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10.1126/science.aad0832 | 41,595,725 | The right kind of dopant The oxygen reduction reaction is an important step in fuel cells and other electrochemical processes but is still largely dependent on precious metal-containing catalysts. Recently explored alternatives include carbon materials that are doped with different, preferably non-precious metal, atoms... | 10.1038/natrevmats.2016.64 | Detailed experimental elucidation of the ORR mechanism by metal-free nitrogen-doped carbon catalysts. |
10.1063/1.4812323 | 20,885,801 | Accelerating the discovery of advanced materials is essential for human welfare and sustainable, clean energy. In this paper, we introduce the Materials Project (www.materialsproject.org), a core program of the Materials Genome Initiative that uses high-throughput computing to uncover the properties of all known inorga... | 10.1038/natrevmats.2015.4 | Introduction of the Materials Project, today's most popular searchable database of density functional theory calculations used by both experimentalists and theorists. |
10.1038/s41467-017-00613-5 | 41,659,122 | Abstract A variety of artificial spinning methods have been applied to produce regenerated silk fibers; however, how to spin regenerated silk fibers that retain the advantages of natural silks in terms of structural hierarchy and mechanical properties remains challenging. Here, we show a bioinspired approach to spin re... | 10.1038/natrevmats.2018.16 | This paper describes improved dry spinning techniques for producing polymorphic and mechanically enhanced regenerated silk fibres. |
10.1126/sciadv.1601939 | 45,388,115 | A nacre-like multilayer filtration membrane is developed by integration of computational simulation and experimental fabrication. | 10.1038/natrevmats.2018.16 | This paper introduces a rational material design strategy to fabricate high-performance water purification membranes. |
10.1126/science.1218764 | 104,341,382 | Hammering Home the Lesson Stomatopods are marine crustaceans that use hammerlike claws for defense and to attack their prey. The claws undergo repeated high-velocity and high-force impacts. Weaver et al. (p. 1275 ; see the Perspective by Tanner ) used a variety of techniques to examine the structure, mechanical behavio... | 10.1038/natrevmats.2018.16 | This paper presents the exceptional damage tolerance mechanism of the stomatopod dactyl club. |
10.1073/pnas.1210105109 | 125,319,447 | Biological communication by means of structural color has existed for at least 500 million years. Structural color is commonly observed in the animal kingdom, but has been little studied in plants. We present a striking example of multilayer-based strong iridescent coloration in plants, in the fruit of Pollia condensat... | 10.1038/natrevmats.2018.16 | This paper demonstrates the origin of structural colour in P. condensata |
10.1073/pnas.0712168105 | 20,864,398 | We have developed a method to detect DNA synthesis in proliferating cells, based on the incorporation of 5-ethynyl-2′-deoxyuridine (EdU) and its subsequent detection by a fluorescent azide through a Cu(I)-catalyzed [3 + 2] cycloaddition reaction (“click” chemistry). Detection of the EdU label is highly sensitive and ca... | 10.1038/nchembio.1296 | This study describes the first alkyne chemical reporter for labeling nucleic acids in cells and animals. |
10.1126/science.287.5460.2007 | 104,066,814 | Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is present... | 10.1038/nchembio.1296 | This study describes the Staundinger ligation reaction between functionalized triarylphosphine reagents and cell-surface glycans that were metabolically labeled with azide-modified monosaccharide reporter. As triarylphosphine and alkyl azides are both abiotic, this study is the first example of a 'bioorthogonal' ligati... |
10.1126/science.1155106 | 45,485,705 | Glycans are attractive targets for molecular imaging but have been inaccessible because of their incompatibility with genetically encoded reporters. We demonstrated the noninvasive imaging of glycans in live developing zebrafish, using a chemical reporter strategy. Zebrafish embryos were treated with an unnatural sugar... | 10.1038/nchembio.1296 | This study describes dynamic bioorthogonal labeling and imaging in whole animals. |
10.1073/pnas.1102458108 | 123,126,988 | The dynamic modification of nuclear and cytoplasmic proteins by the monosaccharide N -acetyl-glucosamine (GlcNAc) continues to emerge as an important regulator of many biological processes. Herein we describe the development of an alkynyl-modified GlcNAc analog (GlcNAlk) as a new chemical reporter of O-GlcNAc modificat... | 10.1038/nchembio.1296 | This study describes a large-scale proteomic analysis of O-GlcNAcylation using chemical reporter labeling. |
10.1073/pnas.1302564110 | 17,576,672 | S-prenylation is an important lipid modification that targets proteins to membranes for cell signaling and vesicle trafficking in eukaryotes. As S-prenylated proteins are often key effectors for oncogenesis, congenital disorders, and microbial pathogenesis, robust proteomic methods are still needed to biochemically cha... | 10.1038/nchembio.1296 | This study describes the proteomic analysis of S-prenylated proteins in mammalian cells using chemical reporter labeling and the discovery of zinc-finger antiviral protein L (ZAPL) farnesylation–dependent antiviral activity. |
10.1073/pnas.0912306107 | 16,885,585 | The functional significance and regulation of reversible S -acylation on diverse proteins remain unclear because of limited methods for efficient quantitative analysis of palmitate turnover. Here, we describe a tandem labeling and detection method to simultaneously monitor dynamic S -palmitoylation and protein turnover... | 10.1038/nchembio.1296 | This study describes dual chemical reporter labeling for the tandem detection of protein turnover and S-palmitoylation dynamics in mammalian cells, which revealed accelerated S-palmitoylation in activated T cells. |
10.1002/anie.196305651 | 60,646,267 | Abstract In contrast to the very large number of special methods applicable to syntheses in the heterocyclic series, relatively few general methods are available. The 1,3‐dipolar addition offers a remarkably wide range of utility in the synthesis of five‐membered heterocycles. Here the “1,3‐dipole”, which can only be r... | 10.1038/nchembio.1296 | Early studies of cycloaddition reactions by Huisgen and coworkers provided the foundation for future bioorthogonal reactions. |
