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10.1126/science.1248797
45,550,221
Controlling Quantum Plasmonics Electron tunneling across cavities could potentially induce a quantum mechanical plasmon mode that would be important in nano-electronics, catalysis, nonlinear optics, or single-molecule sensing, but has been expected to occur only at length scales beyond the reach of current state-of-the...
10.1038/ncomms11495
This paper demonstrates control of nanogap plasmons in molecular junctions
10.1126/science.289.5480.739
41,560,733
Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural features, including a bundle of seven transmembrane α helices connected by six loops of varying lengths. We determined the struc...
10.1038/nature08144
This paper presents the first three-dimensional crystal structure of a G-protein-coupled receptor, the visual photoreceptor rhodopsin.
10.1126/science.274.5288.768
83,029,013
Conformational changes are thought to underlie the activation of heterotrimeric GTP-binding protein (G protein)—coupled receptors. Such changes in rhodopsin were explored by construction of double cysteine mutants, each containing one cysteine at the cytoplasmic end of helix C and one cysteine at various positions in t...
10.1038/nature08144
This is the first biophysical study to demonstrate movement of transmembrane segment 6 upon activation of rhodopsin.
10.1126/science.289.5486.1902
41,744,670
Extremely halophilic archaea contain retinal-binding integral membrane proteins called bacteriorhodopsins that function as light-driven proton pumps. So far, bacteriorhodopsins capable of generating a chemiosmotic membrane potential in response to light have been demonstrated only in halophilic archaea. We describe her...
10.1038/nature08059
This paper reports the first observation and characterization of ion-pumping rhodopsins in the domain Bacteria, a discovery enabled by metagenomic sampling and analyses.
10.1111/j.1462-2920.2005.00906.x
104,116,332
Summary Mesophilic crenarchaeota are frequently found in terrestrial and marine habitats worldwide, but despite their considerable abundance the physiology of these as yet uncultivated archaea has remained unknown. From a 1.2 Gb large‐insert environmental fosmid library of a calcareous grassland soil, a 43 kb genomic f...
10.1038/nature08059
This is the first report presenting definitive metagenomic evidence for the occurrence of nitrification-associated genes (encoding ammonia monooxygenase subunits A and B) in non-thermophilic Crenarchaeota.
10.1073/pnas.0708897105
123,065,776
Metagenomics is expanding our knowledge of the gene content, functional significance, and genetic variability in natural microbial communities. Still, there exists limited information concerning the regulation and dynamics of genes in the environment. We report here global analysis of expressed genes in a naturally occ...
10.1038/nature08059
This is the first report of a directed, massively parallel approach that sequenced a sample of the transcriptome in planktonic microbial assemblages by using pyrosequencing.
10.1073/pnas.0808022106
101,027,317
Recently, approaches have been developed to sample the genetic content of heterogeneous environments (metagenomics). However, by what means these sequences link distinct environmental conditions with specific biological processes is not well understood. Thus, a major challenge is how the usage of particular pathways an...
10.1038/nature08059
Canonical correlation analyses identified metabolic pathways in metagenomic data sets that maximally co-varied with multiple environmental variables, revealing co-variation of amino-acid transport and cofactor synthesis across communities and environments.
10.1126/science.1095505
41,741,062
Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cel...
10.1038/nature17040
In this paper, the authors demonstrated that heterotypic ECs, but not stromal cells, support the expansion and differentiation of co-cultured NSCs by producing soluble angiocrine factors.
10.1182/blood.v86.9.3353.bloodjournal8693353
4,580,750
Endothelial cells are a major component of the bone marrow (BM) microenvironment that regulate the trafficking and homing of hematopoietic progenitor and stem cells. In this paper, we provide evidence that BM endothelial cells (BMECs) also support multilineage hematopoiesis by elaboration of soluble cytokines. Hematopo...
10.1038/nature17040
This was the first report of homotypic co-culture of human bone marrow ECs and human haematopoietic cells, and it underscored the capacity of endothelial niches to support the expansion of haematopoietic cells through the production of angiocrine factors in the absence of exogenous factors.
10.1073/pnas.0805980105
59,315,307
Vascular cells contribute to organogenesis and tumorigenesis by producing unknown factors. Primary endothelial cells (PECs) provide an instructive platform for identifying factors that support stem cell and tumor homeostasis. However, long-term maintenance of PECs requires stimulation with cytokines and serum, resultin...
10.1038/nature17040
This report demonstrated that transduction of a non-oncogenic adenoviral E4ORF1 gene enables the serum-free and xenobiotic-free expansion of primary human ECs, sustaining their angiocrine repertoire.
10.1126/science.1244880
107,350,707
Liver regeneration requires spatially and temporally precisely coordinated proliferation of the two major hepatic cell populations, hepatocytes and liver sinusoidal endothelial cells (LSECs), to reconstitute liver structure and function. The underlying mechanisms of this complex molecular cross-talk remain elusive. Her...
10.1038/nature17040
This report provides genetic evidence to show that angiocrine-derived Angiopoietin-2 induces angiogenesis-independent hepatic proliferation and finalizes angiogenesis-dependent liver regeneration by activating its cognate Tie2 receptor and by regulating TGF-β.
10.1161/circulationaha.110.991125
59,281,451
Background— Removal of cardiac endothelial cells (EC) has been shown to produce significant detrimental effects on the function of adjacent cardiac myocytes, suggesting that EC play a critical role in autocrine/paracrine regulation of the heart. Despite this important observation, the mediators of the protective functi...
