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10.4049/jimmunol.171.5.2581 | 78,920,349 | Abstract Murine dendritic cells (DCs) can present Ag in an immunogenic or tolerogenic fashion, the distinction depending on either the occurrence of specialized DC subsets or the maturation or activation state of the DC. Although DC subsets may be programmed to direct either tolerance or immunity, it is not known wheth... | 10.1038/nri1457 | This report shows that IDO-mediated suppression can be upregulated or downregulated by signals from the immune system. |
10.1073/pnas.1018987108 | 39,340,036 | There is no treatment available for vision loss associated with advanced dry age-related macular degeneration (AMD) or geographic atrophy (GA). In a pilot, proof of concept phase 2 study, we evaluated ciliary neurotrophic factor (CNTF) delivered via an intraocular encapsulated cell technology implant for the treatment ... | 10.1038/nrd3745 | This is the first study to demonstrate neuroprotection by CNTF in a Phase II clinical trial. |
10.1083/jcb.200202009 | 20,156,102 | Ras–membrane interactions play important roles in signaling and oncogenesis. H-Ras and K-Ras have nonidentical membrane anchoring moieties that can direct them to different membrane compartments. Ras–lipid raft interactions were reported, but recent studies suggest that activated K-Ras and H-Ras are not raft resident. ... | 10.1038/nrm1105 | A comprehensive comparison of the plasma-membrane interactions of Ras proteins using FRAP. It concludes that activated H-ras and K-ras interact dynamically with different non-raft membrane microdomains. |
10.1091/mbc.01-11-0552 | 81,644,124 | Activation of the epidermal growth factor receptor (EGFR) triggers multiple signaling pathways and rapid endocytosis of the epidermal growth factor (EGF)–receptor complexes. To directly visualize the compartmentalization of molecules involved in the major signaling cascade, activation of Ras GTPase, we constructed fusi... | 10.1038/nrm1105 | This study provides elegant and compelling evidence that Ras proteins enter the endocytic pathway. |
10.2307/2265693 | 123,886,941 | The potential harmful effects of non—indigenous species introduced for biological control remain an important unanswered question, which we addressed by undertaking a literature review. There are few documented instances of damage to non—target organisms or the environment from non—indigenous species released for biolo... | 10.1038/nrg1201 | A rigorous assessment of the risks that are associated with biological control, including non-target effects. |
10.1146/annurev.ento.48.060402.102800 | 18,951,598 | ▪ Abstract Controversy exists over ecological risks in classical biological control. We reviewed 10 projects with quantitative data on nontarget effects. Ten patterns emerged: (a) Relatives of the pest are most likely to be attacked; (b) host-specificity testing defines physiological host range, but not ecological rang... | 10.1038/nrg1201 | An examination of non-target effects in 10 case studies of biological control. |
10.1079/9780851997353.0000 | 15,471,566 | Abstract This book is the result of the 12 keynote addresses, delivered at the third IOBC International Symposium held in Montpellier, France in October 2002, focusing on recent developments in genetics and evolutionary biology, and their relevance to biological control. Chapters are organized around the following them... | 10.1038/nrg1201 | An up-to-date review of genetics and evolutionary biology as applied to biological control. |
10.1002/ps.719 | 18,349,142 | Abstract USDA‐ARS scientists have made important contributions to the molecular genetic analysis of agriculturally important insects, and have been in the forefront of using this information for the development of new pest management strategies. Advances have been made in the identification and analysis of genetic syst... | 10.1038/nrg1201 | A summary of the ways in which molecular genetic approaches are used in pest management. |
10.1073/pnas.100110397 | 104,056,865 | Despite the severe ecological and economic damage caused by introduced species, factors that allow invaders to become successful often remain elusive. Of invasive taxa, ants are among the most widespread and harmful. Highly invasive ants are often unicolonial, forming supercolonies in which workers and queens mix freel... | 10.1038/nrg1201 | An elegant study of the effects of reduced genetic diversity, which led to changes in behaviour that were associated with the invasion biology of Argentine ants. |
10.1126/science.293.5536.1786 | 103,672,424 | In addition to altering global ecology, technology and human population growth also affect evolutionary trajectories, dramatically accelerating evolutionary change in other species, especially in commercially important, pest, and disease organisms. Such changes are apparent in antibiotic and human immunodeficiency viru... | 10.1038/nrg1201 | A review that documents the role of evolution in human civilization. |
10.1038/ncomms8214 | 17,347,900 | Abstract Genetic variation within a species could cause negative epistasis leading to reduced hybrid fitness and post-zygotic reproductive isolation. Recent studies in yeasts revealed chromosomal rearrangements as a major mechanism dampening intraspecific hybrid fertility on rich media. Here, by analysing a large numbe... | 10.1038/nrg.2017.49 | This study provides experimental and genomic evidence that BDMIs are widespread within S. cerevisiae and may help to initiate reproductive barriers in fluctuating environments. |
10.1073/pnas.1323011111 | 107,184,338 | Significance Spontaneous mutations are rare and difficult to observe in large numbers experimentally. By sequencing the genomes of 145 diploid mutation accumulation (MA) lines of the budding yeast Saccharomyces cerevisiae , we identified nearly 1,000 mutations, a larger number than in any prior eukaryotic MA experiment... | 10.1038/nrg.2017.49 | This study provides a direct estimation of the molecular mutation rates in S. cerevisiae from many mutation accumulation lines and different mutation classes. |
10.1534/g3.116.035329 | 125,288,291 | Abstract Gene and genome duplication are the major sources of biological innovations in plants and animals. Functional and transcriptional divergence between the copies after gene duplication has been considered the main driver of innovations . However, here we show that increased phenotypic plasticity after duplicatio... | 10.1038/nrg.2017.49 | This study demonstrates that duplicate genes respond more specifically to stress than singletons, a transcriptional plasticity that is potentially involved in adaptation. |
