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.
An investigation was conducted for the determination of the effects of the forming conditions in the production of Gamma Alumina catalyst support on the crushing strength property. Eight variables were studied , they are ;binder content which is the sodium silicate , Solvent content which is the water, speed of mixing , time of mixing, drying temperature , drying time , calcinations temperature and the calcinations time
Design of the experiments was made by using the response Surface method in Minitab 15 software which supply us 90 experiments .
The results of this investigation show that the crushing strength for the dried Gamma alumina extrudate was affected by the drying temperature and the drying time only and there is no inter
The current research aims to analyze the mathematics book for the first intermediate grade according to the dimensions of mathematical power by answering the following question: What is the percentage of the availability of the dimensions of mathematical power included in the content of the mathematics textbook for first-grade students, average, in its first, and second parts for the academic year 2020-2021, approved by the Iraqi Ministry of Education / General Directorate of Curricula? The research community was determined by middle school mathematics books, and middle school students for middle ,and high school day schools affiliated to the Directorate of Education in Dhi Qar, and by the intentional test, the research sample was s
... Show MoreThe study aimed to identify the E-leadership practice at Princess Nora Bint Abdul Rahman University and to explore the obstacles that are facing the leaders in the implementation of E-leadership, in addition to find mechanisms to improve the practice of electronic driving at the university in light of the Corona pandemic. A descriptive analytical approach was used by depending on a questionnaire to collect the needed data. The study sample consisted of (139) heads of departments, attorneys' colleges and support Deanships universities. The study results showed that E-leadership employment recorded a medium to high degree. Especially at university, that publishing decisions electronically and uses technical means in providing its services.
... Show MoreMany reasons combined behind the Standing of U.S. against Britain in its aggression against Egypt in 1956; the consensus of world opinion on the need to stop the aggression and the fear of the Soviet military intervention which mean a new world war.
United States desired to weaken British influences in the region in general to get new oil gains in the Arabian Gulf and Egypt at the expense of Britain. The exiting of Britain from the area served U.S. strategic interests in the Middle East in general and Egypt in particular to keep the flow of oil for U.S advantage.
The United States wanted to keep its image in the region to apply its future political projects including Eisenhower Project, which intended to take the position of Britis
The research in Islamic history is considered a title for the glory of the nation and a mirror for the intellectual and mental maturity of the men of the Islamic state who played an important role in saving humanity from darkness to light and from ignorance to knowledge and to show their position in building the Islamic state, and to highlight the importance of their conquests of neighboring cities and the expansion of Islam, and for this reason they appear The importance of writing on the topic (The Battle of Dumat al-Jandal and its impact on the era of the Prophethood and the Rightly Guided Caliphate). The reason for choosing this topic was to show the status of Dumat al-Jandal and its importance in the Islamic state and its great role
... Show MoreThe study aimed to prepare a measure of metacognitive thinking commensurate with learning the skill, preparing educational units using the Claus Meyer model for metacognitive thinking, and learning the skill of defending the court in volleyball. To identify the effect of educational units using the model (and Claus Meyer) for metacognitive thinking and learning the skill of defending the court in volleyball. The two researchers used the experimental approach with the design of the experimental and control groups.The research community consisted of students of the second stage / College of Physical Education and Sports Sciences / University of Baghdad for the academic year 2021-2022, whose number is (385) st
... Show MoreThe olive tree, has been used it is important plant for the time being some of their parts on a large scale in the treatment of gastrointestinal disorders and stimulate circulation . Moreover, it is used as antibacterial material and also to address some of the respiratory system, diabetes, food preservation osteoporosis. This study involved the collection of olive leaves from different areas in Baghdad / Iraq. These leaves have been harvested, wash it, then dried and crushed, where the study aimed to identify the active ingredients and chemical elements in the olive leaf as well as its effect on the action of GOT enzyme .The study showed that the aqueous extracts (cold and hot) of the olive leaves powder are acidic in nature pH values
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The research deals with the problems of improvisation in two basic subjects and applied a samples and conclusion. The first topic focuses on the concept of improvisation and spontaneity and clarifies the confusion between them. The second topic deals with the foundations and principles on which the actor is based in his artistic preparation for the purpose of developing his improvisational abilities.
The research focuses on clarifying the dimensions of improvisational techniques and its multiplicity in the modern theater. It analyzes the method of improvisation and its use in the construction and composition of the theatrical performance. It deals with two important experiments, such as the experience of the Russian directo
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The emergence of oil fields and subsequent changes in adjacent land use are known to affect settlements and communities. Everywhere the industry emerges, there is little understanding about the impact of oil fields on land use in the surrounding areas. The oil industry in Iraq is one of the most important industries and is almost the main industry in the Iraqi economic sector, and it is very clear that this industry is spread over large areas, and at the same time adjoins with population communities linked to it developmentally.
The rapid development and expansion of oil extraction activities in various regions has led to many challenges related to land-use planning and management. Here, the problem of research arises on th
... Show MoreThe current research aims to identify the " impact of strategic warheads numbered ( NHT) in the collection average second grade students in the article of history). " To achieve this, I assumed the researcher that there is no different between the statistically significant the average score for the collection of experimental group who teaches the Arab Islamic history on and a strategic warheads numbered and the average score for the collection of the control group who were studying the same article according to the classic method ( traditional) . The study sample consisted of 64 students from the second grade average in the secondary warka bin nawfal in the general Directorate for education first karkh in Baghdad for the annual cources 2
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