10.1038/nature17040
In this paper, the authors provide genetic evidence to demonstrate that selective deletion of Neuregulin-1 in ECs from adult mice impairs myogenic repair, which implies that an angiocrine supply of Neuregulin-1 is essential for cardiac myocyte protection and regeneration.
10.1145/3065386
104,434,219
We trained a large, deep convolutional neural network to classify the 1.2 million high-resolution images in the ImageNet LSVRC-2010 contest into the 1000 different classes. On the test data, we achieved top-1 and top-5 error rates of 37.5% and 17.0%, respectively, which is considerably better than the previous state-of...
10.1038/nature14539
This report was a breakthrough that used convolutional nets to almost halve the error rate for object recognition, and precipitated the rapid adoption of deep learning by the computer vision community.
10.1162/neco.2006.18.7.1527
41,732,085
We show how to use “complementary priors” to eliminate the explaining-away effects that make inference difficult in densely connected belief nets that have many hidden layers. Using complementary priors, we derive a fast, greedy algorithm that can learn deep, directed belief networks one layer at a time, provided the t...
10.1038/nature14539
This paper introduced a novel and effective way of training very deep neural networks by pre-training one hidden layer at a time using the unsupervised learning procedure for restricted Boltzmann machines.
10.1162/neco.1997.9.8.1735
83,559,670
Learning to store information over extended time intervals by recurrent backpropagation takes a very long time, mostly because of insufficient, decaying error backflow. We briefly review Hochreiter's (1991) analysis of this problem, then address it by introducing a novel, efficient, gradient based method called long sh...
10.1038/nature14539
This paper introduced LSTM recurrent networks, which have become a crucial ingredient in recent advances with recurrent networks because they are good at learning long-range dependencies.
10.1073/pnas.1319946111
125,203,403
The elicitation of scientific and technical judgments from experts, in the form of subjective probability distributions, can be a valuable addition to other forms of evidence in support of public policy decision making. This paper explores when it is sensible to perform such elicitation and how that can best be done. A...
10.1038/nenergy.2017.71
This paper provides an overview of the key practices and issues in the use of expert elicitations to inform policy, with examples that include environment and energy applications.
10.1126/science.1092436
83,554,355
Many adult regenerative cells divide infrequently but have high proliferative capacity. We developed a strategy to fluorescently label slow-cycling cells in a cell type–specific fashion. We used this method to purify the label-retaining cells (LRCs) that mark the skin stem cell (SC) niche. We found that these cells rar...
10.1038/nature07043
This paper was the first description of non-invasive labelling of mammalian homeostatic stem cells with a fluorescent protein.
10.1126/science.1124618
62,597,341
Advances in molecular biology, organic chemistry, and materials science have recently created several new classes of fluorescent probes for imaging in cell biology. Here we review the characteristic benefits and limitations of fluorescent probes to study proteins. The focus is on protein detection in live versus fixed ...
10.1038/nature07043
This review provides a comprehensive description of the various possibilities for fluorescent labelling of cells.
10.1634/stemcells.2006-0553
56,695,914
Abstract Validated gene transfer and expression tracers are essential for elucidating functions of mammalian genes. Here, we have determined the suitability and unintended side effects of enhanced green fluorescent protein (EGFP) and DsRed-Express fluorescent protein as expression tracers in long-term hematopoietic ste...
10.1038/nature07043
This paper describes a comprehensive quantitative study of the effects of DsRed-Express on the long-term behaviour of stem cells.
10.1126/science.1110647
104,394,772
Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells...
10.1038/nature09615
References 49 and 50 established the concept of 'surveillant' microglia.
10.1084/jem.20061931
40,882,224
Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targe...
10.1038/nature09615
This study identified a major component of plasma that specifically activates microglia.
10.1126/science.3276004
102,724,754
A crucial question in the study of immunological reactions in the central nervous system (CNS) concerns the identity of the parenchymal cells that function as the antigen-presenting cells in that organ. Rat bone marrow chimeras and encephalitogenic, major histocompatability-restricted T-helper lymphocytes were used to ...
10.1038/nature09615
This study showed that perivascular macrophages are crucial for restimulating antigen-specific T cells in the CNS.
10.1175/jcli3800.1
104,150,974
Abstract Eleven coupled climate–carbon cycle models used a common protocol to study the coupling between climate change and the carbon cycle. The models were forced by historical emissions and the Intergovernmental Panel on Climate Change (IPCC) Special Report on Emissions Scenarios (SRES) A2 anthropogenic emissions of...
10.1038/nature10386
A systematic comparison of model predictions of soil carbon response to climate change.
10.5194/bg-3-397-2006
104,064,499
Abstract. The carbon (C) cycle in boreal regions is strongly influenced by fire, which converts biomass and detrital C mainly to gaseous forms (CO2 and smaller proportions of CO and CH4), and some 1–3% of mass to pyrogenic C (PyC). PyC is mainly produced as solid charred residues, including visually-defined charcoal, a...
10.1038/nature10386
A summary of the current understanding of the formation, properties and fate of fire-residues in natural ecosystems.
10.1126/science.1065635
18,993,868
The pore-forming subunits of canonical voltage-gated sodium and calcium channels are encoded by four repeated domains of six-transmembrane (6TM) segments. We expressed and characterized a bacterial ion channel (NaChBac) from Bacillus halodurans that is encoded by one 6TM segment. The sequence, especially in the pore re...
10.1038/nchembio.2353
This article opened up a new era in structure–function studies of sodium and calcium channels by revealing a family bacterial ancestors of simple structure that can be easily manipulated by molecular biological methods and can be studied by X-ray crystallography.