10.1182/blood.v99.10.3838 | 20,596,826 | CD2+ T lymphocytes obtained from either the donor of bone marrow stromal cells (BMSCs) or a third party were cultured in mixed lymphocyte reactions (MLRs) with either allogeneic dendritic cells (DCs) or peripheral blood lymphocytes (PBLs). When autologous or allogeneic BMSCs were added back to T cells stimulated by DCs... | 10.1038/nature07041 | This study showed the immunosuppressive properties of human bone-marrow stromal cells and became the catalyst for the use of such cells (now known as MSCs) to dampen inflammatory conditions, including graft-versus-host disease. |
10.1677/joe.0.1120345 | 119,600,803 | ABSTRACT It has been shown that the thymus can be regenerated in intact old rats by implanting s.c. a stable analogue of LHRH. Old male rats were given s.c. implants of osmotic pumps containing a solution in citrate buffer of the analogue which was given at a rate of 1 μg/h for 28 days. Some animals were given pumps co... | 10.1038/nature07041 | This paper provided, in an animal model, proof of principle that the thymus can be regenerated in an aged individual by using reversible chemical castration. |
10.4049/jimmunol.175.4.2741 | 62,080,989 | Abstract The thymus undergoes age-related atrophy, coincident with increased circulating sex steroids from puberty. The impact of thymic atrophy is most profound in clinical conditions that cause a severe loss in peripheral T cells with the ability to regenerate adequate numbers of naive CD4+ T cells indirectly correla... | 10.1038/nature07041 | This study showed a fundamentally new clinical approach for treating immunodeficiency states in humans, regenerating the immune system after bone-marrow transplantation or a damaging chemotherapy regimen. |
10.1126/science.1139221 | 83,013,204 | Lymphocytes require sphingosine-1-phosphate (S1P) receptor-1 to exit lymphoid organs, but the source(s) of extracellular S1P and whether S1P directly promotes egress are unknown. By using mice in which the two kinases that generate S1P were conditionally ablated, we find that plasma S1P is mainly hematopoietic in origi... | 10.1038/nature13475 | The authors of this paper demonstrated that the S1P in blood is derived from haematopoietic cells, whereas lymph S1P was not, and clearly demonstrated that S1PR1 expression on lymphocytes was required for their egress. |
10.1126/science.279.5356.1552 | 41,715,227 | The sphingolipid metabolite sphingosine-1–phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding to unidentified receptors on the cell surface. SPP activated the heterotrimeric guanine nucleotide binding protein (G protein... | 10.1038/nature13475 | This paper reported the first identification of a S1P receptor. |
10.1126/science.1215904 | 123,031,860 | A Lipid-Sensing GPCR Sphingosine 1-phosphate (S1P) is a sphingolipid that binds to the G protein–coupled receptor subtype 1 (S1P 1 ) to activate signaling pathways involved in regulation of the vascular and immune systems. Hanson et al. (p. 851 ) determined the crystal structure of S1PR in complex with an antagonist sp... | 10.1038/nature13475 | This was the first crystal structure of the lipid-binding GPCR S1PR1 that indicated that S1P enters the binding pocket by sliding in the plane of the membrane. |
10.2337/db11-1399 | 26,969,771 | Vascular dysfunction that accompanies obesity and insulin resistance may be mediated by lipid metabolites. We sought to determine if vascular ceramide leads to arterial dysfunction and to elucidate the underlying mechanisms. Pharmacological inhibition of de novo ceramide synthesis, using the Ser palmitoyl transferase i... | 10.1038/nature13475 | The authors of this article provided evidence that obesity-induced endothelial dysfunction is due to elevation of ceramide, which de-represses PP2A, leading to dephosphorylation and inhibition of Akt and eNOS. |
10.1126/science.1208248 | 103,218,621 | A molecular mechanism that allows lymphocytes to migrate against a chemokine gradient is revealed. | 10.1038/nature13475 | The authors of this paper explain how lymphocytes migrate into lymphoid tissues against the S1P gradient by GRK2-dependent downregulation of S1PR1. |
10.1126/science.1070238 | 62,169,148 | Blood lymphocyte numbers, essential for the development of efficient immune responses, are maintained by recirculation through secondary lymphoid organs. We show that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolite of the immunosuppressive agent FTY... | 10.1038/nature13475 | This is the first demonstration that the phosphorylated form of FTY720 is an agonist for all S1P receptors, but S1PR2 and that FTY720-P induces lymphopaenia. |
10.1073/pnas.1014154108 | 125,122,641 | Sphingosine 1-phosphate (S1P), a lysophospholipid, has gained relevance to multiple sclerosis through the discovery of FTY720 (fingolimod), recently approved as an oral treatment for relapsing forms of multiple sclerosis. Its mechanism of action is thought to be immunological through an active phosphorylated metabolite... | 10.1038/nature13475 | This study identified non-immunological central nervous system mechanisms of FTY720 efficacy in EAE that depend on the drugs ability to modulate S1PR1 expression in astrocytes. |
10.1126/science.1113640 | 83,012,598 | Lymphocyte egress from the thymus and from peripheral lymphoid organs depends on sphingosine 1-phosphate (S1P) receptor-1 and is thought to occur in response to circulatory S1P. However, the existence of an S1P gradient between lymphoid organs and blood or lymph has not been established. To further define egress requir... | 10.1038/nature13475 | This paper provides compelling evidence that lymphocyte egress depends on the S1P gradient. |
10.1126/scitranslmed.3005765 | 58,025,404 | Decreased activity of serine palmitoyl-CoA transferase is associated with asthma. | 10.1038/nature13475 | This work showed that inhibition of sphingolipid biosynthesis enhances airway hyper-responsiveness. |
