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: Axillary lymph node (ALN) enlargement with diffuse cortical thickening and conserved echogenic hilum may represent a diagnostic and therapeutic challenge. Sonographic strain elastography may help the characterization of borderline ALN.
Aim: To evaluate the strain elastography of borderline ALN and to calculate a cutoff value of strain ratio (SR) that can identify suspicious ALN with the highest sensitivity and specificity to reduce unnecessary invasive procedures.
Subjects and Methods: A prospective study included 45 patients who attended the Breast clinic in Oncology Teaching Hospital with borderline axillary lymphadenopathy (intact hilum and diffusely thic
... Show More
(2)
Toxoplasmosis is the term for infection and disease in man and animal caused by a parasite called Toxoplasma gondii. The more susceptible to infect with toxoplasmosis is the Diabetic patients, due to low level of immunity response. The aim of current study is to investigate the immune status of diabetes mellitus type 2. One hundred and seventy five samples of both diabetes mellitus type 2patients and controls which had been tested by ELISA technique to detect anti-Toxoplasma Abs (IgG and IgM). The positive toxoplasmosis samples were tested to detect the level of TNF alpha and MIG. Results for all samples clarified that seronegative for IgM antibodies while 53 (53%) diabetic patients were seropositive for IgG antibodies and for toxoplasmosis
... Show More
(3)
Background: Vasospasm occurs commonly in the intracranial arteries as a complication of subarachnoid haemorrhage. On the other hand, extracranial Internal carotid artery (ICA) vasospasm is scarce, and it may occur due to mechanical manipulation during cerebral angiography. We report a case of cervical carotid artery vasospasm during diagnostic cerebral angiography, which caused anterior cerebral artery territory hypoperfusion, to discuss potential risk factors. Case description: For a 22-year-old female with a ten-year history of epilepsy on multiple drugs, brain magnetic resonance imaging (MRI) showed frontal periventricular developmental venous anomaly. Diagnostic catheter cerebral angiography was used to better identify the vas
... Show More
(1)
The tax policy is an important tool of fiscal policy tools which is usedasits multiple tools the State seeks to achieve objectives, such as theachievement of economic development.The importance of the research comes from the importance ofeconomic development resulting from economic policies and prudent fiscaland appropriate to the economic situation of Iraq at the moment is the mostimportant tax policy that taxes one of the most important financial instruments.The research aims to clarify the role of tax policy in developing of theIraqi economy.In an effort to achieve the goals researchers tried to prove thehypothesis ((The tax policy and through multiple tools that seeks to contributeto the achievement of economic development in Iraq)).
... Show MoreInterested in many scholars and reseachers the subject of the media and means varied his roleinfluential in the definition of the public of issues and political, cultural, social and because of its spread wide and ability to address the people of all levels effect them in the formation consciousness of those issues and types of this awareness is an awareness of the tax, contribute to media formation consciousness tax through the definition of people what tax and importance of the role of its revenues to supplement the state budget by posting tax laws and regulations of applied and all what respect process account tax, to be in charge of the tax familiar enough about this, which avoid being cheated taxmisleading when rev
... Show More
The rapid development of information technology and its use in all areas has had a positive impact on all areas, and financial markets have had a share of this development through the use of an electronic trading system to settle transactions, enhance transparency and disclosure in all activities of these markets and revitalize their performance.
The reason for choosing this topic is that it is a very important topic for what modern technology addresses in trading operations in financial markets. It is worth noting that these innovations have eliminated the need for direct contact with people, but through the Internet and telephone networks, and the new technology has reduced the costs of building systems
... Show MoreThe research aims to identify the elements of performance supervisory good and effective and availability in the Governmental council through examination and analysis of the reality and practice of censorship in this Council through study and evaluate the characteristics of the regulatory effective upon which the Governmental council in the performance of his work and knowledge of their adequacy by comparing the established criteria , and determine the effect of characteristics supervisory the performance standards for the Governmental council, Based search to two assumptions key to check the level of the relationship and the influence of the dimensions of the con
... Show More
Abstract
The goal of the research is to diagnose some of the negative phenomena which was discovered through the period from (2010 to 2014) as determined by the national strategy to eliminate the corruption which was set out by the joint council of the corruption elimination in Iraq. And to measure the gap in applying the legal rules by the administration, concerning the misconducts and felonies upon the state employments made by the state employee and how far they are applied in the studied sample and to show the nature of the rules and their importance and their role when they are applied in scientific and expertise manner. And to encourage the offices of the general supervisors to adhere to them which will lead t
... Show More
The current study aims to demonstrate the role of strategic renewal in enhancing organizational immunity through strategic renewal mechanisms represented by (Reanimating, Rejuvenation, Venturing, and restructuring). The main idea of this study relates to the extent to which organizations’ immunity is achieved through strategic Renewal mechanisms, by measuring these dimensions with Organizational immunity represented by organizational learning, organizational memory, and organizational DNA. The study population was the headquarters of the Iraqi Ministry of Education, and the sample included (330) individuals from the upper, middle, and lower leadership levels. Several statistical methods were used to deal with the results of the questionna
... Show MoreThis study aimed at highlighting the role of small and medium enterprises in bringing about economic development in Jordan. The study examined the impact of the number, size of investment and the number of jobs provided by these enterprises on the rate of growth in gross domestic product (GDP) as an indicator for economic development. To achieve its objectives, the study adopted descriptive and quantitative analysis. A linear multi regression model was developed with a growth rate of GDP as dependent variable and the number of institutions, size of investment, and the number of job opportunities as independent variables. The study concluded that each increase by one small or medium enterprise lead to an increase in the rate of gr
... Show More