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10.1073/pnas.95.15.8869 | 20,830,090 | The presence of latently infected, resting CD4 + T cells carrying replication-competent HIV-1 has been demonstrated in chronically infected individuals who are antiretroviral therapy naive as well as in those who are receiving highly active antiretroviral therapy (HAART). It is not clear, however, whether the establish... | 10.1038/nrmicro1580 | A study showing that the latent reservoir is established during primary HIV-1 infection. |
10.1126/science.1925601 | 102,720,379 | To better understand the basis for human immunodeficiency virus type 1 (HIV-1) persistence and latency, the form in which viral DNA exists in the peripheral T lymphocyte reservoir of infected individuals was investigated. In asymptomatic individuals, HIV-1 was harbored predominantly as full-length, unintegrated complem... | 10.1038/nrmicro1580 | A seminal study showing that in untreated HIV-1 infection, most of the HIV-1 DNA in resting CD4 + T cells is in an unintegrated form. Rescue of virus from cells with unintegrated HIV-1 DNA could be achieved by cellular activation. |
10.1091/mbc.10.11.3539 | 60,377,944 | Toxoplasma gondii is a member of the phylum Apicomplexa, a diverse group of intracellular parasites that share a unique form of gliding motility. Gliding is substrate dependent and occurs without apparent changes in cell shape and in the absence of traditional locomotory organelles. Here, we demonstrate that gliding is... | 10.1038/nrmicro.2017.86 | This study provides the first time-lapse video microscopy of the three distinct forms of motility of T. gondii tachyzoites. |
10.1242/jcs.50.1.345 | 104,359,917 | The sporozoites of Eimeria tenella and Eimeria acervulina show bending, pivoting and gliding motility. All these types of motility occur intermittently and with decreasing frequency during the life of a sporozoite. Gliding is the only locomotive action expressed by these sporozoites and is only seen when the sporozoite... | 10.1038/nrmicro.2017.86 | References 10–13 provide the basis for the capping model in Apicomplexa. |
10.1126/science.1074553 | 61,640,637 | Obligate intracellular apicomplexan parasites rely on gliding motion powered by their actomyosin system to disperse throughout tissues and to penetrate host cells. Toxoplasma gondii myosin A has been implicated in this process, but direct proof has been lacking. We designed a genetic screen to generate a tetracycline-i... | 10.1038/nrmicro.2017.86 | This study demonstrates the crucial role of MYOA in parasite gliding, invasion and egress. |
10.1083/jcb.200311137 | 123,902,812 | Apicomplexan parasites exhibit a unique form of substrate-dependent motility, gliding motility, which is essential during their invasion of host cells and during their spread between host cells. This process is dependent on actin filaments and myosin that are both located between the plasma membrane and two underlying ... | 10.1038/nrmicro.2017.86 | This research identifies two components of the glideosome associated with the IMC. |
10.1242/jcs.00194 | 80,488,914 | Apicomplexan host cell invasion and gliding motility depend on the parasite's actomyosin system located beneath the plasma membrane of invasive stages. Myosin A (MyoA), a class XIV unconventional myosin, is the motor protein. A model has been proposed to explain how the actomyosin motor operates but little is known abo... | 10.1038/nrmicro.2017.86 | This work revisits the topology of the glideosome within the pellicle and associates the MYOA motor complex with the IMC. |
10.1083/jcb.147.5.937 | 58,554,643 | Most Apicomplexan parasites, including the human pathogens Plasmodium, Toxoplasma, and Cryptosporidium, actively invade host cells and display gliding motility, both actions powered by parasite microfilaments. In Plasmodium sporozoites, thrombospondin-related anonymous protein (TRAP), a member of a group of Apicomplexa... | 10.1038/nrmicro.2017.86 | This study provides genetic evidence of the conserved function of TRAP family members in driving surface protein redistribution across apicomplexans. |
10.1126/science.1204988 | 101,504,442 | The structure of a eukaryotic pathogen adhesin bound to its receptor provides a basis for design of therapeutics. | 10.1038/nrmicro.2017.86 | This study solves the structure of AMA1 in complex with a RON2 peptide, which reveals the buried nature of the interface constituting a solid platform that is necessary to resist to the mechanical forces applied during the penetration of host cells by the parasite. |
10.1126/science.1181369 | 41,754,439 | Chromosomal Mapping The conformation of the genome in the nucleus and contacts between both proximal and distal loci influence gene expression. In order to map genomic contacts, Lieberman-Aiden et al. (p. 289 , see the cover) developed a technique to allow the detection of all interactions between genomic loci in the e... | 10.1038/nrg2883 | References 24 and 25 report a next-generation sequencing-based method to study genome architecture. |
10.1126/science.1178124 | 122,886,750 | Gene fusions play a critical role in cancer progression. The mechanisms underlying their genesis and cell type specificity are not well understood. About 50% of human prostate cancers display a gene fusion involving the 5′ untranslated region of TMPRSS2 , an androgen-regulated gene, and the protein-coding sequences of ... | 10.1038/nrg2883 | The first demonstration that androgen signalling induces proximity between gene fusion partners in prostate cancer. |
10.4049/jimmunol.165.12.7096 | 83,025,056 | Abstract A family of Toll-like receptor (TLR) mediates the cellular response to bacterial cell wall components; murine TLR2 and TLR4 recognize mycoplasmal lipopeptides (macrophage-activating lipopeptides, 2 kDa (MALP-2)) and LPS, respectively. Costimulation of mouse peritoneal macrophages with MALP-2 and LPS results in... | 10.1038/nri2038 | References 13 and 14 are early reports of cooperation between TLRs. |
10.4049/jimmunol.173.12.7548 | 41,205,023 | Abstract Recognition of microbial products through TLRs triggers the expression of several cytokines that regulate innate and adaptive immunity. Signaling by various TLRs is not equivalent and leads to differential gene induction. This study analyzed the responses of human dendritic cells (DCs) and PBMCs stimulated wit... | 10.1038/nri2038 | One of the early studies showing differential and antagonistic functional consequences of the activation of different TLRs. |
