source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1126/science.1213214 | 62,279,733 | Two niches with distinct characteristics work in tandem. | 10.1038/s41580-020-0278-0 | Takeda et al. find that CBCs and +4 cells can directly interconvert |
10.1126/science.1067799 | 104,375,704 | We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This... | 10.1038/s41577-019-0155-2 | This study reports the development of 3C to detect 3D genome organization |
10.1126/science.1068768 | 29,201,609 | Immunoglobulin (Ig) loci are selectively activated for transcription and rearrangement during B lymphocyte development. Using fluorescence in situ hybridization, we show that Ig heavy (H) and Igκ loci are preferentially positioned at the nuclear periphery in hematopoietic progenitors and pro-T cells but are centrally c... | 10.1038/s41577-019-0155-2 | This study provides the first evidence in mammals that gene activity is regulated by nuclear position and that Igh contracts in pro-B cells to facilitate V(D)J recombination |
10.1101/gad.293910.116 | 41,714,723 | Neutrophils are responsible for the first line of defense against invading pathogens. Their nuclei are uniquely structured as multiple lobes that establish a highly constrained nuclear environment. Here we found that neutrophil differentiation was not associated with large-scale changes in the number and sizes of topol... | 10.1038/s41577-019-0155-2 | This study provides the first genome-wide examination of the impact of nuclear lobing on genome organization |
10.1073/pnas.95.4.1511 | 62,356,127 | The lactate dehydrogenase A ( LDH-A ) gene, whose product participates in normal anaerobic glycolysis and is frequently increased in human cancers, has been identified as a c-Myc-responsive gene. It was of interest, therefore, to compare the effect of glucose deprivation in c-Myc-transformed and nontransformed cells. W... | 10.1038/s41573-021-00339-6 | This article provided a link between an oncogene and glucose dependency |
10.1083/jcb.200703099 | 18,025,212 | The idea that conversion of glucose to ATP is an attractive target for cancer therapy has been supported in part by the observation that glucose deprivation induces apoptosis in rodent cells transduced with the proto-oncogene MYC, but not in the parental line. Here, we found that depletion of glucose killed normal huma... | 10.1038/s41573-021-00339-6 | This article provided a link between an oncogene and glutamine dependency |
10.1126/science.aaf5171 | 41,515,600 | Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or ... | 10.1038/s41573-021-00339-6 | This article shows the complexity of the tissue of origin-specific link between RAS and metabolism |
10.1158/1535-7163.mct-13-0870 | 41,665,712 | Abstract Glutamine serves as an important source of energy and building blocks for many tumor cells. The first step in glutamine utilization is its conversion to glutamate by the mitochondrial enzyme glutaminase. CB-839 is a potent, selective, and orally bioavailable inhibitor of both splice variants of glutaminase (KG... | 10.1038/s41573-021-00339-6 | This article describes the development of the clinical stage glutaminase inhibitor CB-839 |
10.1200/jco.2021.39.15_suppl.4501 | 135,584,586 | 4501 Background: Dysregulated metabolism is a hallmark of RCC, driven by overexpression of glutaminase (GLS), a key enzyme of glutamine metabolism. Telaglenastat (Tela) is an investigational, first-in-class, selective, oral GLS inhibitor that blocks glutamine utilization and critical downstream pathways. Preclinically,... | 10.1038/s41573-021-00339-6 | This paper reports the clinical outcome of targeting glutaminase in renal cell carcinoma and failure to meet the primary end point |
10.1038/s41467-019-13561-z | 83,408,125 | Abstract Various methyltransferases and demethylases catalyse methylation and demethylation of N 6 -methyladenosine (m6A) and N 6 ,2′-O-dimethyladenosine (m6Am) but precise methylomes uniquely mediated by each methyltransferase/demethylase are still lacking. Here, we develop m6A-Crosslinking-Exonuclease-sequencing (m6A... | 10.1038/s41592-022-01668-z | This article describes single-base-resolution m6A profiling with m6ACE-seq, the main technology used for training m6Anet |
10.1101/2021.05.20.444035 | 18,007,006 | DNA methylation is a type of epigenetic modification that affects gene expression regulation and is associated with several human diseases. Microarray and short read sequencing technologies are often used to study 5'-methylcytosine (5'-mC) modification of CpG dinucleotides in the human genome. Although both technologie... | 10.1038/s41592-022-01668-z | This preprint describes the Singapore Nanopore Expression project, a comprehensive resource for direct RNA-seq data from human cell lines. |
10.7554/elife.49658 | 83,407,543 | Understanding genome organization and gene regulation requires insight into RNA transcription, processing and modification. We adapted nanopore direct RNA sequencing to examine RNA from a wild-type accession of the model plant Arabidopsis thaliana and a mutant defective in mRNA methylation (m6A). Here we show that m6A ... | 10.1038/s41592-022-01668-z | This article describes the Arabidopsis data we used to demonstrate the generalizability of m6Anet to other species. |
10.1038/s41467-019-11713-9 | 41,715,017 | Abstract The epitranscriptomics field has undergone an enormous expansion in the last few years; however, a major limitation is the lack of generic methods to map RNA modifications transcriptome-wide. Here, we show that using direct RNA sequencing, N 6 -methyladenosine (m 6 A) RNA modifications can be detected with hig... | 10.1038/s41592-022-01668-z | This article describes a set of synthetic sequences that can be used to train and evaluate supervised methods for detection of RNA modifications from direct RNA-seq data. |
10.1038/srep45043 | 124,066,913 | Abstract Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachm... | 10.1038/s41579-020-00449-9 | This paper shows that IAV HA and NA proteins coordinate iterative receptor binding and release, resulting in accelerated viral motility and endocytosis into target cells |
10.7554/elife.43764 | 20,852,049 | Influenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspe... | 10.1038/s41579-020-00449-9 | This paper shows that HA and NA proteins are asymmetrically distributed on filamentous IAV particles, contributing to directional motility |
