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10.1126/science.1100946 | 62,343,595 | To identify previously unknown small molecules that inhibit cell cycle machinery, we performed a chemical genetic screen in Xenopus extracts. One class of inhibitors, termed ubistatins, blocked cell cycle progression by inhibiting cyclin B proteolysis and inhibited degradation of ubiquitinated Sic1 by purified proteaso... | 10.1038/nature07960 | Ubistatins are the first example of small molecules interfering with the recognition of specific ubiquitin chains by ubiquitin receptors. |
10.1126/science.1127119 | 62,561,928 | The mammalian intestine harbors complex societies of beneficial bacteria that are maintained in the lumen with minimal penetration of mucosal surfaces. Microbial colonization of germ-free mice triggers epithelial expression of RegIIIγ, a secreted C-type lectin. RegIIIγ binds intestinal bacteria but lacks the complement... | 10.1038/nature11551 | This study demonstrated that Reg-IIIγ, a C-type lectin produced by Paneth cells in response to the resident microbiota, has microbicidal activity, identifying a new mechanism for sequestration of constituents of the microbiota to the intestinal lumen |
10.1073/pnas.0812681106 | 107,321,141 | A T cell receptor transgenic mouse line reactive to a microbiota flagellin, CBir1, was used to define mechanisms of host microbiota homeostasis. Intestinal IgA, but not serum IgA, was found to block mucosal flagellin uptake and systemic T cell activation in mice. Depletion of CD4 + CD25 + Tregs decreased IgA + B cells,... | 10.1038/nature11551 | References 90 and 91 identify a central role for T reg cells in the induction and maintenance of IgA-producing plasma cells in the intestines, extending the functionality of T reg cells in supporting mutualism to the microbiota |
10.1038/embor.2013.168 | 62,147,214 | In this study, we develop a simple assay to identify mitophagy inducers on the basis of the use of fluorescently tagged mitochondria that undergo a colour change on lysosomal delivery. Using this assay, we identify iron chelators as a family of compounds that generate a strong mitophagy response. Iron chelation‐induced... | 10.1038/nchembio.2287 | A report demonstrating that pharmacologically induced iron depletion activates mitophagy. |
10.1126/science.aaa2397 | 41,774,097 | Fast, continuous, 3D printing Although three-dimensional (3D) printing is now possible using relatively small and low-cost machines, it is still a fairly slow process. This is because 3D printers require a series of steps to cure, replenish, and reposition themselves for each additive cycle. Tumbleston et al. devised a... | 10.1038/nature21003 | This paper details a method for 3D printing of photopolymerizable resins at high speed. |
10.1126/science.aab0129 | 83,353,565 | Making jack jump efficiently In the future, soft-bodied robots may be able to squeeze into tight spaces or work in environments where they could be crushed. However, it is hard to ensure efficient power transmission in a soft-bodied device. One promising solution is to use explosions to drive the robot, using efficient... | 10.1038/nature21003 | This paper highlights the ability to generate graded matrices for soft robots. |
10.1038/ncomms9641 | 125,277,418 | Abstract Discontinuous fibre composites represent a class of materials that are strong, lightweight and have remarkable fracture toughness. These advantages partially explain the abundance and variety of discontinuous fibre composites that have evolved in the natural world. Many natural structures out-perform the conve... | 10.1038/nature21003 | This paper demonstates the power of combining 3D printing with external magnetic fields to produce oriented composite architectures. |
10.1063/1.433153 | 103,800,023 | Using a capillary technique for small samples, the isothermal compressibility κT of water has been measured to −26°C. Accelerating increases of κT at the lower temperatures can be described by an expression of the form κT=Aεγ [where ε= (T−Ts)/Ts], which is known to describe anomalies encountered in the vicinity of a th... | 10.1038/ncomms9998 | This paper presents experimental evidence of a divergence of thermodynamic response functions at a temperature around 228 K in the supercooled regime |
10.1073/pnas.0904743106 | 83,481,929 | Small-angle X-ray scattering (SAXS) is used to demonstrate the presence of density fluctuations in ambient water on a physical length-scale of ≈1 nm; this is retained with decreasing temperature while the magnitude is enhanced. In contrast, the magnitude of fluctuations in a normal liquid, such as CCl 4 , exhibits no e... | 10.1038/ncomms9998 | This paper brings forward both spectroscopic and scattering evidence that water is inhomogeneous in its instantaneous structure at ambient conditions and proposes a unified picture of the ambient and supercooled regimes |
10.1063/1.1724992 | 29,082,930 | Raman frequencies and polarizations and infrared frequencies of water and heavy water have been obtained, and the intermolecular vibrations of water have been related to a five-molecule hydrogen-bonded C2v model consistent with x-ray data. Observed variations of the integrated Raman intensity of the 175-cm—1 hydrogen-b... | 10.1038/ncomms9998 | This paper was the early Raman spectroscopic experimental work on water that generated more than half a century of follow-up studies |
10.1063/1.4902412 | 17,852,002 | Here we present diffraction data that yield the oxygen-oxygen pair distribution function, gOO(r) over the range 254.2–365.9 K. The running O-O coordination number, which represents the integral of the pair distribution function as a function of radial distance, is found to exhibit an isosbestic point at 3.30(5) Å. The ... | 10.1038/ncomms9998 | This paper shows tremendous advances in temperature-dependent X-ray scattering measurements of water where fine details on long-range correlations can be extracted |
10.1073/pnas.0507870102 | 62,231,484 | We investigate, for two water models displaying a liquid–liquid critical point, the relation between changes in dynamic and thermodynamic anomalies arising from the presence of the liquid–liquid critical point. We find a correlation between the dynamic crossover and the locus of specific heat maxima \documentclass[12pt... | 10.1038/ncomms9998 | Here the concept of Widom line is presented as the loci of maxima in the thermodynamic response functions extending from the phase coexistence line into the one-phase region |