10.4049/jimmunol.178.2.1164 | 82,836,244 | Abstract TLRs sense components of microorganisms and are critical host mediators of inflammation during infection. Different TLR agonists can profoundly alter inflammatory effects of one another, and studies suggest that the sequence of exposure to TLR agonists may importantly impact on responses during infection. We t... | 10.1038/nri2038 | A recent report documenting synergy between MyD88- and TRIF-dependent signalling by TLR agonists. |
10.4049/jimmunol.177.6.3515 | 62,183,342 | Abstract Activation of innate immune cells by Trypanosoma cruzi-derived molecules such as GPI anchors and DNA induces proinflammatory cytokine production and host defense mechanisms. In this study, we demonstrate that DNA from T. cruzi stimulates cytokine production by APCs in a TLR9-dependent manner and synergizes wit... | 10.1038/nri2038 | The first description of TLR cooperation in host defence against a protozoan pathogen. |
10.1073/pnas.0308057100 | 121,810,598 | Human neonates infected with herpes simplex virus 1 (HSV-1) develop one of three distinct patterns of infection: ( i ) infection limited to the skin, eye or mouth; ( ii ) infection of the CNS; or ( iii ) disseminated infection. The disseminated form usually involves the liver, adrenal gland, and lung, and resembles the... | 10.1038/nri2038 | References 70 and 71 describe the detrimental effects of specific TLR signals in viral infection. |
10.4049/jimmunol.172.7.4463 | 82,494,409 | Abstract Toll-like receptors (TLRs) are evolutionarily conserved proteins that recognize microbial molecules and initiate host defense. To investigate how TLRs work together to fight infections, we tested the role of TLRs in host defense against the Gram-negative bacterial pathogen, Salmonella. We show that TLR4 is cri... | 10.1038/nri2038 | An early paper describing TLR cooperation in the control of bacterial infection. |
10.4049/jimmunol.177.10.7059 | 20,412,060 | Abstract Host resistance to the intracellular protozoan parasite Trypanosoma cruzi depends on IFN-γ production by T cells and NK cells. However, the involvement of innate immunity in host resistance to T. cruzi remains unclear. In the present study, we investigated host defense against T. cruzi by focusing on innate im... | 10.1038/nri2038 | The first report of cooperation of TRIF- and MyD88-dependent signalling pathways in host defence in vivo |
10.1073/pnas.0507484102 | 62,281,983 | Induction and maintenance of antibody and T cell responses will be critical for developing a successful vaccine against HIV. A rational approach for generating such responses is to design vaccines or adjuvants that have the capacity to activate specific antigen-presenting cells. In this regard, dendritic cells (DCs) ar... | 10.1038/nri2038 | This study describes the effects of coupling a TLR ligand to antigen on the immune response induced to a vaccine antigen in a primate model. |
10.1126/science.1091317 | 19,073,938 | A genetic interaction network containing ∼1000 genes and ∼4000 interactions was mapped by crossing mutations in 132 different query genes into a set of ∼4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions... | 10.1038/nrg2085 | This study describes large-scale mapping of synthetic-lethal genetic interactions in yeast by SGA analysis. The results highlight the utility of genetic networks for discovering gene function and define the topology and general properties of genetic networks. |
10.1093/genetics/121.4.659 | 125,324,071 | Abstract Suppressors of a temperature-sensitive mutation (act1-1) in the single actin gene of Saccharomyces cerevisiae were selected that had simultaneously acquired a cold-sensitive growth phenotype. Five genes, called SAC (suppressor of actin) were defined by complementation tests; both suppression and cold-sensitive... | 10.1038/nrg2085 | One of the first yeast papers to describe synthetic-lethal genetic interactions, with useful references to the early D. melanogaster literature. |
10.1126/science.1065810 | 82,755,186 | In Saccharomyces cerevisiae , more than 80% of the ∼6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analys... | 10.1038/nrg2085 | This paper describes development of the SGA method and its application to synthetic-lethal genetic-interaction mapping. The study also provides the first glimpse of a genetic-interaction network. |
10.1073/pnas.0406614101 | 42,548,223 | Genetic interactions define overlapping functions and compensatory pathways. In particular, synthetic sick or lethal (SSL) genetic interactions are important for understanding how an organism tolerates random mutation, i.e., genetic robustness. Comprehensive identification of SSL relationships remains far from complete... | 10.1038/nrg2085 | The first paper to show that functional genomics data sets can be used to predict genetic interactions. |
10.1063/1.1150069 | 123,443,407 | Small cantilevers allow for faster imaging and faster force spectroscopy of single biopolymers than previously possible because they have higher resonant frequencies and lower coefficients of viscous damping. We have used a new prototype atomic force microscope with small cantilevers to produce stable tapping-mode imag... | 10.1038/nnano.2017.45 | This paper reports the invention of small cantilevers for fast AFM imaging and force spectroscopy. |
10.1073/pnas.1013893107 | 109,035,468 | Understanding how cell adhesion proteins form adhesion domains is a key challenge in cell biology. Here, we use single-molecule atomic force microscopy (AFM) to demonstrate the force-induced formation and propagation of adhesion nanodomains in living fungal cells, focusing on the covalently anchored cell-wall protein A... | 10.1038/nnano.2017.45 | This paper reports using recognition imaging to demonstrate that microbial cell adhesion proteins form nanoclusters under mechanical force. |