10.7554/elife.19027 | 89,962,671 | The evolutionary mechanisms leading to duplicate gene retention are well understood, but the long-term impacts of paralog differentiation on the regulation of metabolism remain underappreciated. Here we experimentally dissect the functions of two pairs of ancient paralogs of the GALactose sugar utilization network in t... | 10.1038/nrg.2017.49 | This paper illustrates the important involvement of duplication in the evolution of transcriptional and metabolic networks by investigating differences in the galactose utilization network among Saccharomyces species. |
10.1038/ng.3847 | 103,997,942 | Abstract Structural rearrangements have long been recognized as an important source of genetic variation, with implications in phenotypic diversity and disease, yet their detailed evolutionary dynamics remain elusive. Here we use long-read sequencing to generate end-to-end genome assemblies for 12 strains representing ... | 10.1038/nrg.2017.49 | The most recent leading paper that presents a comprehensive comparison of evolutionary genome dynamics between domesticated and wild yeasts, using long-read sequencing. |
10.1038/ismej.2016.170 | 91,186,093 | Abstract The budding yeasts are prime models in genomics and cell biology, but the ecological factors that determine their success in non-human-associated habitats is poorly understood. In North America Saccharomyces yeasts are present on the bark of deciduous trees, where they feed on bark and sap exudates. In the Nor... | 10.1038/nrg.2017.49 | This study investigates the genetic determinants and conditions that are required for optimal growth in maple sap, using a functional genomic screen. |
10.1146/annurev.immunol.15.1.177 | 84,427,133 | ▪ Abstract The autosomal recessive human disorder ataxia-telangiectasia (A-T) was first described as a separate disease entity 40 years ago. It is a multisystem disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodefi... | 10.1038/nrm2514 | A comprehensive early review on A-T and the cloning and characteristics of the ATM gene. |
10.1126/science.7792600 | 18,981,767 | A gene, ATM , that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT is characterized by cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities.... | 10.1038/nrm2514 | Describes the identification of the ATM gene, which is defective in A-T. |
10.1126/science.3975628 | 80,302,742 | The cells and tissues of patients with ataxia-telangiectasia (A-T), an inherited disease characterized by a high degree of proneness to cancer, are abnormally sensitive to ionizing radiation. Noncycling cultures of normal human and A-T fibroblasts were exposed to x-rays so that the breakage and rejoining of prematurely... | 10.1038/nrm2514 | Describes the defective gene in A-T which is localized to chromosome 11q. |
10.1146/annurev.phyto.44.070505.143436 | 83,079,451 | Abstract The oomycetes form a phylogenetically distinct group of eukaryotic microorganisms that includes some of the most notorious pathogens of plants. Oomycetes accomplish parasitic colonization of plants by modulating host cell defenses through an array of disease effector proteins. The biology of effectors is poorl... | 10.1038/nrmicro1549 | This review highlights recent findings on the structure of oomycete effectors, such as the RxLR effectors. |
10.1126/science.1104022 | 84,508,291 | Plants are constantly exposed to attack by an array of diverse pathogens but lack a somatically adaptive immune system. In spite of this, natural plant populations do not often suffer destructive disease epidemics. Elucidating how allelic diversity within plant genes that function to detect pathogens (resistance genes)... | 10.1038/nrmicro1549 | The cloning of Hyaloperonospora parasitica ATR1 along with other oomycete avirulence genes resulted in the discovery of the conserved RxLR motif. |
10.1073/pnas.2133080100 | 28,211,015 | When the malaria parasite Plasmodium falciparum infects an erythrocyte, it resides in a parasitophorous vacuole and remarkably exports proteins into the periphery of its host cell. Two of these proteins, the histidine-rich proteins I and II (PfHRPI and PfHRPII), are exported to the erythrocyte cytoplasm. PfHRPI has bee... | 10.1038/nrmicro1549 | This study first defined minimal vacuolar translocation sequences (VTS) of about 35–40 amino acids necessary and sufficient for the export of P. falciparum proteins to the host erythrocyte. |
10.1126/science.1102737 | 83,513,915 | Malaria parasites secrete proteins across the vacuolar membrane into the erythrocyte, inducing modifications linked to disease and parasite survival. We identified an 11–amino acid signal required for the secretion of proteins from the Plasmodium falciparum vacuole to the human erythrocyte. Bioinformatics predicted a s... | 10.1038/nrmicro1549 | This study along with Ref. 21 simultaneously described a host-cell-targeting signal present in hundreds of parasite secretory proteins and thereby predicted a 'secretome' for malarial infection. |
10.1126/science.1107449 | 125,115,903 | Apical membrane antigen 1 from Plasmodium is a leading malaria vaccine candidate. The protein is essential for host-cell invasion, but its molecular function is unknown. The crystal structure of the three domains comprising the ectoplasmic region of the antigen from P. vivax , solved at 1.8 angstrom resolution, shows t... | 10.1038/nrmicro1549 | This is an important paper for the development of a malaria vaccine. |
10.1111/j.1462-2920.2007.01379.x | 82,897,556 | Summary Although soil‐borne bacteria represent the world's greatest source of biological diversity, it is not well understood whether extreme environmental conditions, such as those found in Antarctic habitats, result in reduced soil‐borne microbial diversity. To address this issue, patterns of bacterial diversity were... | 10.1038/nrmicro2281 | An excellent paper looking at the diversity of soil bacteria across a broad latitudinal gradient of Antarctic Peninsula environments. |