10.1126/science.aad2395
41,712,697
A complex channel comes into focus Voltage-gated calcium (Cav) channels are activated in response to membrane potential to initiate calcium-mediated signaling pathways and are associated with diseases such as cardiac arrhythmia and epilepsy. Cav1.1 couples changes in membrane potential to cardiac muscle contraction. It...
10.1038/nchembio.2353
This article (and ref. 19 ) gave the first structural views of a eukaryotic calcium channel. It revealed the subunit architecture of the calcium channel complex and the structure of the central α1-subunit, including the transmembrane fold of the voltage sensor and pore and the ion selectivity filter
10.1073/pnas.1118434109
59,465,859
Voltage-dependent gating of ion channels is essential for electrical signaling in excitable cells, but the structural basis for voltage sensor function is unknown. We constructed high-resolution structural models of resting, intermediate, and activated states of the voltage-sensing domain of the bacterial sodium channe...
10.1038/nchembio.2353
This article presented the first complete, high-resolution model of the resting and activated states of a voltage sensor based on Rosetta Membrane modeling and disulfide locking.
10.15252/embj.201593285
39,089,739
Abstract Voltage‐gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the cry...
10.1038/nchembio.2353
This article showed binding of sodium ions in the selectivity filter of a sodium channel for the first time.
10.1073/pnas.1309452110
102,158,947
Determination of a high-resolution 3D structure of voltage-gated sodium channel Na V Ab opens the way to elucidating the mechanism of ion conductance and selectivity. To examine permeation of Na + through the selectivity filter of the channel, we performed large-scale molecular dynamics simulations of Na V Ab in an exp...
10.1038/nchembio.2353
This article presented molecular dynamic simulations that provide the first description of sodium selectivity and conductance under physiological conditions of ionic composition and membrane potential, and revealed that Glu side chains in the high-field-strength site move inward with each round of sodium transport, cre...
10.1073/pnas.1320907111
40,341,698
Significance Voltage-gated sodium channels are one of the most fundamental electrical components in the nervous system and are key targets for local anesthesia and therapeutics for neurological and cardiac disorders. We have used multimicrosecond simulations to provide molecular-level descriptions of sodium channel fun...
10.1038/nchembio.2353
This article provided evidence from molecular dynamics that dunking of the carboxylate side chains of the Glu residues in the high-field-strength site is coupled to bending of the S6 segments.
10.1085/jgp.201210873
78,590,568
Developing an understanding of the mechanism of voltage-gated ion channels in molecular terms requires knowledge of the structure of the active and resting conformations. Although the active-state conformation is known from x-ray structures, an atomic resolution structure of a voltage-dependent ion channel in the resti...
10.1038/nchembio.2353
This article presented a consensus view of the voltage-dependent activation process of sodium and potassium channels that is consistent with the sliding helix model of voltage sensing.
10.1101/gad.9.10.1250
81,369,236
The transcription factor GATA-1 is expressed in early hematopoietic progenitors and specifically down-regulated in myelomonocytic cells during lineage determination. Our earlier observation that the differentiation of Myb-Ets-transformed chicken hematopoietic progenitors into myeloblasts likewise involves a GATA-1 down...
10.1038/nature08533
This paper, together with refs 19 and 20, established the principle of transcription factor cross-antagonisms.
10.1101/gad.1493506
83,310,645
The mechanism of lineage specification in multipotent stem cells has not been fully understood. We recently isolated progenitors with the eosinophil, basophil, or mast cell lineage potential, all of which originate from granulocyte/monocyte progenitors (GMPs). By using these prospectively purified progenitors, we show ...
10.1038/nature08533
Showed that the order of transcription factor expression can induce different cell fates.
10.1073/pnas.74.12.5463
125,332,567
A new method for determining nucleotide sequences in DNA is described. It is similar to the “plus and minus” method [Sanger, F. & Coulson, A. R. (1975) J. Mol. Biol. 94, 441-448] but makes use of the 2′,3′-dideoxy and arabinonucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific cha...
10.1038/nature24286
Refs 8 9 : The seminal papers by Sanger, Nicklen & Coulson and Maxam & Gilbert describing the first widely adopted methods for DNA sequencing.
10.1093/bioinformatics/bth301
3,423,953
Abstract Summary: A modification to Phred and program to detect heterogeneous positions, which is particularly useful in the identification of mutations and other abnormalities in Phred/Phrap genome assemblies. Availability: The package is made available at http://giscompute.gis.a-star.edu.sg/~charlie/DHetero.html
10.1038/nature24286
phred introduced quantitative, reliable metrics for base quality, substituting human judgement with computers, a process that occurred repeatedly over the course of the HGP.
10.1126/science.287.5461.2196
20,235,656
We report on the quality of a whole-genome assembly of Drosophila melanogaster and the nature of the computer algorithms that accomplished it. Three independent external data sources essentially agree with and support the assembly's sequence and ordering of contigs across the euchromatic portion of the genome. In addit...
10.1038/nature24286
The Celera assembler introduced an overlap–layout–consensus approach to deal with the problems posed by repeats and the millions of reads needed to produce a reliable assembly.
10.1126/science.1079700
62,216,704
Optical approaches for observing the dynamics of single molecules have required pico- to nanomolar concentrations of fluorophore in order to isolate individual molecules. However, many biologically relevant processes occur at micromolar ligand concentrations, necessitating a reduction in the conventional observation vo...
10.1038/nature24286
One of earliest real time observations of DNA synthesis in single molecules, using fluorescently labelled nucleotides and a DNA polymerase anchored in zero-mode waveguides, which with further development led to the PacBio platform.
