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10.1126/science.aaz3691 | 83,069,006 | Stacking solar cells with decreasing band gaps to form tandems presents the possibility of overcoming the single-junction Shockley-Queisser limit in photovoltaics. The rapid development of solution-processed perovskites has brought perovskite single-junction efficiencies >20%. However, this process has yet to enable... | 10.1038/s41565-022-01229-7 | This paper reports tandem solar cells based on a solution-processed perovskite on textured crystalline silicon with an adapted pyramidal texture. |
10.1126/science.267.5195.217 | 4,781,272 | A strategy has been developed for the synthesis of thermoplastic elastomeric polypropylene based on the catalytic activity of the unbridged metallocene bis(2-phenylindenyl)zirconium dichloride [(2-PhInd) 2 ZrCl 2 ]. This catalyst was designed to isomerize between achiral and chiral coordination geometries during the po... | 10.1038/s41570-019-0117-z | An excellent example of modulating tacticity to finely control mechanical properties |
10.1126/science.1062224 | 104,367,171 | Polymerization of isocyanopeptides results in the formation of high molecular mass polymers that fold in a proteinlike fashion to give helical strands in which the peptide chains are arranged in β-sheets. The β-helical polymers retain their structure in water and unfold in a cooperative process at elevated temperatures... | 10.1038/s41570-019-0117-z | A great example of bioinspired chemistry and demonstrates the critical aspect of stereochemistry (helicity) in order to achieve functional, high-order structures |
10.1002/anie.201606750 | 59,741,967 | Abstract In most synthetic elastomers, changing the physical properties by monomer choice also results in a change to the crystallinity of the material, which manifests through alteration of its mechanical performance. Using organocatalyzed stereospecific additions of thiols to activated alkynes, high‐molar‐mass elasto... | 10.1038/s41570-019-0117-z | A striking example of modulating thermomechanical properties by simple cis – trans isomerism of an alkene in the polymer backbone |
10.1038/ncomms6746 | 20,439,549 | Abstract Co-crystallization of polymers with different configurations/tacticities provides access to materials with enhanced performance. The stereocomplexation of isotactic poly( L -lactide) and poly( D -lactide) has led to improved properties compared with each homochiral material. Herein, we report the preparation o... | 10.1038/s41570-019-0117-z | This work demonstrates the potential of stereochemistry to determine function (morphological reorganization of nanostructures) beyond just controlling molecular and/or macroscopic properties of polymers |
10.1002/anie.201410211 | 17,638,018 | Abstract We report the cocrystallization of the regio‐ and stereoregular chiral copolymer poly(limonene carbonate). To the best of our knowledge, this marks the first example of an amorphous, enantiomerically pure polymer that becomes crystalline upon stereocomplexation with its complementary enantiomer. By analyzing X... | 10.1038/s41570-019-0117-z | An excellent example of leveraging stereocomplexation to greatly improve the properties of a biosourced polymer |
10.1126/science.1072873 | 20,607,154 | N -methyl- d -aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we transduced neurons with peptides that disrupted the interaction of NMDARs with the postsynaptic density protein PSD-95. This procedure dissociated NMDARs f... | 10.1038/s41573-020-0086-4 | This article describes the development of the first PSD95 inhibitor NA-1 and how it protects against ischaemic damage in rats |
10.1038/ncomms10467 | 61,735,926 | Abstract Single-molecule magnets display magnetic bistability of molecular origin, which may one day be exploited in magnetic data storage devices. Recently it was realised that increasing the magnetic moment of polynuclear molecules does not automatically lead to a substantial increase in magnetic bistability. Attenti... | 10.1038/s41570-022-00424-3 | A Co(II) single-ion complex is synthesized and shown to possess very slow magnetic relaxation |
10.1126/sciadv.aaw2210 | 122,736,443 | Computational studies of chemical processes taking place over extended size and time scales are inaccessible by electronic structure theories and can be tackled only by atomistic models such as force fields. These have evolved over the years to describe the most diverse systems. However, as we improve the performance o... | 10.1038/s41570-022-00424-3 | Machine-learning force fields based on a simple linear model are shown to accurately capture the potential energy surface of coordination compounds, including magnetic ones |
10.1002/chem.201605102 | 100,338,091 | Abstract An ab initio methodology for the first‐principle derivation of crystal‐field (CF) parameters for lanthanides is described. The methodology is applied to the analysis of CF parameters in [Tb(Pc) 2 ] − (Pc=phthalocyanine) and Dy 4 K 2 ([Dy 4 K 2 O(O t Bu) 12 ]) complexes, and compared with often used approximate... | 10.1038/s41570-022-00424-3 | A computational strategy for the prediction of the crystal-field parameters of lanthanide complexes with ab initio methods is illustrated |
10.1126/science.abl5470 | 133,209,277 | Magnetic effects of lanthanide bonding Lanthanide coordination compounds have attracted attention for their persistent magnetic properties near liquid nitrogen temperature, well above alternative molecular magnets. Gould et al . report that introducing metal-metal bonding can enhance coercivity. Reduction of iodide-bri... | 10.1038/s41570-022-00424-3 | A mixed-valence Dy dimer is synthesized and shown to possess the largest coercive field and exchange coupling ever measured |
10.1126/science.1101077 | 62,394,996 | We demonstrate the ability to measure the energy required to flip the spin of single adsorbed atoms. A low-temperature, high–magnetic field scanning tunneling microscope was used to measure the spin excitation spectra of individual manganese atoms adsorbed on Al 2 O 3 islands on a NiAl surface. We find pronounced varia... | 10.1038/s41570-022-00424-3 | The elemental magnetic excitations of various atomic structures are detected via spin-flip inelastic spectroscopy from a scanning tunnelling microscope setup |