10.1098/rspb.2006.3595 | 103,837,192 | The Antarctic Dry Valleys are regarded as one of the harshest terrestrial habitats on Earth because of the extremely cold and dry conditions. Despite the extreme environment and scarcity of conspicuous primary producers, the soils contain organic carbon and heterotrophic micro-organisms and invertebrates. Potential sou... | 10.1038/nrmicro2281 | An exceptional review of the effects of the abiotic factors that influence microbial activity in Dry Valley soils. |
10.1046/j.1365-2486.2001.00393.x | 41,296,702 | Summary Organic carbon reservoirs and respiration rates in soils have been calculated for most major biomes on Earth revealing patterns related to temperature, precipitation, and location. Yet data from one of the Earth's coldest, driest, and most southerly soil ecosystems, that of the McMurdo Dry Valleys of Antarctica... | 10.1038/nrmicro2281 | This is the first study to report estimates of soil respiration in the Dry Valleys and to consider ecosystem processes in the context of trophic dynamics. |
10.1038/ismej.2008.111 | 41,679,638 | Abstract Antarctic ecosystems are fascinating in their limited trophic complexity, with decomposition and nutrient cycling functions being dominated by microbial activities. Not only are Antarctic habitats exposed to extreme environmental conditions, the Antarctic Peninsula is also experiencing unequalled effects of gl... | 10.1038/nrmicro2281 | An exciting contribution using cutting-edge microarray techniques to survey microbial communities in Antarctic soils. |
10.1126/science.1214453 | 16,793,863 | Close-Up of DNA Methylation In eukaryotes, maintenance of genomic CpG methylation patterns is required for imprinting, retrotransposon silencing, and X-chromosome inactivation. The epigenetic mark needs to be faithfully maintained and propagated during repeated cell divisions in somatic cells by selective methylation o... | 10.1038/nrm4043 | This paper, with reference 144, defines the structural basis for autoinhibitory and active mechanisms for regulation of DNMT1 activity. |
10.1073/pnas.1203701109 | 81,423,839 | Multiple covalent modifications on a histone tail are often recognized by linked histone reader modules. UHRF1 [ubiquitin-like, containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1], an essential factor for maintenance of DNA methylation, contains linked two-histone reader modules,... | 10.1038/nrm4043 | References 157 and 156 report on the mechanism of histone recognition by UHRF1, thereby linking H3K9me3 mark to CG methylation maintanance. |
10.1073/pnas.0710091104 | 82,829,497 | Elevated expression and activation of the focal adhesion kinase (FAK) occurs in a large proportion of human breast cancers. Although several studies have implicated FAK as an important signaling molecule in cell culture systems, evidence supporting a role for FAK in mammary tumor progression is lacking. To directly ass... | 10.1038/nrc3792 | This study shows that mammary epithelial-specific deletion of FAK in PyMT mice prevents the progression of hyperplastic growth to malignant breast carcinomas. It shows the role of FAK in the development of in vivo breast tumours. |
10.1083/jcb.200411155 | 104,110,211 | Focal adhesion kinase (FAK) is a critical mediator of signal transduction by integrins and growth factor receptors in a variety of cells including endothelial cells (ECs). Here, we describe EC-specific knockout of FAK using a Cre-loxP approach. In contrast to the total FAK knockout, deletion of FAK specifically in ECs ... | 10.1038/nrc3792 | References 68 and 83 created FAK-KD knock-in mouse models to test the importance of FAK enzymatic activity during development. FAK-KD is embryonically lethal owing to defective blood vessel formation. |
10.1083/jcb.201307067 | 20,483,216 | Pharmacological focal adhesion kinase (FAK) inhibition prevents tumor growth and metastasis, via actions on both tumor and stromal cells. In this paper, we show that vascular endothelial cadherin (VEC) tyrosine (Y) 658 is a target of FAK in tumor-associated endothelial cells (ECs). Conditional kinase-dead FAK knockin w... | 10.1038/nrc3792 | This study shows that pharmacological inhibition of FAK or endothelial-specific expression of FAK-KD prevents extravasation and spontaneous tumour spread by enhancing endothelial vessel barrier function. |
10.1126/scitranslmed.3008639 | 122,837,592 | FAK inhibitor treatment is effective against Merlin-negative mesothelioma tumors and preferentially targets cancer stem cells. | 10.1038/nrc3792 | This study shows that mesothelioma cells with low expression of the tumour suppressor Merlin are very sensitive to pharmacological FAK inhibition, and it is therefore the first to identify a potential biomarker for patient stratification for chemotherapy. |
10.4049/jimmunol.125.2.711 | 139,054,001 | Abstract To examine the specificity of adoptive chemoimmunotherapy (ACIT) of established syngeneic tumors, two noncross-reactive C57BL/6 tumors were studied: a Friend virus-induced tumor (FBL-3) and a chemically induced virus-negative tumor EL-4(G-). In vitro studies confirmed that these tumors are antigenically distin... | 10.1038/nri1842 | This pioneering paper reports the increased antitumour efficacy of tumour-reactive T cells in a lymphodepleted host. |
10.1126/science.1076514 | 62,136,737 | We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cance... | 10.1038/nri1842 | This paper describes the first successful clinical trail of ACT with TILs following non-myeloablative chemotherapy for the treatment of patients with melanoma. |
10.4049/jimmunol.174.5.2591 | 107,150,912 | Abstract CD4+ T cells control the effector function, memory, and maintenance of CD8+ T cells. Paradoxically, we found that absence of CD4+ T cells enhanced adoptive immunotherapy of cancer when using CD8+ T cells directed against a persisting tumor/self-Ag. However, adoptive transfer of CD4+CD25− Th cells (Th cells) wi... | 10.1038/nri1842 | This paper elucidates the role of CD4 + CD25 + T cells in preventing an otherwise productive antitumour immune response against an established syngeneic tumour. |
10.1084/jem.20050732 | 20,469,104 | Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy of transferred CD8+ T cells, but the specific mechanisms that contribute to this enhanced immunity remain poorly defined. Elimination of CD4+CD25+ regulatory T (T reg) cells has been proposed as a key mechan... | 10.1038/nri1842 | This paper establishes the direct role of the endogenous homeostatic cytokines IL-7 and IL-15 in increasing CD8 + T-cell effector functions in a lymphodepleted environment. |
