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.
In this study, we investigate the behavior of the estimated spectral density function of stationary time series in the case of missing values, which are generated by the second order Autoregressive (AR (2)) model, when the error term for the AR(2) model has many of continuous distributions. The Classical and Lomb periodograms used to study the behavior of the estimated spectral density function by using the simulation.
The resort to the eloquence of the poetic image as a style reveals the poet's creativity and creativity in dealing with external influences, and reflect them with emotional images express a sense of intense emotional imagination, and this imagination stems from the experience of a poetic sense of truth, tasted by the recipient before the creator of the poetic text.
The research dealt with its forefront a definition of the aspects of the study and its variables, the explosive capacity and its relationship to the scoring of football for the halls and highlights the importance of these variables, and the problem of the research consisted that some players fail to score Amie because of the weak power of shots or the slow scoring, so the researchers saw studying this problem and knowing the extent of the influence of the explosive strength During the performance of the skill of scoring with five football, the study aimed to identify the relationship between the explosive strength and the skill of scoring with five football. Researchers assume that there is a statistically significant relationship between t
... Show MoreDue to the increasing interest in the quality of auditing by writers, researchers and regulators of the auditing profession. The matter necessitated a statement of the extent to which the auditor practices professional skepticism, because of its significant impact in discovering errors and material misrepresentations contained in the financial statements in order to give the financial community confidence in them and the success of the audit process. The research aims to clarify the concept and importance of the practice of professional skepticism and its effect on the quality of the auditor's performance in Iraq. To achieve the research objectives, the two re
... Show More The current research aims to: (know the effectiveness of the harvesting strategy in the achievement of the students of the Institute of Fine Arts in environmental art.
- In order to know this effectiveness, the researcher put a main zero hypothesis and derived six sub-hypotheses from it. the usual way; As the research community reached (120) male and female students of the Fine Arts Institutes for the morning study in Baghdad. As for the research sample, it was chosen by the simple random method, and the number was (75) male and female students for the year 2021-2022 AD. The researcher applied a pre-knowledge test for the four groups of research to find out the level of previous experiences of students in the subject of environmen
Aim: This abstract aims to highlight the critical nature of climate change as a pressing challenge facing humanity in the 21st century. It underscores the severe consequences it poses to essential facets of human existence, including water and energy resources, agricultural production, and the broader environmental systems. Method: The abstract primarily utilizes a descriptive approach to emphasize the impact of climate change on the Middle East, particularly the Arab region. It relies on a review of existing knowledge and data related to climate change and its effects on ecosystems and drought patterns. Results: The abstract outlines the direct and indirect repercussions of climate change on human life and the environment. It draws atten
... Show MoreThis experiment was carried out at the Grdarash field belongs to the Agricultural researches directorate/general Agriculture directorate-Erbil in September (2007)، 27 Arabic lambs aged (5-6 months) With average initial weight (39.178 Kg/lamb) were used. Lambs were divided in to (3) groups (9 lambs/group). Control group was fed on (85% barely، 10% bran and 5% straw)، and second and third groups were fed on various by-product in replacement with barely in loss and block shape respectively.
The total gain of three groups were (392708.32، 634826.52 & 445613.72 ID resp
... Show More
This research aims to identify the nutritional status of the individual's relationship to malnutrition using anthropometric measurements such as weight, height and impact on the values ??of the blood study sample included 200 male and 200 female of the inhabitants of the cities of Baghdad and Baquba reviewers Central Mahtbrat
The study aimed to identify the reality of the application of cost accounting system in the contracting institutions in Saudi Arabia, and the extent of the reflection of the application of this system on the effectiveness and efficiency of the general performance of these institutions. Where the research community consists of the contracting institutions operating in the Saudi Arabia, and then a suitable random sample was selected from seventy one institutions. The researchers used the historical method to track the previous studies as well as the descriptive approach to conducting the field study. The study data were analyzed by SPSS statistical program.
The results of this study conclude that there is a
... Show More
Government expenditure represents one of the controlling financial policies in the economic affairs and management of the economic cycle in order to achieve price stability, raise the rate of output growth and decrease the level of unemployment. The price stability represents one of the macroeconomic goals that all countries seek without exception, regardless of the economic philosophy adopted by each country; in addition to this is raising the productive capacity and reaching the actual output to the level of the expected output, that is, the level of output related to the natural unemployment rate or what is sometimes called the Non-inflationary unemployment rate. The restriction of government expenditure (G=T+∆B/iP+∆M/P) is
... Show More