10.1126/science.aat2663 | 104,308,551 | The discovery of new materials can bring enormous societal and technological progress. In this context, exploring completely the large space of potential materials is computationally intractable. Here, we review methods for achieving inverse design, which aims to discover tailored materials from the starting point of a... | 10.1038/s41570-022-00424-3 | A machine-learning method is proposed for the generation of new molecules with target properties based on a continuous interpolation of the chemical space |
10.1007/s13238-020-00733-7 | 59,255,805 | Abstract Over 17 and 160 types of chemical modifications have been identified in DNA and RNA, respectively. The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics. Developing chemical and biological tools to ... | 10.1038/s41576-022-00559-5 | This review summarizes high-throughput NGS-based methods for mapping five forms of DNA modifications and eight forms of RNA modifications, and also summarizes biological discoveries made using these methods |
10.1126/science.abe7489 | 132,451,182 | The discovery of N 6 -methyldeoxyadenine (6mA) across eukaryotes led to a search for additional epigenetic mechanisms. However, some studies have highlighted confounding factors that challenge the prevalence of 6mA in eukaryotes. We developed a metagenomic method to quantitatively deconvolve 6mA events from a genomic D... | 10.1038/s41576-022-00559-5 | This paper describes a machine learning method that can quantitatively deconvolve 6mA events into eukaryotic species of interest and other sources, and warns about bacterial contamination in the study of 6mA in eukaryotic samples |
10.1093/nar/gkab1179 | 133,827,072 | Abstract Methylation on CpG residues is one of the most important epigenetic modifications of nuclear DNA, regulating gene expression. Methylation of mitochondrial DNA (mtDNA) has been studied using whole genome bisulfite sequencing (WGBS), but recent evidence has uncovered technical issues which introduce a potential ... | 10.1038/s41576-022-00559-5 | This paper describes the bias and technical concerns related to BS-seq in mapping 5mC in mtDNA and reports more reliable 5mC levels estimated by machine learning modelling of nanopore data |
10.1126/sciadv.aay3335 | 38,440,303 | N 6 -methyladenine (6mdA) is a widespread DNA modification in bacteria. More recently, 6mdA has also been characterized in mammalian DNA. However, measurements of 6mdA abundance and profiles are often very dissimilar between studies, even when performed on DNA from identical mammalian cell types. Using comprehensive bi... | 10.1038/s41576-022-00559-5 | This article reports that DIP-seq libraries can be contaminated with mammalian mRNA, and that high abundance of m 6 A in mRNA can contribute to false positive 6mA peaks in DIP-seq |
10.1101/gr.231068.117 | 20,438,356 | N6-Methyladenine (m 6 dA) has been discovered as a novel form of DNA methylation prevalent in eukaryotes; however, methods for high-resolution mapping of m 6 dA events are still lacking. Single-molecule real-time (SMRT) sequencing has enabled the detection of m 6 dA events at single-nucleotide resolution in prokaryotic... | 10.1038/s41576-022-00559-5 | This article demonstrates that sequencing technologies tend to make false positive 6mA calls in eukaryotes, and highlights the importance of FDR evaluation for low-abundance modifications |
10.1186/s13059-021-02510-z | 133,863,376 | Abstract Background Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylation from nanopore sequencing reads. Here, we assess the performance of different methylation... | 10.1038/s41576-022-00559-5 | This paper benchmarks computational methods for detecting 5mC in mammalian genomes using nanopore sequencing, and demonstrates that 5hmC levels may contribute to the discrepancy between BS-seq and nanopore sequencing |
10.1200/jco.2017.76.2229 | 62,055,105 | Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1–treatment outcomes may be improved with lower disease burden. In this context, we conducted a phase I study to eva... | 10.1038/s41571-018-0119-7 | Data from this study demonstrated that irradiation of one or a few lesions within a larger disease burden leads to response rates similar to those of historical results obtained with immunotherapy alone. These data suggest that, rather than using subtotal irradiation (irradiation of only one or a few sites), a new stra... |
10.1158/1078-0432.ccr-16-1432 | 62,375,287 | Abstract Purpose: Little prospective data are available on clinical outcomes and immune correlates from combination radiation and immunotherapy. We conducted a phase I trial (NCT02239900) testing stereotactic ablative radiotherapy (SABR) with ipilimumab. Experimental Design: SABR was given either concurrently (1 day af... | 10.1038/s41571-018-0119-7 | Analysis of data from a subset of patients revealing that the location of the irradiated tumour (lung versus liver) is important for eliciting an immune response, raising the issue of tumour-specific and site-specific heterogeneity dictating the likelihood of eliciting antitumour immune priming and responses. Specifica... |
10.1126/science.aao4426 | 62,160,543 | Brain mutations, young and old Most neurons that make up the human brain are postmitotic, living and functioning for a very long time without renewal (see the Perspective by Lee). Bae et al. examined the genomes of single neurons from the prenatal developing human brain. Both the type of mutation and the rates of accum... | 10.1038/s41586-021-03307-7 | Using single-cell sequencing, this study revealed increasing somatic mutations in neurons during human ageing, indicating that even post-mitotic cell types accrue mutations that might trigger age-associated functional decline and degeneration |
10.1073/pnas.1902510116 | 104,172,543 | Accumulation of mutations in somatic cells has been implicated as a cause of aging since the 1950s. However, attempts to establish a causal relationship between somatic mutations and aging have been constrained by the lack of methods to directly identify mutational events in primary human tissues. Here we provide genom... | 10.1038/s41586-021-03307-7 | Using single cell sequencing, L. Zhang and colleagues show increased somatic mutations during normal human ageing occurring in genes and regulatory regions indicating their role in the age-dependent functional decline |
