Sharp boundaries of Dpp signalling trigger local cell death required for Drosophila leg morphogenesis

Article available at http://dx.doi.org/10.1038/ncb1518Morphogens are secreted signalling molecules that govern many developmental processes1. In the Drosophila wing disc, the transforming growth factor (TGF) homologue Decapentaplegic (Dpp) forms a smooth gradient and specifies cell fate by conferring a defined value of morphogen activity. Thus, neighbouring cells have similar amounts of Dpp protein, and if a sharp discontinuity in Dpp activity is generated between these cells, Jun kinase (JNK)-dependent apoptosis is triggered to restore graded positional information2, 3. To date, it has been assumed that this apoptotic process is only activated when normal signalling is distorted. However, we now show that a similar process occurs during normal development: rupture in Dpp activity occurs during normal segmentation of the distal legs of Drosophila. This sharp boundary of Dpp signalling, independently of the absolute level of Dpp activity, induces a JNK—reaper-dependent apoptosis required for the morphogenesis of a particular structure of the leg, the joint. Our results show that Dpp could induce a developmental programme not only in a concentration dependent manner, but also by the creation of a sharp boundary of Dpp activity. Furthermore, the same process could be used either to restore a normal pattern in response to artificial disturbance or to direct a morphogenetic process.This work has been supported by grants from the Dirección General de Investigación Científica y Técnica (BMC 2002-00300), the Comunidad Autónoma de Madrid (08.1/0031/2001.1 and GR/SAL/0147/2004) and an Institutional Grant from the Fundación Ramón Areces. C.M. is a recipient of a Formación del Personal Universitario (F.P.U.) fellowship from the Ministerio de Educación y Ciencia.Peer reviewe

The Gene Regulatory Cascade Linking Proneural Specification with Differentiation in Drosophila Sensory Neurons

Temporal expression profiling of sensory precursor cells reveals how the atonal proneural transcription factor regulates a specialized neuronal differentiation pathway

Prevalence of self-reported constipation in adults from the general population

OBJECTIVE To estimate the prevalence of self-reported constipation and associated factors in the general population of a Brazilian city. METHOD Secondary analysis of an epidemiological study, population-based, cross-sectional study, about bowel habits of Brazilian population. A total of 2,162 individuals were interviewed using two instruments: sociodemographic data and the adapted and validated Brazilian version of the "Bowel Function in the Community" tool. RESULTS There was a prevalence of 25.2% for the self-reported constipation, 37.2% among women and 10.2% among men. Stroke and old age were associated with constipation in the three statistical models used. CONCLUSION The prevalence found showed to be similar to the findings in the literature, although some associated factors obtained here have never been investigated

Robust Target Gene Discovery through Transcriptome Perturbations and Genome-Wide Enhancer Predictions in Drosophila Uncovers a Regulatory Basis for Sensory Specification

CisTarget X is a novel computational method that accurately predicts Atonal governed regulatory networks in the retina of the fruit fly

Illness perceptions mediate the relationship between bowel symptom severity and health-related quality of life in IBS patients

PURPOSE: Irritable bowel syndrome (IBS) is a functional bowel disorder with a large negative impact on HRQOL. The present study examines whether severity of bowel symptoms is directly related to HRQOL, and/or indirectly, mediated by the patients’ illness perceptions. METHODS: Patients were recruited from an IBS support group (N = 123), and data were collected online. HRQOL was measured with the Quality of Life Measure for Persons with IBS and illness perceptions with the brief Illness Perception Questionnaire. Mediation models were tested using the bootstrapping procedure developed by Hayes. RESULTS: Irritable bowel syndrome symptom severity is directly related to total HRQOL and its subscales; after entering the mediator variables (i.e. the patients’ illness perceptions) into the model, this direct association remained only significant for total HRQOL. The relationship between bowel symptom severity and total HRQOL was partially mediated by illness perceptions, and its relationship with each of the HRQOL subscales was fully mediated by the patients’ illness perceptions. Perceived consequences were a mediator of the relationship between bowel symptom severity, total HRQOL as well as its subscales, with the exception of Sexuality. CONCLUSIONS: Bowel symptom severity not only has a direct relationship with HRQOL, but also an indirect relationship via the patients’ cognitive and emotional representations of their illness. In order to better understand this relationship, future research should not only include illness perceptions but also assess cognitive and behavioural coping responses. Clinicians wanting to improve patients’ HRQOL should not only focus on the patients’ symptoms, but also on their illness beliefs and coping responses

Engaging with economic evaluation methods: insights from small and medium enterprises in the UK medical devices industry after training workshops

Background With increased governmental interest in value assessment of technologies and where medical device manufacturers are finding it increasingly necessary to become more familiar with economic evaluation methods, the study sought to explore the levels of health economics (HE) knowledge within small and medium-sized enterprises (SMEs) and to scope strategies they employ to demonstrate the value of their products to purchasers. Methods A short questionnaire was completed by participants attending one of five workshops on product development in the medical device sector that took place in England between 2007 and 2011. From all responses obtained, a large proportion of participants were based in SMEs (N = 43), and these responses were used for the analysis. Statistical analysis using non-parametric tests was performed on questions with approximately interval scales. Qualitative data from participant responses were analysed to reveal emerging themes. Results The questionnaire results revealed that 60 % of SME participants (mostly company directors or managers, including product or project managers) rated themselves as having low or no knowledge of health economics prior to the workshops but the rest professed at least medium knowledge. Clinical trials and cost analyses or cost-effectiveness studies were the most highly cited means by which SMEs aim to demonstrate value of products to purchasers. Purchasers were perceived to place most importance on factors of safety, expert opinion, cost-effectiveness and price. However many companies did not utilise formal decision-making tools to prioritise these factors. There was no significant dependence of the use of decision-making tools in general with respect to professed knowledge of health economics methods. SMEs did not state a preference for any particular aspect of potential value when deciding whether to develop a product. A majority of SMEs stated they would use a health economics tool. Research and development teams or marketing and sales departments would most likely use one. Conclusion This study points to the need for further research into the education requirements of SMEs in the area of Health Technology Assessment and also for investigation into how SMEs engage with existing HTA processes as required by assessors such as NICE