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10.1073/pnas.0605305103
104,397,230
Despite recent progress in visualization experiments, the mechanism underlying chromosome segregation in bacteria still remains elusive. Here we address a basic physical issue associated with bacterial chromosome segregation, namely the spatial organization of highly confined, self-avoiding polymers (of nontrivial topo...
10.1038/ncomms1481
Using CG models and polymer physics concepts an entropy-driven mechanism for DNA segregation in bacterial cells is proposed
10.1126/science.1181369
41,754,439
Chromosomal Mapping The conformation of the genome in the nucleus and contacts between both proximal and distal loci influence gene expression. In order to map genomic contacts, Lieberman-Aiden et al. (p. 289 , see the cover) developed a technique to allow the detection of all interactions between genomic loci in the e...
10.1038/ncomms1481
A polymer model that represents ∼ 1Mb DNA as a CG interaction center was used to explain the interphase DNA organization of the human genome, which is postulated to be fractal globule
10.1073/pnas.072589599
18,109,753
We have used small angle x-ray scattering and computer simulations with a coarse-grained model to provide a time-resolved picture of the global folding process of the Tetrahymena group I RNA over a time window of more than five orders of magnitude. A substantial phase of compaction is observed on the low millisecond ti...
10.1038/ncomms1481
This work used a CG model to infer the structures of T. ribozyme at each stage of collapse dynamics by selecting a conformation that best explain the SAXS profile
10.1073/pnas.1019500108
20,695,761
Quantitative description of how proteins fold under experimental conditions remains a challenging problem. Experiments often use urea and guanidinium chloride to study folding whereas the natural variable in simulations is temperature. To bridge the gap, we use the molecular transfer model that combines measured denatu...
10.1038/ncomms1481
The first demonstration that coarse-grained models can be used to characterize the folding thermodynamics and kinetics of a globular protein in the presence of denaturants
10.1073/pnas.1006760107
61,033,888
We combine experiment and computer simulation to show how macromolecular crowding dramatically affects the structure, function, and folding landscape of phosphoglycerate kinase (PGK). Fluorescence labeling shows that compact states of yeast PGK are populated as the amount of crowding agents (Ficoll 70) increases. Coars...
10.1038/ncomms1481
This work shows that the presence of crowders is critical in shaping the functional state of phosphoglycerate kinase
10.1073/pnas.1003533107
81,422,374
RNA synthesis, carried out by DNA-dependent RNA polymerase (RNAP) in a process called transcription, involves several stages. In bacteria, transcription initiation starts with promoter recognition and binding of RNAP holoenzyme, resulting in the formation of the closed ( R · P c ) RNAP-promoter DNA complex. Subsequentl...
10.1038/ncomms1481
SOP model of RNA polymerase and dsDNA was used to reveal the molecular mechanism of melting of promoter region upon polymerase binding, which is is the first step in transcription initiation
10.1002/prot.22640
102,985,673
Abstract Evaluating the free‐energy landscape of proteins and the corresponding functional aspects presents a major challenge for computer simulation approaches. This challenge is due to the complexity of the landscape and the enormous computer time needed for converging simulations. The use of simplified coarse‐graine...
10.1038/ncomms1481
The study demonstrates how different simulation strategies can be used to obtain insights into dtnamics of complex biological systems
10.26421/qic4.4-3
17,198,588
We study, in the context of quantum information and quantum communication, a configuration of devices that includes (1) a source of some unknown bipartite quantum state that is claimed to be the Bell state $\Phi^+$ and (2) two spatially separated but otherwise unknown measurement apparatus, one on each side, that are e...
10.1038/nature20119
This work introduces the idea of quantum information protocols with untrusted devices.
10.1038/ncomms8127
19,443,919
Abstract The widely popular class of quantum-dot molecular labels could so far not be utilized as standard fluorescent probes in STED (stimulated emission depletion) nanoscopy. This is because broad quantum-dot excitation spectra extend deeply into the spectral bands used for STED, thus compromising the transient fluor...
10.1038/natrevmats.2016.70
This paper demonstrated the possibility of implementing super-resolution microscopy using commercial semiconductor quantum dots.
10.1126/science.1168996
83,357,389
Subwavelength Patterning Microscopists have recently achieved fluorescence imaging at subwavelength resolution by focusing one beam of light in a halo around another beam, thereby quenching the glow of fluorescent dyes in all but the very center of the illuminated spot. Three studies have now adapted this approach to p...
10.1038/natrevmats.2016.70
Appeared simultaneously with references 18 and 19. These papers were the first to demonstrate two-beam super-resolution optical lithography.
10.1002/grl.50948
39,239,691
Ocean acidification (OA) is expected to drive the transition of coral reef ecosystems from net calcium carbonate (CaCO 3 ) precipitating to net dissolving within the next century. Although permeable sediments represent the largest reservoir of CaCO 3 in coral reefs, the dissolution of shallow CaCO 3 sands under future ...
10.1038/nclimate2380
First study to measure CaCO 3 sediment dissolution in situ over a diel cycle with advective flow and increased p CO 2 (ocean acidification scenarios).
10.1261/rna.1184108
101,179,485
We recently showed that the γ-subunit of Kluyveromyces lactis killer toxin (γ-toxin) is a tRNA endonuclease that cleaves , , and 3′ of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm 5 s 2 U). The 5-methoxycarbonylmethyl (mcm 5 ) side chain was important for efficient cleavage by γ-toxin, and defects i...
10.1038/nature07958
This study and ref. 58 implicate the Urm1 thiocarboxylate as a potential sulphur carrier in selective tRNA thiolation.
10.1126/science.1163885
125,151,041
The protein modifier ubiquitin is a signal for proteasome-mediated degradation in eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin-like protein, Pup (Rv2111c), which was specifically conjugated to proteasome ...
