184 research outputs found

    Prehistoric Hopewell Meteorite Collecting : Further Evidence

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    Author Institution: Department of Humanities and Social Studies, Case Institute of Technology, Cleveland, Ohi

    Prehistoric Hopewell Meteorite Collecting : Context and Implications

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    Author Institution: Department of Humanities and Social Studies, Case Institute of Technology, Cleveland, Ohi

    The Abri Schmidt, an Important Upper Palaeolithic Site in Bavaria

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    Author Institution: Cleveland Museum of Natural History and Case Institute of Technology, Cleveland, Ohi

    Brain Activation by Peptide Pro-Leu-Gly-NH2 (MIF-1)

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    MIF-1 (Pro-Leu-Gly-NH2) is a tripeptide for which the therapeutic potential in Parkinson's disease and depression has been indicated by many studies. However, the cellular mechanisms of action of MIF-1 are not yet clear. Here, we show the specific brain regions responsive to MIF-1 treatment by c-Fos mapping, and determine the kinetics of cellular signaling by western blotting of pERK, pSTAT3, and c-Fos in cultured neurons. The immunoreactivity of c-Fos was increased 4 hours after MIF-1 treatment in brain regions critically involved in the regulation of mood, anxiety, depression, and memory. The number of cells activated was greater after peripheral treatment (intravenous delivery) than after intracerebroventricular injection. In cultured SH-SY5Y neuronal cells, c-Fos was induced time- and dose-dependently. The activation of cellular c-Fos was preceded by a transient increase of mitogen-activated protein kinase pERK but a reduction of phosphorylated Signal Transducer and Activator of Transcription (pSTAT3) initially. We conclude that MIF-1 can modulate multiple cellular signals including pERK, and pSTAT3 to activate c-Fos. The cellular activation in specific brain regions illustrates the biochemical and neuroanatomical basis underlying the therapeutic effect of MIF-1 in Parkinson's disease and depression

    Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA

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    Objective: To use deep sequencing to identify novel microRNAs in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. Design: A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate microRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray and computational analysis, validated using 3’-UTR-luciferase reporter plasmids. Protein levels were assessed by western blot and functional analysis by cell adhesion. Results: We identified 990 known microRNAs and 1621 potential novel microRNAs in human osteoarthritic chondrocytes, 60 of the latter were expressed in all samples assayed. MicroRNA-140-3p was the most highly expressed microRNA in osteoarthritic cartilage. Sixteen novel candidate microRNAs were analysed further, of which 6 remained after northern blot analysis. Three novel microRNAs were regulated across models of chondrogenesis, chondrocyte differentiation or cartilage injury. One sequence (novel #11), annotated in rodents as microRNA-3085-3p, was preferentially expressed in cartilage, dependent on chondrocyte differentiation and, in man, is located in an intron of the cartilage-expressed gene CRTAC-1. This microRNA was shown to target the ITGA5 gene directly (which encodes integrin alpha5) and inhibited adhesion to fibronectin (dependent on alpha5beta1 integrin). Conclusion: Deep sequencing has uncovered many potential microRNA candidates expressed in human cartilage. At least three of these show potential functional interest in cartilage homeostasis and osteoarthritis. Particularly, novel #11 (microRNA-3085-3p) which has been identified for the first time in man

    COnstructing Proxy Records from Age models (COPRA)

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    Reliable age models are fundamental for any palaeoclimate reconstruction. Available interpolation procedures between age control points are often inadequately reported, and very few translate age uncertainties to proxy uncertainties. Most available modeling algorithms do not allow incorporation of layer counted intervals to improve the confidence limits of the age model in question. We present a framework that allows detection and interactive handling of age reversals and hiatuses, depth-age modeling, and proxy-record reconstruction. Monte Carlo simulation and a translation procedure are used to assign a precise time scale to climate proxies and to translate dating uncertainties to uncertainties in the proxy values. The presented framework allows integration of incremental relative dating information to improve the final age model. The free software package COPRA1.0 facilitates easy interactive usage

    Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14th century

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    We report genome-wide data for 33 Ashkenazi Jews (AJ), dated to the 14th century, following a salvageexcavation at the medieval Jewish cemetery of Erfurt, Germany. The Erfurt individuals are geneticallysimilar to modern AJ and have substantial Southern European ancestry, but they show more variabilityin Eastern European-related ancestry than modern AJ. A third of the Erfurt individuals carried the samenearly-AJ-specific mitochondrial haplogroup and eight carried pathogenic variants known to affect AJtoday. These observations, together with high levels of runs of homozygosity, suggest that the Erfurtcommunity had already experienced the major reduction in size that affected modern AJ. However, theErfurt bottleneck was more severe, implying substructure in medieval AJ. Together, our results suggestthat the AJ founder event and the acquisition of the main sources of ancestry pre-dated the 14th centuryand highlight late medieval genetic heterogeneity no longer present in modern AJ
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