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.
Many changes took place in a number of Arab countries, most of which ended with the change of the ruling leadership and a new coming. The same change brought about the hopes of the people to turn the page of the past into a democracy through which to overcome the grievances of previous years and achieve justice in all its aspects. The same new grievances have been added to that precedent and justice has not yet been achieved. Here we try to address the justice that is applied in the stages of change or transitional stages, which have been called, ie transitional justice, which has mechanisms and conditions of different application between countries, each of which the conditions applied in them and through a review of these mechanisms bet
... Show More
The mechanical function of the heart is governed by the contractile properties of the cells, the mechanical stiffness of the muscle and connective tissue, and pressure and volume loading conditions on the organ. Although ventricular pressures and volumes are available for assessing the global pumping performance of the heart, the distribution of stress and strain that characterize regional ventricular function and change in cell biology must be known. The mechanics of the equatorial region of the left, ventricle was modeled by a thick-walled cylinder. The tangential (circumferential) stress, radial stress and longitudinal stress in the wall of the heart have been calculated. There are also significant torsional shear in the wall during b
... Show MoreNanocrystalline TiO 2 and CuO doped TiO 2 thin films were successfully deposited on suitably cleaned glass substrate at constant room temperature and different concentrations of CuO (0.05,0.1,0.15,0.2) wt% using pulse laser deposition(PLD) technique at a constant deposition parameter such as : (pulse Nd:YAG laser with λ=1064 nm, constant energy 800 mJ, with repetition rate 6 Hz and No. of pulse (500). The films were annealed at different annealing temperatures 423K and 523 K. The effect of annealing on the morphological and electrical properties was studied. Surface morphology of the thin films has been studied by using atomic force microscopes which showed that the films have good crystalline and homogeneous surface. The Root M
... Show MoreThis 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.
A restrictive relative clause (RRC hereafter), which is also known as a defining relative clause, gives essential information about a noun that comes before it: without this clause the sentence wouldn’t make much sense. A RRC can be introduced by that, which, whose, who, or whom. Givon (1993, 1995), Fox (1987), Fox and Thompson (1990) state that a RCC is used for two main functions: grounding and description. When a RRC serves the function of linking the current referent to the preceding utterance in the discourse, it does a grounding function; and when the information coded in a RRC is associated with the prior proposition frame, the RRC does a proposition-linking grounding function. Furthermore, when a RRC is not used to ground a new di
... Show MoreThis research aims to address the most recent international standard in the field of insurance contracts, the International Financial Reporting Standard (IFRS17) and the theoretical framework of the standard in addition to the most important characteristics of the standard (IFRS17), as well as to identify the paragraphs of the modern standard, with the challenges its application in general and the use of the approach (inputs - operations - outputs) to present the challenges of its application in the Iraqi environment and specifically in the environment of Iraqi insurance sector companies (government), the research is based on the main premise that the identification of the requirements for the application of the International Fin
... Show More
The political participation of the Iraqi woman, gains a big importance equivalent to its role in all other fields. Therefore , it represents a higher value in the democratic orientation in addition to the importance of rising the reality of the woman specifically in the fields that are considered as a scale of the human development like the income, health, and education . The weakness of womenʹs political participation, is something that can't be ignored or neglected if we are looking forward to the rising of the country᾽s reality and achieving the required development in its all aspects. The woman is half of society or more than that due to the burden of raising the generations tasks. This can be achieved by taking part in th
... Show More
Abstract
The research is presented according to an objective study on the ideological problems, especially the distortions that the divine scriptures have been subjected to under a false pretext that does not pertain to religion, namely that the heavenly books of the Torah and the Bible have been damaged or lost as a result of apostasy and persecution, and the writing of these books has been entrusted by people who have been bestowed Holiness, they have the testimony of the Church, so they distorted and omitted it in a manner suitable for securing their good and worldly gains, and the Holy Qur’an mentioned this explicitly, and they continued later, especially the Jews, in distorting the verses of the Holy Qur’an. This researc
... 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 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