10.1038/nature07958
Identifies a non-β-grasp protein in M. tuberculosis that modifies selected protein substrates and targets them for proteasomal degradation.
10.1126/science.1224676
103,771,555
Cancer Stem Cells in Color One of the liveliest debates in contemporary cancer research centers on whether cancer stem cells (CSCs) exist and, if so, how these cells are defined phenotypically. CSCs are hypothesized to be a small population of cells within a tumor that are endowed with the unique capacity to drive tumo...
10.1038/nature12624
Fate mapping of Lgr5 + cells in intestinal adenomas shows that these cells contribute to tumour growth while also forming Lgr5 − progeny, raising the possibility that some adenomas are hierarchically organized.
10.1073/pnas.1005529108
38,800,211
The cancer stem cell (CSC) model proposes that tumors have a hierarchical organization in which only some cells indefinitely self-renew and thereby sustain tumor growth. In addition, the CSC model requires that tumor-initiating cells (TICs) be prospectively isolatable on the basis of their phenotype. Previous studies h...
10.1038/nature12624
This study demonstrates that CD133 enriches tumorigenic cells in only a subset of ovarian cancers and that even in these tumours the effectiveness of the marker changes on passaging.
10.1200/jco.2013.31.15_suppl.11020
58,813,309
11020 Background: ST oncology has been transformed by the linkage of GA with targeted therapeutics. Unfortunately, most STs still have no target detected by clinically available assays. More comprehensive testing platforms are needed to determine GA in ST and thus broaden treatment options. We developed a ST NGS diagno...
10.1038/nature12627
References 59–61 show that next-generation sequencing technology can be applied to stored formalin-fixed, paraffin-embedded tumour samples in a clinical setting.
10.1158/1078-0432.ccr-12-1627
103,912,537
Abstract Purpose: We initiated a personalized medicine program in the context of early clinical trials, using targeted agents matched with tumor molecular aberrations. Herein, we report our observations. Patient and Methods: Patients with advanced cancer were treated in the Clinical Center for Targeted Therapy. Molecul...
10.1038/nature12627
This study demonstrates that matching investigational treatment to genotype results in better response and survival.
10.1126/science.1120411
104,420,153
Covalent organic frameworks (COFs) have been designed and successfully synthesized by condensation reactions of phenyl diboronic acid {C 6 H 4 [B(OH) 2 ] 2 } and hexahydroxytriphenylene [C 18 H 6 (OH) 6 ]. Powder x-ray diffraction studies of the highly crystalline products (C 3 H 2 BO) 6 ·(C 9 H 12 ) 1 (COF-1) and C 9 ...
10.1038/natrevmats.2016.68
The first example of COFs was described in this study using a boronate ester linkage.
10.1126/science.1202747
104,143,909
Microporous covalent organic frameworks, which usually form as insoluble powders, grow as crystalline films on graphene.
10.1038/natrevmats.2016.68
A method to prepare COF films on graphene was demonstrated in this study.
10.1073/pnas.1502875112
62,606,397
Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767...
10.1038/nature18845
This study showed that the composition of the vaginal microbiota early in pregnancy may predict subsequent premature birth, which raises questions about how this community of microbes shapes maternal health and pregnancy outcomes.
10.1126/science.aad2571
125,322,951
Mom's bugs shape of spring immunity In utero, babies are relatively microbe-free but are quickly colonized at birth. These early microbial residents help to shape our immune systems. Gomez de Agüero et al. wondered whether the maternal microbiome also affects the of springs' immune system during gestation. To do this, ...
10.1038/nature18845
A germ-free mouse model of transient microbial colonization demonstrates that exposure of the mother to microbes during pregnancy shapes immunological development and function in the neonate.
10.3402/tellusa.v2i4.8607
101,898,443
A method is given for the numerical solution of the barotropic vorticity equation over a limited area of the earth’s surface. The lack of a natural boundary calls for an investigation of the appropriate boundary conditions. These are determined by a heuristic argument and are shown to be sufficient in a special case. A...
10.1038/nature14956
The first calculation of a numerical weather prediction on an electronic computer.
10.1256/003590002321042135
28,172,789
Abstract Recent verification statistics show a considerable improvement in the accuracy of forecasts from three global numerical weather prediction systems. The improvement amounts to about a 1‐day gain in predictability of mean‐sea‐level pressure and 500 hPa height over the last decade in the northern hemisphere, with...
10.1038/nature14956
Discusses the historical increase of the weather predictive skill of one day lead-time per decade linked to improvements in data assimilation, models and observing systems.
10.1146/annurev-pharmtox-010814-124835
62,289,009
Although the field of pharmacogenetics has existed for decades, practioners have been slow to implement pharmacogenetic testing in clinical care. Numerous publications describe the barriers to clinical implementation of pharmacogenetics. Recently, several freely available resources have been developed to help address t...
10.1038/nature15817
A detailed discussion of a pre-emptive approach to the clinical implementation of pharmacogenetics that contains quantitative information on the use of medications that are subject to genetic actionability.
10.1126/science.1234139
39,219,093
The past decade has brought together substantial advances in human genome analysis and a maturation of understanding of tumor biology. Although there is much progress still to be made, there are now several prominent examples in which tumor-associated somatic mutations have been used to identify cellular signaling path...
10.1038/nature15817
An analysis of the considerations for use of both somatic and inherited germline genetic lesions in prescription of anticancer drugs.
10.1200/jco.2013.48.7215
121,021,090
The scale of tumor genomic profiling is rapidly outpacing human cognitive capacity to make clinical decisions without the aid of tools. New frameworks are needed to help researchers and clinicians process the information emerging from the explosive growth in both the number of tumor genetic variants routinely tested an...