10.1128/jvi.01579-18 | 103,328,709 | Defective viral genomes (DVGs) generated during Sendai virus infections accumulate in the cytoplasm of some infected cells and stimulate antiviral immunity and cell survival. DVGs are packaged and released as defective particles and have a significant impact on infection outcome. We show that the subpopulation of DVG-h... | 10.1038/s41579-020-00449-9 | This paper uses fluorescent in situ hybridization to reveal heterogeneity in the intracellular localization of DVGs compared with full-length genomes during Sendai virus infection |
10.1038/s41467-017-00909-6 | 38,861,090 | Abstract Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report that durin... | 10.1038/s41579-020-00449-9 | This paper uses single-cell analysis to reveal that DVGs promote a MAVS-dependent TNF pro-survival pathway, driving persistence of paramyxoviruses |
10.1126/science.3798106 | 104,442,629 | The HER-2/ neu oncogene is a member of the erb B-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigat... | 10.1038/s41573-022-00579-0 | This work demonstrated that HER2 amplification is a prognostic factor and predictive of outcomes in breast cancer |
10.1038/embor.2013.170 | 104,259,726 | Mechanical forces associated with fluid flow and/or circumferential stretch are sensed by renal epithelial cells and contribute to both adaptive or disease states. Non‐selective stretch‐activated ion channels (SACs), characterized by a lack of inactivation and a remarkably slow deactivation, are active at the basolater... | 10.1038/s41581-019-0143-6 | This article presents evidence that PC2 inhibits PIEZO1 opening in renal epithelial cells through a cytoskeleton-mediated mechanoprotection mechanism |
10.1152/ajprenal.00272.2016 | 41,286,184 | Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening monogenic renal disease. ADPKD results from mutations in either of two proteins: polycystin-1 (also known as PC1 or PKD1) or transient receptor potential cation channel, subfamily P, member 2 (TRPP2, also known as polycystin-2, PC2... | 10.1038/s41581-019-0143-6 | This study demonstrates that PC2 at the primary cilium is activated by both depolarization and an increase in intraciliary calcium |
10.1161/circulationaha.107.710111 | 20,416,619 | Background— When challenged with extracellular fluid shear stress, vascular endothelial cells are known to release nitric oxide, an important vasodilator. Here, we show that the ability of cultured endothelial cells to sense a low range of fluid shear depends on apical membrane organelles, called cilia, and that cilia ... | 10.1038/s41581-019-0143-6 | This research demonstrates that activation of PC1–PC2 by shear stress increases the release of NO by the endothelium |
10.1126/science.aat9819 | 83,390,997 | Mutations in two genes, PKD1 and PKD2 , account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated io... | 10.1038/s41581-019-0143-6 | This report presents the first structural determination of the PC1–PC2 complex |
10.1038/s41467-018-04586-x | 117,609,892 | Abstract PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to respond to ligand(s) and/or mechanical stimuli. Here, we identify a two-residue hydrophobic gate in PKD2L1, and a s... | 10.1038/s41581-019-0143-6 | This study shows that Leu777 in the S6 of PC2 acts as a hydrophobic gate |
10.1128/mcb.25.18.8285-8298.2005 | 101,105,647 | ABSTRACT PKD2, or polycystin 2, the product of the gene mutated in type 2 autosomal dominant polycystic kidney disease, belongs to the transient receptor potential channel superfamily and has been shown to function as a nonselective cation channel in the plasma membrane. However, the mechanism of PKD2 activation remain... | 10.1038/s41581-019-0143-6 | This study provides evidence that EGF activates PC2 currents in renal cells |
10.1242/jcs.02818 | 101,050,538 | Primary cilia play a key role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The affected proteins, polycystin-1 (PC1) and polycystin-2 (PC2), interact with each other and are expressed in cilia. We found that COOH-terminal truncated PC2 (PC2-L703X), lacking the PC1 interaction region, sti... | 10.1038/s41581-019-0143-6 | This report demonstrates that PC2 is targeted to the primary cilium independently of PC1 |
10.1126/science.1193270 | 125,070,423 | Mechanical Responders Identified Although many cells appear to respond to mechanical stimulation through increased conductance of ion channels in the plasma membrane, the actual channels that mediate these effects—which are important in diverse processes from hearing and touch to control of blood pressure—have remained... | 10.1038/s41581-019-0143-6 | This article reports on the discovery of the mechanosensitive PIEZO channels |
10.1126/science.1222538 | 61,482,424 | Distinguishing Right from Left In most vertebrates during embryonic development, rotational movement of the cilia within a structure in the embryo, known as the node, generates unidirectional flow required for future left-right asymmetry of the internal organs. The flow may transport a determinant molecule or provide m... | 10.1038/s41581-019-0143-6 | This study demonstrates that flow-induced PC2 opening in nodal cells is responsible for left–right asymmetry |
10.1101/gr.3715005 | 125,080,545 | We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes ). Parallel searches have been performed with multiple alignments of four insect species (three species of Drosophila and... | 10.1038/s41576-021-00389-x | This paper uses the PhastCons method to give per-base estimates of negative selection within conserved elements using multiple sequence alignments and hidden Markov models |
10.1101/gr.097857.109 | 83,400,000 | Methods for detecting nucleotide substitution rates that are faster or slower than expected under neutral drift are widely used to identify candidate functional elements in genomic sequences. However, most existing methods consider either reductions (conservation) or increases (acceleration) in rate but not both, or as... | 10.1038/s41576-021-00389-x | This paper discusses the pathogenicity scoring method PhyloP using multiple sequence alignments and gives the per-base P value for conservation/acceleration scores per clade that reflect divergence from the neutral rate |