10.1126/science.1187197 | 84,458,275 | Herpes Virus MiRNA Modulation Viruses use a number of strategies to manipulate the cells of their host to ensure a successful infection. Herpesvirus saimiri (HVS) generates highly conserved small noncoding RNAs HSUR 1 and HSUR 2 , which modulate expression of a number of proteins in infected primate T cells. Cazalla et... | 10.1038/nature12986 | This work extends ceRNA crosstalk to viruses and shows that a viral non-coding RNA sequesters and promotes the degradation of a miRNA in infected host cells. |
10.1126/science.aad8857 | 125,291,294 | Close-up view of the nuclear periphery Cell biologists would like to be able to visualize complexes inside cells at molecular resolution. Several limitations, however, have prevented the field from realizing this goal. The thickness of most cells precludes cryo-electron tomography, a technique which itself does not pro... | 10.1038/nature19948 | This work presents an exciting vision of how cryo-electron tomography and sub-tomogram averaging can bridge the gap between the structural biology of isolated complexes and cell biology. |
10.1063/1.1663087 | 86,948,511 | We report on three techniques for replicating relief patterns in dielectric materials for use as substrates for planar integrated optical circuits: embossing with a metal die; casting from a metal die; and casting from a rubber mold. Techniques for overcoating the substrates with light-guiding films and filling of groo... | 10.1038/nature13118 | An early example of replicating microfluidic structures with elastomer materials. |
10.1073/pnas.0810903105 | 123,013,328 | This article describes a method for fabricating 3D microfluidic devices by stacking layers of patterned paper and double-sided adhesive tape. Paper-based 3D microfluidic devices have capabilities in microfluidics that are difficult to achieve using conventional open-channel microsystems made from glass or polymers. In ... | 10.1038/nature13118 | A review of advancements in µPAD devices for diagnostics in developing regions. |
10.1073/pnas.1210182109 | 125,182,633 | Entry of tumor cells into the blood stream is a critical step in cancer metastasis. Although significant progress has been made in visualizing tumor cell motility in vivo, the underlying mechanism of cancer cell intravasation remains largely unknown. We developed a microfluidic-based assay to recreate the tumor-vascula... | 10.1038/nature13118 | This study describes a system that more closely mimics tumour cell intravasation in vitro compared to standard cell biology techniques such as modified Transwell assays. |
10.5194/cp-7-1459-2011 | 84,427,460 | Abstract. The gradual cooling of the climate during the Cenozoic has generally been attributed to a decrease in CO2 concentration in the atmosphere. The lack of transient climate models and, in particular, the lack of high-resolution proxy records of CO2, beyond the ice-core record prohibit, however, a full understandi... | 10.1038/nature11574 | Compiles CO 2 data from a variety of approaches over the past 20 million years, and condenses these into one time series. |
10.1126/science.1062882 | 29,297,029 | In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of... | 10.1038/nature11170 | A study showing the key role that changes in a viral polymerase gene has in H5N1 virulence in a mammalian model. |
10.1126/science.1124513 | 20,706,425 | The hemagglutinin (HA) structure at 2.9 angstrom resolution, from a highly pathogenic Vietnamese H5N1 influenza virus, is more related to the 1918 and other human H1 HAs than to a 1997 duck H5 HA. Glycan microarray analysis of this Viet04 HA reveals an avian α2-3 sialic acid receptor binding preference. Introduction of... | 10.1038/nature11170 | A study describing the haemagglutinin crystal structure of an H5N1 influenza virus and studies of mutations associated with receptor-binding specificity. |
10.1242/dmm.007823 | 123,075,153 | Influenza is a human pathogen that continues to pose a public health threat. The use of small mammalian models has become indispensable for understanding the virulence of influenza viruses. Among numerous species used in the laboratory setting, only the ferret model is equally well suited for studying both the pathogen... | 10.1038/nature11170 | A review of the ferret as a model organism in influenza virus pathogenicity studies. |
10.1126/science.1136212 | 103,749,846 | The 1918 influenza pandemic was a catastrophic series of virus outbreaks that spread across the globe. Here, we show that only a modest change in the 1918 influenza hemagglutinin receptor binding site alters the transmissibility of this pandemic virus. Two amino acid mutations that cause a switch in receptor binding pr... | 10.1038/nature11170 | A study elucidating the importance of the haemagglutinin-receptor-binding region in conferring ferret transmissibility in the 1918 pandemic influenza virus. |
10.1073/pnas.0813172106 | 41,313,161 | The influenza virus genes that confer efficient transmission of epidemic and pandemic strains in humans have not been identified. The rapid spread and severe disease caused by the 1918 influenza pandemic virus makes it an ideal virus to study the transmissibility of potentially pandemic influenza strains. Here, we used... | 10.1038/nature11170 | A study describing the importance of both the 1918 haemagglutinin and polymerase PB2 genes in conferring ferret transmissibility in viruses expressing 1918 pandemic influenza virus genes. |
10.1242/dev.127.24.5253 | 104,423,533 | The developing central nervous system of vertebrates contains an abundant cell type designated radial glial cells. These cells are known as guiding cables for migrating neurons, while their role as precursor cells is less clear. Since radial glial cells express a variety of astroglial characteristics and differentiate ... | 10.1038/nature09611 | This paper highlights the neurogenic potential of radial glia. Using fluorescence-activated cell sorting, radial glia isolated from the embryonic neocortex were shown to generate neurons, as well as astrocytes. |
10.1126/science.1144914 | 81,784,981 | The in vivo potential of neural stem cells in the postnatal mouse brain is not known, but because they produce many different types of neurons, they must be either very versatile or very diverse. By specifically targeting stem cells and following their progeny in vivo, we showed that postnatal stem cells in different r... | 10.1038/nature09611 | This paper shows that in the adult the subventricular zone contains regions that produce different types of interneuron, which contribute to the rostral migratory stream and the olfactory bulb. |
