GSTDTAP

浏览/检索结果: 共11条,第1-10条 帮助

已选(0)清除 条数/页:   排序方式:
Nearest neighbours reveal fast and slow components of motor learning 期刊论文
NATURE, 2020, 577 (7791) : 526-+
作者:  Kollmorgen, Sepp;  Hahnloser, Richard H. R.;  Mante, Valerio
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/03

A new method for analysing change in high-dimensional data is based on nearest-neighbour statistics and is applied here to song dynamics during vocal learning in zebra finches, but could potentially be applied to other biological and artificial behaviours.


Changes in behaviour resulting from environmental influences, development and learning(1-5) are commonly quantified on the basis of a few hand-picked features(2-4,6,7) (for example, the average pitch of acoustic vocalizations(3)), assuming discrete classes of behaviours (such as distinct vocal syllables)(2,3,8-10). However, such methods generalize poorly across different behaviours and model systems and may miss important components of change. Here we present a more-general account of behavioural change that is based on nearest-neighbour statistics(11-13), and apply it to song development in a songbird, the zebra finch(3). First, we introduce the concept of '  repertoire dating'  , whereby each rendition of a behaviour (for example, each vocalization) is assigned a repertoire time, reflecting when similar renditions were typical in the behavioural repertoire. Repertoire time isolates the components of vocal variability that are congruent with long-term changes due to vocal learning and development, and stratifies the behavioural repertoire into '  regressions'  , '  anticipations'  and '  typical renditions'  . Second, we obtain a holistic, yet low-dimensional, description of vocal change in terms of a stratified '  behavioural trajectory'  , revealing numerous previously unrecognized components of behavioural change on fast and slow timescales, as well as distinct patterns of overnight consolidation(1,2,4,14,15) across the behavioral repertoire. We find that diurnal changes in regressions undergo only weak consolidation, whereas anticipations and typical renditions consolidate fully. Because of its generality, our nonparametric description of how behaviour evolves relative to itself-rather than to a potentially arbitrary, experimenter-defined goal(2,3,14,16)-appears well suited for comparing learning and change across behaviours and species(17,18), as well as biological and artificial systems(5).


  
Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition 期刊论文
NATURE, 2020, 577 (7790) : 421-+
作者:  Xue, Jenny Y.;  Zhao, Yulei;  Aronowitz, Jordan;  Mai, Trang T.;  Vides, Alberto;  Qeriqi, Besnik;  Kim, Dongsung;  Li, Chuanchuan;  de Stanchina, Elisa;  Mazutis, Linas;  Risso, Davide;  Lito, Piro
收藏  |  浏览/下载:14/0  |  提交时间:2020/07/03

KRAS GTPases are activated in one-third of cancers, and KRAS(G12C) is one of the most common activating alterations in lung adenocarcinoma(1,2). KRAS(G12C) inhibitors(3,4) are in phase-I clinical trials and early data show partial responses in nearly half of patients with lung cancer. How cancer cells bypass inhibition to prevent maximal response to therapy is not understood. Because KRAS(G12C) cycles between an active and inactive conformation(4-6), and the inhibitors bind only to the latter, we tested whether isogenic cell populations respond in a non-uniform manner by studying the effect of treatment at a single-cell resolution. Here we report that, shortly after treatment, some cancer cells are sequestered in a quiescent state with low KRAS activity, whereas others bypass this effect to resume proliferation. This rapid divergent response occurs because some quiescent cells produce new KRAS(G12C) in response to suppressed mitogen-activated protein kinase output. New KRAS(G12C) is maintained in its active, drug-insensitive state by epidermal growth factor receptor and aurora kinase signalling. Cells without these adaptive changes-or cells in which these changes are pharmacologically inhibited-remain sensitive to drug treatment, because new KRAS(G12C) is either not available or exists in its inactive, drug-sensitive state. The direct targeting of KRAS oncoproteins has been a longstanding objective in precision oncology. Our study uncovers a flexible non-uniform fitness mechanism that enables groups of cells within a population to rapidly bypass the effect of treatment. This adaptive process must be overcome if we are to achieve complete and durable responses in the clinic.