10.1073/pnas.93.24.13770
62,262,989
We show that an electric field can drive single-stranded RNA and DNA molecules through a 2.6-nm diameter ion channel in a lipid bilayer membrane. Because the channel diameter can accommodate only a single strand of RNA or DNA, each polymer traverses the membrane as an extended chain that partially blocks the channel. T...
10.1038/nature24286
The concept of ssDNA modulating an electronic signal while moving through a membrane pore led eventually to practical nanopore sequencing.
10.1126/science.270.5235.484
123,111,153
The characteristics of an organism are determined by the genes expressed within it. A method was developed, called serial analysis of gene expression (SAGE), that allows the quantitative and simultaneous analysis of a large number of transcripts. To demonstrate this strategy, short diagnostic sequence tags were isolate...
10.1038/nature24286
The SAGE method captures 3′ tags from mRNAs, therefore introducing the idea of using a DNA sequencer to count molecules, an idea that has exploded with the later introduction of RNA-seq, chromatin immunoprecipitation followed by sequencing (ChIP–seq) and so on.
10.1017/cbo9780511618611
104,122,158
Fundamentals of Carrier Transport is an accessible introduction to the behaviour of charged carriers in semiconductors and semiconductor devices. It is written specifically for engineers and students without an extensive background in quantum mechanics and solid-state physics. This second edition contains many new and ...
10.1038/natrevmats.2017.53
This is a classic book on carrier transport in materials.
10.1073/pnas.93.15.7436
62,078,778
What electronic structure provides the largest figure of merit for thermoelectric materials? To answer that question, we write the electrical conductivity, thermopower, and thermal conductivity as integrals of a single function, the transport distribution. Then we derive the mathematical function for the transport dist...
10.1038/natrevmats.2017.53
This seminal work formulates the transport distribution function and its desired characteristics for high-performance thermoelectrics.
10.1126/science.aaa4967
62,191,676
Adoptive cell therapy (ACT) is a highly personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity. ACT using naturally occurring tumor-reactive lymphocytes has mediated durable, complete regressions in patients with melanoma, probably by targetin...
10.1038/nature15818
A comprehensive review of the clinical development and potentially transformative impact of adoptive T-cell therapy on cancer by one of its pioneers; see also ref. 42.
10.1126/science.1258096
20,855,444
The advent of facile genome engineering using the bacterial RNA-guided CRISPR-Cas9 system in animals and plants is transforming biology. We review the history of CRISPR (clustered regularly interspaced palindromic repeat) biology from its initial discovery through the elucidation of the CRISPR-Cas9 enzyme mechanism, wh...
10.1038/nature15818
In this review, the researchers who pioneered the application of RNA-guided nucleases to genome engineering show how this transformative technique can make targeted genome editing easy.
10.1126/science.216.4553.1405
62,455,530
The distribution of compositional types among the asteroids is found to vary systematically with heliocentric distance. Seven distinct peaks in the relative proportion of the compositional types E, R, S, M, F, C, P, and D are found from 1.8 to 5.2 astronomical units. The inferred composition of the asteroids in each se...
10.1038/nature12908
This is a comprehensive view of the compositional trends of the asteroid belt that served for decades as the backbone for interpretations of the main belt.
10.1126/science.225.4658.129
59,512,277
Despite the very active deforestation of the last decade, the Amazon Basin is still primarily covered with trees and is a system in equilibrium. The Andes form a barrier at the western end of the basin and, coupled with the prevailing easterly winds, ensure an almost unique precipitation and water-recycling regime. On ...
10.1038/nature10717
One of the first presentations of the Amazon basin from a systems perspective.
10.1111/j.1365-2486.2007.01323.x
60,963,157
Abstract The amount and spatial distribution of forest biomass in the Amazon basin is a major source of uncertainty in estimating the flux of carbon released from land‐cover and land‐use change. Direct measurements of aboveground live biomass (AGLB) are limited to small areas of forest inventory plots and site‐specific...
10.1038/nature10717
Estimates of regional variation and patterns in forest biomass are presented based on a remote sensing approach.
10.1073/pnas.0804619106
125,175,151
We examine the evidence for the possibility that 21st-century climate change may cause a large-scale “dieback” or degradation of Amazonian rainforest. We employ a new framework for evaluating the rainfall regime of tropical forests and from this deduce precipitation-based boundaries for current forest viability. We the...
10.1038/nature10717
A review of climate model predictions for the Amazon basin.
10.1126/science.1092779
103,704,757
Heavy smoke from forest fires in the Amazon was observed to reduce cloud droplet size and so delay the onset of precipitation from 1.5 kilometers above cloud base in pristine clouds to more than 5 kilometers in polluted clouds and more than 7 kilometers in pyro-clouds. Suppression of low-level rainout and aerosol washo...
10.1038/nature10717
A review of understanding of how smoke from biomass burning affects local and regional climate.
10.1098/rstb.2007.0036
82,858,633
Some model experiments predict a large-scale substitution of Amazon forest by savannah-like vegetation by the end of the twenty-first century. Expanding global demands for biofuels and grains, positive feedbacks in the Amazon forest fire regime and drought may drive a faster process of forest degradation that could lea...
10.1038/nature10717
Explores the mechanisms of how land use, fire and climate change interact.
10.1126/science.1176331
62,228,237
Life Histories to Suit Nematode worms can profoundly manipulate their life histories in several ways. For example, Caenorhabditis elegans has two genders: males and hermaphrodites. Some clues for the evolution of this peculiar mating system have been revealed by Baldi et al. (p. 1002 ), who turned females of a related ...