10.1038/nature15817
An overview of databases that can be used to match somatic cancer-specific genetic variants with targeted anticancer drugs.
10.1126/science.1213351
20,808,107
That Sweet Sensation Photosynthesis in the leaf generates sucrose that must be transported via the phloem to other parts of the plant in order, for example, to be incorporated into harvestable produce. Studying Arabidopsis and rice, Chen et al. (p. 207, published online 8 December; see the Perspective by Braun ) identi...
10.1038/nature11909
A FRET (fluorescence (Förster) resonance energy transfer) sucrose nanosensor was used to identify the missing link in phloem loading, that is, the phloem-parenchyma-expressed SWEET sucrose transporters, which are also key susceptibility factors for bacterial pathogens in rice.
10.1073/pnas.0910950106
20,104,100
The most widespread dietary problem in the world is mineral deficiency. We used the nicotianamine synthase ( NAS ) gene to increase mineral contents in rice grains. Nicotianamine (NA) is a chelator of metals and a key component of metal homeostasis. We isolated activation-tagged mutant lines in which expression of a ri...
10.1038/nature11909
These authors showed that increasing nicotianamine levels resulted in increased levels of iron in polished rice and also that the iron is bioavailable using animal feeding studies.
10.1126/science.1132563
20,783,468
Iron deficiency is a major human nutritional problem wherever plant-based diets are common. Using synchrotron x-ray fluorescence microtomography to directly visualize iron in Arabidopsis seeds, we show that iron is localized primarily to the provascular strands of the embryo. This localization is completely abolished w...
10.1038/nature11909
These authors used X-ray fluorescence microprobe spectroscopy to localize iron in seeds and showed that failure to store iron properly in the vacuole via the VIT1 transporter leads to seedling lethality under iron limitation.
10.1073/pnas.0608136104
62,465,436
The arbuscular mycorrhizal (AM) symbiosis is a mutualistic endosymbiosis formed by plant roots and AM fungi. Most vascular flowering plants have the ability to form these associations, which have a significant impact on plant health and consequently on ecosystem function. Nutrient exchange is a central feature of the A...
10.1038/nature11909
A phosphate transporter (MtPT4) was shown to be necessary for Medicago truncatula plants to obtain phosphate delivered via the fungal symbiont and furthermore, that MtPT4 transporter function is essential to maintain the symbiosis.
10.1073/pnas.0802361105
20,744,073
Arsenic poisoning affects millions of people worldwide. Human arsenic intake from rice consumption can be substantial because rice is particularly efficient in assimilating arsenic from paddy soils, although the mechanism has not been elucidated. Here we report that two different types of transporters mediate transport...
10.1038/nature11909
These authors demonstrated that arsenite, a toxic form of soil arsenic, is transported into and within the rice plant by two novel transporters, providing new possible strategies for minimizing arsenic entry into the food chain by altering these transporters.
10.1146/annurev.micro.58.030603.123749
103,829,163
Many microorganisms form symbioses with plants that range, on a continuous scale, from parasitic to mutualistic. Among these, the most widespread mutualistic symbiosis is the arbuscular mycorrhiza, formed between arbuscular mycorrhizal (AM) fungi and vascular flowering plants. These associations occur in terrestrial ec...
10.1038/ncomms1046
This paper reviewed several advancements in the knowledge of arbuscular mycorrhizas and introduced the concept of signal exchanges between the plant and fungus before and after symbiosis establishment
10.1105/tpc.105.035410
62,288,655
Abstract The penetration of arbuscular mycorrhizal (AM) fungi through the outermost root tissues of the host plant is a critical step in root colonization, ultimately leading to the establishment of this ecologically important endosymbiotic association. To evaluate the role played by the host plant during AM infection,...
10.1038/ncomms1046
In this research root epidermal cells were shown to anticipate fungal infection by forming a columnar cytoplasmic aggregation (named the prepenetration apparatus) that subsequently guides the hypha through the plant cell lumen
10.1073/pnas.0608136104
62,465,436
The arbuscular mycorrhizal (AM) symbiosis is a mutualistic endosymbiosis formed by plant roots and AM fungi. Most vascular flowering plants have the ability to form these associations, which have a significant impact on plant health and consequently on ecosystem function. Nutrient exchange is a central feature of the A...
10.1038/ncomms1046
Showed that the functionality of the arbuscule-localized phosphate transporter PT4 is required for correct arbuscule development. Arbuscules in pt4 mutants are degraded by the plant prior to their maturation, suggesting that arbuscule development and life span depend on their efficiency in P transfer
10.1105/tpc.110.074955
125,033,555
Abstract In the symbiotic association of plants and arbuscular mycorrhizal (AM) fungi, the fungal symbiont resides in the root cortical cells where it delivers mineral nutrients to its plant host through branched hyphae called arbuscules. Here, we report a Medicago truncatula mutant, stunted arbuscule (str), in which a...
10.1038/ncomms1046
Reported on a Medicago truncatula mutant, stunted arbuscule (str), impaired in arbuscule development but showing a wild type nodulation phenotype, revealing a SYM independent regulation. STR and STR2 encode half-size ABC transporters that localize in the peri-arbuscular membrane
10.1111/j.1469-8137.2009.03137.x
81,450,955
Commentary p 267
10.1038/ncomms1046
One of the first experimental evidences of the antiquity of AM symbiosis
10.1126/science.1144004
107,221,444
Integrated studies of coupled human and natural systems reveal new and complex patterns and processes not evident when studied by social or natural scientists separately. Synthesis of six case studies from around the world shows that couplings between human and natural systems vary across space, time, and organizationa...
10.1038/nature11157
A framework and case studies for understanding complex patterns and dynamics of coupled human and natural systems.
