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.
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Abstract
The research hypothesizes is that the external Environment
has the responsibility concerning decisions making and behavioral
upon industrial firms. It is, Furthermore, an attempt to review the
problem of closures of private industrial firms in the country, during
the period (1976-1985), i.e. prior to and during the Iraqian- Iranian
war.
The behavioral approach of industrial geography has been
adopted as a theoretical background and the statistical test has
been practiced for the applied purposes.
As result, the research comes out with suggestions,
depending upon previous trials in the field of direction and
formulation of the of the private industrial sector. The chief point
among th
Autorías: Ismael Saleem Abed, Imad Kadhim Khlaif, Salah Mahmood Salman. Localización: Revista iberoamericana de psicología del ejercicio y el deporte. Nº. 5, 2022. Artículo de Revista en Dialnet.
Abstract
financial market occupy very important place in the economic activity all over the world countris, and its importance increased with considerable technological progress in the world of transportation ,communications and information where its impact have spread over the whole world, which led to link the international economy in a kind of international relations so that the open policy became the prevailing trend in national and regional economies within the framework of the new world order.
the international economy has faced the financial crisis, global, that hit all world economies although the United States is the center of the crisis and the starting spark for it w
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In this study, we focused on the random coefficient estimation of the general regression and Swamy models of panel data. By using this type of data, the data give a better chance of obtaining a better method and better indicators. Entropy's methods have been used to estimate random coefficients for the general regression and Swamy of the panel data which were presented in two ways: the first represents the maximum dual Entropy and the second is general maximum Entropy in which a comparison between them have been done by using simulation to choose the optimal methods.
The results have been compared by using mean squares error and mean absolute percentage error to different cases in term of correlation valu
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The research aimed to prepare a psychological counseling program for the coaches of the Sports Care Center in the gymnasium, and to learn about the impact of the psychological counseling program in reducing irrational ideas and causal attribution of the coaches of the Sports Talent Care Center in the gymnasium, to assume that there are statistically significant differences between the results of the tribal and posttests of the research group Experimental in the scale of irrational ideas, and there are statistically significant differences between the results of the tribal and posttests of the experimental research group in the scale of the causal attribution scale, The experimental approach was adopted by designing one experimental
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In the present work effect of recycled heating and cooling on the values of concrete compressive strength due to high temperature of 4000C was studied.
The tests show that the percent of reduction in compressive strength of the samples which exposed to a temperature of 4000C for one cycle was 32.5%, while the reduction was 52.7% for the samples which were exposed to recycled heating and cooling of ten times .
Moreover a study of the effect of specimen sizes on the percentages of compressive strength reduction due to high temperature
... Show MoreIn the city of Hebron, small business industrial organizations face a major challenge related to its ability to reach, attract and sustain a sufficient number of customers in order to ensure its continuity and sustainability. The research problem is summarized in an attempt to reveal how the e-marketing could improve and support the marketing effectiveness of small business industrial organizations in the city of Hebron/Palestine. The importance of this research stems from the fact that it addresses a new knowledge branch of the field of marketing, which is electronic marketing for small business organizations, and the fact that the research highlights appropriate marketing solutions for these organizations in light of the Intern
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Monetary sterilization policies are one of the modern trends of monetary policy in rentier countries, specifically to confront the positive shocks in foreign assets flowing into the national economy and the impact of these shocks on monetary and real variables. And that the Central Bank contains these emergency increases in foreign exchange with the aim of avoiding the impact of this increase on the official local currency through its three main monetary tools, which are the rediscount rate, the legal reserve, and open market operations. As well as the relationship between the central bank and the objective of external balance, which is reflected in the balance of payments balance, the central bank resorts to managing the exchange rate
... Show MoreThe general budget is usually linked to the role of the state in public life and economic activity, whether this role is neutral or interventionist and thus reflects the general objectives that the state seeks to achieve.
for importance of the public budget in clarifying the image of the political state philosophy and its objectives it seeks to achieve on the one hand and clarifying the degree and rank it occupies in the ladder of development among the other countries. This study is intended to highlight the concepts of the general budget and how its concept has evolved since the Middle Ages. Of the importance of the general budget in Iraq was not based on scientific and objective and then the study
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