10.4049/jimmunol.176.9.5255 | 99,542,615 | Abstract IL-2 is a critical T cell growth factor in vitro, but predominantly mediates tolerance in vivo. IL-2 is mainly produced by CD4+ Th cells, but the role of Th cell-derived IL-2 in vivo is controversial. We demonstrate that during immunity to a tumor/self-Ag, the predominant role of Th cell-derived IL-2 was to ma... | 10.1038/nri1842 | References 53 and 54 highlight the role of IL-2 in maintaining the homeostasis and competitive fitness of T Reg cells in vivo |
10.1161/hq1001.098463 | 124,521,437 | High-resolution magnetic resonance imaging (MRI) with flow suppression not only provides useful information on luminal and wall areas of the carotid artery but also can identify the principal tissue components of the carotid atherosclerotic plaque. The effects of intensive lipid-lowering therapy on these MRI tissue cha... | 10.1038/nrd1548 | Although a case-control study, in a relatively small number of patients, this report demonstrated that in addition to plaque size, it is also possible to quantify individual plaque components and to identify changes in plaque composition with intensive lipid-lowering therapy. |
10.1161/hc3601.094303 | 60,114,893 | Background Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fi... | 10.1038/nrd1548 | An elegant demonstration of the use of gadolinium–DTPA-loaded nanoparticles to image fibrin and therefore identify thrombus in vivo |
10.1177/108705710000500507 | 18,787,880 | The interaction between 290 structurally diverse human immunodeficiency virus type 1 (HIV-1) protease inhibitors and the immobilized enzyme was analyzed with an optical biosensor. Although only a single concentration of inhibitor was used, information about the kinetics of the interaction could be obtained by extractin... | 10.1038/nrd838 | An important paper that introduces the concept of screening small-molecule–receptor complexes for affinity and stability using the kinetic data generated by optical biosensors. |
10.1002/aic.690210522 | 41,624,233 | Abstract The penetration of drugs and other micromolecules through intact human skin can be regarded as a process of dissolution and molecular diffusion through a composite, multilayer membrane, whose principal barrier to transport is localized within the stratum corneum. A mathematical model of the stratum corneum as ... | 10.1038/nrd1304 | Rigorous modelling of transdermal transport that provided the foundation for subsequent models. |
10.1002/aic.690410814 | 40,737,996 | Abstract Recently, a large number of new and potentially potent peptide and protein drugs have been developed. Their systemic delivery is difficult because they are rapidly cleared from the bloodstream, are of large molecular size, are vulnerable to proteolytic attack and tend to undergo aggregation, adsorption and den... | 10.1038/nrd1304 | Overview of challenges associated with transdermal delivery of macromolecules, especially in iontophoresis. |
10.1242/dev.128.21.4349 | 104,423,525 | We have investigated the regulation of cell-cycle entry in C. elegans, taking advantage of its largely invariant and completely described pattern of somatic cell divisions. In a genetic screen, we identified mutations in cyd-1 cyclin D and cdk-4 Cdk4/6. Recent results indicated that during Drosophila development, cycli... | 10.1038/nrm1738 | Shows that the C. elegans Rb homologue inhibits cell-cycle progression and that loss of CKI-1 and Rb can suppress the G1-phase arrest of cyd-1 or cdk-4 mutants. |
10.1242/dev.125.18.3585 | 62,604,806 | C. elegans cki-1 encodes a member of the CIP/KIP family of cyclin-dependent kinase inhibitors, and functions to link postembryonic developmental programs to cell cycle progression. The expression pattern of cki-1::GFP suggests that cki-1 is developmentally regulated in blast cells coincident with G1, and in differentia... | 10.1038/nrm1738 | Shows that CKI-1 regulates cell-cycle exit and entry during larval stages. |
10.1242/dev.00916 | 102,998,182 | Maintenance of the stem cell population in the C. elegans germline requires GLP-1/Notch signaling. We show that this signaling inhibits the accumulation of the RNA binding protein GLD-1. In a genetic screen to identify other genes involved in regulating GLD-1 activity, we identified mutations in the nos-3 gene, the pro... | 10.1038/nrm1738 | References 79, 81 and 82 provide important insights into meiotic entry by describing pathways that regulate GLD-1 and GLD-2–GLD-3 in the germ line. |
10.1073/pnas.1608016113 | 38,260,162 | Plastids, the photosynthetic organelles, originated >1 billion y ago via the endosymbiosis of a cyanobacterium. The resulting proliferation of primary producers fundamentally changed global ecology. Endosymbiotic gene transfer (EGT) from the intracellular cyanobacterium to the nucleus is widely recognized as a criti... | 10.1038/nrmicro.2017.137 | Paulinella chromatophora is an amoeba that contains a photosynthetic symbiont. Genomic and transcriptomic data enabled the authors to untangle how many bacterial genes in the genome of P. chromatophora came from phylogenetic sources other than the current symbiont and suggest that HGT from diverse bacteria compensates ... |
10.1126/science.1231707 | 100,504,650 | Hot, Toxic Eukaryote Unusually, the single-celled eukaryote red alga, Galdieria sulphuraria , can thrive in hot, acidic springs. This organism is endowed with extraordinary metabolic talents and can consume a variety of strange carbohydrates, as well as turn on photosynthesis when the food runs out. Schönknecht et al. ... | 10.1038/nrmicro.2017.137 | This study describes the important role that HGT from bacteria has had in enabling the red alga Galdieria to adapt to hot, toxic and acidic environments. |
10.1073/pnas.1603910113 | 38,327,658 | Stable endosymbiosis of a bacterium into a host cell promotes cellular and genomic complexity. The mealybug Planococcus citri has two bacterial endosymbionts with an unusual nested arrangement: the γ-proteobacterium Moranella endobia lives in the cytoplasm of the β-proteobacterium Tremblaya princeps . These two bacteri... | 10.1038/nrmicro.2017.137 | One common argument against the idea of HGT from diverse bacteria compensating for symbiont or organelle gene loss is that complex pathways are impossible to build in a gene-by-gene fashion. This study shows how complex and mosaic pathways can be built sequentially with HGT events from diverse bacteria and that pre-exi... |
