15 resultados para Attaching and effacing lesions type III secretion system
em Aston University Research Archive
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Loss of skeletal muscle in cancer cachexia has a negative effect on both morbidity and mortality. The role of nuclear factor-κB (NF-κB) in regulating muscle protein degradation and expression of the ubiquitin-proteasome proteolytic pathway in response to a tumour cachectic factor, proteolysis-inducing factor (PIF), has been studied by creating stable, transdominant-negative, muscle cell lines. Murine C2C12 myoblasts were transfected with plasmids with a CMV promoter that had mutations at the serine phosphorylation sites required for degradation of I-κBα, an NF-κB inhibitory protein, and allowed to differentiate into myotubes. Proteolysis-inducing factor induced degradation of I-κBα, nuclear accumulation of NF-κB and an increase in luciferase reporter gene activity in myotubes containing wild-type, but not mutant, I-κBα, proteins. Proteolysis-inducing factor also induced total protein degradation and loss of the myofibrillar protein myosin in myotubes containing wild-type, but not mutant, plasmids at the same concentrations as those causing activation of NF-κB. Proteolysis-inducing factor also induced increased expression of the ubiquitin-proteasome pathway, as determined by 'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the β-subunits of the proteasome, protein expression of 20S α-subunits and the 19S subunits MSSI and p42, as well as the ubiquitin conjugating enzyme, E214k, in cells containing wild-type, but not mutant, I-κBα. The ability of mutant I-κBα to inhibit PIF-induced protein degradation, as well as expression of the ubiquitin-proteasome pathway, confirms that both of these responses depend on initiation of transcription by NF-κB. © 2005 Cancer Research UK.
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We have developed a novel multilocus sequence typing (MLST) scheme and database (http://pubmlst.org/pacnes/) for Propionibacterium acnes based on the analysis of seven core housekeeping genes. The scheme, which was validated against previously described antibody, single locus and random amplification of polymorphic DNA typing methods, displayed excellent resolution and differentiated 123 isolates into 37 sequence types (STs). An overall clonal population structure was detected with six eBURST groups representing the major clades I, II and III, along with two singletons. Two highly successful and global clonal lineages, ST6 (type IA) and ST10 (type IB1), representing 64?% of this current MLST isolate collection were identified. The ST6 clone and closely related single locus variants, which comprise a large clonal complex CC6, dominated isolates from patients with acne, and were also significantly associated with ophthalmic infections. Our data therefore support an association between acne and P. acnes strains from the type IA cluster and highlight the role of a widely disseminated clonal genotype in this condition. Characterization of type I cell surface-associated antigens that are not detected in ST10 or strains of type II and III identified two dermatan-sulphate-binding proteins with putative phase/antigenic variation signatures. We propose that the expression of these proteins by type IA organisms contributes to their role in the pathophysiology of acne and helps explain the recurrent nature of the disease. The MLST scheme and database described in this study should provide a valuable platform for future epidemiological and evolutionary studies of P. acnes.
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This chapter contains sections titled: Introduction Structure and Regulation Physiologic Functions of TG2 Disruption of TG2 Functions in Pathologic Conditions Perspectives for Pharmacologic Interventions Concluding Comments Acknowledgements References
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The purpose of this research is to propose a procurement system across other disciplines and retrieved information with relevant parties so as to have a better co-ordination between supply and demand sides. This paper demonstrates how to analyze the data with an agent-based procurement system (APS) to re-engineer and improve the existing procurement process. The intelligence agents take the responsibility of searching the potential suppliers, negotiation with the short-listed suppliers and evaluating the performance of suppliers based on the selection criteria with mathematical model. Manufacturing firms and trading companies spend more than half of their sales dollar in the purchase of raw material and components. Efficient data collection with high accuracy is one of the key success factors to generate quality procurement which is to purchasing right material at right quality from right suppliers. In general, the enterprises spend a significant amount of resources on data collection and storage, but too little on facilitating data analysis and sharing. To validate the feasibility of the approach, a case study on a manufacturing small and medium-sized enterprise (SME) has been conducted. APS supports the data and information analyzing technique to facilitate the decision making such that the agent can enhance the negotiation and suppler evaluation efficiency by saving time and cost.
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The Q parameter scales differently with the noise power for the signal-noise and the noise-noise beating terms in scalar and vector models. Some procedures for including noise in the scalar model largely under-estimate the Q parameter. We propose a simple method for including noise within a scalar model which will allow both the noise-noise dominated limit and the signal-noise dominated limit to be treated consistently. © 2005 Elsevier B.V. All rights reserved.
