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Recycling and metabolic flexibility dictate life in the lower oceanic crust 期刊论文
NATURE, 2020, 579 (7798) : 250-+
作者:  Zhou, Peng;  Yang, Xing-Lou;  Wang, Xian-Guang;  Hu, Ben;  Zhang, Lei;  Zhang, Wei;  Si, Hao-Rui;  Zhu, Yan;  Li, Bei;  Huang, Chao-Lin;  Chen, Hui-Dong;  Chen, Jing;  Luo, Yun;  Guo, Hua;  Jiang, Ren-Di;  Liu, Mei-Qin;  Chen, Ying;  Shen, Xu-Rui;  Wang, Xi;  Zheng, Xiao-Shuang;  Zhao, Kai;  Chen, Quan-Jiao;  Deng, Fei;  Liu, Lin-Lin;  Yan, Bing;  Zhan, Fa-Xian;  Wang, Yan-Yi;  Xiao, Geng-Fu;  Shi, Zheng-Li
收藏  |  浏览/下载:37/0  |  提交时间:2020/05/13

The lithified lower oceanic crust is one of Earth'  s last biological frontiers as it is difficult to access. It is challenging for microbiota that live in marine subsurface sediments or igneous basement to obtain sufficient carbon resources and energy to support growth(1-3) or to meet basal power requirements(4) during periods of resource scarcity. Here we show how limited and unpredictable sources of carbon and energy dictate survival strategies used by low-biomass microbial communities that live 10-750 m below the seafloor at Atlantis Bank, Indian Ocean, where Earth'  s lower crust is exposed at the seafloor. Assays of enzyme activities, lipid biomarkers, marker genes and microscopy indicate heterogeneously distributed and viable biomass with ultralow cell densities (fewer than 2,000 cells per cm(3)). Expression of genes involved in unexpected heterotrophic processes includes those with a role in the degradation of polyaromatic hydrocarbons, use of polyhydroxyalkanoates as carbon-storage molecules and recycling of amino acids to produce compounds that can participate in redox reactions and energy production. Our study provides insights into how microorganisms in the plutonic crust are able to survive within fractures or porous substrates by coupling sources of energy to organic and inorganic carbon resources that are probably delivered through the circulation of subseafloor fluids or seawater.


  
Construction of a human cell landscape at single-cell level 期刊论文
NATURE, 2020, 581 (7808) : 303-+
作者:  Han, Yan;  Reyes, Alexis A.;  Malik, Sara;  He, Yuan
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems(1). However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a '  single-cell HCL analysis'  pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology.


Single-cell RNA sequencing is used to generate a dataset covering all major human organs in both adult and fetal stages, enabling comparison with similar datasets for mouse tissues.


  
Tracking of marine predators to protect Southern Ocean ecosystems 期刊论文
NATURE, 2020
作者:  Kim, Eugene;  Kerssemakers, Jacob;  Shaltiel, Indra A.;  Haering, Christian H.;  Dekker, Cees
收藏  |  浏览/下载:19/0  |  提交时间:2020/07/03

Tracking data from 17 marine predator species in the Southern Ocean are used to identify Areas of Ecological Significance, the protection of which could help to mitigate increasing pressures on Southern Ocean ecosystems.


Southern Ocean ecosystems are under pressure from resource exploitation and climate change(1,2). Mitigation requires the identification and protection of Areas of Ecological Significance (AESs), which have so far not been determined at the ocean-basin scale. Here, using assemblage-level tracking of marine predators, we identify AESs for this globally important region and assess current threats and protection levels. Integration of more than 4,000 tracks from 17 bird and mammal species reveals AESs around sub-Antarctic islands in the Atlantic and Indian Oceans and over the Antarctic continental shelf. Fishing pressure is disproportionately concentrated inside AESs, and climate change over the next century is predicted to impose pressure on these areas, particularly around the Antarctic continent. At present, 7.1% of the ocean south of 40 degrees S is under formal protection, including 29% of the total AESs. The establishment and regular revision of networks of protection that encompass AESs are needed to provide long-term mitigation of growing pressures on Southern Ocean ecosystems.


  
Video-based AI for beat-to-beat assessment of cardiac function 期刊论文
NATURE, 2020, 580 (7802) : 252-+
作者:  Pleguezuelos-Manzano, Cayetano;  Puschhof, Jens;  Huber, Axel Rosendahl;  van Hoeck, Arne;  Wood, Henry M.;  Nomburg, Jason;  Gurjao, Carino;  Manders, Freek;  Dalmasso, Guillaume;  Stege, Paul B.;  Paganelli, Fernanda L.;  Geurts, Maarten H.;  Beumer, Joep;  Mizutani, Tomohiro;  Miao, Yi;  van der Linden, Reinier;  van der Elst, Stefan;  Garcia, K. Christopher;  Top, Janetta;  Willems, Rob J. L.;  Giannakis, Marios;  Bonnet, Richard;  Quirke, Phil;  Meyerson, Matthew;  Cuppen, Edwin;  van Boxtel, Ruben;  Clevers, Hans
收藏  |  浏览/下载:117/0  |  提交时间:2020/07/03

A video-based deep learning algorithm-EchoNet-Dynamic-accurately identifies subtle changes in ejection fraction and classifies heart failure with reduced ejection fraction using information from multiple cardiac cycles.