10.1101/gr.227819.117 | 20,753,642 | Models for predicting phenotypic outcomes from genotypes have important applications to understanding genomic function and improving human health. Here, we develop a machine-learning system to predict cell-type–specific epigenetic and transcriptional profiles in large mammalian genomes from DNA sequence alone. By use o... | 10.1038/s41576-021-00389-x | This paper uses Basenji as a CNN sequence model that predicts regulatory factor binding and expression based on cap analysis gene expression (CAGE) peak data |
10.1093/bioinformatics/btu703 | 125,314,318 | Summary: Annotating genetic variants, especially non-coding variants, for the purpose of identifying pathogenic variants remains a challenge. Combined annotation-dependent depletion (CADD) is an algorithm designed to annotate both coding and non-coding variants, and has been shown to outperform other annotation algorit... | 10.1038/s41576-021-00389-x | This paper presents a pathogenicity scoring method, which is a deep learning (CNN) version of CADD, for coding and non-coding variant fitness impact |
10.1101/735928 | 100,701,413 | After nearly two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no one chromosome has been finished end to end, and hundreds of unresolved gaps persist 1,2 . The remaining gaps include ribosomal rDNA arrays, large near-ide... | 10.1038/s41576-020-0236-x | This landmark study shows that PacBio and ONT long reads are able to generate a de novo genome assembly superior in contiguity to all other genome assemblies (including hg38). Importantly, it reveals the first telomere-to-telomere sequence assembly of a human chromosome and shows that it is possible to resolve megabase... |
10.1038/s41587-020-0503-6 | 41,754,295 | Abstract De novo assembly of a human genome using nanopore long-read sequences has been reported, but it used more than 150,000 CPU hours and weeks of wall-clock time. To enable rapid human genome assembly, we present Shasta, a de novo long-read assembler, and polishing algorithms named MarginPolish and HELEN. Using a ... | 10.1038/s41576-020-0236-x | This study describes the rapid assembly of 11 human genomes using ONT long reads, and it debuts a new assembler (Shasta) and polisher (HELEN). This article provides the methodological basis for scalability in human genome assembly using long reads |
10.1126/science.aax2083 | 62,324,084 | Copy number variants (CNVs) are subject to stronger selective pressure than single-nucleotide variants, but their roles in archaic introgression and adaptation have not been systematically investigated. We show that stratified CNVs are significantly associated with signatures of positive selection in Melanesians and pr... | 10.1038/s41576-020-0236-x | The authors describe large structural variants, originating in Neanderthals or Denisovans, that show signs of adaptation and positive selection in the Melanesian population. In particular, they use long reads to assemble a 386-kb duplication polymorphism that is present in 79% of Melanesians but generally absent from o... |
10.1101/705616 | 38,288,277 | Abstract De novo genome assembly provides comprehensive, unbiased genomic information and makes it possible to gain insight into new DNA sequences not present in reference genomes. Many de novo human genomes have been published in the last few years, leveraging a combination of inexpensive short-read and single-molecul... | 10.1038/s41576-020-0236-x | This article describes a unique and fast genome assembly algorithm called Peregrine that uses PacBio HiFi data. This long-read assembler is able to assemble a human genome in less than 100 minutes or ~30 CPU hours |
10.1073/pnas.1320101110 | 41,512,579 | Significance Isoform identification and discovery are an important goal for transcriptome analysis because the majority of human genes express multiple isoforms with context- and tissue-specific functions. Better annotation of isoforms will also benefit downstream analysis such as expression quantification. Current RNA... | 10.1038/s41576-020-0236-x | This article shows that full-length mRNA transcripts can be sequenced from end to end to identify novel gene isoforms using the PacBio Iso-Seq method. This article also provides a catalogue of the poly(A) transcriptome in human embryonic stem cells using a combination of Iso-Seq and short-read sequencing data |
10.1126/science.aab3516 | 62,137,422 | Axon paths in developing spinal cords Sensory neurons entering the spinal cord take different paths as inputs for pain and proprioception diverge. Working with chick and mouse embryos, Guy et al. found that glycerophospholipids produced by radial glial cells guide these neural fibers, or axons, in the developing spinal... | 10.1038/s41583-019-0168-7 | This very interesting study uncovers a role for lipids in sensory axon guidance |
10.1126/science.279.5347.105 | 58,564,343 | Developing axons reach their final targets as a result of a series of axonal projections to successive intermediate targets. Long-range chemoattraction by intermediate targets plays a key role in this process. Growing axons, however, do not stall at the intermediate targets, where the chemoattractant concentration is e... | 10.1038/s41583-019-0168-7 | This landmark paper, together with that of Zou et al. (2000), provides the first direct experimental evidence for the ‘midline switch’ model |
10.1126/science.aam8999 | 83,498,681 | Identifying single-cell types in the mouse brain The recent development of single-cell genomic techniques allows us to profile gene expression at the single-cell level easily, although many of these methods have limited throughput. Rosenberg et al. describe a strategy called split-pool ligation-based transcriptome sequ... | 10.1038/s41583-019-0168-7 | This article presents one of the recent cell profiling and RNA sequencing studies that illustrate the unknown diversity of spinal cord interneurons. |
10.1046/j.1365-2818.2000.00710.x | 83,318,735 | Lateral resolution that exceeds the classical diffraction limit by a factor of two is achieved by using spatially structured illumination in a wide‐field fluorescence microscope. The sample is illuminated with a series of excitation light patterns, which cause normally inaccessible high‐resolution information to be enc... | 10.1038/s41592-022-01636-7 | Seminal paper for structured illumination microscopy, which was used here to improve the resolution in LSFM. |