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Communication and portability are the two main problems facing the user. An operating system, called PORTOS, was developed to solve these problems for users on dedicated microcomputer systems. Firstly, an interface language was defined, according to the anticipated requirements and behaviour of its potential users. Secondly, the PORTOS operating system was developed as a processor for this language. The system is currently running on two minicomputers of highly different architectures. PORTOS achieves its portability through its high-level design, and implementation in CORAL66. The interface language consists of a set of user cotnmands and system responses. Although only a subset has been implemented, owing to time and manpower constraints, promising results were achieved regarding the usability of the language, and its portability.
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In recent years, freshwater fish farmers have come under increasing pressure from the Water Authorities to control the quality of their farm effluents. This project aimed to investigate methods of treating aquacultural effluent in an efficient and cost-effective manner, and to incorporate the knowledge gained into an Expert System which could then be used in an advice service to farmers. From the results of this research it was established that sedimentation and the use of low pollution diets are the only cost effective methods of controlling the quality of fish farm effluents. Settlement has been extensively investigated and it was found that the removal of suspended solids in a settlement pond is only likely to be effective if the inlet solids concentration is in excess of 8 mg/litre. The probability of good settlement can be enhanced by keeping the ratio of length/retention time (a form of mean fluid velocity) below 4.0 metres/minute. The removal of BOD requires inlet solids concentrations in excess of 20 mg/litre to be effective, and this is seldom attained on commercial fish farms. Settlement, generally, does not remove appreciable quantities of ammonia from effluents, but algae can absorb ammonia by nutrient uptake under certain conditions. The use of low pollution, high performance diets gives pollutant yields which are low when compared with published figures obtained by many previous workers. Two Expert Systems were constructed, both of which diagnose possible causes of poor effluent quality on fish farms and suggest solutions. The first system uses knowledge gained from a literature review and the second employs the knowledge obtained from this project's experimental work. Consent details for over 100 fish farms were obtained from the public registers kept by the Water Authorities. Large variations in policy from one Authority to the next were found. These data have been compiled in a computer file for ease of comparison.
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Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants.
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The prevalence rates of type2 diabetes mellitus (T2DM) continues to rise among British Pakistanis. The aim of this project was to explore T2DM perceptions and any preventative intentions among British Pakistani women and to discover whether they are doing anything to prevent the onset in themselves and their families. Initially a systematic review was conducted to investigate 20 existing prevention interventions and to assess their effectiveness (n=12,419). Mixed methods approach was adopted and three studies were conducted. The first study consisted of two focus groups with T2DM mothers (n=8) and three focus groups with non-T2DM mothers (n=17). The second study consisted of four focus groups young British Pakistani females (n=11). All focus groups were transcribed verbatim and analysed using thematic analysis. Following these a quantitative study was undertaken comprising of a questionnaire survey; 12 prevention-perception items (derived from the qualitative data) and the Illness-Perception Questionnaire Revised (IPQ-R) using participants from the same populations: T2DM mothers (n=41), non-T2DM mother (n=47) and young women (n=42). Results were analysed using multiple/hierarchical regression. The systematic review highlighted that the most effective prevention programmes focussed on behaviour and lifestyle with a combination of support and education to participants. The research studies demonstrated that T2DM was seen as an older person’s disease to be dealt with if/when it happens. T2DM mothers demonstrated knowledge and prevention understanding. There were non-significant relationships between prevention perceptions and T2DM illness perceptions across all three groups. The finding of this thesis emphasised that lifestyle interventions are crucial to aiding T2DM preventions as a good healthy diet and regular physical activity are the key components to T2DM prevention, and the importance of personal experience in perceived severity and lay-beliefs regarding T2DM and on family/cultural influences in British-Pakistanis. The findings of this project can be used to design culturally specific interventions towards preventing T2DM in the British Pakistani community.
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The Global Partnership for Effective Diabetes Management, established to provide practical guidance to improve patient outcomes in diabetes, has developed and modified recommendations to improve glycaemic control in type 2 diabetes. The Global Partnership advocates an individualized therapeutic approach and, as part of the process to customize therapy, has previously identified specific type 2 diabetes patient subgroups that require special consideration. This article builds on earlier publications, expanding the scope of practical guidance to include newly diagnosed individuals with complications and women with diabetes in pregnancy. Good glycaemic control remains the cornerstone of managing type 2 diabetes, and plays a vital role in preventing or delaying the onset and progression of diabetic complications. Individualizing therapeutic goals and treatments to meet glycaemic targets safely and without delay remains paramount, in addition to a wider programme of care to reduce cardiovascular risk factors and improve patient outcomes. © The Author(s) 2013.