10.1126/science.289.5486.1938 | 123,164,227 | The inadvertent activation of the Abelson tyrosine kinase (Abl) causes chronic myelogenous leukemia (CML). A small-molecule inhibitor of Abl (STI-571) is effective in the treatment of CML. We report the crystal structure of the catalytic domain of Abl, complexed to a variant of STI-571. Critical to the binding of STI-5... | 10.1038/nrd1579 | First report of the co-crystal structure of an imatinib analogue in complex with the tyrosine kinase Abl. |
10.1182/blood-2002-09-2896 | 18,634,001 | Abstract Imatinib-treated chronic myeloid leukemia (CML) patients with acquired resistance commonly have detectable BCR-ABL kinase domain mutations. It is unclear whether patients who remain sensitive to imatinib also have a significant incidence of mutations. We evaluated 144 patients treated with imatinib for BCR-ABL... | 10.1038/nrd1579 | This study shows that the type of the imatinib resistance-inducing mutation in BCR–ABL predicts the clinical prognosis for relapsed CML patients. |
10.1182/blood-2002-12-3659 | 123,633,925 | Abstract Imatinib mesylate is a selective Bcr-Abl kinase inhibitor, effective in the treatment of chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses; however, many in blast crisis fail to respond, or relapse quickly. Kinase domain mutations are the most commonly identified mechanism... | 10.1038/nrd1579 | This is the first report demonstrating that many imatinib-restistant Bcr–Abl variants retain sensitivity to a structurally distinct kinase inhibitor. |
10.1158/0008-5472.can-03-1982 | 62,572,585 | Abstract Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47–68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genot... | 10.1038/nrd1579 | This interesting paper reports the reversal of aneuploidy after co-targeting of the EGFR and the closely related HER2 tyrosine kinase. |
10.1126/science.1106209 | 38,598,357 | Type VII collagen defects cause recessive dystrophic epidermolysis bullosa (RDEB), a blistering skin disorder often accompanied by epidermal cancers. To study the role of collagen VII in these cancers, we examined Ras-driven tumorigenesis in RDEB keratinocytes. Cells devoid of collagen VII did not form tumors in mice, ... | 10.1038/nrc1838 | A combination of human genetics and human skin tissue models of cancer were used to identify a potential role for collagen VII, a normal BMZ constituent, in neoplastic invasion. |
10.1101/gad.993902 | 17,581,466 | The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector pro... | 10.1038/nrc1838 | Tranforming actions of Ras were shown to be mediated through Ral in human fibroblasts and through Raf in mouse fibroblasts. |
10.1002/jmri.10181 | 40,064,854 | Abstract The microenvironment within tumors is significantly different from that in normal tissues. A major difference is seen in the chaotic vasculature of tumors, which results in unbalanced blood supply and significant perfusion heterogeneities. As a consequence, many regions within tumors are transiently or chronic... | 10.1038/nrc1713 | A comprehensive review of the distribution, role and methods of measuring the metabolic microenvironment. |
10.1096/fj.00-0029com | 80,751,657 | In this study we investigate the mechanism of intracellular pH change and its role in malignant transformation using the E7 oncogene of human papillomavirus type 16 (HPV16). Infecting NIH3T3 cells with recombinant retroviruses expressing the HPV16 E7 or a transformation deficient mutant we show that alkalinization is t... | 10.1038/nrc1713 | This study showed that in HPV16E7 -transformed cells, NHE1-dependent cellular alkalinization is an early event in neoplastic transformation that drives aerobic glycolysis, proliferation, serum- and anchorage-independent growth and formation of keratinocyte tumours in nude mice. |
10.1083/jcb.200209006 | 39,244,366 | Invasive tumor dissemination in vitro and in vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor–based treatment, suggesting the existence of migratory compensation strategies. In three-dimensional collagen matrices, spindle-shaped prot... | 10.1038/nrc1713 | Describes the use of intravital multiphoton microscopy in cultured cells to study the association between secreted protease activity and cellular functional morphology. |
10.1242/jcs.113.20.3649 | 20,784,789 | The Na(+)/H(+) exchanger NHE1 is involved in intracellular pH homeostasis and cell volume regulation and accumulates with actin in the lamellipodia of fibroblasts. In order to determine the role of NHE1 following epithelial transformation and the acquisition of motile and invasive properties, we studied NHE1 expression... | 10.1038/nrc1713 | The first study to demonstrate that transformation results in a dramatic remodelling of cellular morphology with a redistribution of NHE1 to the tip of the pseudopod, and that motility and transformed cell shape depend on NHE1 activity. |
10.1101/gr.143198.112 | 20,807,387 | We have identified variants present in high-coverage complete sequences of 36 diverse human Y chromosomes from Africa, Europe, South Asia, East Asia, and the Americas, representing eight major haplogroups. After restricting our analysis to 8.97 Mb of the unique male-specific Y sequence, we identified 6662 high-confiden... | 10.1038/nrg.2017.36 | This is the first study of Y-chromosome phylogeny to be based on high-coverage sequencing and reveals the rapid expansion of Y lineages around the time of the expansion of modern humans out of Africa. |
10.1101/gr.186684.114 | 124,126,901 | It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50–100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibrat... | 10.1038/nrg.2017.36 | This large-scale sequence-based study of Y-chromosome variation reports that a strong Y-chromosome, but not mtDNA, bottleneck occurred within the past 10,000 years. |
10.1242/dev.124.20.4133 | 41,733,453 | Notch is involved in the cell fate determination of many cell lineages. The intracellular region (RAMIC) of Notch1 transactivates genes by interaction with a DNA binding protein RBP-J. We have compared the activities of mouse RAMIC and its derivatives in transactivation and differentiation suppression of myogenic precu... | 10.1038/nri1998 | This paper describes RBP-J as an important mediator of Notch1 signalling. |
10.1126/science.1102160 | 38,225,070 | Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1 , a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes... | 10.1038/nri1998 | An analysis of samples from patients with T-cell acute lymphoblastic leukaemia showing that transformation-associated mutations in Notch1 occur in 'hotspots' in a few key domains. |