10.1038/nchembio.2356
This paper identified the first GPCR targets of the ascarosides
10.1038/ncomms12341
42,656,355
Abstract Insect vectors are required for the transmission of many species of parasitic nematodes, but the mechanisms by which the vectors and nematodes coordinate their life cycles are poorly understood. Here, we report that ascarosides, an evolutionarily conserved family of nematode pheromones, are produced not only b...
10.1038/nchembio.2356
This paper was the first to detect ascarosides in an organism other than a nematode, specifically the vector beetle of pinewood nematode
10.1073/pnas.1423951112
104,283,263
Caenorhabditis elegans uses ascaroside pheromones to induce development of the stress-resistant dauer larval stage and to coordinate various behaviors. Peroxisomal β-oxidation cycles are required for the biosynthesis of the fatty acid-derived side chains of the ascarosides. Here we show that three acyl-CoA oxidases, wh...
10.1038/nchembio.2356
This paper directly showed the substrate preference of three ACOX enzymes involved in ascaroside biosynthesis and demonstrated how these play a key role in determining which ascarosides are produced by C. elegans
10.1073/pnas.1608262113
103,197,264
Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze ...
10.1038/nchembio.2356
This paper obtained the first crystal structures of the ACOX enzymes, providing a structural basis for their substrate specificities and also revealing an ATP binding site that regulates enzymatic activity
10.1126/sciadv.1500052
125,328,182
We conducted an analysis of global forest cover to reveal that 70% of remaining forest is within 1 km of the forest’s edge, subject to the degrading effects of fragmentation. A synthesis of fragmentation experiments spanning multiple biomes and scales, five continents, and 35 years demonstrates that habitat fragmentati...
10.1038/nature22899
This paper synthesizes the short-term and long-term impacts of experimental habitat loss on biodiversity and ecosystem functioning.
10.1126/science.aaf8957
125,197,567
Global biodiversity and productivity The relationship between biodiversity and ecosystem productivity has been explored in detail in herbaceous vegetation, but patterns in forests are far less well understood. Liang et al. have amassed a global forest data set from >770,000 sample plots in 44 countries. A positive a...
10.1038/nature22899
This paper describes how the loss of tree diversity will lead to the loss of productivity in forests worldwide and quantifies the potential economic costs.
10.1073/pnas.96.4.1463
125,276,250
Although the effect of biodiversity on ecosystem functioning has become a major focus in ecology, its significance in a fluctuating environment is still poorly understood. According to the insurance hypothesis, biodiversity insures ecosystems against declines in their functioning because many species provide greater gu...
10.1038/nature22899
This paper and ref. 54 provide the theoretical basis for temporal and spatial insurance effects, which are now being tested empirically.
10.1126/science.1197479
38,268,313
Ecosystems worldwide are losing some species and gaining others, resulting in an interchange of species that is having profound impacts on how these ecosystems function. However, research on the effects of species gains and losses has developed largely independently of one another. Recent conceptual advances regarding ...
10.1038/nature22899
This review examines worldwide evidence of the ecosystem effects of losses and gains of particular species or groups of species with a certain function.
10.1002/ece3.601
62,323,516
Abstract People depend on benefits provided by ecological systems. Understanding how these ecosystem services – and the ecosystem properties underpinning them – respond to drivers of change is therefore an urgent priority. We address this challenge through developing a novel risk‐assessment framework that integrates ec...
10.1038/nature22899
This article provides a conceptual basis and case studies for linking functional traits and phylogenetic diversity to ecosystem services.
10.1002/adfm.201203859
45,560,180
Abstract During infection, inflammatory cytokines mobilize and activate dendritic cells (DCs), which are essential for efficacious T cell priming and immune responses that clear the infection. Here, macroporous poly(lactide‐ co ‐glycolide) (PLG) matrices are designed to release the inflammatory cytokines GM‐CSF, Flt3L,...
10.1038/nature21005
This is the first study to incorporate immunological cytokines into a biomaterial scaffold to modulate an immune response.
10.1073/pnas.1106634108
125,155,480
Efforts to extend nanoparticle residence time in vivo have inspired many strategies in particle surface modifications to bypass macrophage uptake and systemic clearance. Here we report a top-down biomimetic approach in particle functionalization by coating biodegradable polymeric nanoparticles with natural erythrocyte ...
10.1038/nature21005
This paper uses cell membranes to camouflage and functionalize polymeric nanoparticles, opening the door to new hybrid biomimetic particles.
10.1126/scitranslmed.aaa1616
67,471,091
Disease type and severity spur specific tissue alterations that can guide formulation of an optimal material for a selected clinical condition.
10.1038/nature21005
This paper introduces the challenge posed by diverse physiological environments and shows they affect the responses of biomaterials in people.
10.1182/blood-2015-03-631747
125,075,040
Abstract Recent genetic analyses of large populations have revealed that somatic mutations in hematopoietic cells leading to clonal expansion are commonly acquired during human aging. Clonally restricted hematopoiesis is associated with an increased risk of subsequent diagnosis of myeloid or lymphoid neoplasia and incr...
10.1038/ncomms15422
This report summarizes data from very recent studies documenting an increasing age-associated appearance of oncogenic mutations in amplified clones of normally differentiating cells without any evidence of immediate or necessary progression to malignancy. These findings established the concept of clonal evolution prece...
10.1182/blood.v94.6.2056.418k13_2056_2064
38,124,208
Chronic myeloid leukemia (CML) is characterized by an increased proliferative activity of the leukemic progenitors that produce an elevated number of mature granulocytes. Nevertheless, cell cycle-active agents, even in very high doses, are alone unable to eradicate the leukemic clone, suggesting the presence of a rare ...
