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 major of DDoS attacks use TCP protocol and the TCP SYN flooding attack is the most common one among them. The SYN Cookie mechanism is used to defend against the TCP SYN flooding attack. It is an effective defense, but it has a disadvantage of high calculations and it doesn’t differentiate spoofed packets from legitimate packets. Therefore, filtering the spoofed packet can effectively enhance the SYN Cookie activity. Hop Count Filtering (HCF) is another mechanism used at the server side to filter spoofed packets. This mechanism has a drawback of being not a perfect and final solution in defending against the TCP SYN flooding attack. An enhanced mechanism of Integrating and combining the SYN Cookie with Hop Count Filtering (HCF) mech
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Background: Dental implants are a suitable option for the replacement of some or all missing teeth. The successful insertion of a biocompatible material into living tissue with little to no evidence of rejection has revolutionized medicine and dentistry. An increase in bone response was observed with local administration of growth hormone around dental implants. Growth hormone may act as a bone stimulant in the placement of endosseous dental implants and enhances osseointegration. The aim of the study was to evaluate immunohistochemically the effect of the topical application of growth hormone on the osseointegration of cpTi implant. Materials and Methods: Eighty titanium screw implants were inserted in the tibia of the forty adult rabbits.
... Show MoreThe research included the introduction to the research and its importance as knee joint is an important joint in the human body that is prone to injury. One such injury is knee roughness injury that occurs as a result of the stress of the knee joint and age. The importance of examining the need for the use of rehabilitation exercises, especially in the watercourse system, is highlighted by the fact that the aquatic environment is one of the most important factors helping to alleviate pain and rehabilitate the knee joint and thereby improve the mobility of those with knee roughness. The problem of research is that rehabilitation exercises have been developed in the watercourse system on the basis of scientific bases with a repetitive and sys
... Show MoreThe research aims to identify intelligence spiritual among a sample of students Baghdad University as well as to identify the differences between students in intelligence spiritual according to variable type (male - female), and variable area of study (Science - a human) and variable (First grade - fourth grade), The research sample consisted of (300) students, were applied scale search - a spiritual Intelligence Scale (prepared by the researcher), has resulted in the search results for: -
The students of the University of Baghdad (sample) enjoyed a high level of spiritual intelligence.
- There are no differences between males and females in the spiritual intelligence.
- There
Abstract
The research problem Focused about extent adoption of the financial reporting obligations and assets of the deferred income tax attributable to the concepts of accounting theory and whether the tax laws or accounting principles as well as local accounting rules to recognize the obligations and assets of deferred income tax in the financial statements, and what is the impact of the financial reporting of liabilities and assets Deferred tax in the quality of accounting information, and research aims to the statement of the accounting concepts of the theory of financial reporting obligations and assets of deferred income tax, view and analyze the differences in reporting, resulting from a discrepanc
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The problem of research lies in answering some of the question: What is the reality of (vital conscience) in some colleges and departments of physical education and sports science in Baghdad from the viewpoint of the teachers? And The aim of the research is to prepare a scale (the vitality of the conscience) and learn about its reality in colleges and departments of physical education and sports science in Baghdad from the viewpoint of teachers and The researcher relied on the descriptive method in the survey method and the relationships related to the nature of the research problem and The sample of the research was senior administrators teaching some colleges and departments of physical education and sports science in Baghdad , Th
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The current research aims to investigate the effect of a specimen of Daniel in the acquisition of concepts for the Arabic language curricula material to the students of the third phase of the Faculty of Basic Education Department of Arabic Language. The sample consists of (93) applications and a student of (47) students in the Division (A), which represents the experimental group which studied the use of a specimen of Daniel, and (46) students in the Division (B), which represents the control group, which studied the traditional way. The subject of unified two groups, which subjects the Arabic language curricula which includes six chapters.
The duration of the experiment is a full semester. The researchers also prepared a tool for mea
The weight of larvae virgins and Alcamlat for males more than the weight of females of the roles themselves that the highest rate of loss in weight of larvae developed to virgins when field conditions were (21.5,22,21.3) mg during June and July and August respectively, recorded the highest degrees of heat and less attributed to moisture
The research aims at recognition of The rate of performing tasks done by the scientific committees in the scientific departments in the University of Baghdad, within the evaluative perspective of the departments’ Heads. To find any statistically significant differences in the responses of the research sample to the rates performance of the scientific committees in scientific departments in the University of Baghdad, within the evaluative perspective of the departments’ Heads, according to the two variables of the social gender; male and females, and field of specialization of Scientific and Humanities. The research sample consisted if (107) heads of the scientific department in the University of Baghdad. The researchers designed a
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