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.
Doxycycline and levofloxacin are heterocyclic organic compounds that are now popularly used to treat some bacterial infections. In this study which was conducted on patients from a private clinic, we compared the use of two commonly used antibiotics for the treatment of diagnosed cases with vaginal chlamydial infection: levofloxacin and doxycycline. Vaginal chlamydial infection is considered to be a very common sexually transmitted infection. It may have minimal symptoms which can lead to neglect by the patient until it leads to some important complications among which is the inability to become pregnant. This indicates early diagnosis and treatment of this infection. By comparing the results of treatment we concluded that there is no much
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The transition of professionals between different sectors is considered as one of sources of
acquisition of technology and will lead to add the practical experience to them. This experience
depending on different factors like: the scientific degree and practical experience by the
professionals, the technology possessed by the transferor sector, the duration that spent by
experienced in transferor sector, the type of work performed by professional….etc.
The research aims to verify the affect of these factors in technology transfer process.
Research reached that the technology transfer process which is depending on the Iraqi competencies
in work is unsatisfied level between Iraqi organizations because there are dif
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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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.
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 MoreBackground: 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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The concept of civil society is one of the relatively recent concepts that have emerged clearly on the political and social arena especially in European countries, where it effectively contributes to the process of democratic transformation through the multiple roles and functions that it exercises, and acts as mediator between the state and the individual. Civil society in essence works to bring about change in society whether it is political, economic, social or cultural .The civil society appeared in Iraq after 2003, as is the case with many concepts that entered Iraq and took upon themselves the building of a democratic Iraq .Accordingly civil society institutions are the entity capable of rebuilding the Iraqi personal
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The 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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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