10.1126/science.1070174 | 123,050,439 | One of the factors postulated to drive the aging process is the accumulation of DNA damage. Here, we provide strong support for this hypothesis by describing studies of mice with a mutation in XPD , a gene encoding a DNA helicase that functions in both repair and transcription and that is mutated in the human disorder ... | 10.1038/s41586-021-03307-7 | J. de Boer and colleagues established that genetic defects in DNA repair accelerate the mammalian ageing process |
10.1038/ncomms10770 | 62,150,364 | Abstract Mouse transgenesis has provided fundamental insights into pancreatic cancer, but is limited by the long duration of allele/model generation. Here we show transfection-based multiplexed delivery of CRISPR/Cas9 to the pancreas of adult mice, allowing simultaneous editing of multiple gene sets in individual cells... | 10.1038/s41576-018-0053-7 | This study first demonstrated the use of the CRISPR–Cas9 platform in a high-complexity, multiplexed format within an autochthonous mouse model |
10.1101/114355 | 91,114,055 | Loss of function screening by CRISPR/Cas9 gene knockout with pooled, lentiviral guide libraries is a widely applicable method for systematic identification of genes contributing to diverse cellular phenotypes. Here, random sequence labels (RSLs) are incorporated into the guide library, which act as unique molecular ide... | 10.1038/s41576-018-0053-7 | References 128 and 129 are early demonstrations of the utility of diversifying sgRNAs with DNA barcodes to enable analyses of individual clones within pooled formats, thereby increasing sensitivity in genetic screens |
10.1111/apt.15415 | 17,120,831 | Linked Content This article is linked to Lenti et al and Walker papers. To view these articles, visit https://doi.org/10.1111/apt.15317 and https://doi.org/10.1111/apt.15394 . | 10.1038/s41572-020-0187-8 | This is the first study exploring diagnostic delay in autoimmune gastritis |
10.1111/apt.15540 | 42,589,345 | Summary Background Autoimmune atrophic gastritis (AAG) is an immune‐mediated disorder characterised by destruction of gastric oxyntic mucosa Aim To explore gastric histopathological evolution in a cohort of AAG patients over a prolonged follow‐up Methods Single centre prospective study enrolling consecutive patients wi... | 10.1038/s41572-020-0187-8 | This paper describes the long-term natural history of autoimmune gastritis, with a description of potential autoimmune gastritis |
10.1111/j.1365-2036.2012.05101.x | 40,309,257 | Summary Background Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. Aims To describe the histological phenotype of autoimmune gastritis , also to test the prognostic impact of OLGA staging in the autoimmune setting. Met... | 10.1038/s41572-020-0187-8 | This paper describes the method for assessing the risk of developing gastric cancer depending on extension and severity of gastric atrophy |
10.1055/a-0859-1883 | 125,266,977 | Main Recommendations Patients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk stratification for these patients. High definition endoscopy with chromoendoscopy (CE) is better than high definition white-light endo... | 10.1038/s41572-020-0187-8 | This paper discusses the latest guidelines for endoscopic surveillance of gastric precancerous lesions |
10.1073/pnas.1205210109 | 80,610,214 | The microenvironment of the cochlea is maintained by the barrier between the systemic circulation and the fluids inside the stria vascularis. However, the mechanisms that control the permeability of the intrastrial fluid–blood barrier remain largely unknown. The barrier comprises endothelial cells connected to each oth... | 10.1038/s41577-018-0056-9 | This study shows that PVMs in the stria vascularis of the cochlea regulate the permeability of the intrastrial fluid–blood barrier to maintain a normal electrolyte balance in the endolymph. This is essential for normal hearing |
10.1038/srep32900 | 101,593,758 | Abstract The aim of the present study was to investigate if macrophage proliferation occurs in the brain during simian immunodeficiency virus (SIV) infection of adult macaques. We examined the expression of the Ki-67 proliferation marker in the brains of uninfected and SIV-infected macaques with or without encephalitis... | 10.1038/s41577-018-0056-9 | This study examines the expression of the proliferation marker Ki-67 in the brains of uninfected and SIV-infected macaques with or without encephalitis. The authors find a significant increase in the number of proliferating PVMs in macaques with SIV encephalitis compared with that in uninfected and SIV-infected animals... |
10.1084/jem.20170074 | 122,983,189 | We examined the transcriptional profiles of macrophages that reside in the islets of Langerhans of 3-wk-old non-obese diabetic (NOD), NOD.Rag1−/−, and B6.g7 mice. Islet macrophages expressed an activation signature with high expression of Tnf, Il1b, and MHC-II at both the transcript and protein levels. These features a... | 10.1038/s41577-018-0056-9 | This paper shows that in the pancreas, islet PVMs express a pro-inflammatory activation signature at steady state that supports diabetogenesis |
10.1039/c6cs00573j | 38,445,722 | This tutorial review outlines the theory and practice of computational modeling applied to understanding and predicting stereoselectivity. | 10.1038/s41570-018-0040-8 | This is a tutorial review outlining the theory and practice of modelling stereoselective reactions |
10.1039/c7sc04679k | 62,131,521 | The utilization of physical organic molecular descriptors for the quantitative description of reaction outcomes in multivariate linear regression models is demonstrated as an effective tool for a priori prediction and mechanistic interrogation. | 10.1038/s41570-018-0040-8 | This presents an overview of MLR methods and a detailed guide on model development |
10.1002/chem.201102785 | 83,268,721 | Abstract A prototypical catalytic cycle for the direct carboxylation of unactivated arene CH bonds with CO 2 based on ruthenium(II) pincer complexes as catalysts is proposed and investigated by density functional theory (DFT) methods. The energetic span model is used to predict the turnover frequency (TOF) of various ... | 10.1038/s41570-018-0040-8 | This is an example of a computationally led design of chemical reactivity that has not yet been tested experimentally |
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/s41570-018-0040-8 | This is an early example of the quantification of favourable non-covalent interactions and their use in correlating catalyst performance |
