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.
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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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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This study was done at Al-Balad City Hospital on 60 diabetic patients (25 male and 35 female). The study included Fasting Blood Sugar and fungal diagnosis (systemic and superficial fungus). The results showed that the high concentration of blood sugar belonged to the group > 70 years among the diabetic patients with high significant differences in comparison with other groups P<0.001 . The result showed that percentage of female systemic fungus infection was higher than male systemic fungus infection ( female 63% and male 24%) and vice versa about superficial fungus infection (female 37% and male 76%) . Data showed that the percentage of nail fungus infection among female diabetic patients was higher than the percentage of male diabetic p
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After the political change in Iraq in 2003, Iraq witnessed a stage of social and political development and the strengthening of the legal foundations of the state system, by the approval of the permanent Iraqi constitution of 2005, and stipulating the quota system.
Iraqi women participated in the parliamentary elections from 2005 until 2021, and despite the participation of Iraqi women in all elections, there are challenges that women in Iraq face that prevent their political participation in general and participation in parliament in particular. There are factors behind this, including those related to Iraqi women themselves, including those concerning the political institution and factors related to the nature of society, and it
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The media plays an important role in a number of functions performed by them. Press is one of those media which had and still have a clear role in addressing the various issues, topics, and events. Journalism is no longer as expressed by owners of the liberal theory – it seeks to raise the instincts – but it began to excite the minds of readers to meet their needs. At the same time, it does not neglect the search for the truth and work to deliver it to readers. Some have identified a set of tasks carried out by the press including the interest in public affairs, the needs of the community, work to provide happiness, what is beneficial and useful and combat the negative phenomenon and to address the deviations facing society. The comi
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The Economist opinion (views) gathered on the great Importance’s of small enterprise on the production sectors at Developed or in developing countries, statistics indicate that these enterprise represent almost 90% of the total enterprises in most economies in the world.
Many of these enterprises have originated in Iraq since the beginning of last century and the question of financing these enterprises remained an issue facing the most of workers in this sector, because of the peculiarty of which are characterized by which as a lack of financial abilities and the difficulty of obtain the sources of financing in Iraq and considered the enterprise as the guarantor of fulfilling Financial obligations. Afte
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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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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
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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