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.
Abstract:
The prose poem of the 1990s is considered one of the important
contributions of the Iraqi poetic scene. The poem found a position in the Iraqi
poetry because of the favor of a group of youth poets who lefty clear traces.
Their linguistic techniques often violate the domain o9f language, significance
and image.
The poems of those youth poets moved the verse towards reality to
drink from its abundant springs in order to stand on a rigid ground. Their
linguistic traces are characterized by paradox and astonishment that are used
by the poet to construct his poem.
The paradox was considered an ideal means for constructing a
poem by some of them. The poem moved towards definitions and these
de
The State company for vegetable oils industry one of the most dynamic
companies in the Iraqi economy and is one of the companies manufacturing(food) that takes astrategic dimension and production within the concept of food security, this as well as to reduce dependence on imports and operation of national manpower.This study aims to describe the performance of the State company for vegetable oils industry for the period (2003-2007) which was characterized by economic and security instability of the country and give an accurate picture of their efficiency and their capacity to produce during this Period.
Recently, that there has been a decline in the levels of female players for this event in recent years compared to developments in the world, as this activity depends to achieve the highest level of performance on the physical capabilities and physiological indicators of the player who It is reflected in the achievement, which results in the loss of time for Iraqi female runners compared to the world champions in the (100) meter hurdles competition, which reflects on the level of achievement. The two researchers used the experimental approach in addressing the research problem, and the experimental design used the method of the two equal groups, the two experiments with the pre and post-tests. Female runner and second experimental group (4)
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This Study Sought to Determine The Relationship and Impact Between The Tax Core Capabilities and Tax Settlement The Study Took Place in The Tax Administration, and Based The Problem Was to Two Hypotheses As Solutions Initial Mocked Content to Explain The Relationship Between The Phenomena, and to Test The Validity of Assumptions And Due To The Fact That The General Authority for Taxes is The Body for The Advancement of The Collection Tax In Iraq Random Sample Was Selected to Represent The Population of The Study, Since The Sample Included 22 Individuals Representing 70% of The Total Community to Study, Represented by The Director General, Agents and Directors of Departments and Branch Managers Managers Working in The General Authority fo
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In the contemporary political history of Iraq, a unique protest broke out on October 1st, 2019. This protest reappeared on October 25th and lasted up to the following weeks making this protest as the most comprehensive and deepest one. It has the possibility of lengthening and the diversification of methods among all the social protesting movements during the century for Iraq. This desperate youth movement presents various images and methods to highlight the image of the protesting movement. The role of the Iraqi woman was clear, which was embodied through the mural paintings expressing her artistic and social role in conveying and expressing the goal of the protest. The aim of the current research is to identify the social artistic implica
... Show MoreThis research aims to identify the impact of the selective model in acquiring the concepts of Kurdish grammar among female students in the eighth grade, and to achieve the goal of research, the researcher selected the experimental design with partial control and dimensional testing; the sample includes basic schools in the Chim district of Chamal/ Sulaymaniyah and randomly selected the basic school (Maha Bad) to be the field of application of the experiment and the random drawing method was chosen: two out of three sections and the number of students of the two sections is (75) students; section (C) represents the experimental group that studied the rules according to the selective model and its number is (37) students, while secti
... Show MoreOne of the globalization results is (VAT) , so it is important to consider its results and impact on the tax system.
The Iraqi economy having wittnisd an acute transition period , still in need for a better care in aim to back it, especialy from the tax system.
The research is concerned with the (VAT) and its details –And for five chapters all the problomes connect are displayed .But yet the new system does not comply with the modern development and this is one of the defects of (VAT) in Iraq.
The history of (VAT)was also studied mentiorned and studied.
As a conclusion (VAT) is one of the m
... Show MoreThe Importance of Effort and its Impact in Building the Society in the Light of
the Holy Book and Sunna.
Thank for God and peace be upon Prophet Muhammad, His hose hold and
Companions.
This research is to refute a fault : that Islam as a religioncalls for laziness and
dependence and this in first, Second, to show the originality of the Islamic method in
building and construction.
This research Starts with an introduction in which I refer to the nature of the
Islamic method and its way of work in life: that it is a divine method that is achieved
by the effort of the people them selfves and not through a divine extraordinary power:
The research explains the shift in the peoples life who were addressed by this<
Abstract
The current research aims to identify the effect of the idea filtering strategy on the achievement of second-intermediate school female students in science. The two researchers adopted the experimental method and the experimental design with partial control in the two groups (experimental group and control group). The two researchers applied the research experience to a sample of students of the second intermediate grade in the school Martyrs of (Jiser Al Aimma for Girls) affiliated with the Baghdad Education Directorate / Rusafa /1 for the academic year (2021/2022), which was chosen intentionally. The number of female students in the research sample was (70) students, with (35) students for the ex
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