10.1046/j.1360-0443.1998.93913758.x | 125,046,486 | ackground. Pathological gambling is becoming an increasing problem in the United States as the number of legalized gambling establishments grows. To examine vulnerability to pathological gambling, we estimated the familial contributions (i.e. inherited factors and/or experiences shared by twin siblings during childhood... | 10.1038/s41572-019-0099-7 | This article was the first to provide estimates of genetic and environmental contributions to pathological gambling. |
10.1111/j.1360-0443.2005.01341.x | 80,940,081 | ABSTRACT Objective The objective is provide a framework concerning the minimum features of reporting efficacy of treatment in the problem gambling field. Research to date has not used uniform outcome measures and it is, therefore, difficult to compare the relative efficacy of various approaches. Some studies emphasize ... | 10.1038/s41572-019-0099-7 | This work presents consensus guidelines for how best to assess for outcomes in trials testing treatments for GD |
10.1126/science.1145593 | 101,075,465 | Shape-memory polymers can revert to their original shape when they are reheated. The stress generated by shape recovery is a growing function of the energy absorbed during deformation at a high temperature; thus, high energy to failure is a necessary condition for strong shape-memory materials. We report on the propert... | 10.1038/s41578-018-0078-8 | A one-way temperature-memory effect is enabled for a nanocomposite with a glass transition covering a broad temperature range |
10.1073/pnas.0600079103 | 107,161,242 | In shape-memory polymers, changes in shape are mostly induced by heating, and exceeding a specific switching temperature, T switch . If polymers cannot be warmed up by heat transfer using a hot liquid or gaseous medium, noncontact triggering will be required. In this article, the magnetically induced shape-memory effec... | 10.1038/s41578-018-0078-8 | A one-way shape-memory effect is magnetically triggered for a nanocomposite by sequentially coupling magnetosensitivity and thermosensitivity |
10.1126/science.1252610 | 62,523,903 | Origami can turn a sheet of paper into complex three-dimensional shapes, and similar folding techniques can produce structures and mechanisms. To demonstrate the application of these techniques to the fabrication of machines, we developed a crawling robot that folds itself. The robot starts as a flat sheet with embedde... | 10.1038/s41578-018-0078-8 | An elegant demonstration is given for the applicability of the reversible shape-memory effect to origami-based methods |
10.1126/science.1066102 | 62,247,536 | The introduction of biodegradable implant materials as well as minimally invasive surgical procedures in medicine has substantially improved health care within the past few decades. This report describes a group of degradable thermoplastic polymers that are able to change their shape after an increase in temperature. T... | 10.1038/s41578-018-0078-8 | A degradable, elastic thermoplastic is designed to exhibit a thermally triggered one-way shape-memory effect with potential medical applications |
10.1126/science.1244989 | 41,505,819 | Salt to Squeeze Simple table salt, NaCl, is the only known stable phase of Na and Cl at ambient conditions. Previous attempts to understand its structure and chemical properties under pressure and at high temperatures revealed phase and bonding transitions, while keeping the balance of one Na to one Cl. Using crystal s... | 10.1038/s41570-020-0213-0 | A good example showing, by using both DFT calculations and diamond anvil cell experiments, that common compounds such as NaCl can assume very different (atypical) compositions under high pressure. |
10.59350/fm16n-ycn69 | 150,875,990 | On February 6th I was alerted to this intriguing article[1] by a phone call, made 55 minutes before the article embargo was due to be released. Gizmodo wanted to know if I could provide an (almost) <sup> † </sup> instant <sup> ‡ </sup> quote. After a few days, this report of a stable compound of... | 10.1038/s41570-020-0213-0 | DFT calculations and diamond anvil cell experiments are used to demonstrate the first example of a stable solid He containing compound. |
10.1073/pnas.0908262106 | 103,637,121 | From detailed assessments of electronic structure, we find that a combination of significantly quantal elements, six of seven atoms being hydrogen, becomes a stable metal at a pressure approximately 1/4 of that required to metalize pure hydrogen itself. The system, LiH 6 (and other LiH n ), may well have extensions bey... | 10.1038/s41570-020-0213-0 | The first DFT study on hydrogen metallization in atypical metal hydrides with hydrogen rich composition, actualizing the pre-compression strategy proposed in Ref. 78. |
10.1073/pnas.1118168109 | 82,898,985 | Hydrogen-rich compounds hold promise as high-temperature superconductors under high pressures. Recent theoretical hydride structures on achieving high-pressure superconductivity are composed mainly of H 2 fragments. Through a systematic investigation of Ca hydrides with different hydrogen contents using particle-swam o... | 10.1038/s41570-020-0213-0 | The first DFT-based computational study predicting that metals can form superhydrides with sodalite H covalent lattices, heralding the recent remarkable discovery of superconducting metal superhydrides. |
10.1126/science.273.5271.95 | 81,706,134 | At high pressure the alkali metals potassium, rubidium, and cesium transform to metals that have a d 1 electron configuration, becoming transition metal-like. As a result, compounds were shown to form between potassium and the transition metal nickel. These results demonstrate that the chemical behavior of the alkali m... | 10.1038/s41570-020-0213-0 | This work demonstrates experimentally how K behaves like a transition metal under pressure; a well-known example of how pressure changes the fundamental properties of elements. |
10.1038/s41467-018-03284-y | 60,079,810 | Abstract Until very recently, helium had remained the last naturally occurring element that was known not to form stable solid compounds. Here we propose and demonstrate that there is a general driving force for helium to react with ionic compounds that contain an unequal number of cations and anions. The corresponding... | 10.1038/s41570-020-0213-0 | This work provides a new mechanism explaining how He can be reactive without forming any local chemical bonds, uncovering potential insertion reactions of He with many ionic compounds. |