10.1073/pnas.1609278114 | 18,663,292 | Light-sheet-based fluorescence microscopy (LSFM) features optical sectioning in the excitation process. It minimizes fluorophore bleaching as well as phototoxic effects and provides a true axial resolution. The detection path resembles properties of conventional fluorescence microscopy. Structured illumination microsco... | 10.1038/s41592-022-01636-7 | A previous effort to combine structured illumination with LSFM using two illumination and one detection objective. |
10.1146/annurev.biochem.77.032207.120833 | 62,607,077 | Collagen is the most abundant protein in animals. This fibrous, structural protein comprises a right-handed bundle of three parallel, left-handed polyproline II-type helices. Much progress has been made in elucidating the structure of collagen triple helices and the physicochemical basis for their stability. New eviden... | 10.1038/s41578-020-0213-1 | This review paper describes the structure and characteristics of collagen triple helices |
10.1002/art.24293 | 61,502,281 | Abstract Objective Chondrocytes, the sole cell type in articular cartilage, maintain the extracellular matrix (ECM) through a homeostatic balance of anabolic and catabolic activities that are influenced by genetic factors, soluble mediators, and biophysical factors such as mechanical stress. Chondrocytes are encapsulat... | 10.1038/s41578-020-0213-1 | This paper describes the structure–function relationship of collagen type VI and cartilage pericellular matrix stiffness |
10.1126/science.1195271 | 20,806,677 | Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis i... | 10.1038/s41577-020-0274-9 | Genome-wide association study of thousands of individuals confirmed that polymorphisms within the HLA class I binding pocket are strongly associated with spontaneous HIV control |
10.1126/science.aav5095 | 38,236,863 | Mutationally constrained epitopes of variable pathogens represent promising targets for vaccine design but are not reliably identified by sequence conservation. In this study, we employed structure-based network analysis, which applies network theory to HIV protein structure data to quantitate the topological importanc... | 10.1038/s41577-020-0274-9 | Network analysis of HIV protein structures identified CD8 + T cell epitopes derived from topologically important regions of the viral proteome that were constrained from mutation, targeted by proliferative responses in spontaneous HIV controllers and presented by common HLA alleles with broad representation in the glob... |
10.1182/blood-2011-10-381996 | 18,777,347 | Abstract True long-term nonprogressors (LTNPs)/elite controllers (ECs) maintain durable control over HIV replication without antiretroviral therapy. Herein we describe 4 unique persons who were distinct from conventional LTNPs/ECs in that they had extraordinarily low HIV burdens and comparatively weak immune responses.... | 10.1038/s41577-020-0274-9 | Characterization of individuals with extraordinary CD8 + T cell-mediated spontaneous control of HIV infection to levels at which replication-competent virus was unable to be recovered, suggesting potential avenues for functional cure, remission or perhaps even clearance of replication-competent HIV reservoirs |
10.1242/dev.149658 | 41,229,028 | How position-dependent cell fate acquisition occurs during embryogenesis is a central question in developmental biology. To study this process, we developed a defined, high-throughput assay to induce peri-gastrulation-associated patterning in geometrically-confined human pluripotent stem cell (hPSC) colonies. We observ... | 10.1038/s41576-018-0040-z | This study employs an in vitro model of a stem-cell-derived, developmentally-relevant, fate-patterning system and demonstrates that reaction diffusion and positional information can work in concert to give rise to emergent complexity in stem cell systems. |
10.1038/ncomms8329 | 101,987,833 | Abstract Reprogramming is a dynamic process that can result in multiple pluripotent cell types emerging from divergent paths. Cell surface protein expression is a particularly desirable tool to categorize reprogramming and pluripotency as it enables robust quantification and enrichment of live cells. Here we use cell s... | 10.1038/s41576-018-0040-z | This study employs mass spectrometry analysis of the surface proteome of reprogramming cells to identify a key marker that can distinguish different reprogramming and PSC states in both murine and human systems |
10.15252/msb.20145141 | 40,595,002 | Abstract The hematopoietic system is a distributed tissue that consists of functionally distinct cell types continuously produced through hematopoietic stem cell ( HSC ) differentiation. Combining genomic and phenotypic data with high‐content experiments, we have built a directional cell–cell communication network betw... | 10.1038/s41576-018-0040-z | This study combines genomic and phenotypic data with high-content experiments to build a directional cell–cell communication network between 12 cell types in human umbilical cord blood. |
10.1126/science.1248882 | 61,027,500 | Predicting stem cell renewal or differentiation Predicting complex mammalian cell behavior is extremely challenging. Dunn et al. developed a computational model that predicts when embryonic stem cells will self-renew or differentiate. The model revealed an essential program governing pluripotency and identifies a minim... | 10.1038/s41576-018-0040-z | This paper reports the development of a data-constrained, computational approach to derive a simple GRN that functionally captures the mouse PSC state |
10.1073/pnas.092258599 | 62,102,921 | Natural killer (NK) cells express inhibitory and activation receptors that recognize MHC class I-like molecules on target cells. These receptors may be involved in the critical role of NK cells in controlling initial phases of certain viral infections. Indeed, the Ly49H NK cell activation receptor confers in vivo genet... | 10.1038/s41590-018-0163-6 | In refs. 45 and 46, the authors identify the MCMV protein m157 as the specific ligand for the NK cell activating receptor Ly49H and thereby for the first time describe a pathogen-specific recognition mechanism for NK cells |