10.1146/annurev-phyto-080615-100204 | 103,827,915 | Plants possess large arsenals of immune receptors capable of recognizing all pathogen classes. To cause disease, pathogenic organisms must be able to overcome physical barriers, suppress or evade immune perception, and derive nutrients from host tissues. Consequently, to facilitate some of these processes, pathogens se... | 10.1038/nrmicro.2017.33 | This review provides an excellent overview of the spatial and temporal effector gene expression profiles in various systems. |
10.1105/tpc.114.131086 | 17,233,814 | Abstract The biotrophic smut fungus Ustilago maydis infects all aerial organs of maize (Zea mays) and induces tumors in the plant tissues. U. maydis deploys many effector proteins to manipulate its host. Previously, deletion analysis demonstrated that several effectors have important functions in inducing tumor expansi... | 10.1038/nrmicro.2017.33 | In this paper, the See1 effector of U. maydis is shown to induce mitotic cell division in infected maize leaf tissue, thus providing a link to tumour formation. |
10.1126/science.1185775 | 59,331,599 | Tailor-Made Tumor The biotrophic smut pathogen Ustilago maydis specifically infects the important crop plant, maize. The pathogen elicits large tumors on all aerial maize organs by redirecting primordia into a tumor pathway, and maize developmental mutants can disrupt tumor progression. Skibbe et al. (p. 89 ) examined ... | 10.1038/nrmicro.2017.33 | The study reveals that U. maydis effectors are expressed in an organ-specific manner and that the colonization of different maize organs by U. maydis requires organ-specific effectors. |
10.1038/ncomms6097 | 19,877,784 | Abstract To cause plant disease, pathogenic fungi can secrete effector proteins into plant cells to suppress plant immunity and facilitate fungal infection. Most fungal pathogens infect plants using very long strand-like cells, called hyphae, that secrete effectors from their tips into host tissue. How fungi undergo lo... | 10.1038/nrmicro.2017.33 | This paper describes an unexpected link between effector gene expression and the motor-dependent retrograde motility of early endosomes. |
10.1105/tpc.110.076265 | 123,963,687 | Abstract Regulation of the cell cycle and morphogenetic switching during pathogenic and sexual development in Ustilago maydis is orchestrated by a concerted action of the a and b mating-type loci. Activation of either mating-type locus triggers the G2 cell cycle arrest that is a prerequisite for the formation of the in... | 10.1038/nrmicro.2017.33 | This study identifies an unprecedented connection between developmental transcription factors and components of the unfolded protein response in the regulation of effector gene expression and effector secretion. |
10.1111/nph.14188 | 122,113,551 | Summary Successful colonization of plants by prokaryotic and eukaryotic pathogens requires active effector‐mediated suppression of defense responses and host tissue reprogramming. Secreted effector proteins can either display their activity in the apoplast or translocate into host cells and function therein. Although c... | 10.1038/nrmicro.2017.33 | This paper describes an assay that enables the detection of effector translocation into plant cells based on in vivo biotinylation. |
10.1126/science.1139522 | 83,443,062 | Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in t... | 10.1038/nri2195 | References 10 and 11 illustrate the crucial role of TLR3-triggered, UNC93B-dependent, induction of type I IFN responses in the control of HSV infection in humans. |
10.1084/jem.20070058 | 122,683,549 | Leukocyte and platelet integrins rapidly alter their affinity and adhesiveness in response to various activation (inside-out) signals. A rare leukocyte adhesion deficiency (LAD), LAD-III, is associated with severe defects in leukocyte and platelet integrin activation. We report two new LAD cases in which lymphocytes, n... | 10.1038/nri2195 | This paper describes the identification of the molecular mechanism that accounts for impaired integrin activation in LAD type III in humans. |
10.1146/annurev.immunol.24.021605.090612 | 18,500,285 | The lymphocytes, T, B, and NK cells, and a proportion of dendritic cells (DCs) have a common developmental origin. Lymphocytes develop from hematopoietic stem cells via common lymphocyte and various lineage-restricted precursors. This review discusses the current knowledge of human lymphocyte development and the phenot... | 10.1038/nri2195 | References 42 and 43 expand on the molecular defects in components of the pre-BCR that are responsible for congenital agammaglobulinaemia. |
10.1101/gad.1346005 | 62,314,462 | Added by telomerase, arrays of TTAGGG repeats specify the ends of human chromosomes. A complex formed by six telomere-specific proteins associates with this sequence and protects chromosome ends. By analogy to other chromosomal protein complexes such as condensin and cohesin, I will refer to this complex as shelterin. ... | 10.1038/nrg2047 | A must-read review on the protein composition of mammalian telomeres and their role in the regulation of telomere length and telomere capping. |
10.1073/pnas.0605442104 | 109,179,182 | The sheltering of chromosome ends from illegitimate DNA repair reactions and telomere length homeostasis are critical for preserving genomic integrity. Growing evidence implicates covalent protein modification by SUMO (small ubiquitin-like modifier) (sumoylation) in the regulation of numerous DNA transactions, includin... | 10.1038/nrg2047 | A role for SUMO proteins in telomerase-mediated telomere elongation is first shown here. |
10.1126/science.1255638 | 61,318,866 | Trashing misfolded membrane proteins Proteins move to and from the inner nuclear membrane (INM) from the rest of the endoplasmic reticulum through the nuclear pores. This movement is tightly controlled. Consequently, the INM accumulates a specific set of proteins required for a variety of functions, including chromosom... | 10.1038/nrm.2016.153 | Together with reference 41, these studies identify a dedicated arm of the ERAD pathway at the INM. |
