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 aim of the research is to present and discuss the subject of the budgeting estimates and how to activate the role of the Federal board of supreme audit in examining these estimates through reference to Articles 6 and 10 of the Federal board of supreme Law, which did not restrict Federal board of supreme in Preventive control on examination process for planning which is prepared from the government units, as the result of a large amount of government units Provisions and the weakness of estimates in most of its items, which rely on personal assessment and not based on scientific and logical basis of the estimate, which leads to the emergence of a deficit is not true in the general budget and this seems clear in most Iraq
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Since the COVID-19 pandemic alarm was made by the severe acute respiratory syndrome (SARS)-coronavirus (CoV) 2, several institutions and agencies have pursued to clarify the viral virulence and infectivity. The fast propagation of this virus leads to an unprecedented rise in the number of cases worldwide. COVID-19 virus is exceptionally contagious that spreads through droplets, respiratory secretions, and direct contact. The enveloped, single-stranded RNA virus has a specific envelop region called (S) region encoding (S protein) that specifically binds to the host cell receptor. Viral infection requires receptors' participation on the host cell membrane's surface, a key- step for the viral invasion of susceptible cells.
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Purpose: The aim of this study was to gain insight into causes of time delays and cost overruns in a selection of thirty case projects in Iraq. Delay factors have been studied in many countries/contexts, but not much data exists from countries under the conditions characterizing Iraq during the last 10-15 years.Design/methodology/approach: A case study approach was adopted, with thirty construction projects selected from the Baghdad region, of different types and sizes. For the case of the study, the participants in the projects provided data about the projects through the data collection tool distributed through the questionnaire directed to them. Statistical data analysis was used to build statistical relationships between time and cost d
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Magnetosphere is a region of space surrounding Earth magnetic field, the formation of magnetosphere depends on many parameters such as; surface magnetic field of the planet, an ionized plasma stream (solar wind) and the ionization of the planetary upper atmosphere (ionosphere). The main objective of this research is to find the behavior of Earth's magnetosphere radius (Rmp) with respect to the effect of solar wind kinetic energy density (Usw), Earth surface magnetic field (Bo), and the electron density (Ne) of Earth's ionosphere for three years 2016, 2017 and 2018. Also the study provides the effect of solar activity for the same period during strong geomagnetic storms on the behavior of Rmp. F
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This paper focuses on the concept of cognition and its clarification in the light of Islamic epistemology. Knowledge passes through two essential parts: conception and assent. Conception explains simple knowledge, while assent explains knowledge involving a judgment. The paper proceeded with the identification of the problem of relationship blurring between cognition and knowledge. The external and inner senses have explained the relationship between the stages of knowledge and cognition. The external senses receive stimuli and form primary conceptions. These conceptions transfer to the first part of the inner senses, which is common sense; it collects the sensations and transmits them to pictorial power. Secondary conceptions are f
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The development in the presentation and presentation of the service in order to distinguish them from the same, was one of the most important reasons to choose the current issue to upgrade the level of service, especially in the Iraqi restaurant sector, which has become today of the important sectors successful. The problem of research was to try to answer a range of questions: to what extent are Iraqi restaurants interested in physical service factors? Do Iraqi restaurants apply physical factors in a way that leads to customer satisfaction? Are Iraqi restaurants interested in the satisfaction of their customers? The objective of the current research is to try to determine the extent to which the
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This study is targeting the new developed materials and techniques and how they were affected by the scientific and technological developments that contributed to revelated new and varied developed materials and techniques. And from the artist’s formulation by using the materials and techniques and through its embodiment and sensor the values, artistic and aesthetic standards by breaking from the familiar in aesthetic contemporary way.
The studies on questioning what’s the role of The New Developed Materials and Techniques in exposing the aesthetic of the art work?
This study is to show the aesthetic of the art work through the new developed materials and techniques. Which was based on descriptive analyzing method and hig
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The study seeks to analyze the perceptions of audience in UAE towards the performance of Emirates Satellite TV Channels. It analyzed the exposure motivations of audience to satellite TV channels, its positive and negative aspects and to what extent they abide by media ethics. A survey is conducted with a sample of four hundred. The study shows significant differences between male and female towards the characteristics of TV channels, its positive and negative aspects and its commitments to media ethics.
The study also shows that the expectancy value model and third person effect model are applicable in studying the perceptions of audience and media people in UAE t
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