10.1073/pnas.1311718110 | 104,352,053 | Significance Water is not only the most important liquid for life on Earth, but also one of the most anomalous liquids. These anomalies become most evident in the supercooled state at subzero temperatures. We show from dielectric and calorimetric studies that water in the deeply supercooled regime, below –120 °C, can e... | 10.1038/ncomms9998 | This paper demonstrates that there is a 2nd glass transition which could be evidence of two liquid phases in the regime close to the temperature where the amorphous phases are metastable |
10.1126/science.1232994 | 38,196,576 | Splitting Singlets Solar cell efficiency is limited because light at wavelengths shorter than the cell's absorption threshold does not channel any of its excess energy into the generated electricity. Congreve et al. (p. 334 ) have developed a method to harvest the excess energy in carbon-based absorbers through a proce... | 10.1038/natrevmats.2017.63 | This study presents the first demonstration of an SF-enhanced PV device with an EQE above 100%. |
10.1126/science.1213986 | 123,030,798 | Photoelectron detection reveals a previously elusive, short-lived paired carrier state of interest in solar light harvesting. | 10.1038/natrevmats.2017.63 | This study presents the observation of ultrafast TT formation with time-resolved photoelectron spectroscopy. |
10.1073/pnas.1204922109 | 83,495,195 | More than 2 y have passed since the BP– Deepwater Horizon oil spill in the Gulf of Mexico, yet we still have little understanding of its ecological impacts. Examining effects of this oil spill will generate much-needed insight into how shoreline habitats and the valuable ecological services they provide (e.g., shorelin... | 10.1038/nature12856 | This article reports that vegetation mortality associated with oiling triggered rapid marsh edge erosion, and emphasizes the importance of vegetation health on marsh stability. |
10.1126/science.1150349 | 29,128,589 | A common assumption is that ecosystem services respond linearly to changes in habitat size. This assumption leads frequently to an “all or none” choice of either preserving coastal habitats or converting them to human use. However, our survey of wave attenuation data from field studies of mangroves, salt marshes, seagr... | 10.1038/nature12856 | This article proposes that maximal economic value of mangrove forests can accommodate competing land uses. |
10.5194/cp-9-191-2013 | 41,007,833 | Abstract. Climate and environments of the mid-Pliocene warm period (3.264 to 3.025 Ma) have been extensively studied. Whilst numerical models have shed light on the nature of climate at the time, uncertainties in their predictions have not been systematically examined. The Pliocene Model Intercomparison Project quantif... | 10.1038/ncomms10646 | Summary of the outcomes from the first co-ordinated model intercomparison project for the Pliocene |
10.1029/2004pa001071 | 20,795,781 | We present a 5.3‐Myr stack (the “LR04” stack) of benthic δ 18 O records from 57 globally distributed sites aligned by an automated graphic correlation algorithm. This is the first benthic δ 18 O stack composed of more than three records to extend beyond 850 ka, and we use its improved signal quality to identify 24 new ... | 10.1038/ncomms10646 | Seminal contribution providing a chronologic framework within which Pliocene palaeoceanographic sequences could be compared |
10.1126/science.1112596 | 29,322,925 | During the warm early Pliocene (∼4.5 to 3.0 million years ago), the most recent interval with a climate warmer than today, the eastern Pacific thermocline was deep and the average west-to-east sea surface temperature difference across the equatorial Pacific was only 1.5 ± 0.9°C, much like it is during a modern El Niño... | 10.1038/ncomms10646 | Established the concept of permanent El Niño conditions during the Pliocene |
10.1126/science.1233137 | 20,554,849 | From Russia with Lovely Data Climate and the atmospheric concentration of CO 2 are closely linked. Brigham-Grette et al. (p. 1421 , published online 9 May) present data from Lake El'gygytgyn, in northeast Arctic Russia, that shows how climate varied between 3.6 and 2.2 million years ago, an important interval in the gl... | 10.1038/ncomms10646 | A unique high resolution record of Pliocene-Pleistocene terrestrial palaeoclimate conditions |
10.5194/cp-9-1495-2013 | 16,860,097 | Abstract. In the Pliocene Model Intercomparison Project (PlioMIP), eight state-of-the-art coupled climate models have simulated the mid-Pliocene warm period (mPWP, 3.264 to 3.025 Ma). Here, we compare the Atlantic Meridional Overturning Circulation (AMOC), northward ocean heat transport and ocean stratification simulat... | 10.1038/ncomms10646 | Multi-model assessment of ocean and thermohaline circulation behaviour during the mid-Pliocene |
10.1073/pnas.1006402107 | 20,370,264 | Catalysis by neutral, organic, small molecules capable of binding and activating substrates solely via noncovalent interactions—particularly H-bonding—has emerged as an important approach in organocatalysis. The mechanisms by which such small molecule catalysts induce high enantioselectivity may be quite different from... | 10.1038/nature21701 | Thought-provoking discussion of the rational implementation of attractive NCIs in asymmetric catalysis. |
10.1002/anie.201503476 | 104,384,359 | Abstract London dispersion, which constitutes the attractive part of the famous van der Waals potential, has long been underappreciated in molecular chemistry as an important element of structural stability, and thus affects chemical reactivity and catalysis. This negligence is due to the common notion that dispersion ... | 10.1038/nature21701 | Intriguing discussion of various manifestations of London dispersion forces in molecular interactions. |
10.1073/pnas.95.21.12088 | 41,452,526 | The nicotinic acetylcholine receptor is the prototype ligand-gated ion channel. A number of aromatic amino acids have been identified as contributing to the agonist binding site, suggesting that cation–π interactions may be involved in binding the quaternary ammonium group of the agonist, acetylcholine. Here we show a ... | 10.1038/nature21701 | Classic physical organic study demonstrating relevance of cation interactions in biological systems. |