10.1126/science.1229568
62,564,104
Stealth Delivery Delivery of therapeutics and imaging agents is hampered by the ability of the innate immune system to recognize and clear foreign particles. "Self" cells are protected from phagocytic clearance by the membrane protein CD47 that interacts with signal regulatory protein-α (SIRPα) on macrophages. Taking a...
10.1038/nbt.3330
An excellent study involving nanoparticle 'camouflaging' or 'biomimicry' for evasion of the MPS, highlighting consequent enhanced tumor accumulation and efficacy.
10.1073/pnas.0600997103
38,419,193
Phagocytosis is a principal component of the body’s innate immunity in which macrophages internalize targets in an actin-dependent manner. Targets vary widely in shape and size and include particles such as pathogens and senescent cells. Despite considerable progress in understanding this complicated process, the role ...
10.1038/nbt.3330
Seminal work on the effect of particle geometry on macrophage uptake, demonstrating that the architectural design parameter of curvature drives phagocytosis.
10.1073/pnas.0608156103
40,286,910
A cell-based screen of chemical libraries was carried out to identify small molecules that control the self-renewal of ES cells. A previously uncharacterized heterocycle, SC1, was discovered that allows one to propagate murine ES cells in an undifferentiated, pluripotent state under chemically defined conditions in the...
10.1038/nature07042
This paper describes the identification of a novel synthetic small molecule that can maintain long-term self-renewal of mouse ES cells in the absence of feeder cells, serum, LIF, BMPs and WNT proteins.
10.1126/science.1134008
83,513,904
We demonstrated microwave-induced cooling in a superconducting flux qubit. The thermal population in the first-excited state of the qubit is driven to a higher-excited state by way of a sideband transition. Subsequent relaxation into the ground state results in cooling. Effective temperatures as low as ≈3 millikelvin a...
10.1038/nature10122
Report of cooling for a flux qubit using an inverse process of state population inversion.
10.1126/science.1189992
45,304,145
Another Cell Culprit in Prostate Cancer A recent controversial hypothesis about the cellular origins of human cancer, the so-called “cancer stem cell hypothesis,” has fueled interest in identifying the specific cell types that give rise to common epithelial cancers. A single, well-defined cell of origin could, in princ...
10.1038/nature09781
This study demonstrates through transduction of isolated cell subsets that basal stem/progenitor cells are an important target cell.
10.5194/fr-1-21-1998
99,507,604
The exoskeleton, consisting of micromeric elements (odontodes) and their derivatives, is characteristic of the most ancient vertebrates. Great morphological and histological variability of discrete exoskeletal microremains makes it difficult to identify them. It is necessary to study not only separate scales or tessera...
10.1038/nature14437
An important review of the tissue structure in Early Palaeozoic microremains.
10.1093/oso/9780198540472.001.0001
149,158,072
Abstract This book presents our current knowledge of the early vertebrates, which were mainly fish, but included some land vertebrates, and lived about 470 to 250 million years ago. It centres on anatomical and phylogenetic questions, but includes information about fossil discovery and preparation, as well as the analy...
10.1038/nature14437
This text is a general overview of early vertebrate anatomy and relationships.
10.1111/j.1469-7580.2009.01046.x
19,169,416
Abstract Most non‐tetrapod vertebrates develop mineralized extra‐oral elements within the integument. Known collectively as the integumentary skeleton, these elements represent the structurally diverse skin‐bound contribution to the dermal skeleton. In this review we begin by summarizing what is known about the histolo...
10.1038/nature14437
This is an updated review of exoskeletal hard tissues in early fishes.
10.1126/science.1208467
58,395,048
Interactions between adhesion molecules support the checkerboard-like patterning of cells in the cochlea.
10.1038/nature11859
In this article, the authors demonstrate how differential sets of heterophilic adhesion molecules can form chequerboard-like patterns in the epithelial sheet.
10.1126/science.1201647
38,751,587
Cycling of active and quiescent states of the hair follicle integrates activator and inhibitor signals for patterning.
10.1038/nature11859
In this article the authors report how local interactions between hair follicles contribute to the global pattern of hair regeneration.
10.1242/dev.025981
41,516,091
The collective migration of cells in the form of cohesive tissues is a hallmark of both morphogenesis and repair. The extrinsic cues that direct these complex migrations usually act by regulating the dynamics of a specific subset of cells, those at the leading edge. Given that normally the function of tissue migration ...
10.1038/nature11859
This paper describes the mechanism by which FGF signals drive morphogenesis in lateral-line organs during their collective migration.
10.1242/dev.070987
62,553,967
The Hippo signaling pathway plays an important role in regulation of cell proliferation. Cell density regulates the Hippo pathway in cultured cells; however, the mechanism by which cells detect density remains unclear. In this study, we demonstrated that changes in cell morphology are a key factor. Morphological manipu...
10.1038/nature11859
References 72 and 73 together demonstrate crucial roles for hippo-related pathways in cellular mechanotransduction, leading to cellular growth and differentiation.
10.1126/science.1162493
62,323,518
A long-standing goal of biology is to map the behavior of all cells during vertebrate embryogenesis. We developed digital scanned laser light sheet fluorescence microscopy and recorded nuclei localization and movement in entire wild-type and mutant zebrafish embryos over the first 24 hours of development. Multiview in ...
10.1038/nature11859
This article is a pioneering study of in toto imaging for cell-lineage tracing.
10.1111/j.1151-2916.2002.tb00334.x
38,354,516
This review represents the authors' view of the evolution of solid‐state ionics over approximately the past 100 years. A brief history, introducing milestones of the development of this discipline, is followed by a short summary of the theory of ionic conduction in the bulk and the more recently developed theory of ion...
10.1038/natrevmats.2016.103
This paper reviews the evolution of solid-state ionics over approximately the past 100 years.
