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.
As long as the place in which a person lives has a meaning and temporal dimensions , memory is the main axis of these dimensions , today , city centers and old historical sectors of cities are abandoned , and began to turn into slums , the contradiction between old and historical sectors led cities to lose their identity while people lost their sense of belongingness to the old sectors where their ancestors used to live . The old city of Hilla used to have social , historical and cultural role on determining the identity . The study problem can be summarized as the ( lack of studies regarding the impact of historical memory related to Hilla old city on social and cultural mobility ) , the study hypothesis claims that the social , histori
... Show MoreBackground: Lumbar disc degeneration (LDD) is a common musculoskeletal disorder that frequently causes low back pain (LBP). In addition to the discomfort of lower back pain, it can accompany pain in one or both legs. The lumbar spine and sacrum, consisting of five vertebrae and one bone, determine the spine's balance. Microelements are essential in bone metabolism and are associated with the prevention of osteoporosis and the alleviation of musculoskeletal pain. Objectives: To examine the correlation between lumbar spinal surgery and the concentrations of microelements, namely zinc and copper. Methods: A case-control study was conducted in Ghazi Al-Hariri Hospital in Baghdad, Iraq, during the period from October 2023 to January 2024
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The study seeks to clarify the role of International Auditing Standard No. (320) of the relative importance in determining responsibility for planning and implementing the process of auditing financial statements and expressing neutral technical opinion through the analytical procedures of the auditor, whose responsibility is to obtain appropriate and reliable audit evidence that helps the auditor to form a general conclusion about whether The financial statements were consistent with the auditor's understanding of the entity. The relative importance contributes to defining the important accounts that help to set priorities for the auditor to set the necessary analytical procedures for these accounts. One of the most important co
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The research aims to identify the mediator role of workplace spirituality in the relationship between psychological capital and entrepreneurial behavior: field research to a sample opinions from employees at the center of the Iraqi ministry of Oil . The importance of the current research emerged from paucity of studies that have attempted to identify and know the nature of the relationship between the variables as well as trying to find the current address and realistic problem directly affects the performance of employees in the Iraqi oil sector.
In order to achieve the goal of research the use of the analytical method (quantitative)
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The study was conducted to detect the effect of addition of 0.03, 0.06 and0.10% potassium sorbate and 0.10, 0.15, 0.20 and 0.30% sodium propionate upon the sensory properties of laboratory made biscuit. The statistical analysis of the results revealed no significant differences (P<0.05) between the propionate treatment (A,B,C,D) and between the sorbate treatment (E,F,G) and the control (H) in most sensory properties of biscuit prior to storage. Upon six month storage of biscuit made with addition of different levels of sodium propionate 20-40C (room temperature) no significant differences (P<0.05) were shown on softness, flakiness and color in comparison with the control . No significant differences (P<0.05) were also
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Background : In order for a tooth to erupt, two obvious requirements are needed. First, there has to be alveolar bone resorption of the bone overlying the crown of the tooth such that an eruption pathway is formed. Second, resorption of bony crypt and apposition of new one, third, there has to be a biological process that will result in the tooth moving through this eruption pathway.The amniotic sac contains a considerable quantity of stem cells. These amniotic stem cells are multipotent and able to differentiate into various tissues, which may be useful for human application. Receptor activator of nuclear factor kappa B ligand (RANKL) is concentrated on bone biology, more specifically bone metabolism. RANKL plays a vital role in osteoclast
... Show MoreObjective: This study aimed to evaluate the effectiveness of the Benson Relaxation Technique (BRT) in reducing pain during femoral artery sheath removal after percutaneous coronary intervention (PCI). Methods and Materials: A randomized controlled trial was conducted at three cardiac centers in Iraq. A total of 58 patients undergoing therapeutic PCI were randomly assigned into two groups: intervention (n=27) and control (n=31). The intervention group received BRT for 10 minutes before and after sheath removal. Pain was assessed using the Visual Analogue Scale (VAS) immediately after the procedure. Demographic data and clinical variables were collected. Data were analyzed using SPSS v26 and non-parametric tests (Mann-Whitney U, Krus
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The current study had investigated how specific physiological parameters and the endurance of offensive skills of elite Iraqi badminton players are influenced using preparatory phase training. The study used a systematic experimental research design to determine the impact of high-intensity interval exercise (HIIE) on technical accuracy and movement efficiency. Maximal oxygen uptake (VO 2 max), blood lactate levels, and other salient physiological variables were taken before and after training. The results indicated that VO 2 max was significantly increased and lactate was reduced which indicated an increase in aerobic and anaerobic capacity. There was also an increased offensive physical endurance among the participants, increased shot eff
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Community pharmacists faced more complex challenges in meeting patients’ medication needs during the pandemic than previously reported in the literature. Objectives To explore the perception and abilities of community pharmacists in managing patients’ needs in terms of medication dispensing during the pandemic, and to examine its effect on improving the patients’ situations. Materials and Methods A cross-sectional study design, validated by 30 experts, was conducted using an electronic survey (Google Form) to assess the effect of the dispensing practice of Iraqi community pharmacists on the patient’s clinical outcomes during the pandemic. The survey was distributed on professional pharmacist’s social media platforms from December
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