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: Infection with sexually
transmitted diseases is broad and includes
bacterial, viral and protozoa infection.
Large number of infected people goes
untreated because of symptomatic or
unrecognized infections.
Patients and methods: Forty five
patients was complaining from infertility
(primary or secondary), consulting
Kammal El-Sammari Hospital for
infertility from May - 2008 to February -
2009. Control group consisted of twenty
fertile women that consulting private clinic
for checking. Four swabs were taken from
each woman in two groups. Two swabs
were taken from posterior fornix of the
vagina (High vaginal swab) and the last
two were taken from endocervical canal.
First swab
الخلفية: العقدية المقيحة المعروفة أيضًا باسم ""(GAS) هي احدى مسببات الأمراض ذات الأهمية الصحية العامة، حيث تصيب 18.1 مليون شخص في جميع أنحاء العالم وتقتل 500000 شخص كل عام. الهدف: حددت هذه المراجعة المقالات المنشورة حول عوامل الخطر واستراتيجيات الوقاية والسيطرة لأمراض المكورات العقدية. المواد والأساليب: تم إجراء بحث منهجي لتحديد الأوراق المنشورة على قواعد البيانات الإلكترونية Web of Science و PubMed و Scopus و Google Scholar في مح
... Show More
The research aims to determine the role of the practices of green human resources management in achieving requirements of environmental citizenship in the workplace, the General Company for Vegetable Oils was chosen for the application of field-side of research which represent one of the important industrial companies in Iraq, which suffers from poor Green human resources management applications, which reflected negatively on the development Environmental citizenship among Employees. The questionnaire use as a tool to collect data and information as well as field presence of the researcher, The research sample included (30) managers of departments and Division ,and through using statistical program (SPSS) the data has been analys
... Show More
(2)
The research aims to explain the role of huge data analyzes in measuring quality costs in the Iraqi company for the production of seed, and the research problem was diagnosed with the weakness of the approved method to measure quality costs, and the weak traditional systems of data analyzes, the researcher in the theoretical aspect relied on collecting sources and previous studies, as well as Adoption of the applied analytical approach in the practical aspect, as a set of financial analyzes were applied within the measurement of quality costs and a statement of the role of data analyzes in the practical side, the research concluded to a set of conc
... Show MoreWith the growing number of patient’s being diagnosed with Parkinson’s disease and Multiple Sclerosis each year it is becoming ever more important to find the cause for these neurological disorders. The present study attempts to shed light on one of the factors that may play a role as a causative agent in these neurological diseases by finding a correlation between the Herpes simplex virus type 1 and 2 in patients with Parkinson’s disease and multiple sclerosis by detecting the virus in these patients using immunological techniques. Sixty patients with neurological diseases (40 patients with Multiple sclerosis and 20 patients with Parkinson’s disease) who’s ages ranged from (17-76) years have been investigated. Samples wer
... Show MoreThe paper aims to build a model that supports organizational sustainability by analyzing the correlations and revealing the impact between the two main variables (entrepreneurial leadership) with its dimensions of proactive outlook, risk, and creativity (Van Zyl & Mathur-Helm, 2007), and (organizational sustainability) with its economic, environmental, and societal dimensions (Hansmann et al., 2012). As well as identifying the level of awareness and informing managers in the General Company for the Automotive and Equipment Industry, of the theoretical implications and performance, and its vital importance to society and the surrounding ecological environment, and drawing attention to that and improving performance, and indicatin
... Show More
The environmental cost management focus on continuous improvement of processes and the various activities of the organization in order to improve the environmental performance by producing an environmentally friendly products lead to a competitive advantage for the organization and supports the activities of their sustainability.
The study was carried out in Bagel cement factory, one of the pioneer projects in Yemen in manufacturing field, The study found the need to develop a separate section for environmental management in order to put plans and environmental policies and the introduction of a special division in the Department of costs cares about Management practices cost and measure environmental costs, also give solu
... Show MoreThe purpose of this study is to investigate the capability of bacterial DNA
compared to bacterial lysate in stimulating arthritis using rat model. One hundred
mid-stream urine specimens were collected during November 2012 to January 2013,
from patients suffering from urinary tract infections attending hospitals in Baghdad,
Iraq. Susceptibility of Staphylococcus aureus isolates to antibiotics was examined.
Twenty five isolates were identified as S. aureus and they developed multi drug
resistance. S. aureus S1 lyaste and its DNA were intra-articulary injected in rats. The
levels of IL-6, anti-ds DNA Ab and leukocytes count were measured. In general, IL-
6, anti-ds DNA Ab and leukocytes count were significantly highe
Abstract
This research aims to the relationship and the effect of concurrent engineering dimensions analyze (product design, process design, and supply chain design) on the dimensions of strategic performance (efficiency, and effectiveness) The research was conducted in public Zora Electrical Industries Company, on a sample of departments and officials, engineers, managers and people in the company amounted to (45) . A questionnaire was used for the purpose of data collection which has been adopted, with the use of statistical methods via computerized system (spss) for processing data , identifying them and testing the research hypotheses. The research
... Show More