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.
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 <
... Show More
The experiment was condncted in greenhouse of Botanical Garden at Biology Garden Dept,College of Education for Pure Science (Ibn-Al-Haitham),University of Baghdad , during the growing season 2013-2014 to study the role of salcylic acid in three concentrations (0.12and24) ppm and two levels of NPKZn fertilizer ( 0. 160) kg.H‾1 and four concentrations of sodium chloride (0.50.100and150) Mmol and the intreaction between salcylic acid and NPKZn on some of morphological parameters of Allium cepa. The experiment was performed with random compelete block design (RCBD)with three replications and the results showed the
... Show MoreBackground 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
... Show More
The article reflects the results of the analysis of the use of metaphors when creating the image of the main character of the story by D. Rubina "You and me under the peach clouds" - a pet, a dog named Kondraty. Through metaphorization, the image of the dog is filled by the author with purely human qualities, thus passing into the category of a full member of the family. The article is a continuation of the study of the work of D. I. Rubina.
The Study aims at evaluating the efficiency of the regional transportation net in Al-mahmoodiya Qadaa center. The bus station of the Qadaa center is suffering from heavy traffic jam, which is due to the ongoing movement of the adjacent provinces, particularly the small cities. They vary in the degree of their link by the regional transportation net that links the province with the centers of big cities. That affects the traffic flow of the civilians of these cities and their daily activities in hierarchical way To achieve the purpose of the study, a questionnaire has been constructed to collect data through selecting a random sample including the passengers who are coming to the bus station in Al-Mahmoodiya center to know the flo
... Show MoreThis research is to take advantage of the performance capabilities which the piano has become famous with and transfer the impact of that advantage to the possibilities of playing the violin. The research aims to introduce the effect of using the piano on the development of the violinists' musical potential. The research, in its literature, focuses on the interpretation of the impact on the possibility of both instruments (piano and violin) in two main sections: the piano (its origin, potential and role in music) and the violin (its origin, potential and role in music). The procedures of the research consisted of presenting a special analysis of a questionnaire consisting of a number of questions presented by the researcher to her resear
... Show More
The research aims to diagnose the causes of the phenomenon of Marketing deception catalog, which is now deployed in the Iraqi market and related to producers and marketers, consumers, regulators and other institutions) and their impact in the areas of prejudice to the consumer protection (product and signifying specifications, price, advertising, packaging), as well as identify differences in the sample responses according to personal variables, it has been the adoption of the resolution as a tool to collect data and information through a sample survey of consumer opinions totaling 108 people in shopping centers in the province of Baghdad and in the Karkh and Rusafa, It was the use of methods selected statistical represented by the arith
... Show MoreThe earthly music has a clear influence on the religious music in the musical culture to read and recite the Holy Quran in the city of Baghdad. This research deals with this subject in an attempt to reveal the influence of the Iraqi maqam in the recitation of Hafiz Khalil Ismail. The methodological framework of the research included the problem of research and its importance as it is useful to the Iraqi schools concerned with the recitation of the Holy Quran in Iraq. The theoretical framework included three sections that serve the literature of its subject: the first is (Iraqi maqam), the second is (the recitation of the Holy Quran) and the third is (the biography of Hafez Khalil Ismail).
The most important procedures
... Show More
Abstract
Heritage represents the center around which poets revolve around and take advantage of its inexhaustible specific, and the connotations that this heritage holds of various values, values and ideas, and the poet Bashar bin Bard from prominent poets who were inspired by that heritage and the culture of the first Abbasid era and whoever and others was worthy of studying and tracking his potentials and capabilities Creativity is based on the inspiration of the legacy of his predecessors, and the development of this legacy and renewal in it. The research methodology required its division into two topics, the first topic, a description of the beauty of women, a description of wine, while the second topic is a description
... Show MoreBack ground: In the present study Pinealoctomy
was used to study the sympathetic innervations of
the pineal gland by the superior cervical ganglion
(SCG) of the albino rat.
Objective: Following Pinealoctomy, it is
expected to observe the Chromatolysis reaction in
some neurons of the SCG if they were to innervate
the pineal gland (i.e. retrograde Chromatolysis
changes).
Methods: Fifty albino rats were used in this study,
Pinealoctomy was done, then after a different time
interval ganglionectomy was done, in order to
study the Chromatolysis in their cell body.
Result: The present study has demonstrated that
the most obvious Chromatolysis reaction in the
neurons which innervate the pineal gland a