54 research outputs found

    Unravelling the structure of the C60 and p-But-calix[8]arene complex

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    Open Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.The structure of the C60 and p-But-calix[8]arene complex has been reinvestigated, showing an unprecedented continuous layered tetragonal array of fullerenes encapsulated by calixarenes. Electron diffraction data revealed the tetragonal symmetry, with a stepped structure observed by AFM and SEM, and the thickness of the basal plane was measured by XRD, as 2 nm. The molecular simulated arrangement of fullerenes accounts for the ability to take up to ca. 11% of fullerenes C70 in place of the smaller fullerene

    Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-kB-dependent manner

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    Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1(-/-) hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease.status: publishe

    Proceedings of the third international molecular pathological epidemiology (MPE) meeting

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    Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods and resources from epidemiology, pathology, biostatistics, bioinformatics and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: 1) the development of new statistical methods to address etiologic heterogeneity; 2) the enhancement of causal inference; 3) the identification of previously unknown exposure-subtype disease associations; and 4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields

    Supplemental Information 3: Raw data from this study

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    Although the existence of coral-reef habitats at depths to 165 m in tropical regions has been known for decades, the richness, diversity, and ecological importance of mesophotic coral ecosystems (MCEs) has only recently become widely acknowledged. During an interdisciplinary effort spanning more than two decades, we characterized the most expansive MCEs ever recorded, with vast macroalgal communities and areas of 100% coral cover between depths of 50–90 m extending for tens of km2 in the Hawaiian Archipelago. We used a variety of sensors and techniques to establish geophysical characteristics. Biodiversity patterns were established from visual and video observations and collected specimens obtained from submersible, remotely operated vehicles and mixed-gas SCUBA and rebreather dives. Population dynamics based on age, growth and fecundity estimates of selected fish species were obtained from laser-videogrammetry, specimens, and otolith preparations. Trophic dynamics were determined using carbon and nitrogen stable isotopic analyses on more than 750 reef fishes. MCEs are associated with clear water and suitable substrate. In comparison to shallow reefs in the Hawaiian Archipelago, inhabitants of MCEs have lower total diversity, harbor new and unique species, and have higher rates of endemism in fishes. Fish species present in shallow and mesophotic depths have similar population and trophic (except benthic invertivores) structures and high genetic connectivity with lower fecundity at mesophotic depths. MCEs in Hawai‘i are widespread but associated with specific geophysical characteristics. High genetic, ecological and trophic connectivity establish the potential for MCEs to serve as refugia for some species, but our results question the premise that MCEs are more resilient than shallow reefs. We found that endemism within MCEs increases with depth, and our results do not support suggestions of a global faunal break at 60 m. Our findings enhance the scientific foundations for conservation and management of MCEs, and provide a template for future interdisciplinary research on MCEs worldwide

    Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring

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    Cardiac rehabilitation for the treatment of women with chest pain and normal coronary arteries

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    Objective: To explore cardiac rehabilitation (CR) as a treatment for psychological and physiological morbidity in women with chest pain and normal coronary arteries (cardiac syndrome X). Design: Sixty-four women aged 57.3 ± 8.6 years (mean ± SD) with cardiac syndrome X were randomly assigned to an 8-week phase III CR exercise program or symptom monitoring control. All women completed the Hospital Anxiety and Depression Scale, Health Anxiety Questionnaire, and Short Form-36 before and after intervention and at the 8-week follow-up. CR patients underwent physical assessment before and after CR. Results: After CR, patients demonstrated improved symptom severity (2.0 ± 0.8 vs 1.26 ± 1.1, P = 0.009), Hospital Anxiety and Depression Scale depression score (8.0 ± 3.4 vs 6.4 ± 3.1, P = 0.04), total Health Anxiety Questionnaire score (12.0 ± 5.5 vs 9.5 ± 6.0, P = 0.008), health worry (4.5 ± 3.1 vs 3.52 ± 2.4, P = 0.025) and interference (2.4 ± 1.8 vs 1.6 ± 1.8, P = 0.004), SF-36 physical functioning (53.1 ± 20.4 vs 62.3 ± 23.9, P = 0.006), energy (36.3 ± 20.7 vs 49.8 ± 19.1, P < 0.001), pain (49.9 ± 20.7 vs 58.1 ± 22.9, P = 0.028), and general health (48.8 ± 17.9 vs 57.6 ± 17.0, P = 0.01) not found among the control women. Improvements were maintained at follow-up. CR patients showed significant improvements in Shuttle Walk Test performance (326.8 ± 111.0 vs 423.6 ± 133.2 m, P < 0.001), diastolic blood pressure (84.7 ± 9.4 vs 79.7 ± 7.3 mm Hg, P = 0.007), and body mass index (29.1 ± 6.0 vs 28.4 ± 6.17 kg/m2, P = 0.003). Conclusions: An 8-week phase III CR program improves exercise tolerance, quality of life, psychological morbidity, symptom severity, and cardiovascular risk factors in women with cardiac syndrome X

    Conceptions of early childhood leadership : driving new professionalism?

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    This study reports the understandings of leadership held by 351 Victorian early childhood leaders (ECLs). Internationally, ECLs are expected to drive quality improvement through mentoring and modelling: a concept associated with distributive leadership. However, ECLs often move into leadership positions by accident and are ill-prepared for their role. Complicating their difficulties are extant perceptions of leadership: many follow models of leadership that prevent them from re-conceptualizing leadership in a new, socially constructed form. This impacts significantly on their ability to influence quality improvement. In this study, ECLs saw relational aspects of their role as particularly important, and were much less concerned with critiquing current quality praxis. They saw their role as important in supporting the development of high-quality practice identified in the National Quality Standards. The paper contends that ECLs play an important role in developing the professions own understandings of quality, and of leadership itself; thus, their lack of engagement in this debate is somewhat concerning. If EC is to continue to evolve as a profession internationally, we need ECLs who excel in quality improvement at the service level, and who are willing to advocate for the ongoing development of professional understandings of quality.18 page(s
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