144 research outputs found

    Trauernormen: historische und gegenwÀrtige Perspektiven

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    "Ziel des Beitrags ist es, eine historische Perspektive auf die Trauer im westlichen Kulturraum zu entwickeln und die darin wirkenden Trauernormen zu verdeutlichen. Den theoretischen Rahmen bildet das Konzept der GefĂŒhlsnormen von Arlie Hochschild. Mit einer Verlagerung von Trauer aus der Gemeinschaft und Öffentlichkeit in die Privatheit - weitgehend losgelöst von festgelegten Ritualen und Praktiken - lĂ€sst sich ein historischer Wandel von Verhaltensnormen hin zu GefĂŒhlsnormen im Rahmen einer Emotionalisierung der Trauer feststellen. Empirische Befunde einer Online-Befragung in der Schweiz und Deutschland verdeutlichen die gegenwĂ€rtigen Trauernormen und individuellen Erfahrungen im Erleben der Trauer. Die Ergebnisse geben u. a. Hinweise auf die Kontrolle von TrauergefĂŒhlen, die Schwierigkeiten, mit anderen ĂŒber die Trauer zu sprechen und eine Unsicherheit im sozialen Umgang mit Trauernden." (Autorenreferat)"The article adopts a historical perspective on grieving in Western culture and traces contemporary grieving norms. Arlie Hochschild's concept of feeling rules provides the theoretical framework. As grieving has shifted from the community and the public sphere to private sphere - where it is no longer embedded in set rituals and practices -, we can also observe a historical shift from behavioral norms to feeling norms in the course of an emotionalization of grieving. Empirical findings from an online survey in Switzerland and Germany elucidate contemporary grieving norms and illustrate individual experiences of grieving. The results indicate, among other things, how the emotions involved in grieving are controlled and what difficulties exist in verbalizing grief to others. They also point to insecurity in social interaction with those grieving." (author's abstract

    Trauernormen: historische und gegenwÀrtige Perspektiven

    Full text link
    "Ziel des Beitrags ist es, eine historische Perspektive auf die Trauer im westlichen Kulturraum zu entwickeln und die darin wirkenden Trauernormen zu verdeutlichen. Den theoretischen Rahmen bildet das Konzept der GefĂŒhlsnormen von Arlie Hochschild. Mit einer Verlagerung von Trauer aus der Gemeinschaft und Öffentlichkeit in die Privatheit - weitgehend losgelöst von festgelegten Ritualen und Praktiken - lĂ€sst sich ein historischer Wandel von Verhaltensnormen hin zu GefĂŒhlsnormen im Rahmen einer Emotionalisierung der Trauer feststellen. Empirische Befunde einer Online-Befragung in der Schweiz und Deutschland verdeutlichen die gegenwĂ€rtigen Trauernormen und individuellen Erfahrungen im Erleben der Trauer. Die Ergebnisse geben u. a. Hinweise auf die Kontrolle von TrauergefĂŒhlen, die Schwierigkeiten, mit anderen ĂŒber die Trauer zu sprechen und eine Unsicherheit im sozialen Umgang mit Trauernden." (Autorenreferat)"The article adopts a historical perspective on grieving in Western culture and traces contemporary grieving norms. Arlie Hochschild's concept of feeling rules provides the theoretical framework. As grieving has shifted from the community and the public sphere to private sphere - where it is no longer embedded in set rituals and practices -, we can also observe a historical shift from behavioral norms to feeling norms in the course of an emotionalization of grieving. Empirical findings from an online survey in Switzerland and Germany elucidate contemporary grieving norms and illustrate individual experiences of grieving. The results indicate, among other things, how the emotions involved in grieving are controlled and what difficulties exist in verbalizing grief to others. They also point to insecurity in social interaction with those grieving." (author's abstract

    eGFP-tagged Wnt-3a enables functional analysis of Wnt trafficking and signaling and kinetic assessment of Wnt binding to full-length Frizzled

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    The Wingless/Int1 (Wnt) signaling system plays multiple, essential roles in embryonic development, tissue homeostasis and human diseases. Although many of the underlying signaling mechanisms are becoming clearer, the binding mode, kinetics and selectivity of 19 mammalian WNTs to their receptors of the class Frizzled (FZD1−10_{1-10}) remain obscure. Attempts to investigate Wnt-FZD interactions are hampered by the difficulties in working with Wnt proteins and their recalcitrance to epitope tagging. Here, we used a fluorescently tagged version of mouse Wnt-3a for studying Wnt-FZD interactions. We observed that the enhanced GFP (eGFP) tagged Wnt-3a maintains properties akin to wild-type Wnt-3a in several biologically relevant contexts. The eGFP-tagged Wnt-3a was secreted in an evenness interrupted (EVI)/Wntless-dependent manner, activated Wnt/ÎČ-catenin signaling in 2D and 3D cell culture experiments, promoted axis duplication in Xenopus embryos, stimulated LDL receptor–related protein 6 (LRP6) phosphorylation in cells and associated with exosomes. Further, we used conditioned medium containing eGFP-Wnt-3a to visualize its binding to FZD and to quantify Wnt-FZD interactions in real time in live cells, utilizing a recently established NanoBRET-based ligand binding assay. In summary, the development of a biologically active, fluorescent Wnt-3a reported here opens up the technical possibilities to unravel the intricate biology of Wnt signaling and Wnt-receptor selectivity

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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    Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

    Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

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    The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

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    Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies
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