10.1126/science.aad7297 | 41,474,627 | Repairing tears in the nuclear envelope The nuclear envelope segregates genomic DNA from the cytoplasm and regulates protein trafficking between the cytosol and the nucleus. Maintaining nuclear envelope integrity during interphase is considered crucial. However, Raab et al. and Denais et al. show that migrating immune ... | 10.1038/nrm.2016.153 | Together with reference 71, these are landmark studies that describe NE rupturing events that are induced by the migration of cells through constrictions and are subsequently repaired by the ESCRT-III machinery. |
10.1073/pnas.0607004104 | 123,151,135 | The vast majority of phylogenetic models focus on resolution of gene trees, despite the fact that phylogenies of species in which gene trees are embedded are of primary interest. We analyze a Bayesian model for estimating species trees that accounts for the stochastic variation expected for gene trees from multiple unl... | 10.1038/nrg3186 | This paper introduces a method for estimating the species tree despite the presence of conflicting gene trees. |
10.1093/genetics/164.4.1645 | 41,597,826 | Abstract The effective population sizes of ancestral as well as modern species are important parameters in models of population genetics and human evolution. The commonly used method for estimating ancestral population sizes, based on counting mismatches between the species tree and the inferred gene trees, is highly b... | 10.1038/nrg3186 | This study describes the multi-species coalescent model. This is the basis for carrying out comparative analyses of individual genomes and phylogeographic studies and for applying species tree methods. |
10.1073/pnas.0913022107 | 20,592,534 | In the absence of recent admixture between species, bipartitions of individuals in gene trees that are shared across loci can potentially be used to infer the presence of two or more species. This approach to species delimitation via molecular sequence data has been constrained by the fact that genealogies for individu... | 10.1038/nrg3186 | This paper describes a Bayesian MCMC method for delimiting species using sequence data from multiple loci under the multi-species coalescent model. |
10.1101/gad.229328.113 | 40,120,827 | More than half of human genes use alternative cleavage and polyadenylation (ApA) to generate mRNA transcripts that differ in the lengths of their 3′ untranslated regions (UTRs), thus altering the post-transcriptional fate of the message and likely the protein output. The extent of 3′ UTR variation across tissues and th... | 10.1038/nrg3813 | This is a detailed study profiling genome-wide alternative polyadenylation sites in mRNAs across 12 human cell lines and tissues. The authors conclude that genes with multiple 3′UTRs tend to vary 3′UTR ratios across tissues, whereas genes with single 3′UTRs vary mRNA expression levels. |
10.1101/gad.1861409 | 79,989,065 | Recent studies have revealed the importance of multiple microRNAs (miRNAs) in promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent oncogenic activity. Genomic amplification and elevated expression of mir-17-92 occur in several human B-cell lymphomas, and enforced mir-17-92 expression in mice coopera... | 10.1038/nrc3166 | References 32 and 33 isolated the oncogenic role of miR-19 from the miR-17 ∼ 92 cluster. Both studies confirmed that miR-19 was sufficient to promote MYC-induced lymphomagenesis. |
10.1073/pnas.1105398108 | 123,456,024 | MicroRNA miR-146a has been implicated as a negative feedback regulator of NF-κB activation. Knockout of the miR-146a gene in C57BL/6 mice leads to histologically and immunophenotypically defined myeloid sarcomas and some lymphomas. The sarcomas are transplantable to immunologically compromised hosts, showing that they ... | 10.1038/nrc3166 | A careful analysis of mir-146a -knockout mice. Mice developed myeloid sarcomas and lymphomas. A link between miR-146a and NF-κB was also described. |
10.1101/gad.2004211 | 36,030,634 | Distant metastases, rather than the primary tumors from which these lesions arise, are responsible for >90% of carcinoma-associated mortality. Many patients already harbor disseminated tumor cells in their bloodstream, bone marrow, and distant organs when they initially present with cancer. Hence, truly effective an... | 10.1038/nrc3166 | A comprehensive study evaluating the antimetastatic role of miR-31 and suggesting the potential use of miR-31 for the treatment of metastatic disease. |
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/nri.2017.90 | This study identified the chemo-sensing proteins gustducin and TRPM5 as components crucial for DCLK1 + tuft cells to sense parasites and secrete IL-25. |
10.1126/scitranslmed.aaf1938 | 101,150,597 | Combined blockade of TSLP, IL-25, and IL-33 may be needed to treat some forms of progressive inflammation and fibrosis. | 10.1038/nri.2017.90 | This study showed partial redundancy of the alarmin proteins in maintaining type 2 responses and that early combinatorial blockade may be efficacious in reducing disease severity. |
10.1126/scitranslmed.aal3694 | 125,256,760 | Development of NASH fibrosis is accompanied by accumulation of hepatic eosinophils and driven by TGF-β and profibrotic type 2 inflammation. | 10.1038/nri.2017.90 | This study demonstrated a previously unappreciated link between hepatic eosinophils, type 2 cytokines and the severity of fibrosis in NAFLD. |
10.1126/science.7973651 | 20,487,984 | The tools of molecular biology were used to solve an instance of the directed Hamiltonian path problem. A small graph was encoded in molecules of DNA, and the "operations" of the computation were performed with standard protocols and enzymes. This experiment demonstrates the feasibility of carrying out computations at ... | 10.1038/nrg3197 | This paper provides the first experimentally shown computation with DNA molecules. |
10.1126/science.1205527 | 19,282,132 | Engineered biological systems that integrate multi-input sensing, sophisticated information processing, and precisely regulated actuation in living cells could be useful in a variety of applications. For example, anticancer therapies could be engineered to detect and respond to complex cellular conditions in individual... | 10.1038/nrg3197 | This paper describes a large-scale control system in human cells that identifies a cancerous cell state on the basis of multiple endogenous miRNA markers and produces a fluorescent or apoptosis-inducing protein following positive detection. |
