1,006 research outputs found

    Concept mapping as a tool to break disciplinary boundaries: isomerism in biological systems

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    O mapeamento conceitual foi utilizado como uma ferramenta para verificar as mudanças conceituais de estudantes de Ensino Médio após a realização de atividades didáticas desenvolvidas durante as aulas de Química. O objetivo pedagógico a ser atingido foi romper as fronteiras que segregam o conhecimento científico em disciplinas isoladas. Os estudantes foram intencionalmente provocados a relacionar conceitos de Química e de Biologia, a fim de compreender melhor e explicar as conseqüências biológicas da isomeria. Os mapas conceituais elaborados pelos estudantes, antes e após as atividades propostas, evidenciaram o aparecimento de relações entre conceitos químicos e biológicos, que foram avaliadas qualitativamente. Este trabalho mostra que os mapas conceituais podem ser utilizados como ferramentas para auxiliar o professor na realização de práticas didáticas interdisciplinares na escola, bem como para acompanhar o progresso dos estudantes em direção à interdisciplinaridade.Concept mapping was used as a tool for checking the conceptual changes caused by didactic activities implemented during chemistry classes in high school. Its pedagogical aim was to break down the boundaries, which segregate scientific knowledge into isolated disciplines. The students were intentionally provoked to merge concepts from chemistry and biology, in order to better understand and explain the biological consequences of isomerism. The concept maps produced by the students before and after the activities confirmed the appearance of relationships among chemical and biological concepts, which were qualitatively evaluated. This work shows that concept maps can be used to follow the students' progress towards interdisciplinarity, and to help the teacher to devise future classroom activities to reinforce and to expand interdisciplinary relationships.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - PIBI

    Joint analysis of stressors and ecosystem services to enhance restoration effectiveness

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    With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes. Cumulative ecosystem stress is highest in near-shore habitats, but also extends offshore in Lakes Erie, Ontario, and Michigan. Variation in cumulative stress is driven largely by spatial concordance among multiple stressors, indicating the importance of considering all stressors when planning restoration activities. In addition, highly stressed areas reflect numerous different combinations of stressors rather than a single suite of problems, suggesting that a detailed understanding of the stressors needing alleviation could improve restoration planning. We also find that many important areas for fisheries and recreation are subject to high stress, indicating that ecosystem degradation could be threatening key services. Current restoration efforts have targeted high-stress sites almost exclusively, but generally without knowledge of the full range of stressors affecting these locations or differences among sites in service provisioning. Our results demonstrate that joint spatial analysis of stressors and ecosystem services can provide a critical foundation for maximizing social and ecological benefits from restoration investments. www.pnas.org/lookup/suppl/doi:10.1073/pnas.1213841110/-/DCSupplementa

    Visceral fat area and cardiometabolic risk: The Kardiovize study

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    BACKGROUND: Visceral fat is associated with adiposity-based complications. Bioimpedance measurement allows estimation of visceral fat area (VFA) in an easy manner. However, a validated cut-off value for VFA by bioimpedance associated with cardiometabolic risk is lacking in European population. AIM: To determine cut-off values of VFA measured via bioimpedance associated with cardiometabolic risk. METHODS: Random cross-sectional Czech population-based sample of 25-64 years old subjects. Receiver Operating Characteristic (ROC) curves were used and the area under the curve (AUC), sensitivity, and specificity were calculated. The Cardiometabolic Disease Staging System (CMDS) was used to classify cardiometabolic risk: Stage 1 - 1 or 2 metabolic syndrome (MetS) components, without impaired fasting glucose (IFG); Stage 2 - MetS or IFG; Stage 3 - MetS with IFG; Stage 4 - type 2 diabetes and/or cardiovascular disease. RESULTS: 2052 participants (54.5% females, median age 49 years) were included. Median VFA (inter-quartile range) were 82.2 cm2 (54.8) in men and 89.8 cm2 (55.6) in women. The best VFA cut-offs associated with Stage 1 in men and women were 71 cm2 (sensitivity = 0.654; specificity = 0.427) and 83 cm2 (sensitivity = 0.705; specificity = 0.556) ; Stage 2: 84 cm2 (sensitivity = 0.673; specificity = 0.551) and 98 cm2 (sensitivity = 0.702; specificity = 0.628) ; Stage 3: 90 cm2 (sensitivity = 0.886; specificity = 0.605) and 109 cm2 (sensitivity = 0.755; specificity = 0.704); Stage 4: 91 cm2 (sensitivity = 0.625; specificity = 0.611) and 81 cm2 (sensitivity = 0.695; specificity = 0.448), respectively. CONCLUSION: A cut-off value of VFA of 71 cm2 in men and 83 cm2 in women exhibited the earliest stage of cardiometabolic risk, and 90 cm2 in men and 109 cm2 in women showed the best performance to detect risk

    The Structure of the NPC1L1 N-Terminal Domain in a Closed Conformation

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    NPC1L1 is the molecular target of the cholesterol lowering drug Ezetimibe and mediates the intestinal absorption of cholesterol. Inhibition or deletion of NPC1L1 reduces intestinal cholesterol absorption, resulting in reduction of plasma cholesterol levels.Here we present the 2.8 Å crystal structure of the N-terminal domain (NTD) of NPC1L1 in the absence of cholesterol. The structure, combined with biochemical data, reveals the mechanism of cholesterol selectivity of NPC1L1. Comparison to the cholesterol free and bound structures of NPC1(NTD) reveals that NPC1L1(NTD) is in a closed conformation and the sterol binding pocket is occluded from solvent.The structure of NPC1L1(NTD) reveals a degree of flexibility surrounding the entrance to the sterol binding pocket, suggesting a gating mechanism that relies on multiple movements around the entrance to the sterol binding pocket

