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 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
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The sciences related to the Book of God are many, and the benefits of every science in it are abundant, and among those sciences is the science of readings, which is for the sake of science and the most honorable, due to its strong attachment to the Book of God Almighty. From this care, and aims to show the attention of scholars to the science of readings in general and the scholars of the fifth century in particular, as the literature on it abounded until it became the principal for those who came after them.
The research consists of an introduction that includes the objectives of the research, the reasons for choosing it, previous studies, research questions, and research terms, then a preface dealing with the im
... 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 MoreThe current research aims to identify the time-management skills based on the post-test of the experimental group as well as to examine the effect of a training program on developing the skills of managing time among the study sample. To achieve the research objectives, the researcher designed a scale of time management skill included (30) paragraphs. The research reached that the training program is significantly effective in managing and organizing time. There are statistically significant differences in pre-posttest between the experimental and control groups.
Contracting cancer typically induces a state of terror among the individuals who are affected. Exploring how chemotherapy and anxiety work together to affect the speed at which cancer cells multiply and the immune system’s response model is necessary to come up with ways to stop the spread of cancer. This paper proposes a mathematical model to investigate the impact of psychological scare and chemotherapy on the interaction of cancer and immunity. The proposed model is accurately described. The focus of the model’s dynamic analysis is to identify the potential equilibrium locations. According to the analysis, it is possible to establish three equilibrium positions. The stability analysis reveals that all equilibrium points consi
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Most of the mosques in the Islamic world fall under specific and known forms and patterns to a large extent, and such patterns have grown and evolved from the few basic and uniform models, but they changed slowly due to the impact with a mixture of changing functional requirements and cultural landscapes because of the variables of time and place to form patterns known and famous in this day across parts of the Islamic world and its borders. There was no exception to these patterns, but small numbers of mosques that were probably the result of personal experiences or improvisational resolutions, or in response to specific or temporary stimuli. However, the emergence of a specific pattern which does not belong to any of these patt
... Show MoreWith the twenty - First century, It becomes clear to us that for 110 years the Japanese - Chinese relations have been witnessing big radical events and developments. ( we take the year of 1949 as the starting date for this relations). In order to prove hypothesis the study divided in to four chapters. - The first chapter deals with explaining the factors of the subject of the Japanese - Chinese relations which described as Indirect threat and aggressive relations from Japan to China after the Second World War by Japanese entering in the American world strategy, in order to destroy the communist china's system which decleard in 1949, because the united states understood that the new system in Beijing could threat American's Interest
... Show MoreAbstract:In this research we prepared nanofibers by electrospinning from poly (Vinyl Alcohol) / TiO2. The spectrum of the solution (Emission) was studied at 772 nm. Several process parameter were Investigated as concentration of PVA, the effect of distance from nozzle tip to the grounded collector (gap distance), and final the effect of high voltage. We find the optimum condition to prepare a narrow nanofibers is at concentration of PVA 16gm, the fiber has 20nm diameter.
The interaction in the city is reflected in the movement of people motivated by their activities and their economic and social goals, which include many variables subject to the planning process in the interpretation of this movement and the mapping of trends of transport intensity through the concept of transport function and its functional relationships with the uses of the earth in the sustainability and effectiveness of the movement of transport and Economic activity and population movement. Transport planners are concerned with the requirements of land use, which are linked to and included in the transport planning process as a factor for the future transport needs. There is a strong relationship between the transport system
... Show MoreThe current research presents a study of the sculptural body in the space of the theatrical show through reviewing most of the ideas, propositions and workings presented by philosophers and directors within the space of the show, that there were various experiences of employing those spatial formations through the mediator (the space) based on sculpturing the body in achieving those formations, which contributed in building a symbolic picture of various structural connotations. That was formulated through the research chapters, which include the first chapter (the methodological framework) which consists of two sections. The first section (the duality of space formation and imaginations). The second section (sculptural body sequences in
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