10.1126/science.1200520 | 20,493,206 | Scalability and noise control are demonstrated in a molecular computer built from DNA. | 10.1038/nrg3197 | In this paper, a large-scale DNA circuit that is based on strand displacement reactions is described. |
10.1073/pnas.1015741108 | 82,299,985 | The widespread natural ability of RNA to sense small molecules and regulate genes has become an important tool for synthetic biology in applications as diverse as environmental sensing and metabolic engineering. Previous work in RNA synthetic biology has engineered RNA mechanisms that independently regulate multiple ta... | 10.1038/nrg3197 | This study described and tested, in the engineering context, an antisense RNA-based regulatory mechanism in bacteria. |
10.1002/bit.20142 | 82,299,989 | Abstract The architecture of gene regulatory networks is reminiscent of electronic circuits. Modular building blocks that respond in a logical way to one or several inputs are connected to perform a variety of complex tasks. Gene circuit engineers have pioneered the construction of artificial gene regulatory networks w... | 10.1038/nrg3197 | This work demonstrated a three-input logic gate on a mammalian promoter. |
10.1073/pnas.0808736106 | 83,179,055 | Self-assembly creates natural mineral, chemical, and biological structures of great complexity. Often, the same starting materials have the potential to form an infinite variety of distinct structures; information in a seed molecule can determine which form is grown as well as where and when. These phenomena can be exp... | 10.1038/nrg3197 | This is the most complex DNA-tiling computation to date, implementing a counter to 17. |
10.1126/science.1206938 | 20,520,051 | Multidimensional RNA structures can act as scaffolds for the spatial organization of bacterial metabolism. | 10.1038/nrg3197 | This paper is an example of nucleic acids nanotechnology use in living cells for improved efficiency of a bioproduction pathway. |
10.1126/science.1214081 | 103,712,863 | Nanorobots Deliver DNA aptamers are short strands that have high binding affinity for a target protein that can be used as triggers for releasing cargo from delivery vehicles. Douglas et al. (p. 831 ) used this strategy to design DNA origami “nanorobots”—complex shaped structures created by manipulating a long DNA stra... | 10.1038/nrg3197 | This study combines DNA nanotechnology with the logic gate concept for selective cell targeting. |
10.1126/science.1172005 | 39,261,167 | One, Two, Three Synthetic biologists take much of their inspiration from computing and electrical engineering, attempting to gain programmability in cells using analogous genetic circuits. Friedland et al. (p. 1199 ; see the Perspective by Smolke ) have constructed complementary Escherichia coli synthetic gene networks... | 10.1038/nrg3197 | An impressive example of recombinase-based circuitry is discussed in this paper that can irreversibly record up to three consecutive events. |
10.4049/jimmunol.165.6.3043 | 61,597,214 | Abstract The costimulatory receptor OX40 has recently been shown to be involved in primary CD4 responses to several defined Ags. However, to date there has been little information regarding the mechanism of action of OX40, such as whether it regulates T cell numbers, reactivity, or both, and whether it contributes to i... | 10.1038/nri1148 | This paper shows that OX40 is essential for the generation of a high frequency of memory CD4+ T cells. |
10.4049/jimmunol.164.5.2320 | 59,124,053 | Abstract Peptide vaccination induces T cell activation and cytotoxic T cell development. In an effort to understand what factors can improve immune responses to peptide vaccination, the role of 4-1BB (CD137) costimulation was examined, since 4-1BB has been shown to promote T cell responses in other systems. 4-1BBL-defi... | 10.1038/nri1148 | This paper, together with references 45 and 46, shows that 4-1BB has an important role in primary and secondary CD8+ T-cell responses to viruses and virus peptides. |
10.4049/jimmunol.168.8.3777 | 78,913,989 | Abstract In this report, we demonstrate that CD28−/− mice are severely impaired in the initial expansion of Db/NP366-374-specific CD8 T cells in response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)−/− mice show no defect in primary T cell expansion to influenza virus. In contrast, 4-1BBL−/− mice show a ... | 10.1038/nri1148 | This paper establishes the sequential action of 4-1BB late in the T-cell response after CD28. |
10.1084/jem.20020319 | 123,473,941 | CD30 is up-regulated in several human diseases and viral infections but its role in immune regulation is poorly understood. Here, we report the expression of a functional soluble CD30 homologue, viral CD30 (vCD30), encoded by ectromelia (mousepox) virus, a poxvirus that causes a severe disease related to human smallpox... | 10.1038/nri1148 | This paper shows that poxvirus produces a homologue of CD30 that can inhibit inflammation controlled by type 1 cytokines. |
10.1084/jem.20021937 | 123,632,756 | Asthma is caused by memory Th2 cells that often arise early in life and persist after repeated encounters with allergen. Although much is known regarding how Th2 cells develop, there is little information about the molecules that regulate memory Th2 cells after they have formed. Here we show that the costimulatory mole... | 10.1038/nri1148 | This paper shows that OX40 directly controls the secondary response of memory T cells and, similar to its action in the primary response, regulates the frequency of effector cells that are generated. |
10.1073/pnas.032662799 | 103,329,884 | The phylogenetic relationships of amoebae are poorly resolved. To address this difficult question, we have sequenced 1,280 expressed sequence tags from Mastigamoeba balamuthi and assembled a large data set containing 123 genes for representatives of three phenotypically highly divergent major amoeboid lineages: Pelobio... | 10.1038/nrg1603 | The first phylogenomic study based on the supermatrix approach that includes more than 100 genes for a relatively broad taxon sampling of eukaryotes. |
