103 research outputs found

    The Evolution of Robust Development and Homeostasis in Artificial Organisms

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    During embryogenesis, multicellular animals are shaped via cell proliferation, cell rearrangement, and apoptosis. At the end of development, tissue architecture is then maintained through balanced rates of cell proliferation and loss. Here, we take an in silico approach to look for generic systems features of morphogenesis in multicellular animals that arise as a consequence of the evolution of development. Using artificial evolution, we evolved cellular automata-based digital organisms that have distinct embryonic and homeostatic phases of development. Although these evolved organisms use a variety of strategies to maintain their form over time, organisms of different types were all found to rapidly recover from environmental damage in the form of wounds. This regenerative response was most robust in an organism with a stratified tissue-like architecture. An evolutionary analysis revealed that evolution itself contributed to the ability of this organism to maintain its form in the face of genetic and environmental perturbation, confirming the results of previous studies. In addition, the exceptional robustness of this organism to surface injury was found to result from an upward flux of cells, driven in part by cell divisions with a stable niche at the tissue base. Given the general nature of the model, our results lead us to suggest that many of the robust systems properties observed in real organisms, including scar-free wound-healing in well-protected embryos and the layered tissue architecture of regenerating epithelial tissues, may be by-products of the evolution of morphogenesis, rather than the direct result of selection

    Stem cells and repair of lung injuries

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    Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung

    What is the value of orthodontic treatment?

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    Orthodontic treatment is as popular as ever. Orthodontists frequently have long lists of people wanting treatment and the cost to the NHS in England was ÂŁ258m in 2010-2011 (approximately 10% of the NHS annual spend on dentistry). It is important that clinicians and healthcare commissioners constantly question the contribution of interventions towards improving the health of the population. In this article, the authors outline some of the evidence for and against the claims that people with a malocclusion are at a disadvantage compared with those without a malocclusion and that orthodontic treatment has significant health benefits. The authors would like to point out that this is not a comprehensive and systematic review of the entire scientific literature. Rather the evidence is presented in order to stimulate discussion and debate

    El Conocimiento DidĂĄctico del Contenido en ciencias: estado de la cuestiĂłn

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    This paper gives a descriptive overview of the literature related to Pedagogical Content Knowledge - PCK - in the sciences. It is expected that this review can contribute to a better understanding of PCK, pointing out what has been investigated about this concept. Specifically, we analyze: a) how PCK is defined, what are its main features and how it has been appropriated by teachers; b) the relationship between PCK, knowledge of the contents to be taught and students learning; c) how PCK was actually used in teachers' training and teachers' evaluation; and, d) the scientific areas in which PCK has been studied. It concludes that PCK is an essential tool for improving the quality of teacher training

    IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

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    <p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.</p> <p>Methods</p> <p>We used an <it>ex vivo </it>culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. <it>In vitro </it>data were correlated with <it>in vivo </it>findings by comparing the results with published expression datasets on human cancer biopsies.</p> <p>Results</p> <p>Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (<it>P </it>= 0.029 - Norway/Stanford and <it>P </it>= 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (<it>P </it>= 0.007 - Bhattacharjee and <it>P </it>= 0.008 - Garber dataset).</p> <p>Conclusion</p> <p>Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.</p> <p>See the related commentary by Werner and Bruchim: <url>http://www.biomedcentral.com/1741-7015/8/2</url></p

    VĂślkisch und sozial? : Neonazistische Agitation gegen die neue EU-FreizĂźgigkeit fĂźr Arbeitnehmerinnen

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    Wnt/β-catenin signalling pathway is crucial for the formation of many tissues and organs during development. In recent years, this pathway has also been found to regulate the biology of stem cells in the intestine and probably in other organs in adult life. Abnormal activation of Wnt/β-catenin signalling, which controls the expression of a high number of genes, is critical for the initiation and progression of most colorectal cancers. In line with this, the gene expression signature induced by activation of the Wnt/β-catenin pathway defines the intestinal stem cells present at the bottom of the crypts and also colon cancer stem cells. This supports the importance of inhibitors of the Wnt/β-catenin pathway as potential agents in colorectal cancer therapy. However, the complexity, wide activity in the organism modulating the biology of several cell types, and characteristics of this pathway have delayed the identification of suitable targets and so, the development of such inhibitors that are only now reaching the clinic.Peer reviewe

    Dental Treatment in a State-Funded Primary Dental Care Facility: Contextual and Individual Predictors of Treatment Need?

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    OBJECTIVE:This study examined individual and contextual factors which predict the dental care received by patients in a state-funded primary dental care training facility in England. METHODS:Routine clinical and demographic data were extracted from a live dental patient management system in a state-funded facility using novel methods. The data, spanning a four-year period [2008-2012] were cleaned, validated, linked by means of postcode to deprivation status, and analysed to identify factors which predict dental treatment need. The predictive relationship between patients' individual characteristics (demography, smoking, payment status) and contextual experience (deprivation based on area of residence), with common dental treatments received was examined using unadjusted analysis and adjusted logistic regression. Additionally, multilevel modelling was used to establish the isolated influence of area of residence on treatments. RESULTS:Data on 6,351 dental patients extracted comprised of 147,417 treatment procedures delivered across 10,371 courses of care. Individual level factors associated with the treatments were age, sex, payment exemption and smoking status and deprivation associated with area of residence was a contextual predictor of treatment. More than 50% of children (<18 years) and older adults (≥65 years) received preventive care in the form of 'instruction and advice', compared with 46% of working age adults (18-64 years); p = 0.001. The odds of receiving treatment increased with each increasing year of age amongst adults (p = 0.001): 'partial dentures' (7%); 'scale and polish' (3.7%); 'tooth extraction' (3%; p = 0.001), and 'instruction and advice' (3%; p = 0.001). Smokers had a higher likelihood of receiving all treatments; and were notably over four times more likely to receive 'instruction and advice' than non-smokers (OR 4.124; 95% CI: 3.088-5.508; p = 0.01). A further new finding from the multilevel models was a significant difference in treatment related to area of residence; adults from the most deprived quintile were more likely to receive 'tooth extraction' when compared with least deprived, and less likely to receive preventive 'instruction and advice' (p = 0.01). CONCLUSION:This is the first study to model patient management data from a state-funded dental service and show that individual and contextual factors predict common treatments received. Implications of this research include the importance of making provision for our aging population and ensuring that preventative care is available to all. Further research is required to explain the interaction of organisational and system policies, practitioner and patient perspectives on care and, thus, inform effective commissioning and provision of dental services
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