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The devising of a general engineering theory of multifunctional diagnostic systems for non-invasive medical spectrophotometry is an important and promising direction of modern biomedical engineering. We aim in this study to formalize in scientific engineering terms objectives for multifunctional laser non-invasive diagnostic system (MLNDS). The structure-functional model as well as a task-function of generalized MLNDS was formulated and developed. The key role of the system software for MLNDS general architecture at steps of ideological-technical designing has been proved. The basic principles of block-modules composition of MLNDS hardware are suggested as well. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).
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We report a distributed multifunctional fiber sensing network based on weak-fiber Bragg gratings (WFBGs) and long period fiber grating (LPG) assisted OTDR system. The WFBGs are applied for temperature, strain, and vibration monitoring at key position, and the LPG is used as a linear filter in the system to convert the wavelength shift of WFBGs caused by environmental change into the power change. The simulation results show that it is possible to integrate more than 4472 WFBGs in the system when the reflectivity of WFBGs is less than {10}^{-5}. Besides, the back-Rayleigh scattering along the whole fiber can also be detected which makes distributed bend sensing possible. As an experimental demonstration, we have used three WFBGs UV-inscribed with 50-m interval at the end of a 2.6-km long fiber, which part was subjected for temperature, strain, and vibration sensing, respectively. The ratio of the intensity of output and input light is used for temperature and strain sensing, and the results show strain and temperature sensitivities are 4.2 \times {10}^{-4}{/\mu \varepsilon } and 5.9 \times {10}^{-3}{{/ {^{\circ }}\textrm {C}}} , respectively. Detection of multiple vibrations and single vibration with the broad frequency band up to 500 Hz are also achieved. In addition, distributed bend sensing which could be simultaneously realized in this system has been proposed.
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Changing the whisker complement on a rodent's snout can lead to two forms of experience-dependent plasticity (EDP) in the neurons of the barrel cortex, where whiskers are somatotopically represented. One form, termed coding plasticity, concerns changes in synaptic transmission and connectivity between neurons. This is thought to underlie learning and memory processes and so adaptation to a changing environment. The second, called homeostatic plasticity, serves to maintain a restricted dynamic range of neuronal activity thus preventing its saturation or total downregulation. Current explanatory models of cortical EDP are almost exclusively neurocentric. However, in recent years, increasing evidence has emerged on the role of astrocytes in brain function, including plasticity. Indeed, astrocytes appear as necessary partners of neurons at the core of the mechanisms of coding and homeostatic plasticity recorded in neurons. In addition to neuronal plasticity, several different forms of astrocytic plasticity have recently been discovered. They extend from changes in receptor expression and dynamic changes in morphology to alteration in gliotransmitter release. It is however unclear how astrocytic plasticity contributes to the neuronal EDP. Here, we review the known and possible roles for astrocytes in the barrel cortex, including its plasticity.
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Aims: Obesity and Type 2 diabetes are associated with accelerated ageing. The underlying mechanisms behind this, however, are poorly understood. In this study, we investigated the association between circulating irisin - a novel my okine involved in energy regulation - and telomere length (TL) (a marker of aging) in healthy individuals and individuals with Type 2 diabetes. Methods: Eighty-two healthy people and 67 subjects with Type 2 diabetes were recruited to this cross-sectional study. Anthropometric measurements including body composition measured by biompedance were recorded. Plasma irisin was measured by ELISA on a fasted blood sample. Relative TL was determined using real-time PCR. Associations between anthropometric measures and irisin and TL were explored using Pearson’s bivariate correlations. Multiple regression was used to explore all the significant predictors of TL using backward elimination. Results: In healthy individuals chronological age was a strong negative predictor of TL (=0.552, p < 0.001). Multiple regression analysis using backward elimination (excluding age) revealed the greater relative TL could be predicted by greater total muscle mass(b = 0.046, p = 0.001), less visceral fat (b = =0.183, p < 0.001)and higher plasma irisin levels (b = 0.01, p = 0.027). There were no significant associations between chronological age, plasmairisin, anthropometric measures and TL in patients with Type 2diabetes (p > 0.1). Conclusion: These data support the view that body composition and plasma irisin may have a role in modulation of energy balance and the aging process in healthy individuals. This relationship is altered in individuals with Type 2 diabetes.