10.1126/science.1169494 | 20,871,148 | We report a strategy to create photodegradable poly(ethylene glycol)–based hydrogels through rapid polymerization of cytocompatible macromers for remote manipulation of gel properties in situ. Postgelation control of the gel properties was demonstrated to introduce temporal changes, creation of arbitrarily shaped featu... | 10.1038/ncomms2271 | Photodegradable hydrogels enabled real-time, "user-defined" manipulation of material properties and, in turn, chondrogenic differentiation of stem cells |
10.1210/en.2010-0890 | 20,693,328 | Abstract The brain has emerged as a target for the insulin-sensitizing effects of several hormonal and nutrient-related signals. The current studies were undertaken to investigate mechanisms whereby leptin lowers circulating blood glucose levels independently of insulin. After extending previous evidence that leptin in... | 10.1038/nature12709 | Hyperglycaemia was normalized by direct infusion of leptin into the brain of rats with uncontrolled, insulin-deficient diabetes, establishing the inherent capacity of the brain to maintain glucose homeostasis without the need for insulin. |
10.1126/science.1099955 | 19,079,482 | For vision, insect and vertebrate eyes use rhabdomeric and ciliary photoreceptor cells, respectively. These cells show distinct architecture and transduce the light signal by different phototransductory cascades. In the marine rag-worm Platynereis , we find both cell types: rhabdomeric photoreceptor cells in the eyes a... | 10.1038/nature07891 | By showing that polychaetes have a 'vertebrate-type' opsin in their brains, this paper reveals how divergent eyes of bilaterians could have evolved from a common ancestor. |
10.1029/pa005i001p00001 | 104,402,893 | Several explanations for the 200 to 280 ppm glacial/interglacial change in atmospheric CO 2 concentrations deal with variations in southern ocean phytoplankton productivity and the related use or nonuse of major plant nutrients. An hypothesis is presented herein in which arguments are made that new productivity in toda... | 10.1038/nature21058 | This paper presented the iron hypothesis—that past variations in atmospheric carbon dioxide were driven by greater iron supply to the Southern Ocean. |
10.1002/2015gb005289 | 103,733,883 | Abstract Numerical models of ocean biogeochemistry are relied upon to make projections about the impact of climate change on marine resources and test hypotheses regarding the drivers of past changes in climate and ecosystems. In large areas of the ocean, iron availability regulates the functioning of marine ecosystems... | 10.1038/nature21058 | This paper was the first to critically appraise how well a range of state-of-the-art ocean models represented the ocean iron cycle. |
10.1146/annurev-marine-121211-172322 | 62,296,056 | Trace metals are required for numerous processes in phytoplankton and can influence the growth and structure of natural phytoplankton communities. The metal contents of phytoplankton reflect biochemical demands as well as environmental availability and influence the distribution of metals in the ocean. Metal quotas of ... | 10.1038/nature21058 | This paper provides a state-of-the-art summary of the iron content of marine phytoplankton determined using a variety of different techniques. |
10.1126/science.1256450 | 83,015,511 | Protein markers of cyanobacterial stress Nutrients including iron, nitrogen, and phosphorus limit primary productivity in the oceans. Determining how abundant cyanobacteria such as Prochlorococcus adapt to nutrient stress across marine settings requires accurate molecular assays. Saito et al. developed a proteomic and ... | 10.1038/nature21058 | This paper was the first to link data on resource stress from proteomic to field measurements of resource concentrations to demonstrate the transitions between iron and nitrogen limitation in the Pacific Ocean |
10.1126/science.1157996 | 83,550,319 | We measured the elastic properties and intrinsic breaking strength of free-standing monolayer graphene membranes by nanoindentation in an atomic force microscope. The force-displacement behavior is interpreted within a framework of nonlinear elastic stress-strain response, and yields second- and third-order elastic sti... | 10.1038/ncomms6678 | A report on the outstanding strength of graphene, a requirement for advanced flexible devices |
10.1126/science.1184014 | 82,962,800 | Heat Flow in Graphene Unsupported graphene sheets show exceptional thermal transport properties, but are these properties maintained when a graphene sheet is in contact with a substrate? Seol et al. (p. 213 ; see the Perspective by Prasher ) measured the thermal conductivity of graphene supported on silicon dioxide and... | 10.1038/ncomms6678 | A report on the outstanding thermal conductivity of graphene, a property useful for thermal management on soft substrates |
10.1126/science.1171245 | 20,674,691 | Growing Graphene The highest quality graphene samples, single-atom-thick layers of carbon, are suspended flakes exfoliated from graphite, but these samples are very small in size (square micrometers). For many electronics applications, larger areas are needed. Li et al. (p. 1312 , published online 7 May) show that grap... | 10.1038/ncomms6678 | A scientific breakthrough demonstrating the growth of large-area monolayer graphene |
10.1073/pnas.0807698106 | 41,270,633 | We demonstrate mass-producible, tetherless microgrippers that can be remotely triggered by temperature and chemicals under biologically relevant conditions. The microgrippers use a self-contained actuation response, obviating the need for external tethers in operation. The grippers can be actuated en masse, even while ... | 10.1038/natrevmats.2017.19 | This paper demonstrates a folding-based method to create 3D microgrippers for biomedical applications. |
10.1126/science.1168375 | 62,219,272 | Flexible, stretchable, and spanning microelectrodes that carry signals from one circuit element to another are needed for many emerging forms of electronic and optoelectronic devices. We have patterned silver microelectrodes by omnidirectional printing of concentrated nanoparticle inks in both uniform and high–aspect r... | 10.1038/natrevmats.2017.19 | This paper introduces a method of nozzle-based 3D printing with conductive inks and presents some examples in free-standing electrical interconnects. |
