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.
Cumulative lifetime lead (Pb) exposure has been associated with accelerated declines in cognition through the free radical generation and epigenetic effects. Several pieces of literature have identified a correlation between exposure to lead and neurodegenerative disorders. Harwich strain Drosophila melanogaster was exposed to lead acetate for two weeks, and changes in pulse transmission by acetylcholinesterase and systemic redox were evaluated. Besides, molecular docking studies of acetylcholinesterase against Quercetin and its most common derivatives contained in food have been performed. Pharmacokinetic studies on Quercetin and its derivatives have also been performed in silico toxicity. The data obtained showed alterations in antioxi
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The paper is concerned with, the behavior of the hydrostatic thrust bearings lubricated with liquid-solid lubricants using Einstein viscosity formula, and taking into account the centrifugal force resulting from high speed. Also studied is the effect of the bearing dimensions on the pressure, flow rate, load capacity, shear stress, power consumption and stiffness.
The theoretical results show an increase in load capacity by (8.3%) in the presence of solid graphite particles with concentration of (16%) by weight as compared with pure oil, with increasing shear stress. .
In general the performance of hydrostatic thrust bearings improve for load carrying capacity, volume flow rate,
... Show Moreملخص البحث باللغة الإنجليزية
The concept of the phenomenon of nuns: an analytical ideological study
Dr. Samia bint Yassin Al-Badri
Department of Islamic Doctrine & Contemporary Ideologies
College of Shariʿah & Islamic Studies
Qassim University
The study of concepts is one of the main pillars of doctrinal studies, in order to understand the formation of the concept, and to understand its contexts in religious sources, in order to be systematically criticized; So, this research came with the title:
The concept of the phenomenon of nuns, an analytical doctrinal study
The study concluded with resu
... Show MoreThe Arabic pronouns received a lot of attention from the ancient Arab grammarians, so they explained their origins, the different forms of their structure, and the aspects of the Arabs’ use of them, and explained the aspects and reasons for these uses, with what they had of linguistic insight, which guided them to clarify the truth of these pronouns.
And recently, this research seeks new knowledge of the development of the structure of the nominative pronouns (he), (she), (them), (taa), and (waw) between dialects and towards classical Arabic, by analyzing the structure of these pronouns into their components. Its linguistic formulas are traced from the ancient Arabic texts, and by ancient I mean the texts of the era of linguistic ci
Highway network could be considered as a function of the developmental level of the region, that it is representing the sensitive nerve of the economic activity and the corner stone for the implementation of development plans and developing the spatial structure. The main theme of this thesis is to show the characteristics of the regional highway network of Anbar and to determine the most important effective spatial characteristics and the dimension of that effect negatively or positively. Further this thesis tries to draw an imagination for the connection between highway network as a spatial phenomenon and the surrounded natural and human variables within the spatial structure of the region. This thesis aiming also to determine the natu
... Show MoreThe current research studies (representations of metaphysics in the works of potter Jason Walker) a concept that refers to To a large extent, by conveying a sense of reality to the recipient by conveying ideas, contents, and connotations. A variety of center hit, dispersion, and rejection of everything that prevails, so our position on the closed text has shifted To the open text, through the role played by cross-pollination in the works of the potter (Jason Walker), which established a clear hypothetical vision of the image represented in the construction of the ceramic work and the thought that was embodied in that image represented by the nature of its unrealistic formations for those ceramic artworks. It is thus considered a logical
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Constructing The Psychological Tranquility Scale of the University of Baghdad Students
The research aimed to :
- Constructing the Psychological Tranquility Scale of the University of Baghdad Students.
- Appointing the psychological content standard for the accepting Answer of student about the scale.
The research Sample was (414) boy and girl from Baghdad University Students for the Studying year (2008-2009), So the Scale of the Psychological Tranquility Scale was bilt on them in good psychometric properties from truth Factor analyzing which was its super saturation was reached to (50) item from its items a value more than the super sutution norm (0,30) for kaizer, also the firm value was Relaibility for the scale by the way
This research study focuses on fundamental questions. It deals with the content of the critical reviews through which the most important sources that undermine the renaissance of the Islamic human society can be concluded. It is the vague fetishization of the sacred between religion, politics, and ideas, which members of society live in and which raised the dust of closed-minded fanaticism that led to the return of deviant extremism. It is oppression, violence, and domination, all of which are professional tools in the manufacture of the ideology of extremism in all its forms. Here, the idea matured in giving a human, intellectual and philosophical overview that mixed the required drawing in the formulation of scientific cont
... Show MoreIn this paper, a new approach was suggested to the method of Gauss Seidel through the controlling of equations installation before the beginning of the method in the traditional way. New structure of equations occur after the diagnosis of the variable that causes the fluctuation and the slow extract of the results, then eradicating this variable. This procedure leads to a higher accuracy and less number of steps than the old method. By using the this proposed method, there will be a possibility of solving many of divergent values equations which cannot be solved by the old style.
MR Younus, Nasaq Journal, 2022