  
Detecting Slow Slip Events From Seafloor Pressure Data Using Machine Learning 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2020, 47 (11)
作者:  He, Bing;  Wei, Meng;  Watts, D. Randolph;  Shen, Yang
收藏  |  浏览/下载:10/0  |  提交时间:2020/05/13
slow slip events  seafloor geodesy  machine learning  seafloor pressure data  New Zealand  
Hydrothermal (NN)-N-15-N-15 abundances constrain the origins of mantle nitrogen 期刊论文
NATURE, 2020, 580 (7803) : 367-+
作者:  Zhao, Steven;  Jang, Cholsoon;  Liu, Joyce;  Uehara, Kahealani;  Gilbert, Michael;  Izzo, Luke;  Zeng, Xianfeng;  Trefely, Sophie;  Fernandez, Sully;  Carrer, Alessandro;  Miller, Katelyn D.;  Schug, Zachary T.;  Snyder, Nathaniel W.;  Gade, Terence P.;  Titchenell, Paul M.;  Rabinowitz, Joshua D.;  Wellen, Kathryn E.
收藏  |  浏览/下载:16/0  |  提交时间:2020/05/13

Nitrogen is the main constituent of the Earth'  s atmosphere, but its provenance in the Earth'  s mantle remains uncertain. The relative contribution of primordial nitrogen inherited during the Earth'  s accretion versus that subducted from the Earth'  s surface is unclear(1-6). Here we show that the mantle may have retained remnants of such primordial nitrogen. We use the rare (NN)-N-15-N-15 isotopologue of N-2 as a new tracer of air contamination in volcanic gas effusions. By constraining air contamination in gases from Iceland, Eifel (Germany) and Yellowstone (USA), we derive estimates of mantle delta N-15 (the fractional difference in N-15/N-14 from air), N-2/Ar-36 and N-2/He-3. Our results show that negative delta N-15 values observed in gases, previously regarded as indicating a mantle origin for nitrogen(7-10), in fact represent dominantly air-derived N-2 that experienced N-15/N-14 fractionation in hydrothermal systems. Using two-component mixing models to correct for this effect, the (NN)-N-15-N-15 data allow extrapolations that characterize mantle endmember delta N-15, N-2/Ar-36 and N-2/He-3 values. We show that the Eifel region has slightly increased delta N-15 and N-2/Ar-36 values relative to estimates for the convective mantle provided by mid-ocean-ridge basalts(11), consistent with subducted nitrogen being added to the mantle source. In contrast, we find that whereas the Yellowstone plume has delta N-15 values substantially greater than that of the convective mantle, resembling surface components(12-15), its N-2/Ar-36 and N-2/He-3 ratios are indistinguishable from those of the convective mantle. This observation raises the possibility that the plume hosts a primordial component. We provide a test of the subduction hypothesis with a two-box model, describing the evolution of mantle and surface nitrogen through geological time. We show that the effect of subduction on the deep nitrogen cycle may be less important than has been suggested by previous investigations. We propose instead that high mid-ocean-ridge basalt and plume delta N-15 values may both be dominantly primordial features.


  
Microbiome analyses of blood and tissues suggest cancer diagnostic approach 期刊论文
NATURE, 2020, 579 (7800) : 567-+
作者:  Shao, Zhengping;  Flynn, Ryan A.;  Crowe, Jennifer L.;  Zhu, Yimeng;  Liang, Jialiang;  Jiang, Wenxia;  Aryan, Fardin;  Aoude, Patrick;  Bertozzi, Carolyn R.;  Estes, Verna M.;  Lee, Brian J.;  Bhagat, Govind;  Zha, Shan;  Calo, Eliezer
收藏  |  浏览/下载:56/0  |  提交时间:2020/07/03

Microbial nucleic acids are detected in samples of tissues and blood from more than 10,000 patients with cancer, and machine learning is used to show that these can be used to discriminate between and among different types of cancer, suggesting a new microbiome-based diagnostic approach.


Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. Following recent demonstrations that some types of cancer show substantial microbial contributions(1-10), we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas(11) (TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma  100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.