10.1126/science.1260960 | 125,170,119 | Popping materials and devices from 2D into 3D Curved, thin, flexible complex three-dimensional (3D) structures can be very hard to manufacture at small length scales. Xu et al. develop an ingenious design strategy for the microfabrication of complex geometric 3D mesostructures that derive from the out-of-plane buckling... | 10.1038/natrevmats.2017.19 | This paper introduces a mechanical assembly approach that allows formation of complex 3D mesostructures from 2D precursors by controlled buckling processes. |
10.1126/science.aaa2397 | 41,774,097 | Fast, continuous, 3D printing Although three-dimensional (3D) printing is now possible using relatively small and low-cost machines, it is still a fairly slow process. This is because 3D printers require a series of steps to cure, replenish, and reposition themselves for each additive cycle. Tumbleston et al. devised a... | 10.1038/natrevmats.2017.19 | This paper introduces continuous liquid interface production techniques for high speed, 3D printing of photopolymerizable resins. |
10.1073/pnas.1515602112 | 62,628,732 | Assembly of 3D micro/nanostructures in advanced functional materials has important implications across broad areas of technology. Existing approaches are compatible, however, only with narrow classes of materials and/or 3D geometries. This paper introduces ideas for a form of Kirigami that allows precise, mechanically ... | 10.1038/natrevmats.2017.19 | This paper describes kirigami-inspired concepts for the mechanically guided assembly of 3D mesostructures from 2D membrane precursors. |
10.1126/scitranslmed.aaf7704 | 62,650,198 | A new, mechanically elastic biomaterial can be custom 3D-printed, is surgically friendly, and promotes robust bone regeneration. | 10.1038/natrevmats.2017.19 | This paper describes classes of synthetic osteoregenerative biomaterials for 3D bioprinting of versatile, hyperelastic ‘bone’ constructs. |
10.1126/science.1215309 | 125,262,538 | Smooth Operator When thin sheets are compressed they can buckle and wrinkle, such as when the edges of a sheet of paper, or two areas of skin, are pushed together. Variations in local thickness and stiffness will alter the buckling patterns, but controlling this in a simple and predictable way is difficult. Kim et al. ... | 10.1038/natrevmats.2017.19 | This paper describes a method of halftone gel lithography to create spatially varying 2D patterns of swelling in gel sheets for transformation into desired 3D shapes. |
10.1002/2013jc009693 | 19,444,370 | Abstract The mean structure and variability of the currents east of Mindanao are investigated through 2 year mooring observations at about 8°N, 127°3'E from December 2010 to December 2012. The strong southward Mindanao Current (MC) exists in the upper 600 m with a maximum mean velocity of 73 cm/s and a standard deviati... | 10.1038/nature14504 | Confirms the existence of the Mindanao Undercurrent and reveals its strong 60–80-day variability using observations spanning two years. |
10.1029/2012gl052575 | 104,381,324 | Thermocline waters of the tropical southwest Pacific can be traced back to the center of the South Pacific basin and have a potential influence on equatorial surface conditions and on the characteristics of the El Niño Southern Oscillation on decadal timescales. The Solomon Sea is traversed by this influential flow, an... | 10.1038/nature14504 | A hydrographic survey across the southern Solomon Sea allows a complete estimate of the NGCU transports down to 2,000 m, as well as counter currents, inflows and outflows between the Solomon and Coral Seas. |
10.1175/2010jpo4462.1 | 61,648,772 | Abstract Satellite altimeter sea surface height (SSH) data from the past 17 yr are used to investigate the interannual-to-decadal changes in the bifurcation of the North Equatorial Current (NEC) along the Philippine coast. The NEC bifurcation latitude migrated quasi decadally between 10° and 15°N with northerly bifurca... | 10.1038/nature14504 | Shows a decadal modulation in the characteristics of the NEC bifurcation, which is determined by wind forcing in the 12°–14° N band that contains variability not fully representable by the Niño-3.4 index. |
10.3189/172756406781812005 | 98,106,670 | Abstract Glaciers in China are primarily located in the Tibetan Plateau (TP) and surrounding high mountains. The Chinese Glacier Inventory indicates that there are 46 377 glaciers in western China. Meteorological records indicate that air temperature in western China has risen by 0.2˚C per decade since 1951, and 1998 w... | 10.1038/nature09364 | Most of the glaciers in western China are in a state of retreat. |
10.1111/j.1574-0862.2009.00379.x | 103,898,838 | Abstract This article examines how expected changes in climate are likely to affect agriculture in China. The effects of temperature and precipitation on net crop revenues are analyzed using cross‐sectional data consisting of both rainfed and irrigated farms. Based on survey data from 8,405 households across 28 provinc... | 10.1038/nature09364 | Global warming is likely to be harmful to rainfed farms but beneficial to irrigated farms. |
10.1073/pnas.0608537103 | 81,301,509 | Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM and that insulin resistance is strongly associated with ... | 10.1038/nature13478 | This study reported ethnic differences in the prevalence of NAFLD and insulin resistance. |
10.1073/pnas.1113359108 | 104,157,667 | Insulin resistance is associated with nonalcoholic fatty liver disease (NAFLD) and is a major factor in the pathogenesis of type 2 diabetes. The development of hepatic insulin resistance has been ascribed to multiple causes, including inflammation, endoplasmic reticulum (ER) stress, and accumulation of hepatocellular l... | 10.1038/nature13478 | This paper reports that intracellular diacylglycerol, associated with PKCε activation, is the strongest predictor of insulin resistance in obese patients. |
10.1073/pnas.121164498 | 42,652,883 | Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to alterations in fat metabolism. Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied ... | 10.1038/nature13478 | This paper reports that overexpression of LpL in liver resulted in liver-specific triglyceride accumulation and liver-specific insulin resistance, whereas muscle-specific overexpression of LpL resulted in muscle-specific triglyceride accumulation and muscle-specific insulin resistance. |