10.1084/jem.20101831 | 62,250,296 | Recognition of mouse cytomegalovirus (MCMV)–infected cells by activating NK cell receptors was first described in the context of Ly49H, which confers resistance to C57BL/6 mice. We investigated the ability of other activating Ly49 receptors to recognize MCMV-infected cells in mice from various H-2 backgrounds. We obser... | 10.1038/s41590-018-0163-6 | In ref. 56, additional receptors of the Ly49 family are reported to specifically recognize MCMV via the viral ligand m04 in mouse strains other than C57BL/6, highlighting the general importance of this recognition mode of NK cells |
10.1182/blood-2004-05-2058 | 19,095,612 | Expression of the activating CD94/NKG2C killer lectin-like receptor (KLR) specific for HLA-E was analyzed in peripheral blood lymphocytes (PBLs) from healthy adult blood donors; the expression of other natural killer (NK) cell receptors (ie, CD94/NKG2A, KIR, CD85j, CD161, NKp46, NKp30, and NKG2D) was also studied. Huma... | 10.1038/s41590-018-0163-6 | In ref. 59, the authors report for the first time dominant imprinting of HCMV on the NK cell population and note the striking population expansion of NKG2C + NK cells, setting the stage for further studies of this population in humans |
10.4049/jimmunol.162.1.305 | 139,040,879 | Abstract The CD94/NKG2 receptors expressed by subpopulations of NK cells and T cells have been implicated as receptors for a broad range of both classical and nonclassical HLA class I molecules. To examine the ligand specificity of CD94/NKG2 proteins, a soluble heterodimeric form of the receptor was produced and used i... | 10.1038/s41590-018-0163-6 | The studies in refs. 68–70 describe HLA-E as the ligand for receptors of the NKG2 family and how the presentation of leader peptides on HLA-E allows NK cells to surveil the expression of classical HLA class I |
10.4049/jimmunol.164.10.5019 | 81,985,079 | Abstract Human CMV has evolved multiple strategies to interfere with immune recognition of the host. A variety of mechanisms target Ag presentation by MHC class I molecules resulting in a reduced class I cell-surface expression. This down-regulation of class I molecules is expected to trigger NK cytotoxicity, which wou... | 10.1038/s41590-018-0163-6 | In refs. 78,79, the authors demonstrate how the HCMV protein gpUL40 can substitute for leader peptides derived from HLA class I to upregulate HLA-E and thereby protect HCMV against lysis by NKG2A + NK cells |
10.4049/jimmunol.1002151 | 19,211,654 | Abstract The thymic medulla represents a key site for the induction of T cell tolerance. In particular, autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) provide a spectrum of tissue-restricted Ags that, through both direct presentation and cross-presentation by dendritic cells, purge the... | 10.1038/s41577-019-0238-0 | Together with Yano et al. (2008), this study is the first to show that AIRE + mTECs are not terminally differentiated cells but rather give rise to phenotypically distinct subsets characterized by high levels of KRT10 expression. |
10.1126/science.1075958 | 41,666,351 | Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire - deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue– restricted antigens in me... | 10.1038/s41577-019-0238-0 | This study is the first to uncover the functional role of AIRE in promiscuous gene expression and central tolerance induction. |
10.1101/gad.194282.112 | 110,856,590 | In eukaryotes, the replication of chromosome DNA is coordinated by a replication timing program that temporally regulates the firing of individual replication origins. However, the molecular mechanism underlying the program remains elusive. Here, we report that the telomere-binding protein Taz1 plays a crucial role in ... | 10.1038/s41594-020-0400-1 | This paper shows that Taz1 controls the replication timing of a subset of late origins by directly binding to telomeric repeats found proximal to origins |
10.1101/gad.178491.111 | 38,310,142 | One of the long-standing questions in eukaryotic DNA replication is the mechanisms that determine where and when a particular segment of the genome is replicated. Cdc7/Hsk1 is a conserved kinase required for initiation of DNA replication and may affect the site selection and timing of origin firing. We identified rif1Δ... | 10.1038/s41594-020-0400-1 | This paper reveals that global replication timing in S pombe is controlled by Rif1 in a Taz1-independent fashion |
10.1101/gad.231258.113 | 123,027,868 | Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by dire... | 10.1038/s41594-020-0400-1 | This paper shows that the budding yeast protein Rif1 controls DNA replication genome-wide and that Rif1 exerts this control through PP1-mediated dephosphorylation of the MCM complex early in the cell cycle |
10.1126/science.1192759 | 103,699,234 | A Hot Dipole In a ferroelectric material, there is an alignment of local electric dipole moments that produces a net overall electric polarization. This state is accompanied by a decrease in symmetry, which can be restored by heating above a critical temperature. In contrast, through a combination of theory and experim... | 10.1038/s41563-023-01513-4 | This article presents evidence for local symmetry breaking in PbTe using the X-ray PDF technique. |
10.1242/jcs.108.11.3463 | 83,384,460 | Point mutations in the keratin intermediate filament genes for keratin 5 or keratin 14 are known to cause hereditary skin blistering disorders such as epidermolysis bullosa simplex, in which epidermal keratinocytes are extremely fragile and the skin blisters on mild trauma. We show that in 2 phenotypically diverse case... | 10.1038/s41572-020-0210-0 | This paper demonstrates thermolability of the keratin cytoskeleton, which manifests clinically as increased blistering and skin fragility in warm conditions |
10.1038/ncomms14839 | 20,419,999 | Abstract Terminal cobalt(IV)–oxo (Co IV –O) species have been implicated as key intermediates in various cobalt-mediated oxidation reactions. Herein we report the photocatalytic generation of a mononuclear non-haem [(13-TMC)Co IV (O)] 2+ ( 2 ) by irradiating [Co II (13-TMC)(CF 3 SO 3 )] + ( 1 ) in the presence of [Ru I... | 10.1038/s41570-020-0197-9 | This paper described the first thorough spectroscopic characterization of a Co( iv )–oxo complex |
