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: This study aimed to apply a high-power pulsed alexandrite laser in vitro, the researchers tested different exposure periods, pulse lengths, and laser fluencies to see which dosage was most successful against S. aureus bacteria, which had developed resistance to many antibiotics. Method: Three bacteria samples were exposed to laser beams for 30 seconds with a 5ms pulse duration and a laser fluency of 5J/cm2. The process was repeated with laser fluencies of 10, 15, and 20. Results: The study was carried out by using different doses of Alexandrite laser. Results: There are significant differences (p = 0.05) in the mean number of bacteria colonies exposed for 30 and 60 seconds at any laser fluencies utilized in the present i
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Planning for a city with human identity considers the needs of human being that exist in the traditional cities where it was so easy creating place there, on the other hand, modern cities refuse these values and reduce the human characters of urban fabric elements , and the searching for the concept of " Urban Coherence " considers the knowledge about urban theory, especially Morphological attitudes finding three sides of making the coherence of dense urban fabric which are " Functional Complementarily , Formal Complementarily ,
Contextual complementarily “and the differentiation of these sides within the variety of spatial structural patterns between the organic type of traditional city and the gridiron type of modern city. To
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This study was conducted in the Faculty of Agricultural Engineering Sciences - University of Baghdad in the field of sheep and goats in the Department of Animal Production. Effect of different concentrations of bovine albumin on some semen characteristics of frozen rams. Used in this experiment, 3 rams and their ages ranging from 2.5-3 years. The sample of the semen was diluted with Tris dilution with the addition of 10 ml of egg yolk per 100 ml, the sample by 1:1 with the tris and then the collection of sperm samples (Pooling) after the semen was divided into four treatments Control and bovine albumin at concentrations of 5, 7.5 and 10% and then complete dilution 10: 1, at 5C, dilution 20: 1, containing 5% glycerol per 100 ml. The results
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Urban Balance is one of the important indicators that leads to an assessment of the urbanization process in a particular country , province or even a city that is multi-centered. By examining the data related to Anba province, it was found that the value of this indicator is equal to 0.96, which is less than the absolute one, and therefore the urbanization in the province is distributed collectively
The development of a mathematical or statistical model for estimating urban growth is a complex process due to the overlap between indicators or variables that can be adopted to calculate estimate growth rates Al-Qaim city has been considered as an example to develop a statistical method by which changes
... Show MorePseudomonas aeruginosa is an opportunistic pathogen responsible for serious infections. At least three different exopolysaccharides, alginate, polysaccharide synthesis locus (Psl), and pellicle exopolysaccharide (Pel) make up the biofilm matrix in P. aeruginosa . The effect of temperature on the biofilm formation and gene expression was examined by microtiter plate and real-time quantitative polymerase chain reaction (qRT-PCR). To be able to determine the effect of temperature on biofilm formation and gene expression of P. aeruginosa, 303 clinical and environmental samples were collected. Pseudomonas aeruginosa was isolated from 61 (20.1%) and 48 (15.8%) of the clinical and e
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Background: The aims of the study were to evaluate the unclean/clean root canal surface areas with a histopathological cross section view of the root canal and the isthmus and to evaluate the efficiency of instrumentation to the isthmus using different rotary instrumentation techniques. Materials and Methods:The mesial roots of thirty human mandibular molars were divided into six groups, each group was composed of five roots (10 root canals)which prepared and irrigated as: Group one A: Protaper system to size F2 and hypodermic syringe, Group one B: Protaper system to size F2 and endoactivator system, Group two A:Wave One small then primary file and hypodermic syringe, Group two B:Wave One small then primary file and endoactivator system, Gr
... Show MoreThe duration of the contract is a legal term first provided for in French Amendment Decree No. 131/2016, and given the increasing importance of time in contracts, we have chosen to study the legal rules governing time at the formative stage by drawing on changes in French law compared to both Iraqi and Egyptian laws. Article 1102 of French Amendment Decree No. 131/2016 stipulates that: "Everyone is free to contract or not to contract, to choose the person with whom he contracts, and to determine the content and form of the contract within the limits established by law." Contractual freedom does not permit a breach of the rules relating to public order), as well as article 1104, which provides for (contracts must be nego
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Abstract
The aim of the current research is to identify the level of administrative applications of expert systems in educational leadership departments in light of the systems approach. To achieve the objectives of the research, the descriptive-analytical and survey method was adopted. The results showed that the level of availability of the knowledge base for expert systems in educational leadership departments (as inputs) was low. The level of availability of resources and software for expert systems in educational leadership departments (as transformational processes) came to be low, as well as the level of availability of the user interface for expert systems in educational leadership departments (as outputs
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