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.
Kp index correlates with the many magnetosphere properties, which are used to measure the level of magnetic activity. In the solar system, the two different planets, Mercury with weak magnetic field and Jupiter with strong magnetic field, are selected for this study to calculate the planet's magnetosphere radius (RMP) which represents the size of magnetosphere compared with solar activity through Kp index, through two types of geomagnetic conditions; quiet and strong for the period (2016-2018). From the results, we found that there are reversible relations between them during strong geomagnetic storms, while there are direct relations during quiet geomagnetic conditions. Also it is found that the
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Stick- slip is the continuous stopping& release of the Bit/BHA due to the irregular down-hole rotation prompted by the existing relationship between the friction torque and the torque applied from the surface to free the bit.
Friction coefficient between BHA and wellbore is the main player of stick slip amount, which can be mitigated by support a good lubricators as additives in drilling mud.
Mathematical (or empirical) solves should be done through adjusting all parameters which supposed to reduce stick- slip as low as possible using different models, one of the main parameters is drilling mud. As per Nanoparticles drilling fluid is a new technology that offers high performance
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Irisin is a novel myokine and adipokine, its role during pregnancy and its association with some metabolic risk factors especially pre-pregnancy body mass index (pre-BMI) need more evaluation. The aim of the study is to find whether the pre-BMI could predict irisin levels during normal pregnancy and to clarify associations of irisin with some pathological parameters.
Irisin levels were estimated by ELISA in sera of 59 normal pregnant women who enrolled from December 2016 to May 2017 at Maternity Hospital, Zakho city, Kurdistan region (Iraq). Thirty-two normal-weight pregnant (pre-BMI≤24.9 kg/m2, Age=24.03 mean±3.7standard deviation) and 27 overweight/obese-pregnant (pre-BMI>25 kg/m2, Age=27.6 mean±3.9
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Background: Anaemia is a major public health concern and is one of the most prevalent health issue in women within reproductive age group.
Objective: to assess maternal knowledge related to anaemia during pregnancy.
Type of the study: A cross –sectional study.
Method: The study including 200 mothers who attended selected primary health care centres, Baghdad during November and December 2015, they completed a previously prepared questionnaire coveringsocio-demographic characteristics and knowledge regarding anaemia in 4 main domains. The responses were analysed by using frequency, percentage and percent score for each statement a
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Background Numerous studies indicated that workers in the health sector suffer from work stress, hassles, and mental health problems associated with COVID-19, which negatively affect the completion of their job tasks. These studies pointed out the need to search for mechanisms that enable workers to cope with job stress effectively. Objectives This study investigated psychological flow, mental immunity, and job performance levels among the mental health workforce in Saudi Arabia. It also tried to reveal the psychological flow (PF) and mental immunity (MI) predictability of job performance (JP). Method A correlational survey design was employed. The study sample consisted of 120 mental health care practitioners (therapists, psychologists, co
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This research Sought to identify the correlation relationships and the impact of each of the job description and perceived organizational support, Excellent Job performance of the heads of academic departments in the faculties of the University of Sulaymaniyah Iraqi Kurdistan Region, totaling (89) as President, and to achieve this was Default plan includes research variables as well as the formulation of a number of preparation fundamental assumptions, and researchers used a questionnaire for this purpose as a tool head of the collection of data and information, as it was distributed (80) copies, and the number of retrieved them (76) a copy of a valid statistical analysis, as well as conducting personal i
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The results of previous scientific studies showed that knowledge is something and application is something else, that's why teachers' preparation programs focused, in the present time, on special standards for knowledge and performance, i.e., who has knowledge is not necessary able to apply it in his life or in his field of work, which led to the existence of a gap between knowledge and application. Based on that, those interested in (teachers' preparation) reconsidered their work evaluation, thus the concept of competency appeared at the end of the sixties of the past century to address the negative in teachers' preparation.
The following contains a number of competency features in teachers' preparation programs:
Teachers' effec
The mysterious letters, the philosophy of existence and the meaning of these letters in the Qur'an is one of the mysterious issues that has always occupied the minds of Interpreters. Each Interpreter has tried to provide his own interpretation and understanding of these mysterious letters. Since these letters are part of the surah of the Qur'an and at the same time, the appearance of these letters, unlike other verses, does not indicate meaning, the commentators have approached these verses with their preconceptions. In this article, an attempt has been made to investigate the role of pre-interpreters of descriptors in a descriptive and analytical method in finding the meaning of syllables. However, each of them has tried to interpret th
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Planning budgets are one of the methods used by the administration in controlling the elements of costs represented by (direct material costs, direct wage costs, and indirect manufacturing costs), and their importance lies in that they reflect what the activity of the economic unit should be in the future. In order to achieve the objectives of the economic unit and to solve this problem, the research was based on the following hypothesis (the role of planning budgets in controlling the elements of costs). , and thus the ability to reduce these costs and thus achieve profits by increasing sales and increasing market share, and the need to urge the state to support the company and the manufacturing sector, which helps and contributes
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