Mining Disease Courses across Organizations: A Methodology Based on Process Mining of Diagnosis Events Datasets

Berlín (Alemania) (23-27 julio 2019)This work was supported in part by grants TRA2015-63708-R and TRA2016-78886-C3-1-R (Spanish Government) and Topus (Madrid Regional Government)

IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors

<p>Abstract</p> <p>Background</p> <p>Hepatoblastoma (HB) is an embryonal liver neoplasm of early childhood with a poor prognosis for patients with distant metastases and vascular invasion. We and others have previously shown that the overexpression of <it>insulin-like growth factor 2 </it>(<it>IGF2</it>), loss of imprinting at the <it>IGF2</it>/<it>H19 </it>locus, and amplification of <it>pleomorphic adenoma gene 1 </it>(<it>PLAG1</it>) are common features in HB, suggesting a critical role of the IGF axis in hepatoblastomagenesis. In this study, we investigated the role of the insulin-like growth factor binding protein 3 (IGFBP3), a known competitor of the IGF axis, in pediatric liver cancers.</p> <p>Results</p> <p>The <it>IGFBP3 </it>gene was highly expressed in normal pediatric livers but was heavily downregulated in four HB cell lines and the majority of HB primary tumors (26/36). Detailed methylation analysis of CpG sites in the <it>IGFBP3 </it>promoter region by bisulfite sequencing revealed a high degree of DNA methylation, which is causatively associated with the suppression of <it>IGFBP3 </it>in HB cell lines. Consequently, the treatment of HB cell lines with 5-aza-2'-deoxycytidine resulted in DNA demethylation and reactivation of the epigenetically silenced <it>IGFBP3 </it>expression. Interestingly, <it>IGFBP3 </it>promoter methylation predominantly occurred in metastatic HB with vascular invasion. Restoring <it>IGFBP3 </it>expression in HB cells resulted in reduced colony formation, migration, and invasion.</p> <p>Conclusion</p> <p>This study provides the first direct evidence that the reactivation of <it>IGFBP3 </it>decreases aggressive properties of pediatric liver cancer cells and that <it>IGFBP3 </it>promoter methylation might be used as an indicator for vessel-invasive tumor growth in HB patients.</p

Interface Excitons in Krmnen Clusters : The Role of Electron Affinity in the Formation of Electronic Structure

The formation of the electronic structure of small Kr_m clusters (m<150) embedded inside Ne_N clusters (1200<N<7500) has been investigated with the help of fluorescence excitation spectroscopy using synchrotron radiation. Electronically excited states, assigned to excitons at the Ne/Kr interface, 1i and 1'i were observed. The absorption bands, which are related to the lowest spin-orbit split atomic Kr 3P1 and 1P1 states, initially appear and shift towards lower energy when the krypton cluster size m increases. The characteristic bulk 1t and 1't excitons appear in the spectra, when the cluster radius exceeds some critical value, R_cl>Delta_1i . Kr clusters comprising up to 70 atoms do not exhibit bulk absorption bands. We suggest that this is due to the penetration of the interface excitons into the Kr_m cluster volume, because of the negative electron affinity of surrounding Ne atoms. From the energy shift of the interface absorption bands with cluster size an unexpectedly large penetration depth of delta_1i =7.0+/-0.1 A is estimated, which can be explained by the interplay between the electron affinities of the guest and the host cluster

The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1 and regulates the stability of UHRF1

Aberrant DNA methylation is often associated with cancer and the formation of tumors; however, the underlying mechanisms, in particular the recruitment and regulation of DNA methyltransferases remain largely unknown. In this study, we identified USP7 as an interaction partner of Dnmt1 and UHRF1 in vivo. Dnmt1 and USP7 formed a soluble dimer complex that associated with UHRF1 as a trimeric complex on chromatin. Complex interactions were mediated by the C-terminal domain of USP7 with the TS-domain of Dnmt1, whereas the TRAF-domain of USP7 bound to the SRA-domain of UHRF1. USP7 was capable of targeting UHRF1 for deubiquitination and affects UHRF1 protein stability in vivo. Furthermore, Dnmt1, UHRF1 and USP7 co-localized on silenced, methylated genes in vivo. Strikingly, when analyzing the impact of UHRF1 and USP7 on Dnmt1-dependent DNA methylation, we found that USP7 stimulated both the maintenance and de novo DNA methylation activity of Dnmt1 in vitro. Therefore, we propose a dual role of USP7, regulating the protein turnover of UHRF1 and stimulating the enzymatic activity of Dnmt1 in vitro and in vivo

Specimens, slips and systems: Daniel Solander and the classification of nature at the world's first public museum, 1753-1768.

The British Museum, based in Montague House, Bloomsbury, opened its doors on 15 January 1759, as the world's first state-owned public museum. The Museum's collection mostly originated from Sir Hans Sloane (1660-1753), whose vast holdings were purchased by Parliament shortly after his death. The largest component of this collection was objects of natural history, including a herbarium made up of 265 bound volumes, many of which were classified according to the late seventeenth-century system of John Ray (1627-1705). The 1750s saw the emergence of Linnaean binomial nomenclature, following the publication of Carl Linnaeus' Species Plantarum (1753) and Systema Naturae (1758). In order to adopt this new system for their collections, the Trustees of the British Museum chose to employ the Swedish naturalist and former student of Linnaeus, Daniel Solander (1733-1782) to reclassify the collection. Solander was ordered to devise a new system for classifying and cataloguing Sloane's natural history collection, which would allow both Linnaeans and those who followed earlier systems to access it. Solander's work was essential for allowing the British Museum to realize its aim of becoming a public centre of learning, adapting the collection to reflect the diversity of classificatory practices which were existent by the 1760s. This task engaged Solander until 1768, when he received an offer from Joseph Banks (1743-1820) to accompany him on HMS Endeavour to the Pacific

Advance of the "vagina-guardian"

Der türkische Premier Erdoğan zeigt sich besorgt um das Bevölkerungswachstum – und prescht mit kontroversen Erklärungen für ein neues Abtreibungsgesetz voran. Frauenrechtsverbände sind empört und kündigen Demonstrationen an.1 page(s

Brutus remains in cover

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