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.
This research deals with the color bias and its effect on maids in Mississippi in Kathryn Stockett''s (2003) The Help. The ill-treatment and negligence of Afro-American maids received from the white women who employed them in Mississippi that must have affected directly or indirectly on their personality and may eventually lead to suffering. They live in an atmosphere of struggle to free themselves from the complicated relationships between black and white. Afro-American maids pledged to liberate themselves from social oppression by protesting through writing a book which chronicles their stories in slave masters’ homes to make their presence felt as human being equal to their white masters.
Recently, a new secure steganography algorithm has been proposed, namely, the secure Block Permutation Image Steganography (BPIS) algorithm. The new algorithm consists of five main steps, these are: convert the secret message to a binary sequence, divide the binary sequence into blocks, permute each block using a key-based randomly generated permutation, concatenate the permuted blocks forming a permuted binary sequence, and then utilize a plane-based Least-Significant-Bit (LSB) approach to embed the permuted binary sequence into BMP image file format. The performance of algorithm was given a preliminary evaluation through estimating the PSNR (Peak Signal-to-Noise Ratio) of the stego image for limited number of experiments comprised hiding
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The research aims to determine the role of the training strategy with its dimensions of (strategic analysis, formulation of training strategy, implementation of training strategy, evaluation) in the pioneering performance of the organization with its dimensions of (pre-planning , renewal and modernization, efficiency, effectiveness). Important and modern in pioneering performance and training strategy, and in recognition of the importance of the subject and the expected results of the surveyed banks, an analysis was made of the data obtained through field visits in addition to the questionnaire and interviews ,and the most prominent results that were reached were taking the research sample into consideration all the requirements of the trai
... Show MoreThe present study discusses the problem based learning in Iraqi classroom. This method aims to involve all learners in collaborative activities and it is learner-centered method. To fulfill the aims and verify the hypothesis which reads as follow” It is hypothesized that there is no statistically significant differences between the achievements of Experimental group and control group”. Thirty learners are selected to be the sample of present study.Mann-Whitney Test for two independent samples is used to analysis the results. The analysis shows that experimental group’s members who are taught according to problem based learning gets higher scores than the control group’s members who are taught according to traditional method. This
... Show MoreThis study is at the heart of the pragmatic theory, as this research seeks to highlight the concept of necessity, and what the researchers have tended to do is that the development that has acquired integrated pragmatics is only for the development of the subject of necessity, as it is one of the contents of the saying, and this is what made Decroux define it as the semantic element that Concerning the saying, as for Grace; He paid great attention to the conversational imperative, and understood the requirement by clues or suggestions, as it is an element known for its absence and presence in the linguistic structures included in the text when reading or when understanding. This study has paved the way for clarifying the concept of necessi
... Show MoreLimited importance of research in a stand on the most important difficulties faced by both faculty and parents to communicate with each process to follow up on their children, and the analysis and inventory of the obstacles that hinder the educational process, and work to develop a vision of how to address these constraints and the important role of technology in the treatment of problems of the society so as to develop frameworks future to minimize the errors and the problems they face, and the development outlook for future generations in order to promote the educational level, especially that Iraq is going through a change in conditions in all sectors. Through the questionnaire, which includes questions set that was made on a sample o
... Show MoreThe research was titled: Approval of the Imam of the Nuclear of Iraqis through the curriculum of the students.
The research revolves around the study of the weight of the imam nuclear jurisprudence in which the views of the Iraqi jurists of the Imam Shafi'i agreed through the book of students' approach to the nuclear imam, the research included a brief translation of the nuclear imam, and the definition of his place in the Shafi'i school, and then the definition of Iraqi jurists and then study the jurisprudence The course of research is only three issues, and compared with the views of imams, and the statement of the most correct opinion, and God and the conciliator.
researcher
This research deals with the perceived and the imagined in the texts of Yusef Al-Sayegh, considering language as the most important source in literature and theatrical criticism, and given the importance of the subject, the researcher monitored many philosophical and psychological opinions and theories related to (the perceived and the imagined), and they were discussed and their compatibility with the Iraqi theatrical t As for the second chapter, where (the theoretical framework), it included two topics, and the first topic was about the concept of the perceived and the imagined, and the second topic was about Youssef Al-Sayegh and the structure of the theatrical text.
In the third chapter, where (research procedures), the research
The research, which was drawn from his doctoral thesis (People's Policy towards Vietnam 1949-1979), discussed the roots of the connections between the Chinese and Vietnamese communists since the 1920s, the presence of Ho Chi Minh and other Vietnamese communists in China, their influence by the revolutionary struggle of the Chinese Communist Party and their establishment of a group of The Vietnamese Revolutionary Societies and the Indo-Chinese Communist Party until the outbreak of the Vietnamese Revolution and their success in declaring the establishment of the Democratic Republic of Vietnam in 1946. Keywords: Ho Chi Minh, Chinese Communist Party, Indo-Chinese Communist Party, Democratic Republic of Vietnam, Chou En Lai.