10.1073/pnas.0705408104 | 124,914,690 | We examined the hypothesis that insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidemia, associated with the metabolic syndrome, by altering the distribution pattern of postprandial energy storage. Following ingestion of two high carbohydrate mixed meals, net muscle glycogen synthesis... | 10.1038/nature13478 | In this paper the authors demonstrate that selective insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidaemia and NAFLD. |
10.1073/pnas.1205675109 | 99,009,017 | To examine the role of intramyocellular lipid (IMCL) accumulation as well as circulating cytokines, branched-chain amino acids and acylcarnitines in the pathogenesis of muscle insulin resistance in healthy, young, lean insulin-resistant offspring of parents with type 2 diabetes (IR offspring), we measured these factors... | 10.1038/nature13478 | This study provides evidence that skeletal muscle insulin resistance in young lean insulin-resistant offspring of parents with type 2 diabetes can be attributed to increased intramyocellular lipid content. |
10.1073/pnas.1110105108 | 20,618,007 | Skeletal muscle insulin resistance has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and atherogenic dyslipidemia associated with the metabolic syndrome by altering the distribution pattern of postprandial energy storage. We conducted a study to examine this hypothesis by reversing mus... | 10.1038/nature13478 | The authors of this paper demonstrate that reversal of muscle insulin resistance in healthy young lean insulin-resistant individuals with a single 45 minute bout of elliptical exercise reversed the abnormal pattern of energy distribution of energy storage following carbohydrate ingestion, thus offering strong evidence ... |
10.1073/pnas.1219456110 | 16,900,929 | Comparative gene identification 58 (CGI-58) is a lipid droplet-associated protein that promotes the hydrolysis of triglyceride by activating adipose triglyceride lipase. Loss-of-function mutations in CGI-58 in humans lead to Chanarin–Dorfman syndrome, a condition in which triglyceride accumulates in various tissues, in... | 10.1038/nature13478 | The authors of this study demonstrate the importance of compartmentation of DAG in modulating hepatic insulin resistance. |
10.2337/diabetes.54.3.603 | 101,920,647 | To examine the mechanism by which moderate weight reduction improves basal and insulin-stimulated rates of glucose metabolism in patients with type 2 diabetes, we used 1H magnetic resonance spectroscopy to assess intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) content in conjunction with hyperinsulinemic-eug... | 10.1038/nature13478 | This study demonstrates that moderate (<10%) body weight reduction in obese patients with type 2 diabetes eating a 1,200 calorie hypocaloric diet corrected fasting plasma glucose concentrations, normalized rates of hepatic glucose reversed NAFLD and reversed hepatic insulin resistance independent of changes in circulat... |
10.2337/diabetes.51.3.797 | 123,455,442 | We examined the effect of three months of rosiglitazone treatment (4 mg b.i.d.) on whole-body insulin sensitivity and in vivo peripheral adipocyte insulin sensitivity as assessed by glycerol release in microdialysis from subcutaneous fat during a two-step (20 and 120 mU · m−2 · min−1) hyperinsulinemic-euglycemic clamp ... | 10.1038/nature13478 | This study demonstrated that thiazolidinediones improve insulin sensitivity in patients with type 2 diabetes be decreasing hepatic steatosis and promoting a redistribution of fat to the subcutaneous fat compartment. |
10.1073/pnas.0308177101 | 61,488,308 | Pyrroloindoline and bispyrroloindoline are a subclass of alkaloid structural motifs that commonly exhibit biological activity. An enantioselective organocatalytic approach to the synthesis of pyrroloindoline architecture is described. The addition–cyclization of tryptamines with α,β-unsaturated aldehydes in the presenc... | 10.1038/nature07370 | This paper describes the use of imidazolidinone catalysts for enantioselective Friedel–Crafts reactions with indole nucleophiles for the synthesis of the potassium-channel blocker flustramine B. |
10.1126/science.7367871 | 38,958,122 | Live chimeras between two species of mouse, Mus musculus and Mus caroli , were produced by blastocyst injection. These chimeras were entirely similar to M. musculus ↔ M. musculus chimeras in their somatic tissue organization. This is the first report of completely normal development of interspecific chimeras in mammals... | 10.1038/nature20573 | A pioneering study reporting the first viable interspecies chimaeras generated by injection of M. caroli ICMs into M. musculus blastocysts |
10.1073/pnas.1004584107 | 20,335,266 | Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of c... | 10.1038/nature20573 | A pioneering study demonstrating that a naive human pluripotent state, resembling that of mouse ES cells, could be stabilized in culture |
10.1073/pnas.0610328104 | 103,702,142 | The 1987 Montreal Protocol on Substances that Deplete the Ozone Layer is a landmark agreement that has successfully reduced the global production, consumption, and emissions of ozone-depleting substances (ODSs). ODSs are also greenhouse gases that contribute to the radiative forcing of climate change. Using historical ... | 10.1038/nature10322 | This paper quantified the GWP-weighted reductions in emissions of ozone-depleting substances and was the first to point out the significant climate benefits achieved by the Montreal protocol in relation to those expected from the Kyoto Protocol. |
10.5194/acp-8-389-2008 | 19,317,631 | Abstract. The relationship, on a global basis, between the amount of N fixed by chemical, biological or atmospheric processes entering the terrestrial biosphere, and the total emission of nitrous oxide (N2O), has been re-examined, using known global atmospheric removal rates and concentration growth of N2O as a proxy f... | 10.1038/nature10322 | This paper proposed that the use of fertilizer to grow certain crops for biofuel could result in N 2 O emissions sufficient to offset the avoided CO 2 from fossil fuel combustion. |
