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.
Background: One common undesirable side effect of orthodontic treatment with fixed appliances is the development of incipient caries lesions around brackets, particularly in patients with poor oral hygiene. Different methods have been used to prevent demineralization; the recent effort to improve the resistance against the demineralization is by the application of lasers. Materials and method: Thirty human premolars extracted for orthodontic purposes were used to test the effect of two energy level of ER-YAG laser on enamel resistance to demineralization. The brackets were bonded on the teeth and all the labial surface excluding 2 mm area gingival to the brackets were painted with acid resistance varnish. Three groups were generated. The fi
... Show MoreLaryngoscopy and tracheal intubation are considered the most invasive stimuli in anesthesia. They provoked cardiovascular responses that include hypertension, tachycardia and dysrhythmias. Various pharmacological approaches have been used to blunt or attenuate such pressor responses. The present study was designed to evaluate the effect of medazolom, lignocaine and propranolol as a valuable adjuvant to fentanyl in attenuating hemodynamic responses to endotracheal intubation in normotensive patients. Thirty two patient with physical status I or II according to the score of American Society of Anesthesiologist (ASA), scheduled for elective surgery under standard general anesthesia, were randomly allocated into four groups (8 patients in ea
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The basis of the personality of each individual lies in the early years of his or her life. If the personality of the child has been well organized and if the motives have been fully expressed and effectively directed, the child will have a strong will, happy self-confidence and a strong personality. If there is a failure In the early years, the individual will be unable to meet his responsibilities in life and may be the victim of many psychological disorders. The family is a learning process through which children acquire the customs, traditions, attitudes and values prevailing in their social environment. (Pre-and-after) play and its relationship to parenting methods of (democratic-bullying-overprotection- and neglect), which wi
... Show MoreThe regulatory authorities have implemented various standards to address the risks associated with credit facilities. One important aspect is the use of the Credit Bureau System (CBS), which plays a central role in ensuring banking soundness. Thus, the study seeks to explore the role of CBS in attaining banking soundness as a fundamental principle. The research sample consisted of three Iraqi banks spanning from 2010 to 2022. The research findings indicated that the implementation of CBS had a significant positive impact on achieving Banking Soundness (BS) rates in my bank. Furthermore, the asset quality index's value increased significantly, surpassing the standard value of 5%. It became evident that the banks needed to formulate a well-de
... Show MoreThis study dealt with the basics of financial inclusion in terms of concept, importance and objectives, The empowerment of women financially and bank ,and then the relationship between financial inclusion and women, and determine the requirements of inclusion Financial resources for women. The analytical descriptive method was used for data, which included reviewing and analyzing information and data in economic and financial literature. The study: reached a number of conclusions, the most important of which are Financial inclusion contributes to women's financial and banking support, as there is a positive relationship between financial institutions Banking and women's access to financial and banking services, thus playing a rol
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تدور الدراسة في علم الاقتصاد المنزلي حول احتیاجات الانسان الضروریة لاستمرار الحیاة ومواقف في محیط
الاسرة وتفاعل مع ظروف البیئة المحیطة بھ .والتي تكون دائمة التغییر لذلك یمكن تعریف علوم وفنون الاقتصاد
المنزلي وفنونھ انھا عبارة عن مجموعة منظمة من المعارف والعلوم تتركز في محور الاسرة والمنزل حیث ینمو
ویتطور الانسان بالعلاقات الانسانیة والنواحي الاقتصادیة والاجتماعیة من جھة والنواحي العلمیة وا
The aim of this research was to analyze the financial reporting requirements of segmental information that stipulated by the Iraqi accounting rules, investigating the extent of it compliance with the requirements of the International Financial Reporting Standard No.8 (IFRS 8) and the Statement of Financial Standards No.131 (SFAS 131). Also the research aimed to identify the segmental disclosure practices in listed corporations on Iraq Stock Exchange (ISX), basing on a hypotheses said that “the insufficient of Iraqi financial reporting requirements of segmental information affect<
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The study aimed to exposure young university students and students talk programs offered by satellite TV exposure, as it represents these programs great importance Information Public Knowledge in general And the youth in private Including Posed From Opinions And ideas About Different Issues Raised Which Charges Opinion, And that Through Application Study Survey To Sample From Students of Diyala University, the Researcher display Public Accrediting Theory To Information Which Provided Means Media To achieve Objectives And satisfy Needs And hypotheses . The Problem Search was Determined Through Study of students of Diyala University exposure Programs Talk And measured&
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The economical units in the world face great and rapid challenges in all aspects, a matter that requires facing these challenges throughout continuous improving and developing in their performance to keep their competitive position "place".
The Benchmarking Technique is one of the modern managerial tools that are proved to be successful in application throughout making continuous comparisons between products or services and the best – performance levels the compete with it . This is achieved to develop its performance and give it the competitive criterion with which it faces its competitors.
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A polycrystalline CdTe film has been prepared by thermal evaporation technique on glass substrate at substrate temperature 423 K with 1.0 m thicknesses. The film was heated at various annealing temperature under vacuum (Ta =473, 523 and K). Some of physical properties of prepared films such as structural and optical properties were investigated. The patterns of X-ray diffraction analysis showed that the structure of CdTe powder and all films were polycrystalline and consist of a mixture of cubic and hexagonal phases and preferred orientation at (111) direction.
The optical measurements showed that un annealed and annealed CdTe films had direct energy gap (Eg). The Eg increased with increasing Ta. The refractive index and the real p