10.1146/annurev-psych-010213-115202 | 104,241,367 | Adolescence is a period of formative biological and social transition. Social cognitive processes involved in navigating increasingly complex and intimate relationships continue to develop throughout adolescence. Here, we describe the functional and structural changes occurring in the brain during this period of life a... | 10.1038/nature25750 | This review compiles evidence of social contextual effects on adolescent brain maturation |
10.1073/pnas.1100290108 | 20,570,812 | In the last 60,000 y humans have expanded across the globe and now occupy a wider range than any other terrestrial species. Our ability to successfully adapt to such a diverse range of habitats is often explained in terms of our cognitive ability. Humans have relatively bigger brains and more computing power than other... | 10.1038/nature25750 | This analysis documents the crucial role of social learning in human adaptation. |
10.1111/j.1752-4571.2007.00011.x | 26,832,739 | Abstract We discuss three interlinked issues: the natural pace of environmental change and adaptation, the likelihood that a population will adapt to a potentially lethal change, and adaptation to elevated CO 2 , the prime mover of global change. 1. Environmental variability is governed by power laws showing that ln di... | 10.1038/nature09670 | Using experimental evolution, demonstrates that evolutionary adaptation to climate change can influence the ability of species to take advantage of potentially favourable conditions arising from climate change, including the effects of CO 2 enrichment on growth rate. |
10.1098/rstb.2009.0283 | 57,286,986 | This study addresses the extent and consequences of gene exchange between populations of Darwin's finches. Four species of ground finches ( Geospiza ) inhabit the small island of Daphne Major in the centre of the Galápagos archipelago. We undertook a study of microsatellite DNA variation at 16 loci in order to quantify... | 10.1038/nature09670 | Highlights the potential importance of hybridization in generating genetic variation for adapting to climate change. |
10.1126/science.1112178 | 62,026,128 | The positioning of nucleosomes along chromatin has been implicated in the regulation of gene expression in eukaryotic cells, because packaging DNA into nucleosomes affects sequence accessibility. We developed a tiled microarray approach to identify at high resolution the translational positions of 2278 nucleosomes over... | 10.1038/nature08450 | This paper provides the first high-resolution view of nucleosome positioning and reveals a nucleosome-depleted region that overlaps with transcription-factor binding sites. |
10.1101/gr.076059.108 | 41,690,706 | Chromatin structure is central for the regulation of gene expression, but its genome-wide organization is only beginning to be understood. Here, we examine the connection between patterns of nucleosome occupancy and the capacity to modulate gene expression upon changing conditions, i.e., transcriptional plasticity. By ... | 10.1038/nature08450 | Several concepts in promoter classification developed in this paper are central to my Review. |
10.1126/science.1090701 | 103,710,699 | The conserved histone variant H2AZ has an important role in the regulation of gene expression and the establishment of a buffer to the spread of silent heterochromatin. How histone variants such as H2AZ are incorporated into nucleosomes has been obscure. We have found that Swr1, a Swi2/Snf2-related adenosine triphospha... | 10.1038/nature08450 | This paper provides the first evidence for in vitro insertion of H2A.Z by a remodeller. |
10.1126/science.1123604 | 38,357,852 | Crop domestication frequently began with the selection of plants that did not naturally shed ripe fruits or seeds. The reduction in grain shattering that led to cereal domestication involved genetic loci of large effect. The molecular basis of this key domestication transition, however, remains unknown. Here we show th... | 10.1038/nature07895 | This paper reports the first molecular isolation of a loss-of-shattering gene in a cereal crop species, a trait that is the hallmark of domestication in seed crops. |
10.1126/science.1107891 | 83,121,116 | Domestication promotes rapid phenotypic evolution through artificial selection. We investigated the genetic history by which the wild grass teosinte ( Zea mays ssp. parviglumis ) was domesticated into modern maize ( Z. mays ssp. mays ). Analysis of single-nucleotide polymorphisms in 774 genes indicates that 2 to 4% of ... | 10.1038/nature07895 | This paper reports a genome-wide screen for genes that display a signature of positive selection associated with crop domestication and diversification. |
10.1534/genetics.106.056473 | 29,105,135 | Abstract Rice (Oryza sativa) was cultivated by Asian Neolithic farmers >11,000 years ago, and different cultures have selected for divergent starch qualities in the rice grain during and after the domestication process. An intron 1 splice donor site mutation of the Waxy gene is responsible for the absence of amy... | 10.1038/nature07895 | This paper reports the characterization of a selective sweep in the waxy gene, which underlies the origin and spread of sticky rice. |
10.1177/1461957105066937 | 79,430,110 | The spread of agriculture is here examined from the perspective of changes in the composition of archaeobotantical assemblages. We apply multivariate analysis to a large database of plant assemblages from early Neolithic sites across South-West Asia and Europe and show that there are coherent and meaningful changes in ... | 10.1038/nature07895 | This paper provides a quantitative analysis of crop assemblages and shows the role of selection and drift in the creation of a suitable crop package for new environments. |
10.1177/0309132515580814 | 79,917,856 | Since the 1990s, multilevel models have become popular tools for looking at contextual effects upon health. However, the way that geography is incorporated into these models has received criticism due to somewhat arbitrary definitions of what counts as context, the models’ discrete and, arguably, aspatial view of geogr... | 10.1038/nclimate3318 | Provides specific research design approaches and strategies for developing multi-level models of health outcomes that reflect spatial variability at different scales. |