10.1038/ncomms15422
This study was the first to document the presence of a quiescent population of malignant cells setting the stage for understanding why anti-proliferative agents are not effective longterm in eradicating many human cancers
10.1126/science.1189992
45,304,145
Another Cell Culprit in Prostate Cancer A recent controversial hypothesis about the cellular origins of human cancer, the so-called “cancer stem cell hypothesis,” has fueled interest in identifying the specific cell types that give rise to common epithelial cancers. A single, well-defined cell of origin could, in princ...
10.1038/ncomms15422
This study was the first toproduce human prostate cancers de novo and show that the histological characterization of cancers does not necessarily correlate with the cellular origin of the malignant clone
10.1126/science.1101156
83,459,967
Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for ∼20% of global carbon fixation. We report the 34 million–base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand–base pair plastid and 44 thousand–base pair mitochondrial g...
10.1038/nature08057
This paper describes results from the first diatom genome-sequencing project.
10.1126/science.1076221
123,199,153
Silaffins are uniquely modified peptides that have been implicated in the biogenesis of diatom biosilica. A method that avoids the harsh anhydrous hydrogen fluoride treatment commonly used to dissolve biosilica allows the extraction of silaffins in their native state. The native silaffins carry further posttranslationa...
10.1038/nature08057
This paper describes the isolation of native silaffins from the cell wall and the function of these proteins during silica precipitation.
10.1073/pnas.0811302106
38,240,255
Carbon uptake by marine phytoplankton, and its export as organic matter to the ocean interior (i.e., the “biological pump”), lowers the partial pressure of carbon dioxide ( p CO 2 ) in the upper ocean and facilitates the diffusive drawdown of atmospheric CO 2 . Conversely, precipitation of calcium carbonate by marine p...
10.1038/nature08057
This paper predicts phytoplankton community structure in oceans of the future and the resultant effects on the carbon cycle.
10.1126/science.1056421
83,342,020
We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mo...
10.1038/nature07892
This paper identifies the selective forces acting on the mutation rate of pathogenic bacteria in vivo
10.2307/1935611
20,235,758
Continuous culture populations of the bacterium especially coli and its virulent virus T7 have been studied as a model of a predator—prey in a simple habitat. These organisms maintain apparently stable states of coexistence in: (1) a phage—limited situation where all of the bacteria are sensitive to the coexisting viru...
10.1038/nature07892
This paper demonstrates extremely rapid real-time co-evolution between natural enemies, suggesting that co-evolution is a crucial process in ecology and evolution.
10.1126/science.1174520
59,550,543
An emerging set of methods enables an experimental dialogue with biological systems composed of many interacting cell types—in particular, with neural circuits in the brain. These methods are sometimes called “optogenetic” because they use light-responsive proteins (“opto-”) encoded in DNA (“-genetic”). Optogenetic dev...
10.1038/nchembio.1534
A review that clearly defines two aspects of optogenetics, i.e., the actuators that deliver controlled perturbation and the sensors that report the system response back
10.1126/science.1242366
83,287,007
Oscillation Stabilizes the Progenitor State Transcription factors regulate fate choice between different neural lineages, but the same transcription factors are also expressed in neural progenitor cells. Imayoshi et al. (p. 1203 , published online 31 October) analyzed the details of expression of several transcription ...
10.1038/nchembio.1534
The accurate control of gene expression with light demonstrates the importance of oscillatory versus sustained expression in cell fate
10.1002/anie.201202134
62,072,286
Abstract Spatial and temporal control over chemical and biological processes plays a key role in life, where the whole is often much more than the sum of its parts. Quite trivially, the molecules of a cell do not form a living system if they are only arranged in a random fashion. If we want to understand these relation...
10.1038/nchembio.1534
A recent review dealing with chemical strategies of irreversible and reversible photoactivation for biological applications
10.1128/jvi.79.14.9217-9227.2005
103,334,132
ABSTRACT In the current global AIDS pandemic, more than half of new human immunodeficiency virus type 1 (HIV-1) infections are acquired by women through intravaginal HIV exposure. For this study, we explored pathogenesis issues relevant to the development of effective vaccines to prevent infection by this route, using ...
10.1038/nature08757
Comprehensive tissue analysis of the pathogenesis of transmission and early infection in the nonhuman primate model of vaginal transmission of HIV-1.
10.1128/jvi.79.14.9228-9235.2005
19,306,714
ABSTRACT In the acute stage of infection following sexual transmission of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), virus-specific CD8 + T-lymphocyte responses partially control but do not eradicate infection from the lymphatic tissues (LTs) or prevent the particularly massive depletio...
10.1038/nature08757
Comprehensive tissue analysis after vaginal exposure that revealed the ‘too late and too little’ CD8 T-cell response to prevent massive gut CD4 T-cell depletion in acute SIV infection but a robust response in cervical vaginal tissues that could potentially prevent acquisition if elicited earlier by a vaccine.
10.1126/science.1093137
125,292,203
Heterosexual transmission accounts for the majority of human immunodeficiency virus–1 (HIV-1) infections worldwide, yet the viral properties that determine transmission fitness or outgrowth have not been elucidated. Here we show, for eight heterosexual transmission pairs, that recipient viruses were monophyletic, encod...
10.1038/nature08757
First description of the monophyletic nature of viruses transmitted heterosexually.
