214. Genomic evolution and chemoresistance in germ-cell tumours.
作者: Amaro Taylor-Weiner.;Travis Zack.;Elizabeth O'Donnell.;Jennifer L Guerriero.;Brandon Bernard.;Anita Reddy.;G Celine Han.;Saud AlDubayan.;Ali Amin-Mansour.;Steven E Schumacher.;Kevin Litchfield.;Clare Turnbull.;Stacey Gabriel.;Rameen Beroukhim.;Gad Getz.;Scott L Carter.;Michelle S Hirsch.;Anthony Letai.;Christopher Sweeney.;Eliezer M Van Allen.
来源: Nature. 2016年540卷7631期114-118页
Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types. These tumours also acquire KRAS mutations during the development from precursor to primary disease, and primary testicular GCTs (TGCTs) are uniformly wild type for TP53. In addition, by functional measurement of apoptotic signalling (BH3 profiling) of fresh tumour and adjacent tissue, we find that primary TGCTs have high mitochondrial priming that facilitates chemotherapy-induced apoptosis. Finally, by phylogenetic analysis of serial TGCTs that emerge with chemotherapy resistance, we show how TGCTs gain additional reciprocal loss of heterozygosity and that this is associated with loss of pluripotency markers (NANOG and POU5F1) in chemoresistant teratomas or transformed carcinomas. Our results demonstrate the distinct genomic features underlying the origins of this disease and associated with the chemosensitivity phenotype, as well as the rare progression to chemoresistance. These results identify the convergence of cancer genomics, mitochondrial priming and GCT evolution, and may provide insights into chemosensitivity and resistance in other cancers.
216. Ghost imaging with atoms.
作者: R I Khakimov.;B M Henson.;D K Shin.;S S Hodgman.;R G Dall.;K G H Baldwin.;A G Truscott.
来源: Nature. 2016年540卷7631期100-103页
Ghost imaging is a counter-intuitive phenomenon-first realized in quantum optics-that enables the image of a two-dimensional object (mask) to be reconstructed using the spatio-temporal properties of a beam of particles with which it never interacts. Typically, two beams of correlated photons are used: one passes through the mask to a single-pixel (bucket) detector while the spatial profile of the other is measured by a high-resolution (multi-pixel) detector. The second beam never interacts with the mask. Neither detector can reconstruct the mask independently, but temporal cross-correlation between the two beams can be used to recover a 'ghost' image. Here we report the realization of ghost imaging using massive particles instead of photons. In our experiment, the two beams are formed by correlated pairs of ultracold, metastable helium atoms, which originate from s-wave scattering of two colliding Bose-Einstein condensates. We use higher-order Kapitza-Dirac scattering to generate a large number of correlated atom pairs, enabling the creation of a clear ghost image with submillimetre resolution. Future extensions of our technique could lead to the realization of ghost interference, and enable tests of Einstein-Podolsky-Rosen entanglement and Bell's inequalities with atoms.
218. Quantifying global soil carbon losses in response to warming.
作者: T W Crowther.;K E O Todd-Brown.;C W Rowe.;W R Wieder.;J C Carey.;M B Machmuller.;B L Snoek.;S Fang.;G Zhou.;S D Allison.;J M Blair.;S D Bridgham.;A J Burton.;Y Carrillo.;P B Reich.;J S Clark.;A T Classen.;F A Dijkstra.;B Elberling.;B A Emmett.;M Estiarte.;S D Frey.;J Guo.;J Harte.;L Jiang.;B R Johnson.;G Kröel-Dulay.;K S Larsen.;H Laudon.;J M Lavallee.;Y Luo.;M Lupascu.;L N Ma.;S Marhan.;A Michelsen.;J Mohan.;S Niu.;E Pendall.;J Peñuelas.;L Pfeifer-Meister.;C Poll.;S Reinsch.;L L Reynolds.;I K Schmidt.;S Sistla.;N W Sokol.;P H Templer.;K K Treseder.;J M Welker.;M A Bradford.
来源: Nature. 2016年540卷7631期104-108页
The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.
220. Organization and functions of mGlu and GABAB receptor complexes.
The neurotransmitters glutamate and γ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a large extracellular domain and a mandatory dimeric structure. Recent studies have revealed how these receptors are activated through multiple allosteric interactions between subunit domains. It emerges that the molecular complexity of these receptors is further increased through association with trafficking, effector and regulatory proteins. The structure and composition of these receptors present opportunities for therapeutic intervention in mental health and neurological disorders.
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