10.1146/annurev.energy.30.050504.164507 | 41,641,541 | ▪ Abstract The world's system of protected areas has grown exponentially over the past 25 years, particularly in developing countries where biodiversity is greatest. Concurrently, the mission of protected areas has expanded from biodiversity conservation to improving human welfare. The result is a shift in favor of pro... | 10.1038/nature13947 | This is an important review that explores the different roles of protected areas and the implications of different objectives. |
10.1073/pnas.0509060102 | 121,790,530 | Slowing rates of global biodiversity loss requires preventing species extinctions. Here we pinpoint centers of imminent extinction, where highly threatened species are confined to single sites. Within five globally assessed taxa (i.e., mammals, birds, selected reptiles, amphibians, and conifers), we find 794 such speci... | 10.1038/nature13947 | This was the first global assessment identifying sites that hold crucial populations of an endangered or critically endangered species. |
10.1126/science.291.5501.125 | 125,271,970 | We assessed the impacts of anthropogenic threats on 93 protected areas in 22 tropical countries to test the hypothesis that parks are an effective means to protect tropical biodiversity. We found that the majority of parks are successful at stopping land clearing, and to a lesser degree effective at mitigating logging,... | 10.1038/nature13947 | This was one of the first large-scale analyses on what makes protected areas effective in protecting biodiversity. |
10.1101/066100 | 114,306,624 | Abstract Long sequencing reads generated by single-molecule sequencing technology offer the possibility of dramatically improving the contiguity of genome assemblies. The biggest challenge today is that long reads have relatively high error rates, currently around 15%. The high error rates make it difficult to use this... | 10.1038/nature22011 | This paper shows how long-read sequencing technology coupled with the mega-reads algorithm can be used successfully to tackle a large and complex grass genome, which paves the way for the sequencing of multiple variants. |
10.1101/080796 | 25,933,813 | Advances in genome sequencing and assembly technologies are generating many high quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of op... | 10.1038/nature22011 | This preprint presents open-source assembly methods that preserve genetic variation and have enabled the fast and low-cost assembly of the large and complex wheat genome. |
10.1126/science.1169786 | 20,790,986 | Methylation Mediation Methylation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role in mammalian genomes. Methylation patterns are often inherited across generations, but they can also be dynamic, suggesting that active DNA demethylation pathways exist. One such pathway, best characte... | 10.1038/nbt.2398 | Authors show that 5hmC is present in high levels in Purkinje cells, suggesting a role for 5hmC in neuronal function |
10.1126/science.1170116 | 125,255,278 | Methylation Mediation Methylation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role in mammalian genomes. Methylation patterns are often inherited across generations, but they can also be dynamic, suggesting that active DNA demethylation pathways exist. One such pathway, best characte... | 10.1038/nbt.2398 | This paper showed that 5hmC is present in ESCs and is enzymatically produced through TET-catalyzed oxidation of 5mC |
10.1126/science.1210597 | 20,790,441 | 5-methylcytosine (5mC) in DNA plays an important role in gene expression, genomic imprinting, and suppression of transposable elements. 5mC can be converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) proteins. Here, we show that, in addition to 5hmC, the Tet proteins can generate 5-formylcy... | 10.1038/nbt.2398 | In addition, authors quantified 5fC and 5caC using LC-MS/MS in mouse ESCs and tissues |
10.1126/science.1210944 | 83,432,525 | The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine mo... | 10.1038/nbt.2398 | This paper revealed the first biochemically validated active DNA demethylation pathway |
10.1126/science.1220671 | 62,253,778 | Distinguishing Epigenetic Marks Methylation of the cytosine base in eukaryotic DNA (5mC) is an important epigenetic mark involved in gene silencing and genome stability. Methylated cytosine can be enzymatically oxidized to 5-hydroxymethylcytosine (5hmC), which may function as a distinct epigenetic mark—possibly involve... | 10.1038/nbt.2398 | This paper developed oxBS-Seq for single-base resolution 5hmC sequencing and performed 5hmC mapping in CpG islands |
10.1002/ana.20009 | 41,758,566 | Abstract This report describes the first human study of a novel amyloid‐imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound‐B (PIB), in 16 patients with diagnosed mild AD and 9 controls. Compared with controls, AD patients typically showed marked retention of PIB in areas of association cortex... | 10.1038/nature20412 | This important paper was the first to describe the PET imaging of amyloids in people with AD. |
10.1002/ana.22089 | 45,519,083 | Abstract Objective Alzheimer disease (AD) is characterized by functional impairment in the neural elements and circuits underlying cognitive and memory functions. We hypothesized that fornix/hypothalamus deep brain stimulation (DBS) could modulate neurophysiological activity in these pathological circuits and possibly ... | 10.1038/nature20412 | This paper describes the feasibility of deep-brain stimulation in people and targets regions that are not typically described in studies of disrupted processes in AD; it suggests that complex brain-wide network effects occur in AD. |
10.1126/science.274.5285.209 | 104,227,840 | The central event in the cellular immune response to invading microorganisms is the specific recognition of foreign peptides bound to major histocompatibility complex (MHC) molecules by the αβ T cell receptor (TCR). The x-ray structure of the complete extracellular fragment of a glycosylated αβ TCR was determined at 2.... | 10.1038/nchembio.1391 | The first MHC–TCR co-crystal showing how the TCR recognizes the combination of MHC class I and peptide. |