10.1126/science.299.5609.1037 | 41,723,999 | Following the heme paradigm, it is often proposed that dioxygen activation by nonheme monoiron enzymes involves an iron(IV)=oxo intermediate that is responsible for the substrate oxidation step. Such a transient species has now been obtained from a synthetic complex with a nonheme macrocyclic ligand and characterized s... | 10.1038/s41570-020-0197-9 | The first crystal structure of a synthetic non-haem iron( iv )–oxo complex was reported with the thorough spectroscopic characterization |
10.1002/anie.200900863 | 40,826,178 | Abstract High versus low : The high‐yield generation of a synthetic high‐spin oxoiron(IV) complex, [Fe IV (O)(TMG 3 tren)] 2+ (see picture, TMG 3 tren = 1,1,1‐tris{2‐[N2‐(1,1,3,3‐tetramethylguanidino)]ethyl}amine), has been achieved by using the very bulky tetradentate TMG 3 tren ligand, in order to both sterically pro... | 10.1038/s41570-020-0197-9 | A high-spin ( S = 2) non-haem iron( iv )–oxo complex with a trigonal bipyramidal geometry was synthesized and characterized spectroscopically for the first time |
10.1126/science.1133417 | 41,723,962 | Iron(V)-oxo species have been proposed as key reactive intermediates in the catalysis of oxygen-activating enzymes and synthetic catalysts. Here, we report the synthesis of [Fe(TAML)(O)] – in nearly quantitative yield, where TAML is a macrocyclic tetraamide ligand. Mass spectrometry, Mössbauer, electron paramagnetic r... | 10.1038/s41570-020-0197-9 | This study reports the first spectroscopically well characterized mononuclear non-haem iron( v )–oxo complex, demonstrating that iron( v )–oxo species can be synthesized in non-haem iron models |
10.1126/science.289.5481.938 | 104,346,671 | Iron species with terminal oxo ligands are implicated as key intermediates in several synthetic and biochemical catalytic cycles. However, there is a dearth of structural information regarding these types of complexes because their instability has precluded isolation under ambient conditions. The isolation and structur... | 10.1038/s41570-020-0197-9 | The structural characterization of an iron( iii ) complex with a terminal oxo ligand, which was synthesized by activating dioxygen, was reported for the first time |
10.1002/anie.201904546 | 19,836,482 | Abstract Terminal oxo complexes of late transition metals are frequently proposed reactive intermediates. However, they are scarcely known beyond Group 8. Using mass spectrometry, we prepared and characterized two such complexes: [(N4Py)Co III (O)] + ( 1 ) and [(N4Py)Co IV (O)] 2+ ( 2 ). Infrared photodissociation spec... | 10.1038/s41570-020-0197-9 | In this study, high-valent Co–O complexes were generated in the gas phase and characterized using spectroscopy and quantum-chemical calculations |
10.1126/science.1234070 | 17,706,786 | Balancing Humans with Apes Shared ancestral polymorphisms between species tend to be relatively rare, and studies of trans-species polymorphisms have focused on just a few regions known for balancing selection. Leffler et al. (p. 1578 , published online 14 February) performed genome-wide scans among humans and great ap... | 10.1038/s41576-020-0269-1 | This study reports on many sites with TSPs and ancient balancing selection in genomes of humans and chimpanzees |
10.1073/pnas.1810402116 | 20,408,899 | Red Queen dynamics, involving coevolutionary interactions between species, are ubiquitous, shaping the evolution of diverse biological systems. To date, information on the underlying selection dynamics and the involved genome regions is mainly available for bacteria–phage systems or only one of the antagonists of a euk... | 10.1038/s41576-020-0269-1 | This study of experimental evolution with nematodes and a bacterial pathogen demonstrates the complexity of co-evolutionary interactions emerging in seemingly simple systems |
10.1073/pnas.1710980115 | 20,592,537 | Infectious diseases are often affected by specific pairings of hosts and pathogens and therefore by both of their genomes. The integration of a pair of genomes into genome-wide association mapping can provide an exquisitely detailed view of the genetic landscape of complex traits. We present a statistical method, ATOMM... | 10.1038/s41576-020-0269-1 | This study describes the development of a powerful co-genomics method that utilizes data from an interaction matrix of all combinations of host and parasite genotypes to find the genomic sites that underlie the interaction |
10.1111/1755-0998.12968 | 104,392,983 | Abstract There is an increasing demand for evolutionary models to incorporate relatively realistic dynamics, ranging from selection at many genomic sites to complex demography, population structure, and ecological interactions. Such models can generally be implemented as individual‐based forward simulations, but the la... | 10.1038/s41576-020-0269-1 | This paper describes the implementation of tree-sequence recording into the already multifaceted and powerful SLiM simulation framework, and provides one of the most important schemes needed to model neutral and non-neutral dynamics on genome-scale data |
10.1038/s41586-020-1943-3 | 83,488,365 | Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCG... | 10.1038/s41588-023-01304-2 | This paper summarizes mutational signatures in human cancer and the mutational burden that they contribute. |
10.1126/science.8511591 | 125,130,042 | Mammalian apolipoprotein B (apo B) exists in two forms, each the product of a single gene. The shorter form, apo B48, arises by posttranscriptional RNA editing whereby cytidine deamination produces a UAA termination codon. A full-length complementary DNA clone encoding an apo B messenger RNA editing protein (REPR) was ... | 10.1038/s41588-023-01304-2 | This paper identifies APOBEC1 and establishes its role as the mRNA-editing enzyme for apolipoprotein B, a crucial component of lipoproteins that are responsible for carrying lipids. |
10.1126/science.1260352 | 41,736,289 | Dumping lots of plastics into our oceans Considerable progress has been made in determining the amount and location of plastic debris in our seas, but how much plastic actually enters them in the first place is more uncertain. Jambeck et al. combine available data on solid waste with a model that uses population densit... | 10.1038/s41559-017-0116 | Combines data on waste production with a model that uses population density and economic status to estimate the amount of land-based plastic waste entering the ocean. |
