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.
Administrative procedures in various organizations produce numerous crucial records and data. These
records and data are also used in other processes like customer relationship management and accounting
operations.It is incredibly challenging to use and extract valuable and meaningful information from these data
and records because they are frequently enormous and continuously growing in size and complexity.Data
mining is the act of sorting through large data sets to find patterns and relationships that might aid in the data
analysis process of resolving business issues. Using data mining techniques, enterprises can forecast future
trends and make better business decisions.The Apriori algorithm has bee
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The tourism activity is one of the pillars on which the economy of any country is based , the importance of the tourism sector is reflected in its potential to become an effective development alternative in many countries, especially Iraq ,this has a direct impact on the national economy as an important source in attracting hard currency and eliminating unemployment. Adding the Iraqi Marshlands to the list of effects makes it contribute to diversification of sources of income and stimulating rest of the economic sectors, the potentials and qualifications possessed by Iraq in the field of tourism and monuments have a significant impact on the state budget if they were exploited optimally. The research aims at identifying the contr
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Progesterone is highly used in pregnant women as therapeutic agent to maintain and support pregnancy. To explore the effects of progesterone usage allover gestation till 7days postnatally on mice offspring ovaries development and anogenital distance. Ten pregnant mice were equally divide into control group that was injected with sesame oil which is used as a solvent for progesterone and treated group that is daily intraperitoneally injected with progesterone (dissolved in sesame oil 1: 10) at dose 10.2 mg/kg (the equivalent human dose) all through gestation till7day postnatal then sacrificed and measuring the anogenital distance (the distance between anus and genital papilla). Histological slides were prepared, and Diameters of the ovary, p
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Different cooking conditions were examined for aluminum content in food cooked while wrapped with aluminum foil. The influence of each anticipated factor (the acidity of the cooking medium, type of acids normally used in cuisines namely acetic and tartaric acids, various cooking temperatures, influence of the presence of sodium chloride salt, the effect of cooking oil, and the length of time of cooking) was studied thoroughly as a function of aluminum degraded out of the aluminum foils to the medium. The experimental samples were digested with nitric acid upon fulfillment of examining each factor separately before quantifying aluminum with the sensitive technique of atomic absorption spectroscopy. The outcomes of the study have shown that t
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In this study, the Earth's surface was studied in Razzaza Lake for 25 years, using remote sensing methods. Images of the satellites Landsat 5 (TM) and 8 (OLI) were used to study and determine the components of the land cover. The study covered the years 1995-2021 with an interval of 5 years, as this region is uninhabited, so the change in the land cover is slow. The land cover was divided into three main classes and seven subclasses and classified using the maximum likelihood classifier with the help of training sets collected to represent the classes that made up the land cover. The changes detected in the land cover were studied by considering 1995 as a reference year. It was found that there was a significant reduction in the water mass
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This study examines the analysis of the contents of the international public relations campaign in confronting the Covid-19 virus, which was taken from the (Your Health is a Trust) campaign for the World Health Organization, Iraq office.The research problem revolves around a main question that is, what are the axes of the campaign (Your Health is a Trust) established by the World Health Organization (Iraq office) in the prevention of Covid 19 virus?From this main question, several sub-questions emerged that this study answered on their Facebook page, and the communication activities of the Covid-19 awareness campaign. In the content analysis form, as this form included a number of main themes and main categoriesthat were adopted in analyzin
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Abstract
There has been a heated controversy over the role the financial policy plays and how sufficient it is in affording the financial burden. This burden is known as the operational current expenses which the governments of various countries mainly afford, despite the discrepancy in the government’s economic policy. After the deterioration and deficit in the state budget in all countries nowadays, it was necessary to find an appropri
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Abstract:
This research aims to the importance of oil in achieving economic
security in the Arab. Oil is not an ordinary subject and returns it significance to
the followings:
1. The importance of skipping a source of energy.
2. The importance of oil as raw material for petrochemical industry.
3. The importance of the oil sector as an area of foreign investment
4. The importance of oil in the marketing activities, transport, insurance
and various services
In addition to the importance of oil in general and the Arab oil has
additional strategic advantages such as geographic location, And the
magnitude of reserves and production of heavy investment costs are relatively
simple, And the ability to meet the
The escalating development of technology is one of the distinctive features of the communication environment in the field of sending and receiving satellite broadcasts of television channels in general and Iraqi satellite channels in particular, which contributed to the wide and rapid spread and reaching outside the drawn boundaries and bypassing even natural obstacles, and what is important in this is the communication content that these broadcasts Channels and its impact on the recipient due to the media, cultural, educational and entertainment content it provides, and in our research we will analyze the communication content of the Iraqi satellite channel by choosing one of its dialogue programs that coincided with the events of the l
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كانت وسائل الاعلام- التقليدية والحديثة – وستبقى وسيلة مهمة لتدفق المعلومات والتعبير عن المشاعر ووصف الاحداث وتشكيل الرأي العام المحلي والدولي عن مختلف القضايا التي تهم الافراد والمجتمعات وفي مقدمتها قضايا العنف بمستوياته كافة ،والتطرف الديني والارهاب بكل مسمياته وستحاول هذه الدراسة ان تقدم اجابات عن اسئلة محددة تمثل الاطار النظري لدراسات مسحية ترصد النظريات التي ترسم الاطر النظرية الت
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