215 research outputs found

    Genetics of Mechanosensation in the Heart

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    Mechanosensation (the ultimate conversion of a mechanical stimulus into a biochemical signal) as well as mechanotransduction (transmission of mechanically induced signals) belong to the most fundamental processes in biology. These effects, because of their dynamic nature, are particularly important for the cardiovascular system. Therefore, it is not surprising that defects in cardiac mechanosensation, are associated with various types of cardiomyopathy and heart failure. However, our current knowledge regarding the genetic basis of impaired mechanosensation in the cardiovascular system is beginning to shed light on this subject and is at the centre of this brief review

    Real-time phase-contrast x-ray imaging: a new technique for the study of animal form and function

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    BACKGROUND: Despite advances in imaging techniques, real-time visualization of the structure and dynamics of tissues and organs inside small living animals has remained elusive. Recently, we have been using synchrotron x-rays to visualize the internal anatomy of millimeter-sized opaque, living animals. This technique takes advantage of partially-coherent x-rays and diffraction to enable clear visualization of internal soft tissue not viewable via conventional absorption radiography. However, because higher quality images require greater x-ray fluxes, there exists an inherent tradeoff between image quality and tissue damage. RESULTS: We evaluated the tradeoff between image quality and harm to the animal by determining the impact of targeted synchrotron x-rays on insect physiology, behavior and survival. Using 25 keV x-rays at a flux density of 80 μW/mm(-2), high quality video-rate images can be obtained without major detrimental effects on the insects for multiple minutes, a duration sufficient for many physiological studies. At this setting, insects do not heat up. Additionally, we demonstrate the range of uses of synchrotron phase-contrast imaging by showing high-resolution images of internal anatomy and observations of labeled food movement during ingestion and digestion. CONCLUSION: Synchrotron x-ray phase contrast imaging has the potential to revolutionize the study of physiology and internal biomechanics in small animals. This is the only generally applicable technique that has the necessary spatial and temporal resolutions, penetrating power, and sensitivity to soft tissue that is required to visualize the internal physiology of living animals on the scale from millimeters to microns

    ROS release by PPARβ/δ-null fibroblasts reduces tumor load through epithelial antioxidant response.

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    Tumor stroma has an active role in the initiation, growth, and propagation of many tumor types by secreting growth factors and modulating redox status of the microenvironment. Although PPARβ/δ in fibroblasts was shown to modulate oxidative stress in the wound microenvironment, there has been no evidence of a similar effect in the tumor stroma. Here, we present evidence of oxidative stress modulation by intestinal stromal PPARβ/δ, using a FSPCre-Pparb/d <sup>-/-</sup> mouse model and validated it with immortalized cell lines. The FSPCre-Pparb/d <sup>-/-</sup> mice developed fewer intestinal polyps and survived longer when compared with Pparb/d <sup>fl/fl</sup> mice. The pre-treatment of FSPCre-Pparb/d <sup>-/-</sup> and Pparb/d <sup>fl/fl</sup> with antioxidant N-acetyl-cysteine prior DSS-induced tumorigenesis resulted in lower tumor load. Gene expression analyses implicated an altered oxidative stress processes. Indeed, the FSPCre-Pparb/d <sup>-/-</sup> intestinal tumors have reduced oxidative stress than Pparb/d <sup>fl/fl</sup> tumors. Similarly, the colorectal cancer cells and human colon epithelial cells also experienced lower oxidative stress when co-cultured with fibroblasts depleted of PPARβ/δ expression. Therefore, our results establish a role for fibroblast PPARβ/δ in epithelial-mesenchymal communication for ROS homeostasis

    Decorrelation and efficient coding by retinal ganglion cells

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    An influential theory of visual processing asserts that retinal center-surround receptive fields remove spatial correlations in the visual world, producing ganglion cell spike trains that are less redundant than the corresponding image pixels. For bright, high-contrast images, this decorrelation would enhance coding efficiency in optic nerve fibers of limited capacity. We tested the central prediction of the theory and found that the spike trains of retinal ganglion cells were indeed decorrelated compared with the visual input. However, most of the decorrelation was accomplished not by the receptive fields, but by nonlinear processing in the retina. We found that a steep response threshold enhanced efficient coding by noisy spike trains and that the effect of this nonlinearity was near optimal in both salamander and macaque retina. These results offer an explanation for the sparseness of retinal spike trains and highlight the importance of treating the full nonlinear character of neural codes

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    The Impact of Entrepreneurship Education in Higher Education: A Systematic Review and Research Agenda

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    Using a teaching model framework, we systematically review empirical evidence on the impact of entrepreneurship education (EE) in higher education on a range of entrepreneurial outcomes, analyzing 159 published articles from 2004 to 2016. The teaching model framework allows us for the first time to start rigorously examining relationships between pedagogical methods and specific outcomes. Reconfirming past reviews and meta-analyses, we find that EE impact research still predominantly focuses on short-term and subjective outcome measures and tends to severely underdescribe the actual pedagogies being tested. Moreover, we use our review to provide an up-to-date and empirically rooted call for less obvious, yet greatly promising, new or underemphasized directions for future research on the impact of university-based entrepreneurship education. This includes, for example, the use of novel impact indicators related to emotion and mind-set, focus on the impact indicators related to the intention-to-behavior transition, and exploring the reasons for some contradictory findings in impact studies including person-, context-, and pedagogical model-specific moderator
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