10.1126/science.1102036 | 39,292,628 | We assess the phylogenetic potential of ∼300,000 protein sequences sampled from Swiss-Prot and GenBank. Although only a small subset of these data was potentially phylogenetically informative, this subset retained a substantial fraction of the original taxonomic diversity. Sampling biases in the databases necessitate b... | 10.1038/nrg1603 | References 20 and 22 demonstrate the robustness of the supermatrix approach to a surprisingly high amount of missing data in phylogenomic analyses. |
10.1101/gr.187002 | 101,641,843 | It has been claimed that complete genome sequences would clarify phylogenetic relationships between organisms, but up to now, no satisfying approach has been proposed to use efficiently these data. For instance, if the coding of presence or absence of genes in complete genomes gives interesting results, it does not tak... | 10.1038/nrg1603 | The first application of a supertree method in phylogenomics showing its usefulness for reconstructing bacterial phylogeny in the presence of horizontal gene transfer. |
10.1101/gr.335003 | 86,219,956 | We compared nucleotide usage pattern conservation for related prokaryotes by examining the representation of DNA tetranucleotide combinations in 27 representative microbial genomes. For each of the organisms studied, tetranucleotide usage departures from expectations (TUD) were shared between related organisms using bo... | 10.1038/nrg1603 | A study showing that phylogenetic signal can be retrieved from the distribution of oligonucleotides in prokaryote genomes. |
10.1146/annurev.biophys.093008.131250 | 103,296,844 | When a voltage is imposed across a thin membrane containing a nanoscopic pore, the electric field generated within the pore captures linear ionized polymers, such as nucleic acids, that are present in the solution bathing the pore. The nucleic acid molecule transiently blocks ionic current as it is translocated through... | 10.1038/nnano.2011.129 | This review article provides a historical perspective on the field of nanopore DNA sequencing and elaborates on nanopore-based enzyme-mediated sequencing approaches |
10.1073/pnas.93.24.13770 | 62,262,989 | We show that an electric field can drive single-stranded RNA and DNA molecules through a 2.6-nm diameter ion channel in a lipid bilayer membrane. Because the channel diameter can accommodate only a single strand of RNA or DNA, each polymer traverses the membrane as an extended chain that partially blocks the channel. T... | 10.1038/nnano.2011.129 | This is the first experimental report of electronic detection of a DNA molecule passing through a nanopore (α-haemolysin) and marks the start of the nanopore sequencing field |
10.1073/pnas.1001831107 | 123,166,828 | Nanopore sequencing has the potential to become a direct, fast, and inexpensive DNA sequencing technology. The simplest form of nanopore DNA sequencing utilizes the hypothesis that individual nucleotides of single-stranded DNA passing through a nanopore will uniquely modulate an ionic current flowing through the pore, ... | 10.1038/nnano.2011.129 | Proof-of-principle experiments demonstrating duplex interrupted sequencing using MspA are reported here |
10.1063/1.2980518 | 62,418,182 | We demonstrate high-resolution modification of suspended multilayer graphene sheets by controlled exposure to the focused electron beam of a transmission electron microscope. We show that this technique can be used to realize, on time scales of a few seconds, a variety of features, including nanometer-scale pores, slit... | 10.1038/nnano.2011.129 | This is the first report of nanopore fabrication in a suspended graphene membrane using an electron beam and has led to subsequent studies of DNA translocation through graphene nanopores |
10.1128/jb.170.8.3584-3592.1988 | 61,263,273 | The 16S rRNAs from 29 cyanobacteria and the cyanelle of the phytoflagellate Cyanophora paradoxa were partially sequenced by a dideoxynucleotide-terminated, primer extension method. A least-squares distance matrix analysis was used to infer phylogenetic trees that include green chloroplasts (those of euglenoids, green a... | 10.1038/nrmicro2242 | A classic phylogenetic study using 16S ribosomal RNA sequences that corroborates the hypothesis that chloroplasts belong to the cyanobacterial radiation and shows that heterocyst-forming cyanobacteria constitute a monophyletic group. |
10.1101/gad.5.2.321 | 27,993,259 | Anabaena 7120 mutant 216 fails to differentiate heterocyst. We previously identified a 2.4-kb wild-type DNA fragment able to complement this mutant. We show here that the sequence of this fragment contains a single open reading frame (hetR), encoding a 299-amino-acid protein. Conjugation of deletion subclones of this f... | 10.1038/nrmicro2242 | This work identifies HetR as a key positive regulator of heterocyst differentiation. |
10.1126/science.282.5390.935 | 82,876,487 | Many filamentous cyanobacteria grow as multicellular organisms that show a developmental pattern of single nitrogen-fixing heterocysts separated by approximately 10 vegetative cells. Overexpression of a 54–base-pair gene, patS , blocked heterocyst differentiation in Anabaena sp. strain PCC 7120. A patS null mutant show... | 10.1038/nrmicro2242 | This investigation identifies patS and basic aspects of the PatS-related inhibition of heterocyst differentiation. |
10.1073/pnas.81.5.1561 | 102,342,251 | Wild-type cyanobacteria of the genus Anabaena are capable of oxygenic photosynthesis, differentiation of cells called heterocysts at semiregular intervals along the cyanobacterial filaments, and aerobic nitrogen fixation by the heterocysts. To foster analysis of the physiological processes characteristic of these cyano... | 10.1038/nrmicro2242 | This work develops a method for DNA transfer to heterocyst-forming cyanobacteria, leading to the modern study and genetic manipulation of these organisms. |
10.1101/gad.1100503 | 107,312,284 | It is well known that cell fate decisions in the mouse organizer region during gastrulation ultimately govern gut formation and patterning, left–right axis determination, and development of the central nervous system. Previous studies suggest that signaling pathways activated by Nodal, bone morphogenetic protein (BMP),... | 10.1038/nrm2618 | Shows that cell lineage allocation in the APS is governed by graded levels of nodal–SMAD2 signalling. The conditional deletion of SMAD2 in the epiblast, or lowering nodal expression in the primitive streak by targeted deletion of the primitive streak enhancer element, results in the selective loss of the anterior DE an... |