10.1039/c5ee00058k
20,033,450
Li 2 S is efficiently used for a Li-ion sulfur battery with a dual-phase electrolyte, in which the parasitic polysulfide shuttle process is eliminated.
10.1038/natrevmats.2016.103
This paper is the first report of the feasibility of using a dual-phase electrolyte in a lithium–sulfur battery separated by a LISICON-type solid electrolyte.
10.1002/aenm.201401302
19,857,022
Lithium‐air (Li‐air) batteries have become attractive because of their extremely high theoretical energy density. However, conventional Li‐air cells operating with non‐aqueous electrolytes suffer from poor cycle life and low practical energy density due to the clogging of the porous air cathode by insoluble discharge p...
10.1038/natrevmats.2016.103
This paper provides an overview of recent developments in hybrid and aqueous lithium–air batteries and discusses the benefits of adopting a cell configuration that uses a lithium-ion solid electrolyte to protect the lithium-metal anode.
10.1002/aenm.201601392
83,144,700
A NaSICON‐type Li + ‐ion conductive membrane with a formula of Li 1+ x Y x Zr 2− x (PO 4 ) 3 (LYZP) ( x = 0–0.15) has been explored as a solid‐electrolyte/separator to suppress polysulfide‐crossover in lithium‐sulfur (Li‐S) batteries. The LYZP membrane with a reasonable Li + ‐ion conductivity shows both favorable chemi...
10.1038/natrevmats.2016.103
This paper demonstrates an important approach in controlling the polysulfide-crossover problem in lithium–sulfur batteries with a chemically and electrochemically compatible NASICON-type lithium-ion solid electrolyte.
10.1039/c4ta04419c
18,964,674
Li//Br battery, by using aqueous bromide/tribromide redox pair as positive electrode and a coated lithium metal as negative electrode, exhibits high energy density and good cycling.
10.1038/natrevmats.2016.103
This paper demonstrates a rechargeable lithium–bromine battery platform operated with a lithium-ion solid electrolyte, an aqueous bromine cathode and a non-aqueous lithium anode.
10.1126/science.1439783
82,885,189
Despite decades of intensive investigation, the basic pathophysiological mechanisms responsible for the metabolic derangements associated with diabetes mellitus have remained elusive. Explored here is the possibility that traditional concepts in this area might have carried the wrong emphasis. It is suggested that the ...
10.1038/nature08532
A highly influential commentary that helped switch attention from glucose to lipid metabolism in type 2 diabetes.
10.1084/jem.157.4.1360
101,647,040
An apparent insulin resistance is noted in 3T3-L1 adipocytes after the addition of an endotoxin-induced mediator from macrophages. Examination at the level of the insulin receptor has revealed that the mediator does not effect either the functional ability of the cells to bind insulin or the ability of insulin to stimu...
10.1038/nature21363
This important paper demonstrates that macrophages activated by LPS secrete products that block insulin action in adipocytes.
10.1038/ncomms13280
123,901,154
Abstract Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contribute...
10.1038/nature21363
This study demonstrates the importance of PKR in inflammasome activation, and how cellular metabolism influences this activity.
10.1126/science.1160794
40,742,385
A high-fat diet causes activation of the regulatory protein c-Jun NH 2 -terminal kinase 1 (JNK1) and triggers development of insulin resistance. JNK1 is therefore a potential target for therapeutic treatment of metabolic syndrome. We explored the mechanism of JNK1 signaling by engineering mice in which the Jnk1 gene wa...
10.1038/nature21363
This manuscript shows the pathological role of JNK activity in adipose tissue and demonstrates how this inflammatory input disrupts liver insulin action and glucose metabolism. This paper also addresses the role of JNK1 in macrophages.
10.1073/pnas.1409229111
41,584,337
Significance Muscle insulin resistance is a major factor in the pathogenesis of type 2 diabetes, but the underlying cellular mechanisms are yet unclear. This study found that muscle diacylglycerol content was temporally associated with protein kinase Cθ activation and impairment of insulin signaling in human skeletal m...
10.1038/nature21363
This study shows that in human subjects lipid-induced insulin resistance in muscle is associated with DAG–PKC activation.
10.2337/db13-1398
29,290,479
Statins reduce lipid levels and are widely prescribed. Statins have been associated with an increased incidence of type 2 diabetes, but the mechanisms are unclear. Activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3)/caspase-1 inflammasome, promotes insulin resistance, a precursor of type 2 dia...
10.1038/nature21363
This study demonstrates a direct link between a statin and inflammasome activation, showing a mechanism by which statins may act as pro-inflammatory agents.
10.1098/rsta.2008.0111
105,343,753
The compositional variations among the chondrites inform us about cosmochemical fractionation processes during condensation and aggregation of solid matter from the solar nebula. These fractionations include: (i) variable Mg–Si–RLE ratios (RLE: refractory lithophile element), (ii) depletions in elements more volatile t...
10.1038/nature10901
This paper discusses how the compositions of terrestrial planets may change during the later stages of their accretion.
10.1126/science.1113634
123,436,506
New high-precision samarium-neodymium isotopic data for chondritic meteorites show that their 142 Nd/ 144 Nd ratio is 20 parts per million lower than that of most terrestrial rocks. This difference indicates that most (70 to 95%) of Earth's mantle is compositionally similar to the incompatible element–depleted source o...
10.1038/nature10901
Here the 142 Nd/ 144 Nd for chondritic meteorites is shown to be 20 parts per million less than that of most terrestrial rocks.
10.1126/science.1179386
38,376,311
A Smooth(ened) Path to Drug Resistance The Hedgehog (Hh) signaling pathway has emerged as a key contributor to the growth of medulloblastoma, an aggressive brain tumor. GDC-0449, a drug that ramps down this signaling pathway by binding to the Hh pathway component Smoothened, was recently shown to induce rapid and drama...