10.1038/s41467-018-06172-7 | 123,920,976 | Abstract Adaptor protein 4 (AP-4) is an ancient membrane trafficking complex, whose function has largely remained elusive. In humans, AP-4 deficiency causes a severe neurological disorder of unknown aetiology. We apply unbiased proteomic methods, including ‘Dynamic Organellar Maps’, to find proteins whose subcellular l... | 10.1038/s41580-018-0094-y | This is the first example of how MS-based organellar maps of the cell can be used to pinpoint the molecular basis of a genetic disorder, in this case the neurodegenerative AP-4 deficiency syndrome |
10.1126/science.aal3321 | 104,257,315 | Mapping the proteome Proteins function in the context of their environment, so an understanding of cellular processes requires a knowledge of protein localization. Thul et al. used immunofluorescence microscopy to map 12,003 human proteins at a single-cell level into 30 cellular compartments and substructures (see the ... | 10.1038/s41580-018-0094-y | This study presents the first near proteome-wide spatial map of human cells, at unprecedented resolution in terms of the number of organelles and structures that were mapped, which represents the Cell Atlas component of the HPA. This study provides localization data for more than 12,000 human proteins and revealed a ve... |
10.1126/science.1260088 | 20,691,552 | Overcoming the limits of the microscope The resolution of a light microscope is limited. Physicists have long since worked out what these limits are and which parameters determine the spatial resolution. Many groups have nevertheless made numerous attempts to overcome these resolution limits. Rather than improving the ... | 10.1038/s41583-019-0250-1 | This article first reports the concept of expansion microscopy based on an exogenous hydrogel polymer |
10.1126/scitranslmed.aah6518 | 29,088,023 | Bone clearing and light-sheet microscopy enables visualization and quantification of fluorescent single cells in intact bone. | 10.1038/s41583-019-0250-1 | This article reports clearing of whole bone with preserved marrow and imaging endogenous fluorescence with single-cell resolution throughout the marrow by light-sheet microscopy |
10.7554/elife.12059 | 62,032,498 | Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. W... | 10.1038/s41583-019-0250-1 | This article describes the first applications of crowdsourcing of connectome tracing through the Web-based CATMAID framework |
10.1038/s42003-021-01674-5 | 17,563,076 | Abstract Biases in data used to train machine learning (ML) models can inflate their prediction performance and confound our understanding of how and what they learn. Although biases are common in biological data, systematic auditing of ML models to identify and eliminate these biases is not a common practice when appl... | 10.1038/s41576-021-00434-9 | This article proposes a set of data modifications that can be used to identify overestimated performance in supervised ML with paired-input data, such as protein–protein interactions, where examples occur in many pairs |
10.1111/ecog.02881 | 20,736,105 | Ecological data often show temporal, spatial, hierarchical (random effects), or phylogenetic structure. Modern statistical approaches are increasingly accounting for such dependencies. However, when performing cross‐validation, these structures are regularly ignored, resulting in serious underestimation of predictive e... | 10.1038/s41576-021-00434-9 | This study demonstrates blocking as an effective strategy for estimating the performance of ML models on data with complex dependency structures |
10.1073/pnas.102102699 | 19,194,558 | In the context of cancer diagnosis and treatment, we consider the problem of constructing an accurate prediction rule on the basis of a relatively small number of tumor tissue samples of known type containing the expression data on very many (possibly thousands) genes. Recently, results have been presented in the liter... | 10.1038/s41576-021-00434-9 | The authors present prediction of cancer outcome from expression of a small number of genes as an example of how supervised feature selection performed before cross-validation leads to performance overestimation |
10.1126/science.1129139 | 41,703,516 | The role of the adaptive immune response in controlling the growth and recurrence of human tumors has been controversial. We characterized the tumor-infiltrating immune cells in large cohorts of human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. Collectively, the immunologic... | 10.1038/s41573-018-0007-y | This article is the first demonstration of the dependence of tumour progression and invasion on the intratumoural adaptive immunity. T cell infiltrates and IFNγ signatures have predictive value superior to TNM with respect to the natural history of primary cancers |
10.1126/science.aad0095 | 125,331,168 | Is cancer immunotherapy a private affair? Immune checkpoint blockade, a relatively new cancer treatment, substantially extends the survival of a subset of patients. Previous work has shown that patients whose tumors harbor the largest number of mutations—and thus produce a large number of “neoantigens” recognized as fo... | 10.1038/s41573-018-0007-y | This article is the first to show that patients with metastatic melanoma with high mutational burden, neoantigen load and expression of cytolytic markers in their tumours are more likely to respond to anti-CTLA4 immunotherapy |
10.1158/0008-5472.can-08-2654 | 102,249,379 | Abstract A role for the immune system in controlling the progression of solid tumors has been established in several mouse models. However, the effect of immune responses and tumor escape on patient prognosis in the context of human cancer is poorly understood. Here, we investigate the cellular and molecular parameters... | 10.1038/s41573-018-0007-y | This paper presents the first description of the immune hot (optimal), altered-excluded, altered-immunosuppressed and cold (absent) tumours |
10.1200/jco.2017.73.7379 | 83,018,159 | Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor. Methods Patients with unresectable ... | 10.1038/s41573-018-0007-y | This paper presents the first randomized trial evaluating the combination of an oncolytic virus with a checkpoint inhibitor and showing a significantly higher objective response rate for T-VEC plus ipilimumab versus ipilimumab alone |
