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.
Tuberculosis (TB) still remains an important medical problem due to high levels of morbidity and mortality worldwide. A series of innate immune mechanisms that create a cytokine network control the pathogenesis of tuberculosis and this response has the capacity to modify the host genomic DNA structure through epigenetic mechanisms such as DNA methylation which could constantly alter the local gene expression pattern that can modulate the metabolism of the tissues and the immune-response. Interferon-gamma (IFN-γ) is an important pro-inflammatory cytokine regulator of the innate immune response to TB. This study aims to determine DNA methylation patterns of INF-γ gene promoter and measure serum IFN- γ level in newly diagnosed TB patient
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Introduction & Aim: Long-term diabetes mellitus (DM) is known to have a deleterious impact on bone health, resulting in change in bone mineral density, bone turnover, and bone quality, all of which increase the risk of fractures. The aim of. this study was to link immunological and pro-inflammatory cytokine (I.L-6, I.L-1, and TNF-alpha) markers in patients.with type 1 diabetes to Their connection to bones formation (sPINP) and bone resorption parameters (sCTX). Materials & Methods: This study included 80 patients suffering from T1DM in the age range of 20-45 years. The patients were assayed for their biochemical (Vitamin D and HbA1c), Immunological (IL-6, IL-1 and TNF-alpha) parameters, as well as bone formation and resor
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Abstract:
The purpose of this research is measuring relationship level and impact between Organizational Factors and their Dimensions (Leadership, Organizational Structure, Organizational Culture), and Talent Management Strategies (Talent Recruitment,Talent performance management, Talent Development, Talent Retention ). it was relied on the Questionnaire form as a basic instrument in collecting the Data by using (Likert) instrument ,which was distributed on the research Sample which number was (100) individual included (Managers of schools, assistants (scientific and Administration ) and teachers in Four schools of Talents in Iraq (Baghdad , AL-Nagaf , AL-Basra, Mesan). All fo
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The economic units always sought to maintain its market position and Trchinh the technology management and modern methods that will support success factors .vdila about it has become a customer and one profitability analysis of the most practical way benefit of economic units as modern management focus their attention on achieving this satisfaction, as the customers make up the axis of the success of every organization and that there are many government units aiming to profit directs attention to customers and the number of these units increased continuously. The administration used the customer profitability analysis in order to obtain information to assist in making and decision-making process. How to use modern tec
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The housing sector in Iraq has suffered from multiple problems, the most prominent of which is the failure of the housing market to achieve housing production that faces population increases and a high number of households.
The research aims to foresight the future of the housing sector, and to identify the expectations of experts in the development of the housing sector and housing production, in order to overcome the obstacles and problems.
Foresight does not mean forecasting about future events, but rather it is a process and skill aimed at familiarity with providing sufficient knowledge to achieve the desired future goals, Accordingly, adopting a method of future foresight will reduce error, surprise and s
... Show MoreWe can conclude that version A is substantially genuine while version B is spurious. an Attempt has been made above to show relevance of this to our understanding of the agreement itself .
The central issue of sunna to which recourse was to be had must of course be connected with development of the meaning of the word sunna from the broader (way of Proceeding ) and (generally agreed practice).
Any sweeping judgements about the invalidity of reports transmitted by shiis or supposed shii are out of place. theestablishment of realistic criteria for the appreciation of early sources for Islamic history is subject which is still in Its infancy
The theory of the psychologist’s Piaget states that man passes through four stages; other says that mankind passes through five. At each stage, human learn new characteristics, values, skills, and cultures from different environment that differ from one society to another. Therefore, the cultures of societies vary according to the diversity of the environments. These environments also vary depending on the circumstances surrounding them, e.g., in war environment, the individual learns what he does not learn from living in safe environment. As the environment changes, the communicative message also changes. This message is subject to person, groups, organizations and parties and directed to a diverse audience in its orientations and bel
... Show MoreThis study has came as a result to discover on the references of the educational theories which leads the professors in the educational art departments in the Iraqi universities through knowing these ideological references indeed in an important slice of the society. This slice is: the members of professoriate. The study goal knows the ideological references to these theories for the professors in these departments.
In order to approve the research's goals. The researcher has selected a sample contains (50) professoriate members in these departments in the Iraqi universities which they have the educational art profession among the next scientific degrees (assistant teacher. teacher. assistant professor & professor).
The resea
The aim of the current research is to develop the social studies curriculum at the primary stage in light of the standards of the next generation, which was represented in three main dimensions (pivotal ideas, scientific practices, and comprehensive concepts). The researcher designed a tool for the study, which is a content analysis card in the light of (NGSS) standards, based on the previous main dimensions. The descriptive analytical approach was adopted in analyzing the social studies curriculum for the primary stage to determine the degree to which the standards of the next generation are available, as well as to establish the theoretical framework related to the research variables. To develop the social studies curriculum in light o
... Show MoreThe implicit pattern is one of the cultural patterns that are present in both the text and theatrical presentation and the reading of the implicit pattern cannot take place without cognitive references, whether audio or visual as well as historical references and the natural, social and psychological dimensions of communities and individuals.
The researcher, in this study, attempted to focus on the axis of the aesthetic preoccupations of the implicit pattern in the theatrical presentation and the definition of the implicit pattern. Methodologically speaking, the research problem focused on revealing the outlines and the main features in the aesthetic preoccupations that shape the i
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