10.1038/nchembio.1776
The first report of acquired resistance to a Smoothened inhibitor in the clinic.
10.1073/pnas.0602852103
38,591,313
Sterol synthesis is required for Sonic hedgehog (Shh) signal transduction. Errors in Shh signal transduction play important roles in the formation of human tumors, including medulloblastoma (MB). It is not clear which products of sterol synthesis are necessary for Shh signal transduction or how they act. Here we show t...
10.1038/nchembio.1776
The first observation that oxysterols can modulate Hedgehog signaling through SMO.
10.1126/science.1222879
80,252,594
Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 angstrom structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to kno...
10.1038/nchembio.1776
The structure of WNT bound to the Frizzled CRD revealed a hydrophobic groove that binds the palmitoyl moiety of WNT.
10.1073/pnas.1103824108
123,144,249
The global distribution of soil animals and the relationship of below-ground biodiversity to above-ground biodiversity are not well understood. We examined 17,516 environmental 18S rRNA gene sequences representing 20 phyla of soil animals sampled from 11 locations covering a range of biomes and latitudes around the wor...
10.1038/nature13855
This study of soils taken from a range of biomes and latitudes showed that cosmopolitan soil animals are extremely rare, and that there is a lack of coupling between aboveground and soil animal diversity at a global scale.
10.1073/pnas.0507535103
125,284,254
For centuries, biologists have studied patterns of plant and animal diversity at continental scales. Until recently, similar studies were impossible for microorganisms, arguably the most diverse and abundant group of organisms on Earth. Here, we present a continental-scale description of soil bacterial communities and ...
10.1038/nature13855
This study showed that continental scale patterns of soil bacterial diversity and richness are largely explained by soil pH, diversity and richness being greater in neutral than acidic soils.
10.1073/pnas.1204306109
62,065,800
The pulse of carbon dioxide (CO 2 ) resulting from the first rainfall after the dry summer in Mediterranean ecosystems is so large that it is well documented at the landscape scale, with the CO 2 released in a few days comparable in magnitude to the annual net carbon exchange of many terrestrial ecosystems. Although th...
10.1038/nature13855
This study showed that sudden increases in soil water availability following rainfall events after prolonged drought cause rapid and sequential resurrection of distinct, phylogenetically clustered groups of microorganisms, and that these rapid microbial responses are associated with significant pulses of CO 2 productio...
10.1126/science.1101865
62,375,494
The loss of biodiversity can have significant impacts on ecosystem functioning, but the mechanisms involved lack empirical confirmation. Using soil microcosms, we show experimentally that functional dissimilarity among detritivorous species, not species number, drives community compositional effects on leaf litter mass...
10.1038/nature13855
This study showed that functional dissimilarity among detritivorous species, not species number, drives community compositional effects on decomposition and soil respiration.
10.1073/pnas.1305198110
20,430,224
Intensive land use reduces the diversity and abundance of many soil biota, with consequences for the processes that they govern and the ecosystem services that these processes underpin. Relationships between soil biota and ecosystem processes have mostly been found in laboratory experiments and rarely are found in the ...
10.1038/nature13855
This study showed that soil food web properties strongly and consistently predict processes of carbon and nitrogen cycling across land use systems and geographic locations, and they were a better predictor of these processes than agricultural land use intensity.
10.1111/ele.12115
62,189,007
Abstract The roots of most land plants are colonised by mycorrhizal fungi that provide mineral nutrients in exchange for carbon. Here, we show that mycorrhizal mycelia can also act as a conduit for signalling between plants, acting as an early warning system for herbivore attack. Insect herbivory causes systemic change...
10.1038/nature13855
This study showed that plants that were not attacked by aboveground aphids induced defence responses when connected by arbuscular mycorrhizal fungi to plants that were attacked by aphids, suggesting that mycorrhizal networks may enable plants to anticipate insect attack by defence induction.
10.1111/j.1461-0248.2012.01801.x
62,154,989
Abstract Root herbivory can greatly affect the performance of aboveground insects via changes in plant chemistry. These interactions have been studied extensively in experiments where aboveground and belowground insects were feeding on the same plant. However, little is known about how aboveground and belowground organ...
10.1038/nature13855
This study showed that feeding on plants by aboveground insects changed soil fungal community composition, which influenced both plant-feeding and carnivorous insects on plants that colonized this soil; indicating that aboveground multitrophic interactions are affected by those of the past through a legacy effect on so...
10.1126/science.1208473
20,371,845
Plants and their associated fungi reward partners that offer the best resources to sustain mutualism in complex systems.
10.1038/nature13855
This study showed that both plants and mycorrhizal fungi have control over mutual interactions and that plants may favour cooperating fungi over cheaters; findings suggest that the rhizosphere is a market place where goods are exchanged by equal partners, rather than where goods are stolen.
10.1073/pnas.1202319109
83,104,982
Global change is challenging plant and animal populations with novel environmental conditions, including increased atmospheric CO 2 concentrations, warmer temperatures, and altered precipitation regimes. In some cases, contemporary or “rapid” evolution can ameliorate the effects of global change. However, the direction...
10.1038/nature13855
This study showed that adaptive plant responses to drought stress are governed by rapid responses of soil microbial communities and suggests that plants may benefit from associations with diverse soil microbial communities when faced with rapid environmental change.
10.1111/j.1461-0248.2010.01474.x
18,974,150
Ecology Letters (2010) 13: 803–809 Abstract The enemy release hypothesis is a common explanation for species invasions, suggesting that introduced species benefit from leaving behind natural enemies in the native range. However, any such advantage may attenuate over time. In this study, we test a prediction of this mor...
