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.
The importance of economic and technical feasibility studies include all of the investor, the society, the banks, the project and the government. As it will assist in achieving the optimal use of the available economic incomes on the national level and arranging the projects in priority which participates in achieving the government benefit without wasting the amounts .This is the research goal So, the research covered its theoretical aspect, of SAIs and the economic and technical feasibility studies then the role of the auditors in auditing those studies Then a mechanism was proposed includes a guidebook that provides guidelines for organizing the process of preparing and auditi
... Show MoreWomen issues occupy an important place in international and development projects and programs. This is one of the goals of 21 Century announced during universal summit conference in 2000. The goals are : teaching children, reducing the average of the dead, in addition to the main goal which is reducing the poor level in 2015.
The increasing number of countries that adopt democratic policies, economic freedom and openness lead to heighten and develop the role of women in different ways. As a result, many feminism journals have appeared. Since journals help people to make decisions about public issues as well as acquiring new knowledge, it stimulates women to make decisions.
Feminism journalism takes a new trend. It has become specia
Background: Ulcerative colitis is a chronic inflammatory condition characterized by relapsing and remitting episodes of inflammation limited to the mucosal layer of the colon.Loop ileostomy might be helpful in the management of the disease.
Objective: To evaluate the role of loop ileostomy in the management of ulcerative colitis.
Methods: Between Januarys 2008 and January 2018, patients with fulminant ulcerative colitis resistant to medical therapy had been referred to our surgical unit and were included in our study. Assessment of the patients’ medical status (serum electrolytes, total serum protein, complete blood count, erythrocyte sedimentation rate, general stool exam,and abdominal ultrasound
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Background: The altered status of some essential trace elements observed in diabetes could have deleterious influences on the health of the diabetics. Objectives: To estimate and study the potential role of serum Selenium in type 1, type 2 diabetics and healthy subjects; and its relation with lipid profile and glycemic index. Methods: A case control designed study was carried out at the National Diabetes Center (NDC) / Al-Mustansiria University; on a total of 94 participants formed of 32 type 1 diabetics, 32 type 2 diabetics and 30 healthy control participants. Data collected about age, sex and BMI; also, blood samples examined for FPG, HbA1C, serum total cholesterol, HDL cholesterol, non-HDL cholesterol, serum triglyceride and sera were
... Show MoreThe research aims to demonstrate the role of organizational justice as an independent variable in influencing the achievement of development of the sense of psychological ownership of workers as a dependent variable. The current research variables were distinguished as being effective variables in terms of the field and affecting the achievement of success for organizations. In order to achieve this goal, it was applied on a sample of employees in the Iraqi Ministry of Transport employees, whose number reached (84) individuals, and the data were collected through the questionnaire as a main tool, to come out with a set of conclusions that contribute to raising the levels of the researched company, and based on the importance of the
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The operator ψ has been introduced as an associated set-valued set function. Although it has importance for the study of minimal open sets as well as minimal I-open sets. As a result of this study, we introduce minimal I^*-open sets . In this study, several characterizations of minimal I^*-open sets are also investigated. This study also discusses the role of minimal I^*-open sets in the *-locally finite spaces. In an aspect of topological invariant, the homeomorphic images of minimal I^*-open set has been discussed here.
Objectives: The aim of the study was, to assess the nurse's role regarding cardiovascular drug
administration in Erbil city.
Methodology: A descriptive survey was conducted in Hawler teaching and Rizgari teaching Hospitals. The
number of samples is 50 nurses; the period of the study was started from 15th of November 2008 up to
the end of March 2009. A questionnaire was developed by investigators based on extensive review of
available studies and literatures. Data were collected through application of observational check list
consist of two part, part one was demographic sheet and part two about nurse’s responsibility regarding
medication administration which include (before, during, after drug administration). Data
The pathogenicity of S. saprophyticus was studied in mice. A group of white mice were injected transurethrally using a catheter with S. saprophyticus S67 cell suspension in a concentration reached 109 CFU/ml. concomitantly, the role of its peptidoglycan in the pathogenicity was studied by injecting another group of mice with 0.3 mg/0.2 ml of partially purified S. saprophyticus S67 peptidoglycan extract. After autopsy, kidneys and urinary bladder showed several histopathological changes both in cells and peptidoglycan injected mice, included: hydropic degeneration, glomerulus shrinkage, congestion of renal vessels, infiltration of inflammatory cells, and dekeratinization in urinary bladder.
The purpose of this study is to explore whether the adoption of Beyond Budgeting (BB) as a management accounting practice (MAP) contributes to developing intellectual capital (IC) and creating value in Iraqi companies. This requires an understanding of the views of the Iraqi managers about the nature of the information provided by this practice, which may be used to determine whether this information is relevant in the management of IC in the context of Iraq. This research aims also to explore the challenges of the adoption of the BB in planning and controlling IC in Iraq. The study adopts a qualitative approach and an interpretive paradigm. It also adopts a semi-structured interview method of collecting data from executive managers
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