10.1126/science.1150369 | 41,714,939 | Increasing quantities of atmospheric anthropogenic fixed nitrogen entering the open ocean could account for up to about a third of the ocean's external (nonrecycled) nitrogen supply and up to â¼3% of the annual new marine biological production, â¼0.3 petagram of carbon per year. This input could account for the produ... | 10.1038/nature10322 | This paper provides a semi-quantitative synthesis of the influence atmospheric anthropogenic nitrogen has on the balance of GHG exchange in the open ocean. |
10.1073/pnas.1006282107 | 42,535,307 | Emissions of a broad range of greenhouse gases of varying lifetimes contribute to global climate change. Carbon dioxide displays exceptional persistence that renders its warming nearly irreversible for more than 1,000 y. Here we show that the warming due to non-CO 2 greenhouse gases, although not irreversible, persists... | 10.1038/nature10322 | This paper points out how the warming associated with a pulsed GHG emission persists longer than the emission lifetime owing to timescales associated with the movement of heat throughout the climate system, particularly into and out of the ocean. |
10.1073/pnas.170278997 | 40,217,787 | A common view is that the current global warming rate will continue or accelerate. But we argue that rapid warming in recent decades has been driven mainly by non-CO 2 greenhouse gases (GHGs), such as chlorofluorocarbons, CH 4 , and N 2 O, not by the products of fossil fuel burning, CO 2 and aerosols, the positive and ... | 10.1038/nature10322 | This paper was one of the first to point out that reductions in non-CO 2 GHG emissions could reduce the rate of global warming during the next half-century and lessen the potential for drastic climate change. |
10.1073/pnas.1006463107 | 45,573,548 | Stimulation of terrestrial plant production by rising CO 2 concentration is projected to reduce the airborne fraction of anthropogenic CO 2 emissions. Coupled climate–carbon cycle models are sensitive to this negative feedback on atmospheric CO 2 , but model projections are uncertain because of the expectation that fee... | 10.1038/nature10322 | Much is being learned about how the biosphere will respond to enhanced CO 2 concentrations, and this study, in summarizing results from over a decade of exposing a forest to enhanced CO 2 concentrations, shows how nitrogen limitations limit long-term CO 2 fertilization effects even in the eastern United States. |
10.1073/pnas.0509541102 | 62,439,491 | Activating the immune system to trigger a specific response is a major challenge in vaccine development. In particular, activating sufficient cytotoxic T lymphocyte-mediated cellular immunity, which is crucial for the treatment of many diseases including cancer and AIDS, has proven to be especially challenging. In this... | 10.1038/nature08604 | In this paper, ketal-crosslinked acid-sensitive nanoparticles are functionalized with anti-DEC205 antibodies, providing multiple levels of nanoparticle functionality. |
10.1073/pnas.0509404103 | 41,090,899 | T cells are activated by recognition of foreign peptides displayed on the surface of antigen presenting cells (APCs), an event that triggers assembly of a complex microscale structure at the T cell–APC interface known as the immunological synapse (IS). It remains unresolved whether the unique physical structure of the ... | 10.1038/nature08604 | In this paper, surface patterning methods are used to demonstrate the importance of ultrastructural organization of the interface between a T cell and a dendritic cell. |
10.1126/science.1060331 | 103,786,601 | Intracellular zinc is thought to be available in a cytosolic pool of free or loosely bound Zn(II) ions in the micromolar to picomolar range. To test this, we determined the mechanism of zinc sensors that control metal uptake or export in Escherichia coli and calibrated their response against the thermodynamically defin... | 10.1038/nature08300 | In this paper, the tight zinc affinities of two zinc sensors, ZntR and Zur, are estimated and used to infer a low concentration of available zinc in the bacterial cytoplasm. |
10.1073/pnas.0600928103 | 27,595,707 | We have generated probes of metal binding to zinc fingers (ZFs) that provide tools to study zinc trafficking in vivo . In this study, we used these probes to examine zinc binding by the Zap1 transcription factor of Saccharomyces cerevisiae . Zap1 contains two zinc-regulated activation domains (ADs), AD1 and AD2. AD2 is... | 10.1038/nature08300 | In this paper, by exploiting constructs in which zinc occupancy of two of Zap1's zinc-fingers is coupled to energy transfer between fluorescent reporters, Zap1 is inferred to detect zinc directly through metal binding in vivo |
10.1146/annurev.biophys.37.032807.125811 | 84,345,042 | This review highlights insights gained from computational studies on protein-metal recognition. We systematically dissect the various factors governing metal binding affinity and selectivity in proteins starting from (a) the intrinsic properties of the metal and neighboring metal cations (if present), to (b) the primar... | 10.1038/nature08300 | From computational studies, it is inferred that in the absence of metallochaperones the specificity of a metal for a set of ligands in a protein depends mainly on the metal's abundance in the locality. |
10.1126/science.1070925 | 40,426,507 | Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein. In humans, SPP activity is required to generate signal sequence–derived human lymphocyte antigen–E epitopes that are recognized by the immune system, and to process hepatitis C viru... | 10.1038/nature08146 | Human SPP was isolated by affinity purification and the protein identified in this paper |
10.1126/science.1150755 | 104,091,102 | Regulated intramembrane proteolysis by members of the site-2 protease (S2P) family is an important signaling mechanism conserved from bacteria to humans. Here we report the crystal structure of the transmembrane core domain of an S2P metalloprotease from Methanocaldococcus jannaschii . The protease consists of six tran... | 10.1038/nature08146 | This paper reports the first crystal structure of a metalloprotease |
10.1073/pnas.0609773104 | 21,894,313 | Intramembrane proteases catalyze peptide bond cleavage of integral membrane protein substrates. This activity is crucial for many biological and pathological processes. Rhomboids are evolutionarily widespread intramembrane serine proteases. Here, we present the 2.3-Å-resolution crystal structure of a rhomboid from Esch... | 10.1038/nature08146 | This paper describes the crystal structure of GlpG in two different conformations |