Accurate assessment of cardiac function is crucial for the diagnosis of cardiovascular disease(1), screening for cardiotoxicity(2) and decisions regarding the clinical management of patients with a critical illness(3). However, human assessment of cardiac function focuses on a limited sampling of cardiac cycles and has considerable inter-observer variability despite years of training(4,5). Here, to overcome this challenge, we present a video-based deep learning algorithm-EchoNet-Dynamic-that surpasses the performance of human experts in the critical tasks of segmenting the left ventricle, estimating ejection fraction and assessing cardiomyopathy. Trained on echocardiogram videos, our model accurately segments the left ventricle with a Dice similarity coefficient of 0.92, predicts ejection fraction with a mean absolute error of 4.1% and reliably classifies heart failure with reduced ejection fraction (area under the curve of 0.97). In an external dataset from another healthcare system, EchoNet-Dynamic predicts the ejection fraction with a mean absolute error of 6.0% and classifies heart failure with reduced ejection fraction with an area under the curve of 0.96. Prospective evaluation with repeated human measurements confirms that the model has variance that is comparable to or less than that of human experts. By leveraging information across multiple cardiac cycles, our model can rapidly identify subtle changes in ejection fraction, is more reproducible than human evaluation and lays the foundation for precise diagnosis of cardiovascular disease in real time. As a resource to promote further innovation, we also make publicly available a large dataset of 10,030 annotated echocardiogram videos.


  
Mass-spectrometry-based draft of the Arabidopsis proteome 期刊论文
NATURE, 2020
作者:  Vasanthakumar, Ajithkumar;  Chisanga, David;  Blume, Jonas;  Gloury, Renee;  Britt, Kara;  Henstridge, Darren C.;  Zhan, Yifan;  Torres, Santiago Valle;  Liene, Sebastian;  Collins, Nicholas;  Cao, Enyuan;  Sidwell, Tom;  Li, Chaoran;  Spallanzani, Raul German;  Liao, Yang;  Beavis, Paul A.;  Gebhardt, Thomas;  Trevaskis, Natalie;  Nutt, Stephen L.;  Zajac, Jeffrey D.;  Davey, Rachel A.;  Febbraio, Mark A.;  Mathis, Diane;  Shi, Wei;  Kallies, Axel
收藏  |  浏览/下载:37/0  |  提交时间:2020/07/03

Plants are essential for life and are extremely diverse organisms with unique molecular capabilities(1). Here we present a quantitative atlas of the transcriptomes, proteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis thaliana. Our analysis provides initial answers to how many genes exist as proteins (more than 18,000), where they are expressed, in which approximate quantities (a dynamic range of more than six orders of magnitude) and to what extent they are phosphorylated (over 43,000 sites). We present examples of how the data may be used, such as to discover proteins that are translated from short open-reading frames, to uncover sequence motifs that are involved in the regulation of protein production, and to identify tissue-specific protein complexes or phosphorylation-mediated signalling events. Interactive access to this resource for the plant community is provided by the ProteomicsDB and ATHENA databases, which include powerful bioinformatics tools to explore and characterize Arabidopsis proteins, their modifications and interactions.


A quantitative atlas of the transcriptomes, proteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis thaliana provides a valuable resource for plant research.


  
Loss of p53 drives neuron reprogramming in head and neck cancer 期刊论文
NATURE, 2020, 578 (7795) : 449-+
作者:  Lipson, Mark;  39;ane
收藏  |  浏览/下载:23/0  |  提交时间:2020/07/03

MicroRNAs from head and neck cancer cells, shuttled to sensory neurons by extracellular vesicles, cause a shift to an adrenergic neuronal phenotype that promotes tumour progression.


The solid tumour microenvironment includes nerve fibres that arise from the peripheral nervous system(1,2). Recent work indicates that newly formed adrenergic nerve fibres promote tumour growth, but the origin of these nerves and the mechanism of their inception are unknown(1,3). Here, by comparing the transcriptomes of cancer-associated trigeminal sensory neurons with those of endogenous neurons in mouse models of oral cancer, we identified an adrenergic differentiation signature. We show that loss of TP53 leads to adrenergic transdifferentiation of tumour-associated sensory nerves through loss of the microRNA miR-34a. Tumour growth was inhibited by sensory denervation or pharmacological blockade of adrenergic receptors, but not by chemical sympathectomy of pre-existing adrenergic nerves. A retrospective analysis of samples from oral cancer revealed that p53 status was associated with nerve density, which was in turn associated with poor clinical outcomes. This crosstalk between cancer cells and neurons represents mechanism by which tumour-associated neurons are reprogrammed towards an adrenergic phenotype that can stimulate tumour progression, and is a potential target for anticancer therapy.