10.1242/dev.005967 | 59,542,645 | The specification of a subset of epiblast cells to acquire a neural fate constitutes the first step in the generation of the nervous system. Little is known about the signals required for neural induction in the mouse. We have analysed the role of BMP signalling in this process. We demonstrate that prior to gastrulatio... | 10.1038/nrm2618 | Shows that BMP signalling in the epiblast is required to maintain epiblast pluripotency and to repress precocious NE differentiation. |
10.1242/dev.01711 | 38,966,366 | Blimp1, a zinc-finger containing DNA-binding transcriptional repressor,functions as a master regulator of B cell terminal differentiation. Considerable evidence suggests that Blimp1 is required for the establishment of anteroposterior axis formation and the formation of head structures during early vertebrate developme... | 10.1038/nrm2618 | References 131 and 132 show that BLIMP1 (also known as PRDM1) is a marker for lineage restricted PGCs. Both papers show that targeted deletions of BLIMP1 lead to the complete loss of PGCs. |
10.1111/j.1348-0421.1998.tb02280.x | 60,760,686 | Abstract Fimbriae preparation from Actinobacillus actinomycetemcomitans was found to contain an abundant low‐molecular‐weight protein (termed Flp) with an apparent molecular mass of approximately 6.5 kDa, in addition to a small amount of 54‐kDa protein. Immunogold electron microscopy localized the Flp protein at the ba... | 10.1038/nrmicro1636 | The first study to identify Flp (Flp1) as the major structural component of Flp pili in A. actinomycetemcomitans |
10.1046/j.1365-2958.2001.02422.x | 104,391,455 | Actinobacillus actinomycetemcomitans , a Gram‐negative bacterium responsible for localized juvenile periodontitis and other infections such as endocarditis, produces long fibrils of bundled pili that are believed to mediate non‐specific, tenacious adherence to surfaces. Previous investigations have implicated an abunda... | 10.1038/nrmicro1636 | Identification of the Flp-subfamily of type IVb prepilins and in-depth phylogenetic analysis of type IV prepilins. |
10.1099/mic.0.26364-0 | 62,553,312 | Homologues of the protein constituents of the Klebsiella pneumoniae ( Klebsiella oxytoca ) type II secreton (T2S), the Pseudomonas aeruginosa type IV pilus/fimbrium biogenesis machinery (T4P) and the Methanococcus voltae flagellum biogenesis machinery (Fla) have been identified. Known constituents of these systems incl... | 10.1038/nrmicro1636 | A comprehensive study examining the phylogenetic relationships between the conserved components of T2S, T4P and archaeal flagellar biogenesis system proteins. |
10.1073/pnas.1237223100 | 81,124,969 | Actinobacillus actinomycetemcomitans is a Gram-negative coccobacillus that has been associated with localized aggressive periodontitis and infections of the heart, brain, and urinary tract. Wild-type clinical isolates have the remarkable ability to adhere tenaciously and nonspecifically to solid surfaces such as glass,... | 10.1038/nrmicro1636 | This study shows that the tad genes of A. actinomycetemcomitans are required for colonization, persistence and bone loss in rats inoculated through the natural route of infection. |
10.1126/science.286.5441.950 | 84,427,523 | Posttranscriptional gene silencing (PTGS) is a nucleotide sequence–specific defense mechanism that can target both cellular and viral mRNAs. Here, three types of transgene-induced PTGS and one example of virus-induced PTGS were analyzed in plants. In each case, antisense RNA complementary to the targeted mRNA was detec... | 10.1038/nri1227 | The first evidence that small ∼ 25-nucleotide RNAs might be the mediators of post-transcriptional gene silencing mediated by dsRNA. |
10.1084/jem.20050625 | 107,242,437 | The role of innate immune recognition by intestinal epithelial cells (IECs) in vivo is ill-defined. Here, we used highly enriched primary IECs to analyze Toll-like receptor (TLR) signaling and mechanisms that prevent inappropriate stimulation by the colonizing microflora. Although the lipopolysaccharide (LPS) receptor ... | 10.1038/nri2075 | A landmark study revealing a mechanism by which initial intestinal endotoxin exposure at birth downregulates subsequent responses, paving the way for commensal interactions. |
10.4049/jimmunol.177.3.1956 | 83,299,158 | Abstract Human newborns are susceptible to microbial infection and mount poor vaccine responses, yet the mechanisms underlying their susceptibility are incompletely defined. We have previously reported that despite normal basal expression of TLRs and associated signaling intermediates, human neonatal cord blood monocyt... | 10.1038/nri2075 | Shows, in human neonatal cord blood, that high plasma adenosine levels and increased mononuclear-cell sensitivity to adenosine action results in greatly increased cellular cAMP concentrations that impair TLR2-mediated TNF production but preserve production of IL-6. |
10.1084/jem.20031272 | 87,176,569 | To gain insight into the inability of newborns to mount efficient Th1 responses, we analyzed the molecular basis of defective IL-12(p35) expression in human neonatal monocyte-derived dendritic cells (DCs). Determination of IL-12(p35) pre-mRNA levels by real-time RT-PCR revealed that transcriptional activation of the ge... | 10.1038/nri2075 | Shows that expression of IL-12 p35 by human neonatal DCs is regulated at the chromatin level by a defect in nucleosome remodelling. |
10.4049/jimmunol.174.2.777 | 39,051,367 | Abstract Infection by Listeria monocytogenes causes serious morbidity and mortality during the neonatal period. Previous studies established that immunostimulatory CpG oligodeoxynucleotides (ODN) can increased the resistance of adult mice to many infectious pathogens, including Listeria. This work examines the capacity... | 10.1038/nri2075 | Shows that administration of CpG ODNs can protect newborn mice from subsequent challenge with L. monocytogenes |
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