10.1038/nature13855
This study showed that non-native plant species introduced longer ago in New Zealand induce more soil pathogenic activity than species introduced more recently, indicating that negative soil feedback toward introduced plant species increases with time since introduction, which may ultimately contribute to their control...
10.1073/pnas.0905446106
125,187,240
Invasive species can quickly transform biological communities due to their high abundance and strong impacts on native species, in part because they can be released from the ecological forces that limit native populations. However, little is known about the long-term dynamics of invasions; do invaders maintain their do...
10.1038/nature13855
This study showed that introduced exotic plant species produce less phytotoxins with increasing time since introduction, which had strong impacts on soil community functioning; results suggest that effects of invasive species on soil biodiversity may change over time due to evolutionary processes in the plants.
10.1073/pnas.242606799
38,332,408
Micro-RNAs ( miR genes) are a large family of highly conserved noncoding genes thought to be involved in temporal and tissue-specific gene regulation. MiRs are transcribed as short hairpin precursors (≈70 nt) and are processed into active 21- to 22-nt RNAs by Dicer, a ribonuclease that recognizes target mRNAs via base-...
10.1038/nature10888
This article reports miRNA deregulation in cancer and is the first evidence of the role of miRNAs in cancer.
10.1073/pnas.0602266103
107,273,305
MicroRNAs (miRNAs) represent a newly discovered class of posttranscriptional regulatory noncoding small RNAs that bind to targeted mRNAs and either block their translation or initiate their degradation. miRNA profiling of hematopoietic lineages in humans and mice showed that some miRNAs are differentially expressed dur...
10.1038/nature10888
This article reports overexpression of a single miRNA can cause cancer in vivo
10.1073/pnas.1304988111
123,279,115
Significance Skin tanning is a protective response of epidermal cells involving increased melanin formation. Overexposure to sun can cause sunburn and even skin cancer, and such conditions are partly attributable to the accumulation of toxic side products of melanin and its intermediates. In this study, we reveal the i...
10.1038/nchembio.1548
This recent study identified IFN-γ as a hypopigmenting factor by stalling melanosome maturation process and established a physiological and pathological relevance of this effect in multiple models
10.1111/j.1600-0625.2007.00666_1.x
104,031,352
Abstract: The pathobiology of vitiligo has been hotly disputed for as long as one remembers, and has been a magnet for endless speculation. Evidently, the different schools of thought – ranging, e.g. from the concept that vitiligo essentially is a free‐radical disorder to that of vitiligo being a primary autoimmune dis...
10.1038/nchembio.1548
These two papers (refs. 94 and 95) summarize the caveats in interpreting the observations on vitiligo in light of one theory and propose interplay of several confounding factors in vitiligo etiopathogenesis
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/nature08538
This first study of the tracer compound PIB in humans describes both the retention of PIB in areas of Alzheimer's-disease-affected brains known to contain amyloid and an inverse relationship between the PIB PET signal and cerebral glucose metabolism, measured by fluorodeoxyglucose PET.
10.1002/ana.20730
20,521,912
Abstract Objectives Amyloid‐β 42 (Aβ 42 ) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Aβ 42 is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Aβ 42 “sink,” hindering transport of solub...
10.1038/nature08538
This study illustrates an inverse relationship between mean cortical retention of PIB and cerebrospinal-fluid A β 42 concentrations among both demented and non-demented subjects, suggesting that brain amyloid deposition results in low cerebrospinal-fluid A β 42 and that amyloid imaging and cerebrospinal-fluid A β 42 mi...
10.1126/science.1230200
20,427,217
Honeybees Can't Do It Alone The majority of food crops require pollination to set fruit with the honeybee providing a pollination workhorse, with both feral and managed populations an integral component of crop management (see the Perspective by Tylianakis , published online 28 February). Garibaldi et al. (p. 1608 , pu...
10.1038/nature20588
This study is the first to show consistent benefits from wild insects to crop pollination across the globe and that those benefits cannot be replaced by increasing the abundance of a single managed species such as honeybees
10.1111/ele.12082
20,557,918
Abstract Bees provide essential pollination services that are potentially affected both by local farm management and the surrounding landscape. To better understand these different factors, we modelled the relative effects of landscape composition (nesting and floral resources within foraging distances), landscape conf...
10.1038/nature20588
This study is based on detailed spatial modelling of data from 39 crop systems globally to understand the relative influence of landscape composition, landscape configuration, farm management and their interactions on wild bee abundance and richness
10.1111/ele.12128
41,510,029
Abstract In Europe, agri‐environmental schemes ( AES ) have been introduced in response to concerns about farmland biodiversity declines. Yet, as AES have delivered variable results, a better understanding of what determines their success or failure is urgently needed. Focusing on pollinating insects, we quantitatively...
10.1038/nature20588
This is the first study to provide an overview of the effectiveness of a range of agri-environment options for supporting local pollinator richness and abundance
10.1098/rspb.2015.1740
83,284,171
Ecological intensification has been promoted as a means to achieve environmentally sustainable increases in crop yields by enhancing ecosystem functions that regulate and support production. There is, however, little direct evidence of yield benefits from ecological intensification on commercial farms growing globally ...
10.1038/nature20588
The first to test farm-scale ‘ecological intensification’, this study found no decrease in the crop yield over a five year rotation cycle on a large English farm, despite taking up to 8% of land out of production to support ecological functions
10.1126/science.1178239
19,035,729
Facile Fluorination Fluorine atoms have become a useful substituent in pharmaceuticals. However, they remain challenging to introduce synthetically because present methods for carbon-fluorine bond formation require either corrosive conditions or somewhat exotic, and thus expensive, reagents. A sticking point has been t...
10.1038/nature10108
Reports the first functional-group-tolerant Pd-catalysed Ar−F bond formation using aryl triflates and fluoride.