  
The strength and pattern of natural selection on gene expression in rice 期刊论文
NATURE, 2020, 578 (7796) : 572-+
作者:  Lipson, Mark;  Ribot, Isabelle;  Mallick, Swapan;  Rohland, Nadin;  Olalde, Inigo;  Adamski, Nicole;  Broomandkhoshbacht, Nasreen;  Lawson, Ann Marie;  Lopez, Saioa;  Oppenheimer, Jonas;  Stewardson, Kristin
收藏  |  浏览/下载:19/0  |  提交时间:2020/07/03

Levels of gene expression underpin organismal phenotypes(1,2), but the nature of selection that acts on gene expression and its role in adaptive evolution remain unknown(1,2). Here we assayed gene expression in rice (Oryza sativa)(3), and used phenotypic selection analysis to estimate the type and strength of selection on the levels of more than 15,000 transcripts(4,5). Variation in most transcripts appears (nearly) neutral or under very weak stabilizing selection in wet paddy conditions (with median standardized selection differentials near zero), but selection is stronger under drought conditions. Overall, more transcripts are conditionally neutral (2.83%) than are antagonistically pleiotropic(6) (0.04%), and transcripts that display lower levels of expression and stochastic noise(7-9) and higher levels of plasticity(9) are under stronger selection. Selection strength was further weakly negatively associated with levels of cis-regulation and network connectivity(9). Our multivariate analysis suggests that selection acts on the expression of photosynthesis genes(4,5), but that the efficacy of selection is genetically constrained under drought conditions(10). Drought selected for earlier flowering(11,12) and a higher expression of OsMADS18 (Os07g0605200), which encodes a MADS-box transcription factor and is a known regulator of early flowering(13)-marking this gene as a drought-escape gene(11,12). The ability to estimate selection strengths provides insights into how selection can shape molecular traits at the core of gene action.


Phenotypic selection analysis is used to estimate the type and strength of selection that acts on more than 15,000 transcripts in rice (Oryza sativa), which provides insight into the adaptive evolutionary role of selection on gene expression.


  
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:16/0  |  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.


  
AQP5 enriches for stem cells and cancer origins in the distal stomach 期刊论文
NATURE, 2020, 578 (7795) : 437-+
作者:  Athukoralage, Januka S.;  McMahon, Stephen A.;  Zhang, Changyi;  Grueschow, Sabine;  Graham, Shirley;  Krupovic, Mart;  Whitaker, Rachel J.;  Gloster, Tracey M.;  White, Malcolm F.
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

LGR5 marks resident adult epithelial stem cells at the gland base in the mouse pyloric stomach(1), but the identity of the equivalent human stem cell population remains unknown owing to a lack of surface markers that facilitate its prospective isolation and validation. In mouse models of intestinal cancer, LGR5(+) intestinal stem cells are major sources of cancer following hyperactivation of the WNT pathway(2). However, the contribution of pyloric LGR5(+) stem cells to gastric cancer following dysregulation of the WNT pathway-a frequent event in gastric cancer in humans(3)-is unknown. Here we use comparative profiling of LGR5(+) stem cell populations along the mouse gastrointestinal tract to identify, and then functionally validate, the membrane protein AQP5 as a marker that enriches for mouse and human adult pyloric stem cells. We show that stem cells within the AQP5(+) compartment are a source of WNT-driven, invasive gastric cancer in vivo, using newly generated Aqp5-creERT2 mouse models. Additionally, tumour-resident AQP5(+) cells can selectively initiate organoid growth in vitro, which indicates that this population contains potential cancer stem cells. In humans, AQP5 is frequently expressed in primary intestinal and diffuse subtypes of gastric cancer (and in metastases of these subtypes), and often displays altered cellular localization compared with healthy tissue. These newly identified markers and mouse models will be an invaluable resource for deciphering the early formation of gastric cancer, and for isolating and characterizing human-stomach stem cells as a prerequisite for harnessing the regenerative-medicine potential of these cells in the clinic.


AQP5 is identified as a marker for pyloric stem cells in humans and mice, and stem cells in the AQP5(+) compartment are shown to be a source of invasive gastric cancer in mouse models.


  
A human liver cell atlas reveals heterogeneity and epithelial progenitors 期刊论文
NATURE, 2019, 572 (7768) : 199-204
作者:  Aizarani, Nadim;  Saviano, Antonio;  Sagar;  Mailly, Laurent;  Durand, Sarah;  Herman, Josip S.;  Pessaux, Patrick;  Baumert, Thomas F.;  Gruen, Dominic
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27