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.
Laryngoscopy 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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Background: Pain due to muscular cramp during hemodialysis is one of the most common problems experienced by patient undergoing hemodialysis, and is associated with poor outcomes of patients. The main aim of this study was to comparing the effects of lavender oil and olive oil massage on Pain due to muscular cramp during hemodialysis.
Methods: In this random clinical trial, 60 hemodialysis patients were enrolled randomly and allocated to two groups with 30 members in Lordegan and Brojen hospitals, Shahrekord, Iran. The intervention included flora massage on the lower leg muscles so that the first group received olive oil massage (10 drops) and the second group received lavender oil massage (10 dr
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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 MoreThe 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 MoreObjective (s): To determine factors associated with the pregnancy complications (Maternal age, education,
obstetrical history, gravidity, birth space interval, and smoking).
Methodology: A cross-sectional study conducted at Al- washash & Bab-almoadham primary health care
centers. The sample was (non probability convenient sample) which included (550) pregnant women. The
study started from 1st April 2014 to 1
st of April 2015. The data was collected by direct interview using
special questionnaire to obtain socio-demographic information.
Results: the result shows that mean age of the subjects was 26.5± 4.39 years, 57.8% were housewives, the
sample included 103 premature uterine contractions, 98 pregnancy induce
BackgroundThe diagnosis and important aspects in treating acute abdomen during pregnancy tend to be delayed due to the peculiar physiological features of pregnancy and the restrictions imposed on imaging diagnostic techniques such as x-ray and CT.Aim of the studyTo identify the most common causes of acute abdomen during pregnancy and identifying the approaches for early diagnosis and to take a correct decision for surgery and assigning the complications that may occur during and/or after surgery for the mother and the fetus.Patients and Methods This is a prospective study that involves data obtained from 91 pregnant patients admitted in the surgical wards in Baghdad teaching hospital during the period from January 2008 to December 2009 .
... Show MoreCoronavirus 2019 (COVID-19) pandemic led to a massive global socio-economic tragedy that has impacted the ecosystem. This paper aims to contextualize urban and rural environmental situations during the COVID-19 pandemic in the Middle East and North Africa (MENA) Region.
An online survey was conducted, 6770 participants were included in the final analysis, and 64% were females. The majority of the participants were urban citizens (74%). Over 50% of the urban residents significantly (
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This study concluded detection of Toxoplasma gondii in milk, immunologically by using Elisa and nested PCR)nPCR (based on B1 gene, also to investigate the effect of toxoplasmosis, parity, breed and flock on some milk composition in the Iraqi local and Shami goats in the middle of Iraq. A total of 80 milk samples of the lactating goats were collected. Results of this study showed the prevalence of Toxoplasmosis was 21.25% and 28.75% by Elisa and nPCR respectively without significant differences. The sensitivity of Elisa was a low (30.43%) whereas the specificity was a high (82.45%). The degree of agreement estimated by Kappa coefficient revealed a slight agreement (0.14) between two methods. The results indicated that goats infected
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Biosignal analysis is one of the most important topics that researchers have tried to develop during the last century to understand numerous human diseases. Electroencephalograms (EEGs) are one of the techniques which provides an electrical representation of biosignals that reflect changes in the activity of the human brain. Monitoring the levels of anesthesia is a very important subject, which has been proposed to avoid both patient awareness caused by inadequate dosage of anesthetic drugs and excessive use of anesthesia during surgery. This article reviews the bases of these techniques and their development within the last decades and provides a synopsis of the relevant methodologies and algorithms that are used to analyze EEG sig
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