  
DNA clamp function of the monoubiquitinated Fanconi anaemia ID complex 期刊论文
NATURE, 2020, 580 (7802) : 278-+
作者:  Wu, Thomas D.;  39;Gorman, William E.
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

The ID complex, involving the proteins FANCI and FANCD2, is required for the repair of DNA interstrand crosslinks (ICL) and related lesions(1). These proteins are mutated in Fanconi anaemia, a disease in which patients are predisposed to cancer. The Fanconi anaemia pathway of ICL repair is activated when a replication fork stalls at an ICL2  this triggers monoubiquitination of the ID complex, in which one ubiquitin molecule is conjugated to each of FANCI and FANCD2. Monoubiquitination of ID is essential for ICL repair by excision, translesion synthesis and homologous recombination  however, its function remains unknown(1,3). Here we report a cryo-electron microscopy structure of the monoubiquitinated human ID complex bound to DNA, and reveal that it forms a closed ring that encircles the DNA. By comparison with the structure of the non-ubiquitinated ID complex bound to ICL DNA-which we also report here-we show that monoubiquitination triggers a complete rearrangement of the open, trough-like ID structure through the ubiquitin of one protomer binding to the other protomer in a reciprocal fashion. These structures-together with biochemical data-indicate that the monoubiquitinated ID complex loses its preference for ICL and related branched DNA structures, and becomes a sliding DNA clamp that can coordinate the subsequent repair reactions. Our findings also reveal how monoubiquitination in general can induce an alternative protein structure with a new function.


Cryo-EM structures of the FANCI-FANCD2 complex bound to DNA reveal that monoubiquitination triggers structural changes that enable the complex to function as a sliding DNA clamp and coordinate the repair of DNA interstrand crosslinks.


  
A simple dynamic model explains the diversity of island birds worldwide 期刊论文
NATURE, 2020
作者:  Li, Junxue;  Wilson, C. Blake;  Cheng, Ran;  Lohmann, Mark;  Kavand, Marzieh;  Yuan, Wei;  Aldosary, Mohammed;  Agladze, Nikolay;  Wei, Peng;  Sherwin, Mark S.;  Shi, Jing
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

Colonization, speciation and extinction are dynamic processes that influence global patterns of species richness(1-6). Island biogeography theory predicts that the contribution of these processes to the accumulation of species diversity depends on the area and isolation of the island(7,8). Notably, there has been no robust global test of this prediction for islands where speciation cannot be ignored(9), because neither the appropriate data nor the analytical tools have been available. Here we address both deficiencies to reveal, for island birds, the empirical shape of the general relationships that determine how colonization, extinction and speciation rates co-vary with the area and isolation of islands. We compiled a global molecular phylogenetic dataset of birds on islands, based on the terrestrial avifaunas of 41 oceanic archipelagos worldwide (including 596 avian taxa), and applied a new analysis method to estimate the sensitivity of island-specific rates of colonization, speciation and extinction to island features (area and isolation). Our model predicts-with high explanatory power-several global relationships. We found a decline in colonization with isolation, a decline in extinction with area and an increase in speciation with area and isolation. Combining the theoretical foundations of island biogeography(7,8) with the temporal information contained in molecular phylogenies(10) proves a powerful approach to reveal the fundamental relationships that govern variation in biodiversity across the planet.


Using a global molecular phylogenetic dataset of birds on islands, the sensitivity of island-specific rates of colonization, speciation and extinction to island features (area and isolation) is estimated.


  
Genomic basis for RNA alterations in cancer 期刊论文
NATURE, 2020, 578 (7793) : 129-+
作者:  Petitprez, Florent;  39;han
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Transcript alterations often result from somatic changes in cancer genomes(1). Various forms of RNA alterations have been described in cancer, including overexpression(2), altered splicing(3) and gene fusions(4)  however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)(5). Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed '  bridged'  fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.


  
Understanding uneven urban expansion with natural cities using open data 期刊论文
LANDSCAPE AND URBAN PLANNING, 2018, 177: 281-293
作者:  Long, Ying;  Zhai, Weixin;  Shen, Yao;  Ye, Xinyue
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Urban expansion  Social media  Head/tail division  New data  Open data  China  
Clean Cities Now: Vol. 17, No. 1, Spring 2013 (Brochure) 科技报告
来源:US Department of Energy (DOE). 出版年: 2013
作者:  Sutor, J.;  Tucker, E.;  Thomas, J.
收藏  |  浏览/下载:3/0  |  提交时间:2019/04/05
CLEAN CITIES  ELECTRIC VEHICLES  BIODIESEL  COMPRESSED NATURAL GAS  PROPANE  IDLE REDUCTION  E85  ETHANOL  ALTERNATIVE FUELS DATA CENTER  AFDC  NEW YORK  MISSOURI  ARIZONA  ILLINOIS  COCA-COLA  ALABAMA  CONNECTICUT  CALIFORNIA  IDAHO  20TH ANNIVERSARY  Ma