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 research aims to shed light on the amount of proceeds annual tax for each of the way the contract total and percentage of completion method - see which is better - as well as the current problems arising from the application method of the contract in full in settling accounts tax - to identify problems - related to postpone settling accounts tax in accordance with the way the contract fully and determine the advantages and disadvantages of each of the methods through practical application , and then use the results as inputs to help in the decision to confirm the continuation of the GCT using a full decade in settling accounts tax for long-term construction contracts or forgo them.
Were the result of research the existence of
... Show MorePraise be to God, Lord of the worlds, and peace and blessings be upon our master Muhammad and his family and companions as follows:
For God Almighty has swapped for every age a group of religious scholars who give news to the narrators, so that they can lie against the Sunnah of the Mustafa, who is among those who memorized Ibn Al-Mulqin, as he followed the ruler in his book Al-Badr Al-Munir in the Hadith of Al-Sharh Al-Kabeer, and our research included two topics, which we explained in the first topic: The sequels in which the teacher's son Al-Malqin disagreed, and we discussed in the second topic: the followings in which Ibn Al-Malqin agreed to rule.
This research included important results, th
The study aims to achieve several objectives, including follow-up scientific developments and transformations in the modern concepts of the Holistic Manufacturing System for the purpose of identifying the methods of switching to the entrances of artificial intelligence, and clarifying the mechanism of operation of the genetic algorithm under the Holonic Manufacturing System, to benefit from the advantages of systems and to achieve the maximum savings in time and cost of machines Using the Holistic Manufacturing System method and the Genetic algorithm, which allows for optimal maintenance time and minimizing the total cost, which in turn enables the workers of these machines to control the vacations in th
... Show More
The aim of the study is to reveal the effect of the constructivist learning Model on the achievement and reflective thinking of the fifth grade literary Preparatory students in History subject. A random sample was chosen which consisted of 64 students divided into experimental and control groups, each group consisted of 32 students. The experimental group was taught via the constructivist learning model, and the control group was taught via the traditional method. The experiment was lasted for Eight weeks, each week taught two lessons. The researcher adopted the experimental design with partial control. The two groups were equalized statistically. The researcher used two instruments, the achievement test and the reflective thinking test.
... Show MoreThe principle of rights and duties is part of the reform project of the Commander of the Faithful Ali ibn Abi Talib, to build a state of institutions whose foundations have been built on Quranic rules, a prophetic biography, and his diligence in doing so in accordance with the requirements of interests and evil, and his certainty in determining the most important and important, and research analytical study of speeches Imam Ali and his career, in this study (the principle of rights and duties) of the ruler and the parish because of their role in the reform process, which depends on the demolition and construction together, as it is the responsibility of the ruler to demolish all constructed corrupt and contrary to the principles of Islam
... Show MoreThis paper describes the first occurrence of the monogenetic trematode Silurodiscoides
mediacanthus (Achmerow, 1952) in Iraq from gills of the cyprinid fish Barbus luteus from
Diyala river, Diyala province, Iraq. The description and measurements of this parasite were
given. In addition, key for the identification of the three species of Silurodiscoides, so far
recorded from freshwater fishes of Iraq, is included.
The aim of the research is to measure the length between the variable the efficiency of the tax examiner with its dimensions represented by (scientific questions, practical process (experience), training and development, impartiality and independence, ethics of the profession) and the approved variable discovering the artificial adaptation of profits, and the degree of arrangement of those dimensions its importance and priority, and the research problem has been identified In a main question that is there any effect of copying the images of the image examiner in discovering the adaptation, the financial statements and reports of the companies (X, Y) and the banks (A, B) were relied on in the interpretation of the results, t
... Show MoreThe problem of research is that there are differences between learners in processing in formation in general and there is variation at the learners level perform scrolling skill of the passes up and down by the volley ball .Therefore the researchers decided to conduct astudy through which identify the relationship between information processing and the skill of scrolling from the top and bottom by the volleyball. The researchers used the descriptive approach by themethod of interconnectivity .Asampleconsist of21 students from first staye in collage of physical education and sports science for Girls(university of Baghdad) and attest has been applied(process information and scroll up and down) on the research sample after the required
... Show More
The aim of the study is to reveal the effect of the constructivist learning Model on the achievement and reflective thinking of the fifth grade literary Preparatory students in History subject. A random sample was chosen which consisted of 64 students divided into experimental and control groups, each group consisted of 32 students. The experimental group was taught via the constructivist learning model, and the control group was taught via the traditional method. The experiment was lasted for Eight weeks, each week taught two lessons. The researcher adopted the experimental design with partial control. The two groups were equalized statistically. The researcher used two instruments, the achievement test and the reflective thinking test.
... Show MoreThe research aims to reveal the availability of skills to develop the tax assessor when carrying out the tax examination process. The study was conducted in the branches of the General Tax Authority in the province of Baghdad (the General Authority for Taxes, Adhamiya branch, the General Authority for Taxes, Rusafa branch, Al-Bayaa branch, New Baghdad tax branch) was approved The descriptive approach to achieve the research objectives represented by answering the following two questions: 1- What are the necessary skills that should be available in the performance of the tax examiner? 2- Are the skills of developing a tax evaluator available? The two researchers used the closed questionnaire as a tool for their research. The quest
... Show More