10.1126/science.1138659 | 83,017,798 | We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic reg... | 10.1038/s41583-022-00576-7 | This study conducts comparative genomic hybridization in simplex and multiplex families with ASD and establishes that de novo CNVs significantly contribute to ASD risk |
10.1126/science.1224989 | 101,458,839 | Expression patterns of the diverse genes disrupted in autism spectrum disorders in the developing brain give a fresh perspective on the underlying biology. | 10.1038/s41583-022-00576-7 | This review describes the rationale for and approaches to leveraging convergence among ASD genes to identify not only relevant molecules and pathways but also when and where they act in the developing human brain |
10.1126/science.aaz6063 | 62,398,384 | The number of disease risk genes and loci identified through human genetic studies far outstrips the capacity to systematically study their functions. We applied a scalable genetic screening approach, in vivo Perturb-Seq, to functionally evaluate 35 autism spectrum disorder/neurodevelopmental delay (ASD/ND) de novo los... | 10.1038/s41583-022-00576-7 | This paper conducted in vivo transcriptional screening of a large number of ASD risk genes using single-cell transcriptomics and CRISPR technology. |
10.1126/science.1089071 | 123,937,569 | We often think of neurodevelopmental disorders as beginning before birth, and many certainly do. A handful, however, strike many months after birth, following a period of apparently normal growth and development. Autism and Rett syndrome are two such disorders, and here I consider some of their similarities at the phen... | 10.1038/s41583-022-00576-7 | This early commentary proposes that ASD genetic risk may mechanistically converge at the synapse |
10.1038/s41598-018-19333-x | 20,650,932 | Abstract We found tremendous inequality across gene and protein annotation resources. We observed that this bias leads biomedical researchers to focus on richly annotated genes instead of those with the strongest molecular data. We advocate that researchers reduce these biases by pursuing data-driven hypotheses. | 10.1038/s41583-022-00576-7 | This paper analyses multiple annotation databases and finds significant inequalities across genes that have become more prominent over time, highlighting a self-perpetuating cycle that may be driven by the tendency of researchers to focus their efforts on richly annotated genes rather than those with the strongest mole... |
10.1126/science.aat8464 | 62,296,004 | Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of... | 10.1038/s41583-022-00576-7 | This study describes molecular data resources generated by the PsychENCODE Consortium from adult human brain tissue, and conducts a deconvolution analysis of bulk and single-cell expression data that finds that the majority of expression variation across bulk brain tissue samples is attributable to varying proportions ... |
10.1126/science.1100658 | 61,509,790 | Retroviral DNA can be subjected to cytosine-to-uracil editing through the action of members of the APOBEC family of cytidine deaminases. Here we demonstrate that APOBEC-mediated cytidine deamination of human immunodeficiency virus (HIV) virion RNA can also occur. We speculate that the natural substrates of the APOBEC e... | 10.1038/s41577-020-0391-5 | This study describes the identification of APOBEC-mediated RNA editing as a mechanism restricting HIV-1 replication |
10.1073/pnas.1210659109 | 83,009,800 | Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular virus neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protei... | 10.1038/s41577-020-0391-5 | These authors identify an important role for the ubiquitin–proteasome pathway in cytosolic neutralization of viral capsids |
10.1155/2017/2913297 | 6,748,715 | Reports suggesting a pathogenic role of autoantibodies directed against glutamic acid decarboxylase 65 (GAD65Abs) in cerebellar ataxias (CAs) are reviewed, and debatable issues such as internalization of antibodies by neurons and roles of epitopes are discussed. GAD65 is one of two enzymes that catalyze the conversion ... | 10.1038/s41582-020-0359-x | A comprehensive review of the potential role of GAD antibodies in cerebellar ataxia |
10.1038/ismej.2010.161 | 103,639,747 | Abstract Complex microbial populations are organized in relation to their environment. In the intestine, the inner lining (mucosa) is a potential focal point for such organization. The proximal murine colon contains mucosal folds that are known to be associated with morphologically distinct microbes. To identify these ... | 10.1038/s41575-020-00397-y | A study revealing the taxonomic specificity of mucosa-associated and lumenal microbiota in the mouse proximal colon |
10.1038/s41467-019-11140-w | 103,190,409 | Abstract Proteolytic homeostasis is important at mucosal surfaces, but its actors and their precise role in physiology are poorly understood. Here we report that healthy human and mouse colon epithelia are a major source of active thrombin. We show that mucosal thrombin is directly regulated by the presence of commensa... | 10.1038/s41575-020-00397-y | This study demonstrates that a host mediator (protease) control the physical properties of gut biofilms and its spatial exclusion from the gut epithelium |
10.1046/j.1365-2567.2003.01700.x | 16,699,602 | Summary It is critical, both for the host and for the long‐term benefit of the bacteria that colonize the gut, that bacterial overgrowth with subsequent bacterial translocation, which may lead to sepsis and death of the host, be avoided. Secretory IgA (sIgA) is known to be a key factor in this process, agglutinating ba... | 10.1038/s41575-020-00397-y | This study suggests a role for host IgA in the formation of gut biofilms and discusses the concept of ‘immune-inclusion/exclusion’ for IgA |
10.1177/08959374970110011801 | 27,936,977 | The human colonic ecosystem is an extremely complex environment comprised of several hundred different strains of bacteria. Studies were undertaken to determine whether these organisms formed metabolic or genotypically distinct assemblages in the gut microbiota in relation to polysaccharide fermentation. Measurements o... | 10.1038/s41575-020-00397-y | This study is the origin of our perception of the gut microbiota as a biofilm community, and proposes that a biofilm phenotype influences the microbially cooperative metabolism of carbohydrates within the gastrointestinal tract |