10.1073/pnas.1314705111 | 41,741,573 | Significance High concentrations of floating plastic debris have been reported in remote areas of the ocean, increasing concern about the accumulation of plastic litter on the ocean surface. Since the introduction of plastic materials in the 1950s, the global production of plastic has increased rapidly and will continu... | 10.1038/s41559-017-0116 | Provides a first-order approximation of how much plastic pollution there is in surface waters resulting in a global map of high-density areas. |
10.1073/pnas.1519019113 | 83,389,815 | Plastics are persistent synthetic polymers that accumulate as waste in the marine environment. Microplastic (MP) particles are derived from the breakdown of larger debris or can enter the environment as microscopic fragments. Because filter-feeder organisms ingest MP while feeding, they are likely to be impacted by MP ... | 10.1038/s41559-017-0116 | Provides data to illustrate multigenerational effects of microplastic in an invertebrate model illustrating potential ecological impact in marine ecosystems. |
10.1126/science.aaf1648 | 41,739,173 | Tuft cells help contain parasites Trillions of microbes inhabit our guts, including worms and other parasites. Epithelial cells that line the gut orchestrate parasite-targeted immune responses. Howitt et al. now identify a key cellular player in immunity to parasites: tuft cells (see the Perspective by Harris). Tuft ce... | 10.1038/s41577-019-0176-x | In this study the protist Tritrichomonas is shown to potently stimulate the TRPM5-dependent tuft cell–ILC2 circuit |
10.1002/cne.21768 | 20,841,320 | Abstract To determine the role in chemosensation of intestinal solitary cells that express taste receptors and Trpm5, we carried out a microarray study of the transcriptome of FACS‐sorted transgenic mouse intestinal cells expressing enhanced green fluorescent protein (eGFP) under the control of the Trpm5 promoter and c... | 10.1038/s41577-019-0176-x | This article presents the first expression profiling of tuft cells using a Trpm5 –GFP reporter, revealing chemosensory–immune–neuronal programmes |
10.1083/jcb.201010127 | 125,051,435 | The unique morphology of tuft cells was first revealed by electron microscopy analyses in several endoderm-derived epithelia. Here, we explore the relationship of these cells with the other cell types of the intestinal epithelium and describe the first marker signature allowing their unambiguous identification. We demo... | 10.1038/s41577-019-0176-x | This paper presents a detailed characterization of small intestine tuft cell markers and development |
10.1101/310110 | 72,327,760 | Summary Initiation of immune responses requires innate immune sensing, but immune detection of the helminths, protists, and allergens that stimulate type 2 immunity remains poorly understood. In the small intestine, type 2 immune responses are regulated by a tuft cell-ILC2 signaling circuit. Tuft cells express componen... | 10.1038/s41577-019-0176-x | This study presents an RNA sequencing profiling of tuft cells and identification of Tritrichomonas -induced succinate–SUCNR1-mediated activation |
10.1073/pnas.1720758115 | 41,665,779 | The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 ( Sucnr1 ) is specifica... | 10.1038/s41577-019-0176-x | This study identifies succinate–SUCNR1-mediated tuft cell activation by succinate-producing microbiota |
10.1038/s41467-017-02291-9 | 62,620,314 | Abstract Reversible anionic redox has rejuvenated the search for high-capacity lithium-ion battery cathodes. Real-world success necessitates the holistic mastering of this electrochemistry’s kinetics, thermodynamics, and stability. Here we prove oxygen redox reactivity in the archetypical lithium- and manganese-rich la... | 10.1038/s41560-018-0097-0 | This work proved redox reactivity of bulk lattice oxygen in Li-rich NMC using hard-XPS and further correlated it with the issues of hysteresis and sluggish kinetics |
10.1038/s41467-017-02041-x | 83,359,186 | Abstract Lithium-rich layered transition metal oxide positive electrodes offer access to anion redox at high potentials, thereby promising high energy densities for lithium-ion batteries. However, anion redox is also associated with several unfavorable electrochemical properties, such as open-circuit voltage hysteresis... | 10.1038/s41560-018-0097-0 | This work proved redox reactivity of bulk lattice oxygen in Li-rich NMC using STXM and further correlated it with cation migration to explain voltage hysteresis |
10.1111/pai.12584 | 40,525,135 | Abstract Targeting the IgE pathway is a clinically validated strategy for treating IgE‐mediated diseases. Omalizumab, an anti‐IgE antibody, which binds to free IgE and prevents the binding of IgE to FcεRI on mast cells and basophils has been approved for severe persistent allergic asthma and chronic spontaneous (idiopa... | 10.1038/s41573-021-00266-6 | Explains the strategy of depleting IgE-committed B cells by targeting membrane IgE |
10.1111/all.13460 | 41,770,380 | Abstract Background The skin of atopic dermatitis ( AD ) patients presents a significant dysbalance of the microbiome with a high colonization by Staphylococcus aureus ( S. aureus ), which positively correlates with the severity of the disease. Objective Understanding the role of epidermal dendritic cells (DC) as link ... | 10.1038/s41573-021-00266-6 | The first report that epidermal DCs isolated from AD skin are tolerant to S. aureus derived signals |
10.1126/science.aaw6985 | 125,231,427 | Organoids are microscopic self-organizing, three-dimensional structures that are grown from stem cells in vitro. They recapitulate many structural and functional aspects of their in vivo counterpart organs. This versatile technology has led to the development of many novel human cancer models. It is now possible to cre... | 10.1038/s41587-022-01398-9 | A Review discussing the use of organoids as tumor models that recapitulate the original tumor characteristics. |
10.1073/pnas.211053698 | 62,257,322 | Mammalian cells can respond to damage or stress by entering a state of arrested growth and altered function termed cellular senescence. Several lines of evidence suggest that the senescence response suppresses tumorigenesis. Cellular senescence is also thought to contribute to aging, but the mechanism is not well under... | 10.1038/s41568-019-0156-2 | This is the first study to have shown that senescence can be pro-tumorigenic |