10.1002/bies.201300007 | 19,875,402 | Abstract The significance of horizontal gene transfer (HGT) in eukaryotic evolution remains controversial. Although many eukaryotic genes are of bacterial origin, they are often interpreted as being derived from mitochondria or plastids. Because of their fixed gene pool and gene loss, however, mitochondria and plastids... | 10.1038/nrmicro.2017.137 | This study presents the weak-link model, which posits that foreign genes enter eukaryotic genomes at unprotected stages of their development; the model thus expands previous models for multicellular sexual eukaryotes. |
10.1126/science.1156407 | 40,542,079 | Horizontal gene transfer in metazoans has been documented in only a few species and is usually associated with endosymbiosis or parasitism. By contrast, in bdelloid rotifers we found many genes that appear to have originated in bacteria, fungi, and plants, concentrated in telomeric regions along with diverse mobile gen... | 10.1038/nrmicro.2017.137 | This is one of the first studies to describe massive HGT to an animal genome with details on gene localization, structure and function. |
10.1073/pnas.1517242113 | 83,221,548 | Horizontal gene transfer (HGT) among bacteria, archaea, and viruses is widespread, but the extent of transfers from these lineages into eukaryotic organisms is contentious. Here we systematically identify hundreds of genes that were likely acquired horizontally from a variety of sources by the early-diverging fungal ph... | 10.1038/nrmicro.2017.137 | This comprehensive analysis of HGT events in Microsporidia and Cryptomycota fungi detects dozens of novel HGT candidates, including parallel acquisitions that enable these pathogenic fungi to scavenge nucleosides and nucleotides from their hosts. |
10.1126/science.1127344 | 41,664,802 | We introduce a method for optically imaging intracellular proteins at nanometer spatial resolution. Numerous sparse subsets of photoactivatable fluorescent protein molecules were activated, localized (to ∼2 to 25 nanometers), and then bleached. The aggregate position information from all subsets was then assembled into... | 10.1038/nmeth.2843 | This is one of the three studies that introduced super-resolution localization microscopy based on localizing single fluorophores. This strongly increased the interest in understanding and optimizing localization precision and accuracy |
10.1126/science.1153529 | 125,226,607 | Recent advances in far-field fluorescence microscopy have led to substantial improvements in image resolution, achieving a near-molecular resolution of 20 to 30 nanometers in the two lateral dimensions. Three-dimensional (3D) nanoscale-resolution imaging, however, remains a challenge. We demonstrated 3D stochastic opti... | 10.1038/nmeth.2843 | This study is one of the first to use an engineered PSF in the context of localization microscopy to improve the axial localization precision. The authors used astigmatism to encode the axial position of the emitter in the PSF shape |
10.1128/mcb.24.7.2627-2636.2004 | 85,668,686 | ABSTRACT Caspase 8 is required not only for death receptor-mediated apoptosis but also for lymphocyte activation in the immune system. FLIP(L), the long-splice form of c-FLIP, is one of the specific substrates for caspase 8, and increased expression of FLIP(L) promotes activation of the NF-κB signaling pathway. The syn... | 10.1038/nri1787 | An important study showing that p43cFLIP can recruit TRAF2 more efficiently than cFLIP L . This might indicate that cFLIP L is an important caspase-8 substrate following T-cell activation. |
10.1084/jem.190.12.1891 | 60,303,057 | Triggering of Fas (CD95) by its ligand (FasL) rapidly induces cell death via recruitment of the adaptor protein Fas-associated death domain (FADD), resulting in activation of a caspase cascade. It was thus surprising that T lymphocytes deficient in FADD were reported recently to be not only resistant to FasL-mediated a... | 10.1038/nri1787 | References 26–28 describe the requirement of caspase activity, and specifically caspase-8, for T cell activation. |
10.1084/jem.192.11.1661 | 109,156,742 | Ligation of the Fas (CD95) receptor leads to an apoptotic death signal in T cells, B cells, and macrophages. However, human CD34+–derived dendritic cells (DCs) and mouse DCs, regardless of their maturation state, are not susceptible to Fas-induced cell death. This resistance correlates with the constitutive expression ... | 10.1038/nri1787 | An important demonstration that CD95 might provide activation signals rather than inducing cell death of DCs, because they express high levels of cFLIP. |
10.1084/jem.178.6.2231 | 38,533,759 | The Fas gene encodes a cell surface molecule that is a member of the the nerve growth factor/tumor necrosis factor receptor family of proteins and can mediate programmed cell death (apoptosis) in certain transformed cell lines. To characterize further the biological function of Fas, particularly with regard to its func... | 10.1038/nri1787 | The first study showing that CD95 can co-stimulate resting T cells. |
10.1101/gad.1063703 | 125,150,277 | Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We gener... | 10.1038/nri1787 | The first description of a conditional Casp8 knockout mouse showing that caspase-8 is required for T-cell survival and activation. |
10.1084/jem.20050117 | 109,117,125 | Apoptosis-related genes play important roles in thymocyte maturation. We show that cellular FLICE-like inhibitory protein (c-FLIP), a procaspase-8–like apoptotic regulator, plays an essential role in the efficient development of mature T lymphocytes. Mice conditionally lacking c-FLIP in T lymphocytes display severe def... | 10.1038/nri1787 | References 84 and 85 show the requirement of cFLIP for T-cell survival and activation. |
10.1126/science.1232458 | 41,740,034 | DNA Sensing Is a (c)GAS DNA is normally localized to the nucleus, and so its cytoplasmic localization sends off alarm bells to the immune system because it indicates that a virus may have entered. But how does the immune system actually detect the DNA (see the Perspective by O'Neill )? Sun et al. (p. 786 , published on... | 10.1038/nrmicro.2016.45 | This paper demonstrates that cGAS is a key cytosolic DNA sensor that produces the second messenger cGAMP to activate the host IFN response. |