10.1126/science.1168676
119,986,367
In the early stages of viral infection, outcomes depend on a race between expansion of infection and the immune response generated to contain it. We combined in situ tetramer staining with in situ hybridization to visualize, map, and quantify relationships between immune effector cells and their targets in tissues. In ...
10.1038/nature08757
Report of the tissue-compartment-specific nature of the cellular immune response that reveals the importance of the relative numbers of both immune effectors and infected targets in determining whether viral infection is cleared, and the extent of control if infection is not cleared.
10.1126/science.280.5364.717
103,444,233
Direct evidence for the effect of local strain at a surface on the bonding strength for adsorbates is presented. Scanning tunneling microscopy revealed that adsorbed oxygen atoms on Ru(0001) surfaces are located preferentially on top of nanometer-size protrusions above subsurface argon bubbles, where tensile strain pre...
10.1038/natrevmats.2017.59
Direct evidence for the effect of strain on adsorption properties.
10.1126/science.aah6133
104,405,978
An activity lift for platinum Platinum is an excellent but expensive catalyst for the oxygen reduction reaction (ORR), which is critical for fuel cells. Alloying platinum with other metals can create shells of platinum on cores of less expensive metals, which increases its surface exposure, and compressive strain in th...
10.1038/natrevmats.2017.59
This study shows that the large tensile strain of the Pt(110) facet promotes oxygen reduction catalysis.
10.1126/science.347.6227.1274-c
82,742,275
A decade on from the completion of the Human Genome, the Human Protein Atlas, a multinational research project supported by the non-profit Knut and Alice Wallenberg Foundation, recently launched (November 6, 2014) an open source tissue-based interactive map of the human proteome. A team of multidisciplinary researchers...
10.1038/nature19949
This paper provides an integrative analysis of the human proteome through large-scale antibody localization and transcriptomics; the findings are organized in an accompanying database.
10.1126/science.1210148
62,634,319
The effect of lipids and nucleotides on the soluble head domain and membrane base domain is examined in an intact adenosine triphosphatase.
10.1038/nature19949
An elegant demonstration of native mass spectrometry in structural studies of intact membrane complexes.
10.1126/science.1221483
82,752,230
Dynamic Assembly Structural characterization of protein complexes has yielded significant insight into biological function; however, most structural techniques require stable, homogenous samples. This presents a challenge in characterizing transient signaling complexes. Herzog et al. (p. 1348 ) used chemical cross-link...
10.1038/nature19949
This study pioneered the use of chemical crosslinking to reveal the topology of an important phosphatase complex.
10.1126/science.1255784
41,667,229
The thermal stability of proteins can be used to assess ligand binding in living cells. We have generalized this concept by determining the thermal profiles of more than 7000 proteins in human cells by means of mass spectrometry. Monitoring the effects of small-molecule ligands on the profiles delineated more than 50 t...
10.1038/nature19949
In this paper, isobaric chemical labelling was used to measure the proportion of proteins that bound to a drug as a function of temperature, on a proteome-wide scale.
10.1126/science.aad0189
29,223,227
Expanded proteomic analysis of metabolism Combined analysis of large data sets characterizing genes, transcripts, and proteins can elucidate biological functions and disease processes. Williams et al. report an exceptionally detailed characterization of mitochondrial function in a genetic reference panel of recombinant...
10.1038/nature19949
A demonstration of the combined use of proteomics and genetics to interrogate mitochondrial function.
10.1101/262295
10,274,571
Abstract Motivation Advances in genome sequencing and genomics research are bringing us closer to a new era of personalized medicine, where healthcare can be tailored to the individual’s genetic makeup, and to more effective diagnosis and treatment of rare genetic diseases. Much of this progress depends on collaboratio...
10.1038/nature15816
This paper describes an international system for sharing genomic cases to aid in gene discovery.
10.1126/science.1229164
41,548,700
Single-Cell Sequencing With the rapid progress in sequencing technologies, single-cell sequencing is now possible, promising insight into how cell-to-cell heterogeneity affects biological behavior. Achieving adequate genome coverage remains a challenge because single-cell sequencing relies on genome amplification that ...
10.1038/nature21350
Refs 18–23 introduce and develop single-cell genome sequencing, which has applications in the inference of cancer evolution.
10.1126/science.aad7038
20,438,553
Visualizing gene expression in nuclei Gene expression can vary greatly within a single cell. Using techniques that they developed for sequencing single nuclei and labeling proliferating cells in vivo, Habib et al. performed RNA sequencing of 1402 single nuclei from the adult mouse hippocampus. Combining this approach w...
10.1038/nature21350
This paper adapts RNA-seq to the nuclei of single cells, with applications in rare cells and other challenging samples.
10.1126/science.aaa6090
104,392,664
Multiplexed RNA imaging in single cells The basis of cellular function is where and when proteins are expressed and in what quantities. Single-molecule fluorescence in situ hybridization (smFISH) experiments quantify the copy number and location of mRNA molecules; however, the numbers of RNA species that can be simulta...
10.1038/nature21350
Refs 105 and 106 develop multiplexed RNA-FISH (ref. 105) or in situ sequencing (ref. 106) to enable the spatial mapping of a large number of different transcripts at single-cell resolution.
10.1073/pnas.74.11.4772
122,932,211
ATP-dependent DNA supercoiling catalyzed by Escherichia coli DNA gyrase was inhibited by oxolinic acid, a compound similar to but more potent than nalidixic acid and a known inhibitor of DNA replication in E. coli . The supercoiling activity of DNA gyrase purified from nalidixic acid-resistant mutant ( nalA R ) bacteri...