10.1126/science.1095522 | 125,271,763 | CD8 T lymphocytes recognize peptides of 8 to 10 amino acids presented by class I molecules of the major histocompatibility complex. Here, CD8 T lymphocytes were found to recognize a nonameric peptide on melanoma cells that comprises two noncontiguous segments of melanocytic glycoprotein gp100 PMEL17 . The production of... | 10.1038/nchembio.1391 | This study shows the concept of peptide splicing yielding new peptides for MHC class I antigen presentation. These peptides are not genetically encoded but are the result of proteasomal degradation and proteasomal ligation into a new combination to result post-translationally in a new peptide sequence. |
10.1126/science.1172308 | 62,603,250 | The Grim RIPper Cells can undergo regulated cell death through distinct processes known as apoptosis and necrosis. Regulation of apoptosis is better understood than that of necrosis. In a screen for gene products that participate in control of necrosis in cells treated with TNF (tumor necrosis factor), D.-W. Zhang et a... | 10.1038/nature14191 | This paper along with refs 9 and 10 identified RIPK3 as a key regulator of TNF-induced necroptosis. |
10.1073/pnas.1200012109 | 103,810,778 | Tumor necrosis factor (TNF) is an important inflammatory cytokine and induces many cellular responses, including inflammation, cell proliferation, apoptosis, and necrosis. It is known that receptor interacting protein (RIP) kinases, RIP1 and RIP3, are key effectors of TNF-induced necrosis, but little is known about how... | 10.1038/nature14191 | This paper along with ref. 19 identified MLKL as an essential mediator of necroptosis downstream of RIPK3. |
10.4049/jimmunol.1400499 | 123,040,121 | Abstract RIP1 (RIPK1) kinase is a key regulator of TNF-induced NF-κB activation, apoptosis, and necroptosis through its kinase and scaffolding activities. Dissecting the balance of RIP1 kinase activity and scaffolding function in vivo during development and TNF-dependent inflammation has been hampered by the perinatal ... | 10.1038/nature14191 | This article along with ref. 53 (and ref. 65) showed that knock-in mice expressing kinase inactive Ripk1 alleles are viable and protected from TNF-induced SIRS. |
10.1126/science.1249361 | 104,157,349 | Life and Cell Death Trying to protect animals from one form of cell death may lead to death by another. Two protein kinases, known as RIPK1 and RIPK3 promote signaling that leads to cell death by necroptosis. However, Newton et al. (p. 1357 , published online 20 February; see the Perspective by Zhang and Chan ) found t... | 10.1038/nature14191 | This study showed that RIPK3 D161N knock-in mice die during embryogenesis due to caspase-8 dependent apoptosis, suggesting that RIPK3-kinase activity inhibits caspase-8 during development. |
10.1126/science.1058827 | 104,106,139 | Glial cells express a variety of neurotransmitter receptors. Notably, Bergmann glial cells in the cerebellum have Ca 2+ -permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–type glutamate receptors (AMPARs) assembled without the GluR2 subunit. To elucidate the role of these Ca 2+ -permeable AMPARs, we... | 10.1038/nature09612 | This paper shows that Ca 2+ -permeable AMPA receptors on glia are required for proper structural and functional relationships between Bergmann glia and glutamate-mediated synapses in the cerebellum. |
10.1126/science.291.5504.657 | 41,622,054 | Although astrocytes constitute nearly half of the cells in our brain, their function is a long-standing neurobiological mystery. Here we show by quantal analyses, FM1-43 imaging, immunostaining, and electron microscopy that few synapses form in the absence of glial cells and that the few synapses that do form are funct... | 10.1038/nature09612 | References 38 and 39 show that synapse formation and function are powerfully affected by astrocytes in culture. This is the first report that these processes are not only controlled by neuronal mechanisms but can also be directed by glia. |
10.1126/scisignal.2004235 | 41,038,009 | Hyperglycemia restricts the formation of new blood vessels by preventing VEGFR2 from responding to its angiogenic ligand VEGF. | 10.1038/nature13312 | Mechanistic evidence of the anti-angiogenic effect of high glucose and ROS in diabetes. |
10.1126/science.1242454 | 125,118,429 | Lymphocyte Metabolism Lymphocytes are highly dynamic cells, undergoing extensive proliferation upon infection and then reducing in number upon pathogen clearance. Lymphocytes also circulate through many different tissue environments that vary in their nutrient and oxygen availability. Recent studies have revealed chang... | 10.1038/nature13312 | Refs 50-55 highlight emerging concepts of metabolism and its importance in T-cell function and development. |
10.1182/blood-2013-04-495515 | 82,949,993 | Key Points T cells activated during GVHD increase their dependence upon fatty acid oxidation. This dependence is not observed following acute activation or during normal immune reconstitution, suggesting novel therapeutic targets. | 10.1038/nature13312 | Shows the ability of T eff to adopt a different metabolic phenotype inflicted by external cues. |
10.1126/science.1136370 | 20,482,650 | Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. T... | 10.1038/nature06796 | This study is a superb example of linkage analysis in a large kindred identifying a novel gene, LRP6 , associated with both premature coronary artery disease and components of the metabolic syndrome. |
10.1126/science.1103333 | 83,271,447 | Female gender affords relative protection from cardiovascular disease until the menopause. We report that estrogen acts on estrogen receptor subtype alpha to up-regulate the production of atheroprotective prostacyclin, PGI 2 , by activation of cyclooxygenase 2 (COX-2). This mechanism restrained both oxidant stress and ... | 10.1038/nature06796 | This paper shows the atheroprotective effects of PGI 2 and activation of its receptor, with the interesting twist that the effect is limited to female mice (as a result of oestrogen-receptor-α -stimulated production of PGI 2 ). The study has implications for the cardiovascular complications of COX2 inhibition and for t... |