10.1126/science.1229963 | 41,621,469 | DNA Sensing Is a (c)GAS DNA is normally localized to the nucleus, and so its cytoplasmic localization sends off alarm bells to the immune system because it indicates that a virus may have entered. But how does the immune system actually detect the DNA (see the Perspective by O'Neill )? Sun et al. (p. 786 , published on... | 10.1038/nrmicro.2016.45 | The authors find that on cytosolic DNA stimulation, cGAMP acts as a second messenger by binding to STING to activate IRF3 and trigger the production of type I IFNs. |
10.1126/science.1230949 | 107,310,031 | Parainfluenza 5 and MDA5 Our immune system and the viruses that infect us are in a constant arms race, with one side always trying to outwit the other. One example is the inhibition of host protein MDA5, a member of the retinoic acid–inducible gene 1 (RIG-I)–like receptor (RLR) family of innate immune sensors, by the V... | 10.1038/nrmicro.2016.45 | The authors find that V proteins from paramyxoviruses directly bind to the innate immune sensor MDA5 to unfold its ATP-hydrolysis domain, which prevents its activation. |
10.1126/science.aab3291 | 83,360,974 | Viral oncogenes remove the host's STING Cancer-causing viruses, such as the human papilloma virus (HPV) that causes cervical cancer, account for 12% of human cancers. One way they can cause cancer is by targeting tumor suppressor proteins in the host. Now Lau et al. report that DNA tumor viruses can also thwart the hos... | 10.1038/nrmicro.2016.45 | This study shows that the oncoproteins of certain DNA viruses are potent inhibitors of DNA sensors, which suggests that some viral oncogenes have evolved dual function during the co-evolution of host and virus. |
10.1126/science.1132998 | 104,095,857 | Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5). We showed that influenza A virus infection does not... | 10.1038/nrmicro.2016.45 | This paper demonstrates that single-stranded RNA bearing 5′-phosphates is a RIG-I ligand, which enables RIG-I to distinguish between 'self' and 'non-self'. |
10.1126/science.1199478 | 61,251,415 | A viral homolog of a host microbial sensor inhibits viral detection by the host and subsequent antiviral immunity. | 10.1038/nrmicro.2016.45 | This paper shows that ORF63 of KSHV is a viral homologue of the receptor NLRP1 and subverts the function of NLRP1 and several other NLR members. |
10.1126/science.288.5463.140 | 1,778,953 | African trypanosomes, the cause of sleeping sickness, need massive amounts of myristate to remodel glycosyl phosphatidylinositol (GPI) anchors on their surface glycoproteins. However, it has been believed that the parasite is unable to synthesize any fatty acids, and myristate is not abundant in the hosts' bloodstreams... | 10.1038/nrmicro1617 | The first report of FA synthesis by BSF T. brucei that also describes the different end products of synthesis by BSFs and PCFs. |
10.1111/j.1742-4658.2005.05049.x | 82,721,227 | A survey of the three kinetoplastid genome projects revealed the presence of three putative front‐end desaturase genes in Leishmania major , one in Trypanosoma brucei and two highly identical ones (98%) in T. cruzi . The encoded gene products were tentatively annotated as Δ8, Δ5 and Δ6 desaturases for L. major , and Δ6... | 10.1038/nrmicro1617 | Reports the specificities of L. major T. cruzi and T. brucei PUFA desaturases and predicts the pathways present in trypanosomatids. |
10.1098/rstb.1997.0113 | 121,988,474 | Insect–transmitted protozoan parasites of the order Kinetoplastida, suborder Trypanosomatina, include Trypanosoma brucei (aetiological agent of African sleeping sickness), Trypanosoma cruzi (aetiological agent of Chagas’ disease in South and Central America) and Leishmania spp. (aetiological agents of a variety of dise... | 10.1038/nrmicro1617 | Reviews the structures of abundant trypanosomatid cell-surface GPI anchors and glycoconjugates. |
10.4049/jimmunol.158.12.5890 | 139,040,515 | Abstract Components of Trypanosoma cruzi able to induce the production of IL-12 and other proinflammatory cytokines by macrophages were identified. Murine inflammatory macrophages were cultured with live parasites or with cellular components from different developmental forms of T. cruzi (i.e., trypomastigotes, amastig... | 10.1038/nrmicro1617 | Shows that the unsaturated fatty groups in the GPI anchor are essential for the pro-inflammatory activity of T. cruzi mucin. |
10.1111/j.1528-1167.2011.03024.x | 20,265,082 | Summary Despite the development of various new antiepileptic drugs (AEDs) since the early 1990s, the available evidence indicates that the efficacy and tolerability of drug treatment of epilepsy has not substantially improved. What are the reasons for this apparent failure of modern AED development to discover drugs wi... | 10.1038/nrd4126 | This is the first review to show that modern AEDs fail to address important unmet treatment needs of patients with epilepsy. |
10.1111/j.1528-1167.2007.01458.x | 27,045,541 | Summary Purpose: Current treatments for epilepsy may control seizures, but have no known effects on the underlying disease. We sought to determine whether early treatment in a model of genetic epilepsy would reduce the severity of the epilepsy phenotype in adulthood. Methods: We used Wistar albino Glaxo rats of Rijswij... | 10.1038/nrd4126 | This is the first study to show the anti-epileptogenic activity of an AED in a genetic model of epilepsy. |
10.1002/ana.21331 | 4,621,269 | Abstract Objective Tuberous sclerosis complex (TSC) represents one of the most common genetic causes of epilepsy. TSC gene inactivation leads to hyperactivation of the mammalian target of rapamycin signaling pathway, raising the intriguing possibility that mammalian target of rapamycin inhibitors might be effective in ... | 10.1038/nrd4126 | This study describes the anti-epileptogenic or disease-modifying activity of the mTOR inhibitor rapamycin in a model of tuberous sclerosis, which stimulated clinical trials with this drug. |
10.1126/science.1076510 | 83,012,873 | The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppr... | 10.1038/nrd4126 | This important study identifies a subpopulation of excitatory pyramidal neurons displaying depolarizing GABA responses in the subicular zone of the hippocampus as the likely pacemaker neurons that initiate epileptic discharges. |
