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 purpose of this study is to assess the performance of government units (Iraqi hospitals) by trying to determine the possibility of the current governmental accounting system to provide information on the performance reports of government units. In order to improve the efficiency of hospital resources management, the services provided by the hospital should be subject to performance measurement and evaluation The importance of the health sector in the provision of services, in order to raise the efficiency of the performance of services provided by government units has reached the researcher a set of conclusions, the most important
- The financial reports produced by the accounting s
(1)
University libraries seek to evaluate their performance in order to correct their path and adjust it in the right direction. Therefore, they use (performance indicators), which are a tool used by institutions to evaluate the weaknesses and strengths in their work and the reasons for failure to achieve some goals sometimes. They convert (goals, procedures and actions) into a formula that can be measured mathematically, which contributes to the library determining the gap between its current performance and what those libraries are supposed to be on, clarifying the path that the library is following, controlling the risks that may befall it, and thus enhancing the process of continuous improvement to avoid areas of failure and weakness becaus
... Show MoreThe current research aims to verify the role of strategic intelligence as an explanatory variable in organizational success as a respondent variable in the colleges of the University of Fallujah, the research community. (Dean, Associate Dean, Section Head, Division Officer, Unit Officer), The researcher used the questionnaire as the main tool to collect data that included (50) items, in addition to using personal interviews and field observations as aids in data collection. The researcher relied on statistical programs (SPSS V.25; Excel V (16) In the treatment and analysis of data through the use of the most appropriate statistical methods (arithmetic mean, standard deviation, difference coefficient, determinatio
... Show More
The current research seeks to identify the role of the marketing intelligence system in its dimensions (customer intelligence, market intelligence, competitor intelligence, insurance product intelligence, sales representatives) and its reflection on improving the quality of the insurance service provided by the National Insurance Company represented in its dimensions (reliability, response, tangibility, Safety, the spirit of empathy, communication) adopted in the current research, and based on that, the research came as an attempt to find out the extent to which the research sample company can apply the approach of the marketing intelligence system and its impact on improving the quality of the insurance service provided to custo
... Show More
(14)
(10)
(50)
(43)
Background: To elucidate the possible role of human cytomegalovirus in pregnancy loss through induction of certain pro-inflammatory adhesion molecules.
Methods: Paraffin embedded sections of curate samples were obtained from 34 women had spontaneous abortion, and 5 women had elective termination of pregnancy (as control), and then subjected for immunohistochemistry analysis to detect human cytomegalovirus (HCMV) early protein and VCAM-1 molecule.
Results: Nine out of 34 women with spontaneous abortion were positive for HCMV early protein, with a
significantly higher expression of VCAM-1 in HCMV positive cases as compared with HCMV negative and the control groups (p = 0.05, 0.001 respectively).
Conclusion: HCMV infection may p
Background: Swine influenza (also Called pig influenza, swine flu, hog flu and pig flu) is an infection by any one of several types of swine influenza virus (SIV) or S-OIV (Swine-Origin influenza virus) is any strain of the influenza family of viruses that is endemic in pigs. Patients and Methods:- Ninety patients with there families suspected of swine flu who were admitted to Central Teaching Hospital of Pediatric in Baghdad seventy one from Baghdad Al-Kerkh, twelve from Baghdad Al-Rasafa and seven other Iraqi Governorate (1 in Suleimaniya, 2 in Baquba, 4 in Anbar) they were included in a prospective study started from the 1st October till the 30 th of November 2009. Results:- The study revealed from )90( suspected cases the H1N1 Virus Pos
... Show MoreFunctional dyspepsia is one of the most common gastrointestinal symptoms and attributed to various causes including Helicobacter pylori infection. AIM OF THE STUDY: To correlate Helicobacter pylori infection to functional dyspepsia and to identify the possible risk factors for this infection. PATIENTS AND METHODS: Fifty patients who were referred to the endoscopy unit for dyspepsia symptoms, secondary gastric causes of dyspepsia were excluded during endoscopy, gastric biopsies were taken for histopathological study and for bedside urease test for detection of Helicobacter pylori infection. RESULTS: 62% of non-ulcer dyspeptic patients were infected with Helicobacter pylori, 74.2% of the patients were above 30 years old, female gender patient
... Show More