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 current research aims to identify: 1. The level of mathematical construct among the Department of Mathematics students in the colleges of education and basic education. 2. The level of effective mathematical operations in both sides of the brain at the Department of Mathematics students in the colleges of education and basic education. 3. The strength and direction of the correlation between the mathematical construct and effective mathematical operations on both sides of the brain at the Department of Mathematics students in the colleges of Education and Basic Education. To investigate the research objectives, the researcher formulated zero-main hypothesis for each aim and from the same hypothesis, three sub-zero hypotheses are deri
... Show MoreThis study aims to impact statement played by banking governance according to the decisions of the Basel Committee in achieving the strategic objectives of the banks, But order to achieve the this goal has been the adoption of two hypotheses in addition to the two main hypotheses as sub answered preliminary The study seeks to verify their health and two (no correlation relationship and impact between Banking governance and achieve strategic objectives), has been tested hypotheses. Study has reached
... Show More
(1)
The Necessity of College of Education for Woman from the Point of view of Students
Time is very important in educational institutions. It is also one of our contemporary problem ‚as time is a clear – cut and limited factor‚ it demands that administrators should monitor it by administering and monitoring the principles of time.
Hence‚ the researcher attempts to identify the skills of administrating time and the reasons that cause the waste of time of the Heads of Departments at university of Baghdad.
Significance of the research:
Time is very important to all educational administrators and one of them is the institutions of Higher education. One of the
... Show MoreThe plant licorice is considered important plants as nutritionally and medically and economically, as a rich in phytochemical, vitamins and minerals, and being widely available, Research indicated the presence of many nutrients such as (proteins, Carbohydrates, vitamins and minerals) as well as presence of Glycyrrhizin which responsible of sweet taste, that allowing the possibility to use it as natural intensity sweetener with few calories in Sweetening of many food. This research is aimed to study the Stability of Glycyrrhizin toward the various manufacturing conditions such as (thermal treatment, pH of foods and microwaves), so three factorial experiments was implemented to find out the Stability as following: 100C° - 121C° - Microwa
... Show MoreThe research aims to identify the extent to which Iraqi private banks practice profit management motivated by reducing the taxable base by increasing the provision for loan losses by relying on the LLP it model, which consists of a main independent variable (net profit before tax) and independent sub-variables (bank size, total debts to total equity, loans granted to total obligations) under the name of the variables governing the banking business. (Colmgrove-Smirnov) was used to test the normal distribution of data for all banks during the period 2017-2020, and then find the correlation between the main independent variable sub and the dependent variable by means of the correlation coefficient person, and then using the multiple
... Show More
Abstract
This study aims to find the relationships between social capital (social network, social trust, shared goals) and knowledge sharing (knowledge Donating, knowledge collecting) as independent variables and their impact on improving the quality of educational services (academic staffs quality, Quality of teaching methods and study curriculums). This research is an important, because it attempts to identify the relationship between social capital and the knowledge sharing and their effect on improving the quality of educational service for universities. The study problem was determined in several questions related to the nature of the correlation relationship - the impact between the different independent variables (
... Show More
(1)
This study research to Showing The impact of the integration process on the quality of Insurance service and analyze the impact financially to determine whether there is any impact on the quality of the insurance service, in addition to identifying the obstacles that impede the merger between the insurance companies, insurance and the appropriate proposals for its' application and benefit from the benefits achieved.
The importance of The study lies in the fact that it is an important and vital spotlight that is becoming increasingly important in the world to confront the various difficulties and crises that have occurred recently in light of the liberalization of international trade, globalization a
... Show More
(1)
(Social values) are of great importance in the lives of nations and peoples as they are the frame of reference that governs the relations of members of society to each other and regulates their life affairs.
And the Prophet of Islam (may God’s prayers and peace be upon him) has told about a group of (social values) such as: spreading peace, feeding food, being fair in dealing with others, and clarifying what a Muslim should have towards his Muslim brother from the safety of the chest and refraining from harming him with the tongue and hand, and so on. Ethics and behaviors that are directly and closely related to (social values).
The best book that abounds with these (social valu
... Show More