10.1002/ana.23567 | 82,060,084 | Abstract Objective: Epilepsy is a common neurological disorder characterized by recurrent seizures often unresponsive to pharmacological treatment. Brain inflammation is considered a crucial etiopathogenetic mechanism of epilepsy that could be targeted to control seizures. Specific inflammatory mediators overexpressed ... | 10.1038/nrd4126 | This paper describes how the human recombinant IL-1βR antagonist anakinra terminates seizures, prevents their recurrence and resolves seizure-associated BBB breakdown in an animal model, supporting the use of specific anti-inflammatory drugs for the treatment of refractory seizures. |
10.1083/jcb.122.3.553 | 38,266,963 | The role of human dynamin in receptor-mediated endocytosis was investigated by transient expression of GTP-binding domain mutants in mammalian cells. Using assays which detect intermediates in coated vesicle formation, the dynamin mutants were found to block endocytosis at a stage after the initiation of coat assembly ... | 10.1038/nrm3266 | Demonstrates that dynamin mutants with impaired GTP binding and hydrolysis exert dominant-negative effects on clathrin-mediated endocytosis. |
10.1126/science.1140621 | 20,455,767 | Dynamin 1 is a neuron-specific guanosine triphosphatase thought to be critically required for the fission reaction of synaptic vesicle endocytosis. Unexpectedly, mice lacking dynamin 1 were able to form functional synapses, even though their postnatal viability was limited. However, during spontaneous network activity,... | 10.1038/nrm3266 | Reveals using dynamin 1-knockout mice that, contrary to expectations, dynamin 1 is not required for the making of synaptic vesicles but rather serves to enhance the efficiency of this clathrin-mediated process at synapses. |
10.1242/jcs.115.3.575 | 104,222,317 | Survivin is a member of the inhibitor of apoptosis gene family that has been implicated in both apoptosis inhibition and regulation of mitosis. However, the subcellular distribution of survivin has been controversial and variously described as a microtubule-associated protein or chromosomal passenger protein. Here, we ... | 10.1038/nrc968 | Reconciles earlier discrepant findings on the subcellular localization of survivin to multiple compartments of the mitotic apparatus. |
10.1182/blood.v100.7.2463 | 21,689,635 | The inhibitor of the apoptosis protein (IAP) survivin is expressed in proliferating cells such as fetal tissues and cancers. We previously reported that survivin is expressed and growth factor regulated in normal adult CD34+ cells. Herein, we examined survivin expression in CD34+ cells before and after cell cycle entry... | 10.1038/nrc968 | Demonstration that survivin gene expression can occur independently of mitotic progression in interphase bone-marrow progenitor cells. |
10.1091/mbc.e02-02-0092 | 28,266,471 | Aurora B regulates chromosome segregation and cytokinesis and is the first protein to be implicated as a regulator of bipolar attachment of spindle microtubules to kinetochores. Evidence from several systems suggests that Aurora B is physically associated with inner centromere protein (INCENP) in mitosis and has geneti... | 10.1038/nrc968 | A survivin homologue in Xenopus laevis controls the enzymatic activity of Aurora kinase, a multifunctional regulator of mitosis. |
10.1073/pnas.072586399 | 85,607,623 | Although standard anticancer chemotherapeutic drugs have been designed to inhibit the survival or growth of rapidly dividing tumor cells, it is possible to enhance the efficacy of such drugs by targeting the proliferating host endothelial cells (ECs) of the tumor vasculature. A theoretical advantage of this strategy li... | 10.1038/nrc968 | Demonstration that survivin can reduce the effectiveness of anti-angiogenic therapy in cancer treatment. |
10.1083/jcb.200112126 | 125,062,263 | Ezrin, radixin, and moesin (ERM) regulate cortical morphogenesis and cell adhesion by connecting membrane adhesion receptors to the actin-based cytoskeleton. We have studied the interaction of moesin and ezrin with the vascular cell adhesion molecule (VCAM)-1 during leukocyte adhesion and transendothelial migration (TE... | 10.1038/nri1268 | This paper describes the active role of endothelial cells during leukocyte firm adhesion, building an adhesion-receptor-based, actin-dependent docking structure to promote transmigration. |
10.1126/science.281.5373.105 | 18,638,610 | Actin filament assembly at the cell surface of the pathogenic bacterium Listeria monocytogenes requires the bacterial ActA surface protein and the host cell Arp2/3 complex. Purified Arp2/3 complex accelerated the nucleation of actin polymerization in vitro, but pure ActA had no effect. However, when combined, the Arp2/... | 10.1038/nri1268 | The protein ActA from Listeria monocytogenes recruits cellular machinery and directly induces actin polymerization, constituting the basis of actin-dependent, intracellular bacteria-independent movement. |
10.1126/science.1080115 | 102,392,637 | Cell contact is required for efficient transmission of human T cell leukemia virus– type 1 (HTLV-I) between cells and between individuals, because naturally infected lymphocytes produce virtually no cell-free infectious HTLV-I particles. However, the mechanism of cell-to-cell spread of HTLV-I is not understood. We show... | 10.1038/nri1268 | The first evidence on the role of the cytoskeleton on cell–cell spreading of viral particles. |
10.1126/science.1216338 | 18,937,989 | Dissecting DNA Repair Covalent modification of proteins can be a crucial regulatory event. Poly(ADP-ribose) polymerase 1 (PARP-1) (ADP, adenosine diphosphate) synthesizes poly(ADP-ribose), which is attached to and regulates proteins involved in DNA repair. Langelier et al. (p. 728 ; see the Perspective by Gagné et al. ... | 10.1038/nrm.2017.53 | This article reports the crystal structure of PARP1 bound to a DNA DSB and proposes a mechanism for the DNA-dependent activation of PARP1. |
10.1073/pnas.0406182101 | 80,322,116 | The metabolism of poly(ADP-ribose) (PAR) is critical for genomic stability in multicellular eukaryotes. Here, we show that the failure to degrade PAR by means of disruption of the murine poly(ADP-ribose) glycohydrolase (PARG) gene unexpectedly causes early embryonic lethality and enhanced sensitivity to genotoxic stres... | 10.1038/nrm.2017.53 | This article reports the essential role of PARG in degradation of PAR. |
10.1093/nar/gku088 | 102,402,091 | Abstract Poly(ADP-ribose) polymerases (PARP) attach poly(ADP-ribose) (PAR) chains to various proteins including themselves and chromatin. Topoisomerase I (Top1) regulates DNA supercoiling and is the target of camptothecin and indenoisoquinoline anticancer drugs, as it forms Top1 cleavage complexes (Top1cc) that are tra... | 10.1038/nrm.2017.53 | This article elucidates the interaction of PARP1 and TDP1 and its important role in the repair of TOP1-abortive complexes. |
