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: The role of prophylactic antibiotics remains controversial. It is clear that actively facial fractures are considered as clean contaminated and should be treated with therapeutic antibiotics; however, there is widespread variability in the use, type, timing, and duration of prophylactic antibiotic administrated in practice today. There is an adverse effect of increased antibiotic resistance, as well as costs, it is important to review the current evidence for the role of prophylactic antibiotics in compound facial fractures. The purpose of this study is to evaluate the role and significance of preoperative, perioperative and postoperative antibiotic prophylaxis for patients when there is already an infective focus, such as co
... Show More
Patients with decompensated cirrhosis have typically prescribed a combination of therapeutic and prophylactic medications. Polypharmacy increases the probability of medication errors and drug related problems. Clinical pharmacists are highly effective at identifying, resolving, and preventing clinically important drug-related problems in their patients' care. The objectives of the study were the identification and classification of drug-related problems, as well as the discussion of these problems with health care providers (physicians, pharmacists, and nurses) and patients. Reduce their incidence as effectively as possible and educate all research participants on the significance of following their prescribed drug regimen
... Show More
Neuro-ophthalmology, bridging neurology and ophthalmology, highlights the nervous system’s crucial role in vision, encompassing afferent and efferent pathways. The evolution of this field has emphasized the importance of neuroanatomy for precise surgical interventions, presenting educational challenges in blending complex anatomical knowledge with surgical skills. This review examines the interplay between neuroanatomy and surgical practices in neuro-ophthalmology, aiming to identify educational gaps and suggest improvements.
A literature search across databases such as PubMed, Scopus, and W
The principal objective of this study is to demonstrate how green quality management and product life cycle costing may help an organization gain a competitive advantage. Green quality management's influence on increasing product quality and meeting environmental criteria, as well as tracking the activities of product life cycle before, during, and after production, is demonstrated. Orienting these activities toward the production of eco-friendly products that fulfill the needs of customers, hence increasing organization's market share. We found from our study that proposed framework can help organizations improve their competitiveness. Green quality management contributes to environmental protection and the provision of high-qualit
... Show More
(1)
The first chapter includes introduce the research and the problem of the research that there are negligence of some educational institutions and schools management , some parents and supervisors .Also there are some educators who believes that school activities are obstacles means to learning and prevent pupils from studying and understanding the subjects. That may due to social , psychological and educational reasons
The purposes of the researches come from the reports of supervision visits which indicate a lot of difficulties faced by pupils and teachers related to education activities and its influence on in education and the necessity of indentify these difficulties and remedy them
... Show MoreThe acute phase response is a major pathophysiologic phenomenon that accompanies inflammation whether acute or chronic. Complement (C3 and C4) and C - reactive protein (CRP) are positive acute phase proteins (+ ve APPs ). Their production takes place in hepatocyte and the blood concentration of these parameters are increased in osteoarthritis (OA). Chloroquine (CQ) is a diprotic weak base traditionally used to treat malaria. Recently the phosphate salt of CQ is used to decrease this type of (+ve APPs) . In this study, patients who suffered from knee osteoarthritis (KOA) are treated with oral dosage form of chloroquine phosphate (CQP) for one month, twice daily. Our results demonstrate that CQP improves the patient status by decreas
... Show More
The aggregation capacity of human reb blood cells lies between that of the non- aggregated arythrocyte and the remarkably full sedimentation. As the ability to aggregate is atributed to many factors such as the availability of macromolecules and plasma lipids, the role of plasm lipid profile on RBC aggregation and sedimentation changes in normal and diabetic patients is studied.Also serum lipid profile measurement (Total cholesterol, Triglyceride, HDL, LDL, VLDL) in normal and diabetic subjects were made. The principle of measurement includes detecting the transmitted laser light through a suspension of 10% diluted red blood cells in plasma. In all diabetics, the raulux formation and sedimentation rate is enhanced.
Objective: To measure the effect of the pharmacist-led medication reconciliation service before hospital discharge on preventing potential medication errors. Methods: This behavioral interventional study took place in a public teaching hospital in Iraq between December 2022 and January 2023. It included inpatients who were taking four or more medications upon discharge from the internal medicine ward and the cardiac care unit. The researcher provided the patients with a medication reconciliation form and reconciliation form (including medication regimen and pharmacist instructions) before discharging them home. Any discrepancies between the patients’ understanding and the actual medication recommendations prescribed by the physici
... Show More
(3)
(2)