10.1073/pnas.0810647105 | 20,033,815 | The origin of the eukaryotic genetic apparatus is thought to be central to understanding the evolution of the eukaryotic cell. Disagreement about the source of the relevant genes has spawned competing hypotheses for the origins of the eukaryote nuclear lineage. The iconic rooted 3-domains tree of life shows eukaryotes ... | 10.1038/nature09486 | An important contribution, using a state of the art phylogenetic repertoire, to show that the host that acquired the mitochondrion was an archaebacterium (a prokaryote). |
10.1098/rstb.2002.1191 | 102,550,549 | Mitochondria and chloroplasts are energy-transducing organelles of the cytoplasm of eukaryotic cells. They originated as bacterial symbionts whose host cells acquired respiration from the precursor of the mitochondrion, and oxygenic photosynthesis from the precursor of the chloroplast. The host cells also acquired gene... | 10.1038/nature09486 | Presents compelling bioenergetic reasons, necessary and sufficient, to account for the retention of genes involved in membrane-associated electron transport in mitochondria (and chloroplasts). |
10.1182/blood-2010-04-281931 | 4,804,973 | Abstract Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen r... | 10.1038/nature22395 | First report of a clinical response to CD19 CAR therapy in non-Hodgkin lymphoma. |
10.1126/scitranslmed.3002842 | 104,325,590 | Adoptively transferred gene-modified T cells expand in vivo, eliminate leukemic cells, and form functional memory cells in patients. | 10.1038/nature22395 | First report of clinical response to CD19 in CAR therapy in chronic lymphocytic leukaemia. |
10.1126/scitranslmed.3005930 | 125,148,850 | Five adults with chemotherapy-refractory B-ALL were induced into molecular remissions after treatment with CD19 CAR-targeted T cells. | 10.1038/nature22395 | First report of clinical responses to CD19 CAR therapy in acute lymphoblastic leukaemia. |
10.1126/scitranslmed.aaj2013 | 45,559,873 | Universal gene-edited CAR19 T cells eliminate infant leukemia. | 10.1038/nature22395 | Talen-mediated TCR deletion enables CD19 CAR therapy with donor T cells in allogeneic recipients. |
10.1126/science.aaf6756 | 20,628,129 | Engineering T cells to treat autoimmunity Autoimmune diseases such as lupus and rheumatoid arthritis lack therapies that specifically target only the disease-causing cells. Inspired by the clinical success of using chimeric antigen receptor T cells to treat certain types of cancers, Ellebrecht et al. asked whether a si... | 10.1038/nature22395 | CAR T cells can treat autoimmunity in a murine model of pemphigus vulgaris. |
10.1002/anie.201604802 | 20,745,595 | Abstract A new strategy for achieving stable Co single atoms (SAs) on nitrogen‐doped porous carbon with high metal loading over 4 wt % is reported. The strategy is based on a pyrolysis process of predesigned bimetallic Zn/Co metal–organic frameworks, during which Co can be reduced by carbonization of the organic linker... | 10.1038/natrevmats.2017.75 | A work describing in situ-formed single atoms stabilized on nitrogen-doped porous carbon, which suggests the possibility of the tailorability of MOF-templated nanostructures at the atomic level. |
10.1073/pnas.1218705110 | 83,404,678 | Intracellular delivery of macromolecules is a challenge in research and therapeutic applications. Existing vector-based and physical methods have limitations, including their reliance on exogenous materials or electrical fields, which can lead to toxicity or off-target effects. We describe a microfluidic approach to de... | 10.1038/nature19764 | In this paper, rapid mechanical deformation of cells through microfluidic constrictions was shown to achieve efficient intracellular delivery of a wide range of molecular cargo. |
10.1126/science.7904084 | 79,438,603 | After injury to the cell membrane, rapid resealing of the membrane occurs with little loss of intracellular contents. This process has been studied by measurement of the rate of dye loss after membrane puncture in both the sea urchin embryo and 3T3 fibroblasts. Resealing of disrupted cell membranes requires external ca... | 10.1038/nature19764 | This groundbreaking paper alerted the research community to the active and responsive nature of cell plasma membrane repair, which was previously attributed to passive resealing. |
10.1073/pnas.0909350107 | 59,380,435 | A generalized platform for introducing a diverse range of biomolecules into living cells in high-throughput could transform how complex cellular processes are probed and analyzed. Here, we demonstrate spatially localized, efficient, and universal delivery of biomolecules into immortalized and primary mammalian cells us... | 10.1038/nature19764 | This study expanded the use of nanoneedles for co-delivery of diverse biomolecules. |
10.1073/pnas.84.23.8463 | 28,035,675 | Scrape loading and sonication loading are two recently described methods of introducing macromolecules into living cells. We have tested the efficacy of these methods for transfection of mammalian cells with exogenous DNA, using selection systems based either on resistance to the drug G418 (Geneticin) or on acquisition... | 10.1038/nature19764 | This pioneering paper demonstrated DNA transfection of mammalian cells by ultrasound. |
10.1126/science.1198469 | 83,477,215 | Bacteria of the genus Clostridium promote the induction of suppressor T cells in the colons of mice. | 10.1038/nature10208 | This paper describes a link between Clostridium spp. and T reg cells in the gut and, together with references 47 and 48, provides compelling evidence that colonization with distinct commensal bacteria results in the accumulation of different effector T cells in the intestine. |
10.1126/science.1156725 | 19,612,981 | Chromosomal rearrangements that create gene fusions are common features of human tumors. The prevailing view is that the resultant chimeric transcripts and proteins are abnormal, tumor-specific products that provide tumor cells with a growth and/or survival advantage. We show that normal endometrial stromal cells conta... | 10.1038/nature08452 | This paper identifies chimaeric RNA and protein from JAZF1 and JJAZ1 genes in normal and transformed endometrial cells. |