10.1073/pnas.0511043103 | 104,021,854 | Atherosclerosis regression is an important clinical goal. In previous studies of regression in mice, the rapid loss of plaque foam cells was explained by emigration to lymph nodes, a process reminiscent of dendritic cells. In the present study, plaque-containing arterial segments from apoE −/− mice were transplanted in... | 10.1038/nature06796 | This study explored the molecular physiology of plaque regression, and it indicates that activation of CCR7 promotes egress of dendritic cells from plaques, thereby inducing plaque regression. |
10.1111/j.1751-1097.2011.00901.x | 104,028,541 | Abstract The blue light photoreceptor phototropin mediates crucial processes in plants leading to optimization of photosynthesis. Phototropin comprises two flavin mononucleotide‐binding LOV (light‐, oxygen‐, or voltage‐sensitive) domains. The LOV domains undergo a photocycle upon illumination, in which two intermediate... | 10.1038/nchembio.1633 | Detection of a flavin semiquinone intermediate in the LOV adduct forming reaction. |
10.1073/pnas.1311077110 | 123,281,384 | The flavin adenine dinucleotide cofactor has an unusual bent configuration in photolyase and cryptochrome, and such a folded structure may have a functional role in initial photochemistry. Using femtosecond spectroscopy, we report here our systematic characterization of cyclic intramolecular electron transfer (ET) dyna... | 10.1038/nchembio.1633 | Ultrafast spectroscopy characterizes rapid electron exchange between flavin and adenine rings of FAD in various redox states of PL. Implications for redox processes that could trigger signal propagation in CRYs. |
10.1126/science.1223710 | 39,300,642 | Modulating the Clock Because of the close association of the circadian clock with a wide range of physiological processes, identification of clock-modulating small molecules may prove useful for the treatment of circadian-related disorders, which include circadian sleep disorders, cardiovascular disease, cancer, and me... | 10.1038/nchembio.1633 | Small molecule screen for disrupted circadian gene expression identifies CRY as primary binder and potential therapeutic target. |
10.1098/rsif.2013.0638 | 20,166,287 | The radical pair model proposes that the avian magnetic compass is based on radical pair processes in the eye, with cryptochrome, a flavoprotein, suggested as receptor molecule. Cryptochrome 1a (Cry1a) is localized at the discs of the outer segments of the UV/violet cones of European robins and chickens. Here, we show ... | 10.1038/nchembio.1633 | Powerful behavioral assays correlate bird magnetic orientation with CRY activation in the eye through antibodies that recognize the CRY C-terminus. |
10.1110/ps.03259908 | 104,387,250 | Abstract Although phenomenlogical models that account for cooperativity in allosteric systems date back to the early and mid‐60's (e.g., the KNF and MWC models), there is resurgent interest in the topic due to the recent experimental and computational studies that attempted to reveal, at an atomistic level, how alloste... | 10.1038/nature13001 | A thoughtful, comprehensive review that synthesizes the ‘old’ and ‘new’ views of allostery with experimental and computational case studies from the literature. |
10.1126/science.1585178 | 103,935,523 | The oxygen affinity of hemoglobin varies linearly with the chemical potential of water in the bathing medium, as seen from the osmotic effect of several neutral solutes, namely sucrose, stachyose, and two polyethyleneglycols (molecular weights of 150 and 400). The data, analyzed either by Wyman linkage equations or by ... | 10.1038/nature13001 | Groundbreaking experimental work demonstrating the large energetic effects of hydration on haemoglobin conformation and thus protein allostery. |
10.1073/pnas.0700329104 | 83,244,409 | Transcription factors and other allosteric cell signaling proteins contain a disproportionate number of domains or segments that are intrinsically disordered (ID) under native conditions. In many cases folding of these segments is coupled to binding with one or more of their interaction partners, suggesting that intrin... | 10.1038/nature13001 | The first paper to propose and demonstrate that intrinsic disorder can be used by proteins to mediate allosteric coupling. |
10.1126/science.1145724 | 41,653,591 | Agricultural soil erosion is thought to perturb the global carbon cycle, but estimates of its effect range from a source of 1 petagram per year –1 to a sink of the same magnitude. By using caesium-137 and carbon inventory measurements from a large-scale survey, we found consistent evidence for an erosion-induced sink o... | 10.1038/nature12350 | This paper estimated the net effect of erosion given sources and sinks induced by the transported material. |
10.1073/pnas.1107891109 | 20,576,110 | Forest ecosystems store approximately 45% of the carbon found in terrestrial ecosystems, but they are sensitive to climate-induced dieback. Forest die-off constitutes a large uncertainty in projections of climate impacts on terrestrial ecosystems, climate–ecosystem interactions, and carbon-cycle feedbacks. Current unde... | 10.1038/nature12350 | This is a comprehensive analysis of mechanisms causing drought-related tree mortality. |
10.1126/science.1076347 | 123,171,640 | Ecosystem responses to increased variability in rainfall, a prediction of general circulation models, were assessed in native grassland by reducing storm frequency and increasing rainfall quantity per storm during a 4-year experiment. More extreme rainfall patterns, without concurrent changes in total rainfall quantity... | 10.1038/nature12350 | This is a classic paper showing the importance of precipitation variability (compared to mean precipitation) for net primary production. |
10.1126/science.1197931 | 120,547,522 | Spin Control Controlling and manipulating the spin of an electron is a central requirement for applications in spintronics. Some of the challenges researchers are facing include efficient creation of spin currents, minimization of Joule heating, and extending the lifetime of electronic spins, which is especially import... | 10.1038/nature10681 | This study demonstrated electrical read-out of both 31 P and 29 Si nuclear spin states in silicon, using the hyperfine interaction with donor electrons. |
10.1126/science.285.5432.1390 | 81,824,866 | The gene expression profile of the aging process was analyzed in skeletal muscle of mice. Use of high-density oligonucleotide arrays representing 6347 genes revealed that aging resulted in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic ge... | 10.1038/ncomms6659 | Through gene expression analysis of skeletal muscle of aged and caloric restricted mice several proteasome-related genes are found to be upregulated |
