207 research outputs found

    Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at 7 y in Chilean children of normal birth weight.

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    BACKGROUND: In low-birth-weight girls, obesity increases the risk of premature adrenarche and metabolic complications. However, the consistency of this association in normal-birth-weight children and its potential mediators remain unknown. OBJECTIVES: The objectives were to assess the associations between obesity indicators and dehydroepiandrosterone sulfate (DHEAS) at 7 y of age and to evaluate the role of hormonal markers on these associations. DESIGN: We assessed in 969 participants (6.9 y; 48% girls; all Tanner I) in the Growth and Obesity Chilean Cohort Study the associations between DHEAS and weight, BMI, waist circumference (WC), waist-to-height ratio, skinfold thickness, and percentage total fat (bioimpedance) and determined whether these associations were related to insulin, insulin-like growth factor I (IGF-I), and leptin. We also compared BMI and height growth from 0 to 7 y of age in nonobese and obese children with normal and high DHEAS (≥75th percentile) at 7 y. RESULTS: DHEAS concentrations were similar between girls (30.3 ±1.86 μg/dL) and boys (29.4 ±1.73 μg/dL) (P > 0.05); 17.3% of children were obese (BMI-for-age z score ≥2 SD). Adiposity indicators were positively and similarly associated with DHEAS [ie, BMI, β standardized regression coefficient: 0.23 (95% CI: 0.17, 0.29); WC, β standardized regression coefficient: 0.23 (95% CI: 0.16, 0.30)]; these associations were only partially related to IGF-I and leptin. Obese children had twice the risk of high DHEAS (OR: 2.16; 95% CI: 1.51, 3.09); at 7 y, obese children with high DHEAS were fatter and more centrally obese than their counterparts (P 0.05). None of the results differed by sex (P > 0.05). CONCLUSION: In children of normal birth weight, obesity is positively associated with DHEAS at 7 y of age

    Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

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    This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

    On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes

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    The sensitivity of a search for sources of TeV neutrinos can be improved by grouping potential sources together into generic classes in a procedure that is known as source stacking. In this paper, we define catalogs of Active Galactic Nuclei (AGN) and use them to perform a source stacking analysis. The grouping of AGN into classes is done in two steps: first, AGN classes are defined, then, sources to be stacked are selected assuming that a potential neutrino flux is linearly correlated with the photon luminosity in a certain energy band (radio, IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino production in AGN, this correlation is motivated by hadronic AGN models, as briefly reviewed in this paper. The source stacking search for neutrinos from generic AGN classes is illustrated using the data collected by the AMANDA-II high energy neutrino detector during the year 2000. No significant excess for any of the suggested groups was found.Comment: 43 pages, 12 figures, accepted by Astroparticle Physic

    Detection of Atmospheric Muon Neutrinos with the IceCube 9-String Detector

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    The IceCube neutrino detector is a cubic kilometer TeV to PeV neutrino detector under construction at the geographic South Pole. The dominant population of neutrinos detected in IceCube is due to meson decay in cosmic-ray air showers. These atmospheric neutrinos are relatively well-understood and serve as a calibration and verification tool for the new detector. In 2006, the detector was approximately 10% completed, and we report on data acquired from the detector in this configuration. We observe an atmospheric neutrino signal consistent with expectations, demonstrating that the IceCube detector is capable of identifying neutrino events. In the first 137.4 days of livetime, 234 neutrino candidates were selected with an expectation of 211 +/- 76.1(syst.) +/- 14.5(stat.) events from atmospheric neutrinos

    Ubiquitous Expression of CUG or CAG Trinucleotide Repeat RNA Causes Common Morphological Defects in a Drosophila Model of RNA-Mediated Pathology

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    Expanded DNA repeat sequences are known to cause over 20 diseases, including Huntington’s disease, several types of spinocerebellar ataxia and myotonic dystrophy type 1 and 2. A shared genetic basis, and overlapping clinical features for some of these diseases, indicate that common pathways may contribute to pathology. Multiple mechanisms, mediated by both expanded homopolymeric proteins and expanded repeat RNA, have been identified by the use of model systems, that may account for shared pathology. The use of such animal models enables identification of distinct pathways and their ‘molecular hallmarks’ that can be used to determine the contribution of each pathway in human pathology. Here we characterise a tergite disruption phenotype in adult flies, caused by ubiquitous expression of either untranslated CUG or CAG expanded repeat RNA. Using the tergite phenotype as a quantitative trait we define a new genetic system in which to examine ‘hairpin’ repeat RNA-mediated cellular perturbation. Further experiments use this system to examine whether pathways involving Muscleblind sequestration or Dicer processing, which have been shown to mediate repeat RNA-mediated pathology in other model systems, contribute to cellular perturbation in this model

    The History of Makassan Trepang Fishing and Trade

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    The Malayan term trepang describes a variety of edible holothurians commonly known as sea cucumbers. Although found in temperate and tropical marine waters all over the world, the centre of species diversity and abundance are the shallow coastal waters of Island Southeast Asia. For at least 300 years, trepang has been a highly priced commodity in the Chinese market. Originally, its fishing and trade was a specialized business, centred on the town of Makassar in South Sulawesi (Indonesia). The rise of trepang fishing in the 17th century added valuable export merchandize to the rich shallow seas surrounding the islands of Southeast Asia. This enabled local communities to become part of large trading networks and greatly supported their economic development. In this article, we follow Makassan trepang fishing and trading from its beginning until the industrialization of the fishery and worldwide depletion of sea cucumbers in the 20th century. Thereby, we identify a number of characteristics which trepang fishing shares with the exploitation of other marine resources, including (1) a strong influence of international markets, (2) the role of patron-client relationships which heavily influence the resource selection, and (3) the roving-bandit-syndrome, where fishermen exploit local stocks of valuable resources until they are depleted, and then move to another area. We suggest that understanding the similarities and differences between historical and recent exploitation of marine resources is an important step towards effective management solutions

    Search for neutralino dark matter with the AMANDA neutrino detector

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