10.1101/gr.5660607 | 40,504,781 | This report presents systematic empirical annotation of transcript products from 399 annotated protein-coding loci across the 1% of the human genome targeted by the Encyclopedia of DNA elements (ENCODE) pilot project using a combination of 5′ rapid amplification of cDNA ends (RACE) and high-density resolution tiling ar... | 10.1038/nature08452 | This paper identifies and characterizes chimaeric RNAs in normal tissue and transformed cell lines mapping in the 1% of the human genome analysed by the ENCODE studies. |
10.1002/adma.200290020 | 103,776,396 | Abstract Super‐hydrophobic surfaces, with a water contact angle (CA) greater than 150°, have attracted much interest for both fundamental research and practical applications. Recent studies on lotus and rice leaves reveal that a super‐hydrophobic surface with both a large CA and small sliding angle (α) needs the cooper... | 10.1038/natrevmats.2017.36 | The first paper to illustrate that the micro- or nanohierarchical structure is key to the lotus effect. |
10.1002/adma.200501961 | 83,388,269 | Abstract Recent achievements in the construction of surfaces with special wettabilities, such as superhydrophobicity, superhydrophilicity, superoleophobicity, superoleophilicity, superamphiphilicity, superamphiphobicity, superhydrophobicity/superoleophilicity, and reversible switching between superhydrophobicity and su... | 10.1038/natrevmats.2017.36 | Four superwetting and antiwetting states in air systems were developed. |
10.1002/anie.201506866 | 104,098,475 | Abstract Oil/water separation membranes with different wettability towards water are attractive for their economic efficiency and convenience. The key factor for the separation process is the roughness‐enhanced wettability of membranes based on the intrinsic wetting threshold (IWT) of water, that is, the limitation of ... | 10.1038/natrevmats.2017.36 | The design of superlyophobic and superlyophilic surfaces based on intrinsic wetting thresholds for liquids was proposed. |
10.1115/1.2910737 | 59,888,854 | Pool boiling of saturated water at 1 atm pressure has been investigated. In the experiments, copper surfaces prepared by following a well-defined procedure were used. The cumulative number density of the cavities and their shapes were determined with an optical microscope. The surface had a mirror finish and had a surf... | 10.1038/natrevmats.2016.92 | This boiling study investigates how the intrinsic contact angle of a smooth surface affects nucleation, HTC and CHF. |
10.1063/1.3200951 | 83,389,214 | Heterogeneous nucleation of water plays an important role in a wide range of natural and industrial processes. Though heterogeneous nucleation of water is ubiquitous and an everyday experience, spatial control of this important phenomenon is extremely difficult. Here we show for the first time that spatial control in t... | 10.1038/natrevmats.2016.92 | This condensation study is the first to demonstrate spatial control of the nucleation of water. |
10.1038/srep13145 | 39,447,682 | Abstract We report the counterintuitive mechanism of increasing boiling heat transfer by incorporating low-conductivity materials at the interface between the surface and fluid. By embedding an array of non-conductive lines into a high-conductivity substrate, in-plane variations in the local surface temperature are cre... | 10.1038/natrevmats.2016.92 | This boiling study demonstrates the high CHF and high HTC behaviour of biconductive surfaces. |
10.1243/09576500260049034 | 104,388,619 | The paper reviews progress in dropwise condensation research from 1930 to the present. Particular attention is given to heat transfer measurements, theory, transition and effects of surface material. Although it has been known since the 1930s that heat transfer coefficients for dropwise condensation of steam are much h... | 10.1038/natrevmats.2016.92 | This is a comprehensive review of dropwise condensation research since 1930. |
10.1126/science.aac4255 | 20,795,570 | Gut microbes affect immunotherapy The unleashing of antitumor T cell responses has ushered in a new era of cancer treatment. Although these therapies can cause dramatic tumor regressions in some patients, many patients inexplicably see no benefit. Mice have been used in two studies to investigate what might be happenin... | 10.1038/nature18848 | Together with refs 125 and 126, this study shows that a subset of the microbiota can have an effect on the efficacy of cancer therapy. |
10.1126/scitranslmed.aaa4877 | 62,059,808 | Gut bacterial strains targeted by IgA in undernourished Malawian children produce severe enteropathy in gnotobiotic mice and correlate with health status. | 10.1038/nature18848 | Together with refs 7 and 8, this study shows that IgA-SEQ is a powerful technique for identifying taxa that provide a strong stimulus to the host's immune system. |
10.1126/science.1241165 | 62,606,488 | Protecting the Guts Regulatory T cells (T regs ) in the gut are important sentinels in maintaining the peace between our gut and its trillions of resident bacteria and have been shown to be regulated by specific strains of bacteria in mouse models. Smith et al. (p. 569 , published online 4 July; see the Perspective by ... | 10.1038/nature18848 | Together with refs 39–41, this study identified short-chain fatty acids as strong inducers of T reg cells in the colon. |
10.1126/science.aac4263 | 102,879,255 | Gut microbes make T cells keep the peace Our guts harbor trillions of microbial inhabitants, some of which regulate the types of immune cells that are present in the gut. For instance, Clostridium species of bacteria induce a type of T cell that promotes tolerance between the host and its microbial contents. Ohnmacht e... | 10.1038/nature18848 | Together with refs 78 and 79, this study shows that a subset of T reg cells in the intestine express RORγt and that their development is affected by the microbiota. |
10.1111/j.1945-5100.2000.tb01518.x | 38,263,457 | Abstract— In the primordial solar system, the most plausible sources of the water accreted by the Earth were in the outer asteroid belt, in the giant planet regions, and in the Kuiper Belt. We investigate the implications on the origin of Earth's water of dynamical models of primordial evolution of solar system bodies ... | 10.1038/nature08477 | A breakthrough paper on accretion dynamics, demonstrating the prominence of water delivery to the inner Solar System from Jupiter and beyond. |
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