    The Luminosity Function of Early-Type Galaxies at z~0.75

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    We measure the luminosity function of morphologically selected E/S0 galaxies from z=0.5z=0.5 to z=1.0z=1.0 using deep high resolution Advanced Camera for Surveys imaging data. Our analysis covers an area of 48\Box\arcmin (8×\times the area of the HDF-N) and extends 2 magnitudes deeper (I24I\sim24 mag) than was possible in the Deep Groth Strip Survey (DGSS). At 0.5<z<0.750.5<z<0.75, we find MB5logh0.7=21.1±0.3M_B^*-5\log h_{0.7}=-21.1\pm0.3 and α=0.53±0.2\alpha=-0.53\pm0.2, and at 0.75<z<1.00.75<z<1.0, we find MB5logh0.7=21.4±0.2M_B^*-5\log h_{0.7}=-21.4\pm0.2. These luminosity functions are similar in both shape and number density to the luminosity function using morphological selection (e.g., DGSS), but are much steeper than the luminosity functions of samples selected using morphological proxies like the color or spectral energy distribution (e.g., CFRS, CADIS, or COMBO-17). The difference is due to the `blue', (UV)0<1.7(U-V)_0<1.7, E/S0 galaxies, which make up to 30\sim30% of the sample at all magnitudes and an increasing proportion of faint galaxies. We thereby demonstrate the need for {\it both morphological and structural information} to constrain the evolution of galaxies. We find that the `blue' E/S0 galaxies have the same average sizes and Sersic parameters as the `red', (UV)0>1.7(U-V)_0>1.7, E/S0 galaxies at brighter luminosities (MB<20.1M_B<-20.1), but are increasingly different at fainter magnitudes where `blue' galaxies are both smaller and have lower Sersic parameters. Fits of the colors to stellar population models suggest that most E/S0 galaxies have short star-formation time scales (τ<1\tau<1 Gyr), and that galaxies have formed at an increasing rate from z8z\sim8 until z2z\sim2 after which there has been a gradual decline.Comment: 39 pages, 21 figures, accepted in A

    Dysglycemia and Abnormal Adiposity Drivers of Cardiometabolic-Based Chronic Disease in the Czech Population: Biological, Behavioral, and Cultural/Social Determinants of Health

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    In contrast to the decreasing burden related to cardiovascular disease (CVD), the burden related to dysglycemia and adiposity complications is increasing in Czechia, and local drivers must be identified. A comprehensive literature review was performed to evaluate biological, behavioral, and environmental drivers of dysglycemia and abnormal adiposity in Czechia. Additionally, the structure of the Czech healthcare system was described. The prevalence of obesity in men and diabetes in both sexes has been increasing over the past 30 years. Possible reasons include the Eastern European eating pattern, high prevalence of physical inactivity and health illiteracy, education, and income-related health inequalities. Despite the advanced healthcare system based on the compulsory insurance model with free-for-service healthcare and a wide range of health-promoting initiatives, more effective strategies to tackle the adiposity/dysglycemia are needed. In conclusion, the disease burden related to dysglycemia and adiposity in Czechia remains high but is not translated into greater CVD. This discordant relationship likely depends more on other factors, such as improvements in dyslipidemia and hypertension control. A reconceptualization of abnormal adiposity and dysglycemia into a more actionable cardiometabolic-based chronic disease model is needed to improve the approach to these conditions. This review can serve as a platform to investigate causal mechanisms and secure effective management of cardiometabolic-based chronic disease

    Exploiting inflammation for therapeutic gain in pancreatic cancer

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    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

    Mitoxantrone Induces Natural Killer Cell Maturation in Patients with Secondary Progressive Multiple Sclerosis

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    Mitoxantrone is one of the few drugs approved for the treatment of progressive multiple sclerosis (MS). However, the prolonged use of this potent immunosuppressive agent is limited by the appearance of severe side effects. Apart from its general cytotoxic effect, the mode of action of mitoxantrone on the immune system is poorly understood. Thus, to develop safe therapeutic approaches for patients with progressive MS, it is essential to elucidate how mitoxantrone exerts it benefits. Accordingly, we initiated a prospective single-arm open-label study with 19 secondary progressive MS patients. We investigated long-term effects of mitoxantrone on patient peripheral immune subsets using flow cytometry. While we corroborate that mitoxantrone persistently suppresses B cells in vivo, we show for the first time that treatment led to an enrichment of neutrophils and immunomodulatory CD8low T cells. Moreover, sustained mitoxantrone applications promoted not only persistent NK cell enrichment but also NK cell maturation. Importantly, this mitoxantrone-induced NK cell maturation was seen only in patients that showed a clinical response to treatment. Our data emphasize the complex immunomodulatory role of mitoxantrone, which may account for its benefit in MS. In particular, these results highlight the contribution of NK cells to mitoxantrone efficacy in progressive MS
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