10.1038/nchembio.590
Using aminocoumarins and quinolone antibiotics as probes, this study revealed a second function of DNA gyrase
10.1126/science.1172221
59,633,492
Jamming Protein Translocation Antibiotics are tremendously important drugs in modern medicine, yet we are still learning precisely how they work. SecY is a bacterial membrane protein that is part of a complex that allows protein secretion across the membrane. Van Stelten et al. (p. 753 ; see the Perspective by Breukink...
10.1038/nchembio.590
This work used antibiotics to explore the mechanistic details of protein translocation, which in turn provided insight regarding the origin of toxicity that results in cells struggling during protein secretion
10.1073/pnas.0911674106
125,271,314
β-lactam antibiotics inhibit penicillin binding proteins (PBPs) involved in peptidoglycan synthesis. Although inhibition of peptidoglycan biosynthesis is generally thought to induce cell lysis, the pattern and mechanism of cell lysis can vary substantially. β-lactams that inhibit FtsI, the only division specific PBP, b...
10.1038/nchembio.590
In this work, cephalexin was employed as a chemical tool to explain the relationship between divisome assembly and cell lysis, revealing the mechanistic basis for the requirement of an intact divisome before lysis can take place
10.1126/science.1223269
107,204,179
So Close and So Different In our solar system, the rocky planets have very distinct orbits from those of the gas giants. Carter et al. (p. 556 , published online 21 June) report on a planetary system where this pattern does not apply, posing a challenge to theories of planet formation. Data from the Kepler space telesc...
10.1038/nature13781
The authors of this article describe a system of two planets with very different densities on remarkably close orbits that is precisely characterized using TTVs.
10.1142/s0129183121500285
55,750,047
In the so-called “global polytropic model”, we assume planetary systems in hydrostatic equilibrium and solve the Lane–Emden equation in the complex plane. We thus find polytropic spherical shells providing accommodation to planetary orbits. On the basis of this model, we develop a numerical method which can compute opt...
10.1038/nature13781
This paper describes the masses of dozens of small Kepler planets using radial velocities measured at the Keck Observatory.
10.1073/pnas.0908268106
83,209,647
Great arteries, as well as lungs and skin, contain elastic fibers as important components to maintain their physiological functions. Although recent studies have revealed that a glycoprotein fibulin-4 (FBLN4) is indispensable for the assembly of mature elastic fibers, it remains to be elucidated how FBLN4 takes part in...
10.1038/nature10145
This study shows fibulin-4-dependent recruitment of lysyl oxidase to elastin.
10.1083/jcb.200105046
101,711,906
To elucidate the contribution of the extracellular microfibril–elastic fiber network to vertebrate organogenesis, we generated fibrillin 2 (Fbn2)–null mice by gene targeting and identified a limb-patterning defect in the form of bilateral syndactyly. Digit fusion involves both soft and hard tissues, and is associated w...
10.1038/nature10145
This study demonstrates that fibrillins can act as positive modulators of TGF-β superfamily function.
10.1002/adfm.201202502
83,423,288
Abstract Layered MAX phases are exfoliated into 2D single layers and multilayers, so‐called MXenes. Using first‐principles calculations, the formation and electronic properties of various MXene systems, M 2 C (M = Sc, Ti, V, Cr, Zr, Nb, Ta) and M 2 N (M = Ti, Cr, Zr) with surfaces chemically functionalized by F, OH, an...
10.1038/natrevmats.2016.98
The first computational study on electronic and magnetic properties of all the M2C MXenes.
10.1038/ncomms7544
62,624,234
Abstract High-power Na-ion batteries have tremendous potential in various large-scale applications. However, conventional charge storage through ion intercalation or double-layer formation cannot satisfy the requirements of such applications owing to the slow kinetics of ion intercalation and the small capacitance of t...
10.1038/natrevmats.2016.98
The first report on MXene application in Na-ion hybrid capacitors.
10.1002/anie.201410174
62,651,049
Abstract Lithium–sulfur batteries are amongst the most promising candidates to satisfy emerging energy‐storage demands. Suppression of the polysulfide shuttle while maintaining high sulfur content is the main challenge that faces their practical development. Here, we report that 2D early‐transition‐metal carbide conduc...
10.1038/natrevmats.2016.98
The first report on the use of MXenes in Li–S batteries.
10.1126/science.1241488
20,808,763
Toward Titanium Carbide Batteries Many batteries and capacitors make use of lithium intercalation as a means of storing and transporting charge. Lithium is commonly used because it offers the best energy density, but also because there are difficulties in storing larger cations without disrupting the crystal structure ...
10.1038/natrevmats.2016.98
This is the first demonstration of MXenes being able to host a range of cations, such as Na + + + 2+ 3+ , enabling their use in supercapacitors.
10.1126/science.1162912
125,216,272
The molecular mechanism by which a mechanical stimulus is translated into a chemical response in biological systems is still unclear. We show that mechanical stretching of single cytoplasmic proteins can activate binding of other molecules. We used magnetic tweezers, total internal reflection fluorescence, and atomic f...
10.1038/nature10316
This study demonstrates force-induced binding of vinculin to cryptic sites in talin at the single molecule level.
10.1152/ajpheart.00343.2008
28,057,978
Mechanical stretch, an important growth stimulus, results not only from pulsatile blood flow and diastolic stretch of the ventricles [cyclic stretch (CS)] but also from tissue expansion during growth [constant static stretch (SS)]. We compared growth factor receptor expression and vasculogenic/angiogenic responses of r...
10.1038/nature10316
This study provides evidence that statically and dynamically applied stretches lead to the activation of distinct pathways in stretched endothelial cells.