10.1158/2159-8290.cd-13-0743 | 38,297,518 | Abstract Neoplastic cells rely on the tumor microenvironment (TME) for survival and progression factors. Indeed, senescent and cancer-associated fibroblasts (CAF) express factors that promote tumorigenesis that are collectively referred to as the senescence-associated secretory phenotype (SASP). Despite their importanc... | 10.1038/s41568-019-0156-2 | This reference highlights the important role of p38MAPK in the post-transcriptional regulation of SASP. |
10.1038/ncomms11762 | 20,599,385 | Abstract Age is a significant risk factor for the development of cancer. However, the mechanisms that drive age-related increases in cancer remain poorly understood. To determine if senescent stromal cells influence tumorigenesis, we develop a mouse model that mimics the aged skin microenvironment. Using this model, he... | 10.1038/s41568-019-0156-2 | This study shows that senescent stromal cells recruit myeloid-derived suppressor cells, which creates an immunosuppressive microenvironment in which cancer cells thrive. |
10.1038/s41598-018-19211-6 | 17,990,847 | Abstract Microvesicles (MVs) released by cells are involved in a multitude of physiological events as important mediators of intercellular communication. MVs derived from mesenchymal stem cells (MSCs) contain various paracrine factors from the cells that primarily contribute to their therapeutic efficacy observed in nu... | 10.1038/s41573-021-00139-y | This report shows a path towards large-scale production of exosomes, a major issue for broad therapeutic application, using a 3D cell culture bioprocessing method |
10.1038/s41598-018-36340-0 | 41,642,549 | Abstract The blood-brain barrier (BBB) has long limited therapeutic access to brain tumor and peritumoral tissue. In animals, MR-guided focused ultrasound (MRgFUS) with intravenously injected microbubbles can temporarily and repeatedly disrupt the BBB in a targeted fashion, without open surgery. Our objective is to dem... | 10.1038/s41573-021-00139-y | This is the first clinical study using transcranial MRI-guided FUS for site-specific BBB opening in patients with brain tumours intravenously infused with doxorubicin or temozolomide |
10.1038/s41467-019-10493-6 | 80,189,867 | Abstract Reactive astrocytes evolve after brain injury, inflammatory and degenerative diseases, whereby they undergo transcriptomic re-programming. In malignant brain tumors, their function and crosstalk to other components of the environment is poorly understood. Here we report a distinct transcriptional phenotype of ... | 10.1038/s41568-021-00397-3 | This publication describes a subset of glioma-associated astrocytes characterized by the upregulation of STAT3 in surgical specimen-derived cultures, with some evidence that induction of immune-suppressive cytokines requires interactions with microglia |
10.1242/dev.122820 | 38,873,258 | Congenital anomalies are a significant burden on human health. Understanding the developmental origins of such anomalies is key to developing potential therapies. The Human Developmental Biology Resource (HDBR), based in London and Newcastle, UK, was established to provide embryonic and fetal material for a variety of ... | 10.1038/s41586-021-03620-1 | The HDBR is a biobank that collects and distributes material for research from human embryos (from 4 weeks after conception) and fetuses (up to 22 weeks after conception); shows the range of facilities offered by the HDBR and provides access for prospective users. |
10.1126/science.aba7721 | 62,298,724 | The gene expression program underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of gene expression and chromatin accessibility in fetal tissues. For gene expression, we applied three-level combinatorial indexing to >110 samples representing 15 organs, ultimate... | 10.1038/s41586-021-03620-1 | One of a set of two studies focusing on integrating single-cell gene expression 55 and chromatin accessibility 118 from 15 first- and second-trimester human organs |
10.1126/science.aat1699 | 83,407,590 | Pediatric and adult kidney tumors differ Understanding tumor origins and the similarities and differences between organ-specific cancers is important for determining treatment options. Young et al. generated more than 72,000 single-cell transcriptomes from healthy and cancerous human kidneys. From these data, they dete... | 10.1038/s41586-021-03620-1 | Comparative single-cell analyses of fetal, paediatric and adult kidneys and of Wilms’ tumours, demonstrating the origin of Wilms’ tumour as aberrant nephron development |
10.1126/science.aba6500 | 41,699,592 | The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leverage... | 10.1038/s41586-021-03620-1 | Comparative analyses of fetal skin with healthy and diseased adult skin, revealing the co-option of developmental cell programs in two common inflammatory skin conditions (atopic dermatitis and psoriasis) |
10.1101/gr.253880.119 | 81,917,312 | Aging is a pleiotropic process affecting many aspects of mammalian physiology. Mammals are composed of distinct cell type identities and tissue environments, but the influence of these cell identities and environments on the trajectory of aging in individual cells remains unclear. Here, we performed single-cell RNA-seq... | 10.1038/s41577-021-00646-4 | This article presents single-cell transcriptomics of four mouse organs and characterizes tissue-specific alterations in transcriptional programmes of stromal and immune cells during ageing |
10.1126/sciadv.aaw8330 | 104,391,525 | Age-associated changes in CD4 T-cell functionality have been linked to chronic inflammation and decreased immunity. However, a detailed characterization of CD4 T cell phenotypes that could explain these dysregulated functional properties is lacking. We used single-cell RNA sequencing and multidimensional protein analys... | 10.1038/s41577-021-00646-4 | This article profiles CD4 + T cells from young and old mice and defines cytotoxic, exhausted and activated T reg cells as hallmarks of ageing in the CD4 + T cell compartment |
10.1073/pnas.1907883116 | 62,642,551 | Supercentenarians, people who have reached 110 y of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mono... | 10.1038/s41577-021-00646-4 | This study generates an scRNA-seq dataset for circulating immune cells in supercentenarians and describes accumulation of cytotoxic CD4 + T cells in extremely old individuals |
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