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 relationship between the elements of the climate and the productivity of citrus (kg
/ tree) in the province of Karbala has been determined through the use of simple correlation
coefficient of Pearson (rp) and (t) test. The result for each of oranges, limes and tangerine had
all shown moral and relevant statistical indications; except for relative humidity, which were
not linked to a moral relationship with productivity of tangerine, oranges and limes.As for the
relationship between climatic factors and yield of bitter orange were all not significant
statistically and very weak.
In order to determine the strength of the correlation between fluctuations in the
climatic elements and fluctuations in the productivi
The current research deals with the specificity of the interior design of the classes of art education in the schools of excellence for the province of Muthanna and its center of the city of Samawah. In the first chapter، the problem of research was determined by the lack of internal spaces of the classes of art education to designs that meet the requirements and needs of students in these educational stages. The importance of the research in being an addition to knowledge in the field of interior design and engineering department of the general directorates of the Ministry of Education. The objectives of the research were determined through.
- Identifying the reality of the halls of art education for sch
Purpose :This study seeks to provide the point of view stands on the marketing performance of the banks in the context of Dynamic Equilibrium of marketing. It aims to develop a prototype of measuring marketing performance under the umbrella of marketing dynamic prototype, embodied of the strategic alliance and competition, and the laws and legislation, and to explore any of the dimensions more effective in achieving performance. This study aims to discusses the importance of the Dynamic Equilibrium of marketing and it role in achieving the marketing performance <
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Background and Aim: The aryl hydrocarbon receptor (AhR) plays a pivotal role in spermatogenesis through its regulatory functions in redox balance and gene expression. This study aimed to investigate the effects of resveratrol (RES), a polyphenolic AhR modulator, and CH223191, a selective AhR antagonist, on male reproductive function in rats by assessing sperm quality, oxidative stress, testicular histopathology, and AhR gene expression. Materials and Methods: Forty adult male rats were randomly divided into four groups: (i) Control, (ii) dimethyl sulfoxide (vehicle), (iii) RES (100 mg/kg i.p., twice weekly), and (iv) AhR⁻ (CH223191, 10 mg/kg i.p., twice weekly), treated for 60 days. Post-treatment, sperm motility, survival, viabi
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Summary The objective of the research is to learn the design of a learning educational learning according to the theory of Ausubel in the acquisition of geographical concepts among the students of the fourth primary in the field of geography and the development of their habits of mind. To achieve this, the researcher relied on the two hypotheses the researcher used the design of equal groups the first experimental group was studied according to the design educational educational learning according to the theory and the other is an officer according to the traditional method. The research community consists of fourth grade pupils in primary school day for girls in the Directorate of Education Baghdad, Al-Rusafa, the third academic year 20
... Show Moreم. د. ولاء طارق حميد, Al. Qadisiya journal for the Sciences of Physical Education, 2017
The study focuses on the problem that Iraq is approaching an increasing rate of literacy;the available data refers to a rate of (18% -19%). In addition to the fact that the generalcurrent role of the programs directed to literacy is not actually effective enough to limit the expansion of this rate.
The importance of this study highlights the fact that the Iraqi universities are an important tributary among the tributaries of human development, especially in spreading the education of the voluntary work in literacy field and confirming the connection between the students and their society and their role in solving one of the prominent challenges that face the development, i.e., literacy.
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... Show MoreThis study was conducted in Diyala province for renal failure patients during the periods August 2015 - April 2016. Hundred renal failure patients were enrolled in the study after diagnosis by the consultant physician at Ibn-Sina Center for Dialysis in Baquba Teaching Hospital according to criteria adopted by the World Health Organization for diagnosis of renal failure disease. The number of males in patient’s sample was 61 (61%) and females was 39 (39%) with an age range of 10 – 88 year (44.7 ± 22.1 year). In addition, the study included 50 apparently healthy individuals and considered as a group control, in which the number of males and females was similar (25 individual), with an age range of 18 – 88 year (51.7 ± 17.3 year). The
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It is important to set the background of stiffen arbitration agreement, to understand the real reasons of the fighting. When the Syrians began to lose, raised the masahif and made their announcement, most the qurrar, and so no need to continued fighting.
In their view all that remained was the matter of drawing up formal peace with Ali, Muamiya; Ali would recognize as Amir al-muminin by both Syrian and Iraqis.
The most of the Iraqisfavored settlement for different persons, for example-A'shath, the most power full of the clan leaders of Rabia, his interest by insuring that neither Ali nor Mu
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