10.1111/j.1474-9726.2012.00823.x | 19,038,720 | Summary In organisms with a soma–germ demarcation, the germline must be ‘preserved’ such that harmful damage is not transmitted to the offspring. Keeping the progeny free of damage may be achieved by gametes enjoying elevated, and/or more functional, homeostatic maintenance systems. This possibility was approached here... | 10.1038/ncomms6659 | Although proteasome activity declines in somatic tissues during the ageing process, maturating oocytes and gonads maintain their high activity compared to age-matched somatic tissues |
10.1002/ana.20186 | 100,366,799 | Abstract Environmental toxins have been implicated in the etiology of Parkinson's disease. Recent findings of defects in the ubiquitin‐proteasome system in hereditary and sporadic forms of the illness suggest that environmental proteasome inhibitors are candidate PD‐inducing toxins. Here, we systemically injected six d... | 10.1038/ncomms6659 | Proteasome inhibition in rats causes Parkinson’s Disease-like phenotype, establishing a correlation between impaired proteasome inhibition and the onset of the disease |
10.1146/annurev.med.57.110104.115650 | 123,205,208 | Following the demonstration of the nature of the enzymatic defects in the sphingolipid storage disorders in the mid-1960s, consideration was directed to the development of therapy for patients with these conditions. High on the list of possibilities was enzyme supplementation or replacement. Many years of arduous inves... | 10.1038/nature13476 | This review describes the pioneering development of the first ERTs for LSDs. |
10.1146/annurev.biochem.031209.093756 | 58,485,084 | My postdoctoral training in the biosynthesis of plant polysaccharides at the University of California, Berkeley, led me, rather improbably, to study mucopolysaccharide storage disorders in the intramural program of the National Institutes of Health (NIH). I have traced the path from studies of mucopolysaccharide turnov... | 10.1038/nature13476 | This is a review of the pioneering discovery of cross-correction by lysosomal enzymes that formed the basis for ERT. |
10.1126/science.1174447 | 41,720,395 | Master Controller Cellular organelles allow the localized regulation of specialized processes. Under certain conditions, such as increased growth, organelles may be required to alter their function. Coordinated regulation of the gene networks required for mitochondrial and endoplasmic reticulum function has been observ... | 10.1038/nature13476 | This article reports the discovery of the key role that the transcription factor TFEB has in regulating lysosome biogenesis. |
10.1073/pnas.0608791103 | 83,060,960 | Diverse forms of injury and stress evoke a hypertrophic growth response in adult cardiac myocytes, which is characterized by an increase in cell size, enhanced protein synthesis, assembly of sarcomeres, and reactivation of fetal genes, often culminating in heart failure and sudden death. Given the emerging roles of mic... | 10.1038/nature09783 | This important paper describes the dynamic regulation of miRNA expression during cardiac stress. |
10.1101/gad.1942110 | 103,550,341 | The bicistronic microRNA (miRNA) locus miR-144/451 is highly expressed during erythrocyte development, although its physiological roles are poorly understood. We show that miR-144/451 ablation in mice causes mild erythrocyte instability and increased susceptibility to damage after exposure to oxidant drugs. This phenot... | 10.1038/nature09783 | References 65 and 66 show that miR-451 is required for proper erythroid differentiation, and suggest a potential therapeutic application for targeting miR-451 for degradation. |
10.1126/science.1139089 | 20,428,333 | The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of α–myosin heavy chain (αMHC) and up-regulation of βMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (mi... | 10.1038/nature09783 | The first paper to show a role for an miRNA, miR-208a, in the control of cardiac remodelling, using a genetic knockout. |
10.1126/science.1178178 | 62,449,592 | The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. We found that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA)–modified oligonucleot... | 10.1038/nature09783 | The first report of therapeutically targeting an miRNA for the treatment of a disease in non-human primates. |
10.1126/science.1188308 | 125,167,637 | Devil in the Detail Genetically identical cells in the same environment can show variation in gene expression that may cause phenotypic variation at the single-cell level. But how noisy are most genes? Taniguchi et al. (p. 533 ; see the Perspective by Tyagi ) now report single-cell global profiling of both messenger RN... | 10.1038/nature10315 | This article profiles the transcriptome and proteome with single-molecule sensitivity in single cells, and shows that the protein copy-number distribution of most genes can be well fit with gamma distribution. |
10.1126/science.1119623 | 19,598,880 | We directly observed real-time production of single protein molecules in individual Escherichia coli cells. A fusion protein of a fast-maturing yellow fluorescent protein (YFP) and a membrane-targeting peptide was expressed under a repressed condition. The membrane-localized YFP can be detected with single-molecule sen... | 10.1038/nature10315 | This article monitors the real-time production of individual proteins by imaging newly synthesized YFP molecules, demonstrating translational bursts from a repressed promoter. |
10.1126/science.1141967 | 20,684,684 | Transcription factors regulate gene expression through their binding to DNA. In a living Escherichia coli cell, we directly observed specific binding of a lac repressor, labeled with a fluorescent protein, to a chromosomal lac operator. Using single-molecule detection techniques, we measured the kinetics of binding and... | 10.1038/nature10315 | This article probes specific and nonspecific binding of a transcription factor to DNA, and measures the search time for a transcription factor to reach its target site in a living bacterial cell. |
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