10.1073/pnas.1537100100 | 81,644,060 | The interbacterial communication system known as quorum sensing (QS) utilizes hormone-like compounds referred to as autoinducers to regulate bacterial gene expression. Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is the agent responsible for outbreaks of bloody diarrhea in several countries. We previously... | 10.1038/s41575-020-00397-y | This study reveals that host hormones can activate microbial quorum sensing |
10.1038/s41467-020-14685-3 | 83,306,359 | Abstract Bacterial biofilms, especially those associated with implanted medical devices, are difficult to eradicate. Curli amyloid fibers are important components of the biofilms formed by the Enterobacteriaceae family. Here, we show that a human monoclonal antibody with pan-amyloid-binding activity (mAb 3H3) can disru... | 10.1038/s41575-020-00397-y | This study demonstrates the ability of human immunoglobulins to alter the formation of deleterious biofilms on medical implants |
10.1038/s41522-017-0036-z | 29,282,575 | Abstract Enterococcus faecalis is a leading causative agent of catheter-associated urinary tract infection (CAUTI), the most common hospital-acquired infection. Its ability to grow and form catheter biofilm is dependent upon host fibrinogen (Fg). Examined here are how bacterial and host proteases interact with Fg and c... | 10.1038/s41575-020-00397-y | This study shows that a host protease can act as a defence mechanism against deleterious biofilm growth in mouse bladder |
10.1126/science.aat9931 | 83,515,510 | The gut microbiota is implicated in the metabolism of many medical drugs, with consequences for interpersonal variation in drug efficacy and toxicity. However, quantifying microbial contributions to drug metabolism is challenging, particularly in cases where host and microbiome perform the same metabolic transformation... | 10.1038/s41575-020-00397-y | A comprehensive review of the current knowledge and future directions regarding the role of gut microorganisms in the metabolism of human drugs |
10.1073/pnas.1710465114 | 20,862,194 | Better stewardship of land is needed to achieve the Paris Climate Agreement goal of holding warming to below 2 °C; however, confusion persists about the specific set of land stewardship options available and their mitigation potential. To address this, we identify and quantify “natural climate solutions” (NCS): 20 cons... | 10.1038/s41558-022-01440-3 | This is the first paper to quantify the climate mitigation effects of global NCS and their contribution towards achieving the global climate goals. |
10.1038/s43247-022-00391-z | 135,922,263 | Abstract Meeting the Paris Agreement’s climate objectives will require the world to achieve net-zero CO 2 emissions around or before mid-century. Nature-based climate solutions, which aim to preserve and enhance carbon storage in terrestrial or aquatic ecosystems, could be a potential contributor to net-zero emissions ... | 10.1038/s41558-022-01440-3 | This paper reports that there is a risk that carbon stored by NCS could be lost back to the atmosphere owing to disturbances. |
10.1017/sus.2021.2 | 39,782,236 | Non-technical summary We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in t... | 10.1038/s41558-022-01440-3 | A review article that highlights the strong coupling between gross domestic product (GDP), resource utilization, human well-being and greenhouse gas emissions. |
10.1126/science.aaa7017 | 20,822,256 | Early T cells keep autoimmunity at bay A major challenge faced by the immune system is to react to foreign substances, such as microbes, while simultaneously tolerating the self. Upsetting this balance leads to autoimmunity. Regulatory T cells (T regs ), are a subset of immune cells that help to maintain this balance. ... | 10.1038/s41590-018-0128-9 | This study invokes another layer of a tolerance defect in the Aire-deficient model where T reg cells are inappropriately selected early in life that then help protect against autoimmune responses in the tissues |
10.1084/jem.20171000 | 38,450,830 | During αβT cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection a... | 10.1038/s41590-018-0128-9 | This study helps clarify the potential role for lymphotoxin β signaling in thymic medulla specification. Here a more complex role of lymphotoxin receptor β signaling was unraveled, including a role for both mTECs and dendritic cell populations. |
10.1126/sciimmunol.aan5165 | 59,011,595 | Genetic variations in antigen-peptide processing machinery influence T cell repertoire selection and susceptibility to autoimmune disease. | 10.1038/s41590-018-0128-9 | This translational study finds evidence correlating a SNP risk variant for Sjögren’s syndrome with activity of the thymoproteosome for positive selection. These results suggest that this could be part of the mechanism by which autoimmunity is triggered in this disease. |
10.1084/jem.20150888 | 61,761,184 | A brother and sister developed a previously undescribed constellation of autoimmune manifestations within their first year of life, with uncontrollable bullous pemphigoid, colitis, and proteinuria. The boy had hemophilia due to a factor VIII autoantibody and nephrotic syndrome. Both children required allogeneic hematop... | 10.1038/s41590-018-0128-9 | This study identifies a single family with inheritance of an autoimmune syndrome that correlated with the presence of two mutant ZAP70 alleles. This family provides evidence of hypomorphic Zap70 activity in the generation of autoimmunity |
10.1126/sciimmunol.abb6808 | 60,873,082 | Influenza is a deadly and costly infectious disease, even during flu seasons when an effective vaccine has been developed. To improve vaccines against respiratory viruses, a better understanding of the immune response at the site of infection is crucial. After influenza infection, clonally expanded T cells take up perm... | 10.1038/s41577-021-00583-2 | This study provides evidence that lung-resident T helper cells should be induced by vaccination to support local antibody responses to influenza virus |
