardness strength from 76.5 to be about 86.55 , the Impact value raised from about 0.313 to 0.461 , in addition to that the flexural strength from 2.66 to be about 55 , and the thermal conductivity increases from 2.54 𝑤∕𝑚.℃ to 5.41 𝑤∕𝑚.℃. The results of the present search explains that the composite samples reinforced at rate 20% and 10mm fiber length
... Show MoreThe harmonic oscillator (HO) and Gaussian (GS) wave functions within the binary cluster model (BCM) have been employ to investigate the ground state neutron, proton and matter densities as well as the elastic form factors of two- neutron 6He and 16C halo nuclei. The long tail is a property that is clearly revealed in the density of the neutrons since it is found in halo orbits. The existence of a long tail in the neutron density distributions of 6He and 16C indicating that these nuclei have a neutron halo structure. Moreover, the matter rms radii and the reaction cross section (𝜎𝑅 ) of these nuclei have been calculated using the Glauber model.
The management of the exchange rate of the most important tools of economic policy because of its wide area in achieving stability and economic growth through the provision of stability in the exchange rate of the currency of the country concerned , as well as the impact and influence of money supply and then treat the economic crisis monetary and reduce the risk of currency exchange rate .For the management of the exchange rate in Iraq has passed through several stages , from installation to link to a basket of currencies to float freely , and we are dealing with in this research regard to the achievements of monetary policy , especially after the enjoyment of independence on according to the Iraqi Central Bank Law No. 56 of 2004 and Ma
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Quality is the key to success in today's world, which is based mainly on competition in the provision of high quality services through the application of the modern management method which is called total quality management in organizations. This includes describing the provision of health services and satisfaction of patients . .  
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Pollen grains morphology have been studied for the wild species of the genus Erysimum L. which belong to Crucifereae family in Iraq. These species are E. filifolium Boiss. et Hausskn., E. oleifolium J. Gay, E. repandum L., E. eginense Hausskn. ex Bornm., E. aucheranum J. Gay, E. cheiranthoides L., E. alpestre Ky. ex Boiss., E. kurdicum Boiss. et Hausskn., E. tenellum DC., E. strophades Boiss., E. gladiiferum Boiss. et Hausskn., E. nasturtioides Boiss. et Hausskn. The study was performe by using light microscope . The study reveal that there was only one type of pollen grain named Tricoplate in all studied species . The study also demonstrated that there were differences among pollen grains morphology . The species E. kurdicum , E. alpestre
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Cerebellum (cb) is the most important and sensitive part of the central nervous system (CNS) after cerebrum. The exposure to any infection during embryogenesis produces abnormalities in the cerebellum function and morphology that effect on behavioral of offspring later. In the present study we used 30 mature female pregnant albino rats divided in to three groups, each group contain 10 females: G1 was considered the control group received D.W only, while G2 group treated orally with (2mg/kg /day) suspension of silver nanoparticles (AgNPs) and G3 group treated orally with (20mg/kg/day) AgNPs. The embryos retrieved in different embryonic days from ED12 to ED21. In this study morphometric analysis was measured in the developing albino rats cere
... Show MoreWere collected three types of medicinal plants from their natural habitat after Astkhalasalziot volatile manner steam distillation and determine the quality and quantity of vehicles chemical for each of the oils obtained using a technique JC discouraged when you merge oily thyme and lemon grass against bacteria either when using oils in three did not have a different effect
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