10.1126/science.1206157
125,313,963
Electronic systems with physical properties matched to the human epidermis can be used in clinical monitoring.
10.1038/natrevmats.2016.93
A pioneering application of flexible and stretchable microcontact-printed electronics for biological sensing.
10.1146/annurev-pharmtox-010814-124803
104,277,852
In the past decade, emerging synthetic biology technologies such as chemogenetics have dramatically transformed how pharmacologists and systems biologists deconstruct the involvement of G protein–coupled receptors (GPCRs) in a myriad of physiological and translational settings. Here we highlight a specific chemogenetic...
10.1038/natrevmats.2016.93
This comprehensive review describes powerful chemogenetic approaches to targeted neuromodulation with DREADDs (designer receptors exclusively activated by designer drugs).
10.1128/aem.64.8.2780-2787.1998
61,523,423
ABSTRACT To determine the potential for bacteriophage-mediated gene transfer in the marine environment, we established transduction systems by using marine phage host isolates. Plasmid pQSR50, which contains transposon Tn 5 and encodes kanamycin and streptomycin resistance, was used in plasmid transduction assays. Both...
10.1038/nature08060
This pioneering study was the first to measure transduction rates in the marine environment.
10.1073/pnas.0807707105
122,374,483
The coccolithophore Emiliania huxleyi is one of the most successful eukaryotes in modern oceans. The two phases in its haplodiploid life cycle exhibit radically different phenotypes. The diploid calcified phase forms extensive blooms, which profoundly impact global biogeochemical equilibria. By contrast, the ecological...
10.1038/nature08060
This paper shows that the different life stages of E. huxleyi are a way of avoiding viral mortality.
10.1126/science.1166585
104,254,315
Direct imaging of exoplanetary systems is a powerful technique that can reveal Jupiter-like planets in wide orbits, can enable detailed characterization of planetary atmospheres, and is a key step toward imaging Earth-like planets. Imaging detections are challenging because of the combined effect of small angular separ...
10.1038/nature13784
This paper reports on the discovery of three planetary companions, directly imaged in the near-infrared at two different epochs with the adaptive-optics systems at the Gemini and Keck telescopes, and the corresponding facility near-infrared cameras.
10.1126/science.214.4527.1343
80,095,881
Irradiation of 2,2-bis(2,4,6-trimethylphenyl)hexamethyltrisilane in hydrocarbon solution produces tetramesityldisilene, which can be isolated as a yellow-orange solid stable to room temperature and above in the absence of air. Like the olefins of carbon chemistry, tetramesityldisilene undergoes addition reactions acros...
10.1038/nature08634
Described the synthesis and structure of the first stable (that is, non-dissociating) compound with a double bond between two heavier main group elements and (with ref. 35) effectively overthrew the so-called double bond rule, which holds that heavier main group elements do not form stable double bonds (see refs 10 and...
10.1139/v62-178
123,607,302
It is demonstrated that second-order perturbation theory is useful in determining the manner in which the electron density present in a molecule is changed during a nuclear vibration. Furthermore, it is shown that one nuclear motion will lead to a particularly favorable electronic distortion such that this motion is en...
10.1038/nature08634
Showed how certain vibrational modes permitted symmetry allowed second order Jahn–Teller mixing, which could lead to large geometrical perturbations.
10.1126/science.1141474
83,506,509
In possessing a lone pair of electrons and an accessible vacant orbital, singlet carbenes resemble transition metal centers and thus could potentially mimic their chemical behavior. Although singlet di(amino)carbenes are inert toward dihydrogen, it is shown that more nucleophilic and electrophilic (alkyl)(amino)carbene...
10.1038/nature08634
Reported the first reactions of a carbene with H 2 and NH 3 under ambient conditions.
10.1126/science.1134230
62,207,349
Although reversible covalent activation of molecular hydrogen (H 2 ) is a common reaction at transition metal centers, it has proven elusive in compounds of the lighter elements. We report that the compound (C 6 H 2 Me 3 ) 2 PH(C 6 F 4 )BH(C 6 F 5 ) 2 (Me, methyl), which we derived through an unusual reaction involving...
10.1038/nature08634
Introduced the frustrated Lewis pair concept and showed how a phosphine borane combination could reversibly bind H 2 under near-ambient conditions.
10.1126/science.1176443
27,057,457
Tin Two-Step Doubly and triply bonded carbon compounds have a well-studied tendency to link up with one another and form rings. The rates of these reactions and their relative susceptibilities to acceleration by heat versus light are encapsulated in the decades-old Woodward-Hoffmann rules. More recently, alkene and alk...
10.1038/nature08634
This paper and ref. 58 reported reversible binding of the unsaturated species C 2 H 4 and CO 2 by a main group molecule under ambient conditions.
10.1126/science.1168049
62,671,753
The large-scale practical application of fuel cells will be difficult to realize if the expensive platinum-based electrocatalysts for oxygen reduction reactions (ORRs) cannot be replaced by other efficient, low-cost, and stable electrodes. Here, we report that vertically aligned nitrogen-containing carbon nanotubes (VA...
10.1038/natrevmats.2016.64
The first metal-free catalyst (nitrogen-doped VA-CNT) that showed superior ORR activity to commercial Pt/C.
10.1126/sciadv.1400129
20,719,157
The availability of low-cost, efficient, and durable catalysts for oxygen reduction reaction (ORR) is a prerequisite for commercialization of the fuel cell technology. Along with intensive research efforts of more than half a century in developing nonprecious metal catalysts (NPMCs) to replace the expensive and scarce ...
10.1038/natrevmats.2016.64
The first metal-free catalyst (nitrogen-doped graphene CNT) that showed long-term operational stabilities and comparable gravimetric power densities to the best non-precious metal catalysts in acidic PEM cells.