10.1111/cei.13564 | 35,162,073 | Summary The United Kingdom has a national immunization programme which includes annual influenza vaccination in school-aged children, using live attenuated influenza vaccine (LAIV). LAIV is given annually, and it is unclear whether repeat administration can affect immunogenicity. Because LAIV is delivered intranasally,... | 10.1038/s41577-021-00583-2 | This report shows that pre-existing antigen-specific nasal IgA does not compromise live attenuated influenza vaccine immunogenicity in children |
10.1038/ncomms15221 | 100,350,598 | Abstract Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck ... | 10.1038/s41577-021-00583-2 | This study shows that mucosal vaccine-induced T RM cells enhance antitumour immunity in mice |
10.1126/science.aah5043 | 41,699,635 | In model systems, bacteria present in human pancreatic tumors confer resistance to the anticancer drug gemcitabine. | 10.1038/s41590-020-0761-y | This study identified Gammaproteobacteria species capable of metabolizing the chemotherapy drug gemcitabine to an inactive form and found Gammaproteobacteria species in human PDA |
10.1126/science.1198443 | 62,632,231 | CD40 immunotherapy shows efficacy in treating pancreatic cancer in mice and humans by eliciting antitumor immunity. | 10.1038/s41590-020-0761-y | This study reported clinical responses to CD40 agonism in combination with gemcitabine in patients and identified macrophage-dependent mechanisms that enabled responses to CD40-targeted treatment in mice |
10.1126/scitranslmed.aau9240 | 62,342,140 | Although checkpoint immunotherapies have revolutionized the treatment of cancer, not all tumor types have seen substantial benefit. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy in which very limited responses to immunotherapy have been observed. Extensive immunosuppressive myeloid cell infiltra... | 10.1038/s41590-020-0761-y | This study showed that activation of the myeloid cell surface receptor CD11b reprogrammed immunosuppressive macrophages in the TME and enabled effective antigen presentation, leading to an effective adaptive immune response that synergized with checkpoint immunotherapy |
10.1126/science.aay9189 | 83,453,205 | Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, inc... | 10.1038/s41590-020-0761-y | This study characterized intratumoral bacterial microbiomes across multiple human tumor types, including PDA, and found that different tumor types harbor distinct microbial communities |
10.1126/scisignal.abj9842 | 131,593,232 | αβ T cells are critical components of the adaptive immune system and are capable of inducing sterilizing immunity after pathogen infection and eliminating transformed tumor cells. The development and function of T cells are controlled through the T cell antigen receptor, which recognizes peptides displayed on major his... | 10.1038/s41590-023-01446-9 | A review article that highlights the role of self-peptide MHC recognition in T cell development. |
10.1101/2020.09.22.309229 | 2,537,881 | Recent developments in Oblique Plane Microscopy (OPM) have shown that it can achieve high spatio-temporal resolution. Here we describe a single objective light-sheet microscope based on oblique plane illumination that achieves: (i) large field of view and high-resolution imaging via a custom remote focusing objective; ... | 10.1038/s41592-022-01420-7 | An ongoing project that reports the use of a custom glass-tipped objective lens for high-resolution, single-objective light-sheet microscopy — a critical step towards widespread adoption |
10.1126/sciadv.abi9119 | 128,522,738 | A perfusable vascularized 3D-bioprinted cancer model with stromal cells can be used for personalized therapy and target discovery. | 10.1038/s41568-022-00514-w | This study describes a complex perfusable TME model that includes patient-derived glioblastoma cells, endothelial cells, pericytes, astrocytes and microglia |
10.1002/advs.202200244 | 143,126,385 | Abstract Neuroblastoma (NB) is the most common extracranial tumor in children resulting in substantial morbidity and mortality. A deeper understanding of the NB tumor microenvironment (TME) remains an area of active research but there is a lack of reliable and biomimetic experimental models. This study utilizes a 3D bi... | 10.1038/s41568-022-00514-w | This study describes a perfusable TME model that includes patient-derived neuroblastoma cells, endothelial cells, adipocyte-derived MSCs and induced pluripotent stem cell-derived MSCs |
10.1126/sciadv.aay7513 | 104,211,192 | Glioblastoma multiforme (GBM) is a lethal type of brain tumor that often develop therapeutic resistance over months of chemotherapy cycles. Recently, 3D GBM models were developed to facilitate evaluation of drug treatment before undergoing expensive animal studies. However, for long-term evaluation of therapeutic effic... | 10.1038/s41568-022-00514-w | This study shows that use of a high-resolution tomography platform can markedly improve the imaging of thick 3D bioprinted models |
10.1126/sciadv.abb3308 | 123,452,108 | Understanding the dynamics of circulating tumor cell (CTC) behavior within the vasculature has remained an elusive goal in cancer biology. To elucidate the contribution of hydrodynamics in determining sites of CTC vascular colonization, the physical forces affecting these cells must be evaluated in a highly controlled ... | 10.1038/s41568-022-00514-w | This study describes a computational model that can be used to represent fundamental biological phenomena |
10.1002/smll.202006050 | 18,448,721 | Abstract Glioblastoma multiforme (GBM) is the most lethal primary brain tumor characterized by high cellular and molecular heterogeneity, hypervascularization, and innate drug resistance. Cellular components and extracellular matrix (ECM) are the two primary sources of heterogeneity in GBM. Here, biomimetic tri‐regiona... | 10.1038/s41568-022-00514-w | This study describes the first species-matched 3D bioprinted in vitro models to recapitulate the biophysical heterogeneity of glioblastoma |
10.3389/fimmu.2021.689697 | 84,398,585 | Chimeric antigen receptor (CAR) T cell performance against solid tumors in mouse models and clinical trials is often less effective than predicted by CAR construct selection in two-dimensional (2D) cocultures. Three-dimensional (3D) solid tumor architecture is likely to be crucial for CAR T cell efficacy. We used a thr... | 10.1038/s41568-022-00514-w | This study describes a highly reproducible 3D bioprinted model for preclinical (in vitro) characterization and optimization of CAR T cells for use in personalized therapy |
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