10.1083/jcb.201112132 | 102,880,110 | The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how DDB2 promotes NER in chromatin is poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated fac... | 10.1038/nrm.2017.53 | This report shows the role of PARP1 in mediating NER through the recruitment of DDB2 and the chromatin modifier ALC1. |
10.1038/ncomms12425 | 59,392,859 | Abstract Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved for treatment of advanced ovarian cancer associated with BRCA1 and BRCA2 mutations. BRCA1 - and BRCA2 -mutated cells, which are homologous recombination (HR) deficient, are hypersensitive to PARPi through the mechanism of syntheti... | 10.1038/nrm.2017.53 | This report shows that synthetic viability results from deficiency of both PARP1 and BRCA2. |
10.1126/science.1177321 | 20,236,142 | Damage, Signal, Maneuver Cellular processes, such as transcription and DNA repair, require modification and manipulation of chromosomally associated proteins by a diverse set of chromatin remodeling complexes. The mechanisms by which cells regulate chromatin remodeling are not completely understood. During the response... | 10.1038/nrm.2017.53 | This report shows that PARP1-dependent chromatin remodelling by ALC1 is essential for DNA repair. |
10.1182/blood-2004-03-1224 | 20,030,545 | Abstract Notch1 is known to play a critical role in regulating fates in numerous cell types, including those of the hematopoietic lineage. Multiple defects exhibited by Notch1-deficient embryos confound the determination of Notch1 function in early hematopoietic development in vivo. To overcome this limitation, we exam... | 10.1038/nri3443 | This study shows that Notch 1 is cell-autonomously required for HSC specification. |
10.1182/blood-2008-06-163774 | 39,187,730 | Abstract Canonical Wnt signaling has been implicated in various aspects of hematopoiesis. Its role is controversial due to different outcomes between various inducible Wnt-signaling loss-of-function models and also compared with gain-of-function systems. We therefore studied a mouse deficient for a Wnt gene that seemed... | 10.1038/nri3443 | The first conclusive demonstration of a specific WNT ligand required for HSC patterning. |
10.1084/jem.20120225 | 7,243,054 | Understanding how hematopoietic stem cells (HSCs) are generated and the signals that control this process is a crucial issue for regenerative medicine applications that require in vitro production of HSC. HSCs emerge during embryonic life from an endothelial-like cell population that resides in the aorta-gonad-mesoneph... | 10.1038/nri3443 | This study shows that canonical WNT signalling is required for HSC specification. |
10.1083/jcb.200103132 | 18,824,026 | High molecular weight homologues of gp91phox, the superoxide-generating subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, have been identified in human (h) and Caenorhabditis elegans (Ce), and are termed Duox for “dual oxidase” because they have both a peroxidase homology domain and a gp... | 10.1038/nri1312 | The authors use biochemistry and reverse genetics in Caenorhabditis elegans to show the function of dual oxidase (Duox) in the oxidative modification of the worm cuticle, providing evidence for a general function of Duox in the modification of the extracellular matrix or other extracellular molecules. |
10.1073/pnas.1121299109 | 40,768,384 | The key regulators of intracellular trafficking, Ypt/Rab GTPases, are stimulated by specific upstream activators and, when activated, recruit specific downstream effectors to mediate membrane-transport events. The yeast Ypt1 and its human functional homolog hRab1 regulate both endoplasmic reticulum (ER)-to-Golgi transp... | 10.1038/nrm.2016.74 | Shows that the Ypt1/Rab GTPase also regulates autophagy by interacting with the scaffold protein Atg11 to regulate PAS assembly and subsequent autophagosome formation during selective autophagy. |
10.1083/jcb.201408075 | 67,574,629 | ER-derived COPII-coated vesicles are conventionally targeted to the Golgi. However, during cell stress these vesicles also become a membrane source for autophagosomes, distinct organelles that target cellular components for degradation. How the itinerary of COPII vesicles is coordinated on these pathways remains unknow... | 10.1038/nrm.2016.74 | Shows that the Rab GTPase Ypt1/Rab1 recruits Hrr25/CK1δ to COPII vesicles and to the PAS during non-selective autophagy. Hrr25 is activated by Ypt1 and is required for non-selective autophagy. |
10.1038/embor.2013.40 | 102,174,038 | The selective autophagy receptors Atg19 and Atg32 interact with two proteins of the core autophagic machinery: the scaffold protein Atg11 and the ubiquitin‐like protein Atg8. We found that the Pichia pastoris pexophagy receptor, Atg30, also interacts with Atg8. Both Atg30 and Atg32 interactions are regulated by phospho... | 10.1038/nrm.2016.74 | Lays the foundation for the mechanism by which selective autophagy receptors act by bridging selective cargo and the core autophagy machinery in a phosphoregulated fashion in yeast and mammals. |
10.1038/embor.2013.114 | 103,821,864 | Mitophagy is a process that selectively degrades mitochondria. When mitophagy is induced in yeast, the mitochondrial outer membrane protein Atg32 is phosphorylated, interacts with the adaptor protein Atg11 and is recruited into the vacuole with mitochondria. We screened kinase‐deleted yeast strains and found that CK2 i... | 10.1038/nrm.2016.74 | Provides evidence that CK2 phosphorylates the mitophagy receptor Atg32 and regulates its interaction with Atg11. |
10.1083/jcb.201402128 | 102,185,887 | In selective autophagy, degradation targets are specifically recognized, sequestered by the autophagosome, and transported into the lysosome or vacuole. Previous studies delineated the molecular basis by which the autophagy machinery recognizes those targets, but the regulation of this process is still poorly understoo... | 10.1038/nrm.2016.74 | Demonstrates that two SARs, Atg19 and Atg36, are phosphorylated by Hrr25. Hrr25-mediated phosphorylation enhances the interactions of these receptors with the scaffold protein Atg11, which is required for most selective autophagy pathways. |
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