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.
This study was conducted to evaluate the hydrocarbon biodegradation abilities of Enterobacter cloacae, Staphylococcus aureus, Sphingomonas paucimobilis, and Pentoae species which were isolated from different diesel-contaminated soil samples. The isolates were identified by the Vitek 2 system. Fourier-transform spectroscopy (FT-IR) tested the potential of these isolates to biodegrade the diesel according to the peak areas, a significant decrease in the area of the peaks at 2856-2928 cm−1 corresponds to aliphatic hydrocarbons. The appearance of small peaks at 900-1032 cm−1 refers to substituted benzene derivative compounds. An appearance of some new peaks at 3010- 3030 cm−1 which indicate the presence of alcohol (-OH) and ketones (RC=O)
... Show More
(8)
(5)
The effect of the concentration of the colloidal nanomaterial on their optical limiting behavior is reported in this paper. The colloids of sliver nanoparticles in deionized water were chemically prepared for the two concentrations (31 ppm and 11ppm). Two cw lasers (473 nm Blue DPSS laser and 532 nm Nd:YAG laser) are used to compare the optical limiting performance for the samples. UV–visible spectrophotometer, transmission electron microscope (TEM) and Fourier Transformation Infrared Spectrometer (FTIR) were used to obtain the characteristics of the sample. The nonlinear refractive index was calculated to be in the order of 10-9 cm2/W. The results demonstrate that the observed limiting response is significant for 532nm. In addition, t
... Show MoreThe study of the future of the international system currently appears, according to scientific data and existing facts in light of the emergence of international actors from non-states and international informal institutions, to be heading towards a non-polarity system and this trend is fueled by many variables to reduce polarity, and it is expected in the future that the international system will turn into a non-polarity.
The research specializes in (Usage of the visual elements in the interior designing of indoor swimming pools), the research seeks to provide a study that contributes to providing scientific and knowledge material, as a reference for researchers, students of interior design and architecture, and companies constructing indoor swimming pools.
The objective research is to detect the actual state of the interior design of the indoor swimming pools, and recognize the most important standards and techniques used in its design to provide appropriate design solutions if needed also Proposing a development proposals for the interior design of indoor swimming pools, the theoretical framework of this study, included two sections, The first one ta
This research is determined by the study of the " cognitive references of the directorial imagination and modeling of the theatrical actor performance ." it has described an Iraqi theatrical model, The research began with the great importance of the director's imagination as the basic premise for crystallizing the director's vision according to its cognitive references in creating a solid performance model based on the aesthetic, intellectual and technical bases, It is also contributes to the formation of the theatrical show as a technical framework that presents the show in one unified fabric.
The research sought to reach through the problem of research, which is in the question of: What is the modeling of the
... Show More
The industrial development and raise the level of income that has emerged clearly in the middle of the last century in many rich and medium rich countries has great influence on the risen of the health care level. Which led to a significant increase in the reconstruction of people over 65 years and this in turn has produced markets for products and services through modifications to the existing products to meet their physical needs. The importance of research also has the universal design of a comprehensive actually so that it covers as much as possible from human physical & cultural activities. The importance of research locally is to concentrate on this subject who has not been taken into consideration so far to accommodate the eld
... Show More
Our research which is under the name "Polarization and Communication mechanism in the formation of green industrial products " The problem of the research focuses in identifying what is polarization and its function mechanisms , by displaying the inventive and creative cases of the designer in how to exploit the industrial products and its recycling process to attract the user and recipient by asserting on the values of beauty of the appearance of the industrial product with the attraction Of the user and the recipient with the new function of that product and how its different from the function achieved by the old product , with consideration of nature and its preservation . The results of the research were as following : The designer e
... Show More
Recently, some of Iraq's newly constructed asphalt concrete pavements showed premature failures with significant negative impacts on roadway safety and the economy. Using Nano hydrated lime (NHL) in pavement construction could be one of the possible steps to improve pavement durability. This article discusses how NHL affects the durability of hot mix asphalt. NHL was added in two methods to the asphalt concrete mixture for the wearing course. The first is the dry method, i.e., on the aggregate, whereas the second is the wet addition method, i.e., to the bitumen. The percentages were tried for each additional method; 1, 2, and 3% by weight of aggregate for the dry method and 0.5, 1, and 1.5% by weight of asphalt concrete for the wet
... Show More
(5)
The goal of current research is to identify the difficulties in the application of modern physics in the middle schools of the province of Baghdad schools from the perspective of teachers of physics trends, sample search of (127) teachers, Karkh Third Directorate, and use Researcher questionnaire data collection tool after applying it to teachers who have experience (5) years and more after confirmation of the validity and reliability of the scale (the tool) researcher has used the averages for the purpose of interpreting the results. the results showed that the difficulties have been in the order following: (difficulties related educational environment of modern trends of teaching, curriculum-related dif
... Show MoreThe research aims to define the images of financial aid that it provides within their tasks (central banks to governments) and how it can affect the indicators of banking stability, as well as monitoring the levels of banking stability in the Iraqi economy through the indicators used by the Central Bank of Iraq, and the importance of research in banking stability lies in Iraq, because any decrease in the movement of the aggregate banking stability index will reflect negatively on the financial sector in Iraq. Therefore, the Central Bank sought to provide financial aid to the government through a group of components, some of which are represented by initiatives that contribute to revitalizing the national economy and the other hel
... Show More