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 persons who Allah Ioves them in the holly Quran
Objectivity Study0Dr 0muyad Turky Ali
Allah men tioned in Auran the loving of benevolent and who Allah loves him gave him everything 0the loving of benevolent came fist and after that the loving of justice who remove injustice and after that loving purified and in noeent 0After that mentioning loving of Knighters ( fighters )The eharity with money and to clear up the justice and loving purified is a reason of accessing paradise 0
Abstract
Shorten the research problem that there is no system or model to evaluate the financial performance of the departments of municipalities where it is not possible for a person or institution both to know or to know their success in terms of the financial work of failure and where it is now than those without assessing the financial performed, authorized to be and necessities FATF is the financial performance assessment, which is the work unfinished aspects without Hence the work came in this study to study and diagnose and analyze financial data in a sample of municipal departments in order to develop a model to assess the financ
The Plerion nebula is characterized by its pulsar that fills the center of the supernova remnant with radio and X-ray frequencies. In our galaxy there are nine naked plerionic systems known, of which the Crab Nebula is the best-known example. It has been studied this instance in order to investigate how the pulsar energy affect on the distribution and evolution of the remnant as well as study the pulsar kick velocity and its influence on the remnant. From the obtained results it's found that, the pulsar of the Crab Nebula injects about (2−3)𝑥 1047 erg of energy to the remnant, although this energy is small compared to the supernova explosion energy which is about 1051 erg but still plays a significant role in the distribution and the m
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The energy aimed at examining the mode of energy drinks consumption among athletes in
Baghdad and assessing their drinks were spread greatly among the athletes and students. This
study impression toward such drinks. The study sample comprised of 102 mal athletes aged
between 19-27 years and selected randomly .The obtained results showed that football was
most practiced among the test samples at 40.54% based on twice daily .The athletes
consumed one can each day at 41.18% .As the data on energy drinks was supplied from
friends .The prefared period for drinking was before or during exercise .The athletes thought
that there products can provide energy ,vitamins ,tell ale materials ,does not affect
appetite.The most f
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The current research aims at identifying the new marketing directions that in the picture because if the changes and challenges that face the business nowadays, these effect on the future of the new product.
The problem of the research concentrate on the new marketing activities and how to make it appropriate between the product and the market's need, and to fulfill the needs and desire of the customer and it's importance for achieving the economical goals of the organization for a long relationship with the customer.
The resume of the research is about the impact of nowadays marketing and it's effect on knowing the customer instead of concentrating on the important roll of mark
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Researchers often equate database accounting models in general and the Resources-Events-Agents (REA) accounting model in particular with events accounting as proposed by Sorter (1969). In fact, REA accounting, database accounting, and events accounting are very different. Because REA accounting has become a popular topic in AIS research, it is important to agree on exactly what is meant by certain ideas, both in concept and in historical origin. This article clarifies the analyzing framework of REA accounting model and highlights the differences between the terms events accounting, database accounting, semantically-modeled accounting, and REA accounting. It als
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In this research was conducted to provide a product to analyze the performance sensor fiber optic used to measure and feel the intensity of the electric field results showed obtained that use sensor long gives reactive high electric field strength and a high value for allergic sensor, but that is at the expense of reducing the intensity of the electric field that is detected
In this study the effect of fiber volume fraction of the glass fiber on the thermal conductivity of the polymer composite material was studied. Different fiber volume fraction of glass fibers were used (3%, 6%, 9%, 12%, and 15%). Specimens were made from polyester which reinforced with glass fibers .The fibers had two arrangements according to the direction of the thermal flow. In the first arrangement the fibers were parallel to the direction of the thermal flow, while the second arrangement was perpendicular; Lee's disk method was used for testing the specimens. The experimental results proved that the values of the thermal conductivity of the specimens was higher when the fibers arranged in parallel direction than that when the fibers
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