source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1111/j.1349-7006.1996.tb00288.x | 103,098,826 | MAGE genes encoding tumor antigens recognized by cytotoxic T lymphocytes are appropriate target molecules for specific immunotherapy of cancer. We have investigated whether the demethylating agent 5‐aza‐2′‐deoxycytidine (DAC) induces MAGE‐1, ‐2, ‐3 , and ‐ 6 in normal and malignant lymphoid cells. DAC induced these MAG... | 10.1038/nrc1669 | First demonstration that promoter demethylation is a key element in the induction of expression of CT-X antigens |
10.1111/j.1365-2990.1992.tb00811.x | 4,619,494 | In recent years it has been recognized that cells of the mononuclear phagocyte lineage, macro‐phages and microglia, are a major component of gliosis. We review here studies on the kinetics of the myelomonocytic response to acute excitotoxin induced neuronal degeneration and following the injection of endotoxin (LPS) in... | 10.1038/nri1130 | This review explains the concept that inflammatory reactions in the CNS favour the recruitment and activation of mononuclear phagocytes, even after necrotizing tissue injury. |
10.1126/science.3276004 | 102,724,754 | A crucial question in the study of immunological reactions in the central nervous system (CNS) concerns the identity of the parenchymal cells that function as the antigen-presenting cells in that organ. Rat bone marrow chimeras and encephalitogenic, major histocompatability-restricted T-helper lymphocytes were used to ... | 10.1038/nri1130 | Using bone-marrow chimaeras, the authors show that perivascular mononuclear phagocytes that are derived from the marrow are sufficient to restimulate encephalitogenic T cells in the CNS. |
10.4049/jimmunol.168.4.1940 | 41,113,078 | Abstract Lymphocyte recruitment into the brain is a critical event in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. We developed a novel intravital microscopy model to directly analyze through the skull the interactions between lymphocytes and the endothelium in cerebral venules ... | 10.1038/nri1130 | This paper describes a new intravital-microscopy approach to examine the microvessels of the brain parenchyma, and shows that interaction between encephalitogenic T-cell blasts and unactivated cerebral microvessels is a low-efficiency event. |
10.4049/jimmunol.155.10.5003 | 139,042,676 | Abstract Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for the human demyelinating disease, multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific T lympho... | 10.1038/nri1130 | The first paper to show an essential role for one chemokine in mouse adoptive-transfer experimental autoimmune encephalomyelitis (EAE). |
10.1084/jem.192.6.871 | 56,998,781 | Multiple sclerosis (MS) is believed to be an autoimmune disease in which autoreactive T cells infiltrate the central nervous system (CNS). Animal models of MS have shown that CNS-specific T cells are present in the peripheral T cell repertoire of healthy mice and cause autoimmune disease only when they are activated by... | 10.1038/nri1130 | This paper reports the remarkable observation that T-cell receptor (TCR)-transgenic T cells of a naive phenotype migrate efficiently and spontaneously to the CNS. |
10.1111/j.1750-3639.1991.tb00646.x | 27,070,906 | The central nervous system has long been considered an immunologically privileged site. Nevertheless, cells derived from the bone marrow can and do enter the CNS in a number of circumstances. Derivatives of the monocyte/macrophage lineage appear to enter and take up residence in various structures of the CNS as part of... | 10.1038/nri1130 | This report includes a summary of the early work on the accumulation of activated T-cell blasts in the CNS. |
10.1126/science.1203486 | 62,608,967 | Understanding how the immune system affects cancer development and progression has been one of the most challenging questions in immunology. Research over the past two decades has helped explain why the answer to this question has evaded us for so long. We now appreciate that the immune system plays a dual role in canc... | 10.1038/nrc3397 | An overview of the dual role that immunoediting has in promoting and suppressing tumour growth. |
10.1146/annurev.micro.112408.134019 | 36,196,098 | It has been estimated that viruses are etiological agents in approximately 12% of human cancers. Most of these cancers can be attributed to infections by human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), and Kaposi's sarcoma–associated herpesvirus (KSHV). Prophylact... | 10.1038/nrc3397 | One of the most comprehensive reviews of the state of vaccine research against oncoviruses, with examples from the past, and a look at the future. |
10.1073/pnas.88.9.3734 | 81,169,469 | CENP-A, a centromere-specific 17-kDa protein, has histone-like properties. However, in contrast to the common somatic histones, CENP-A is quantitatively retained in bull spermatozoa, and we have exploited this fact to purify CENP-A to apparent homogeneity. Partial sequence analysis of the purified protein indicates tha... | 10.1038/nrg.2016.157 | The discovery that CenH3 CENP-A is a histone H3 variant. |
10.1126/science.1206880 | 81,048,940 | A specific histone is sufficient for the formation of a functional and heritable centromere in the fruit fly. | 10.1038/nrg.2016.157 | This work describes how CenH3 CID is sufficient to establish functional kinetochores using the LacI–LacO targeting system. |
10.1126/science.1235532 | 125,103,909 | Kinetochore Targeting Chromosomes must be segregated accurately during cell division. This is facilitated by the attachment of mitotic spindle microtubules to the kinetochore at the chromosomal centromere. The centromere is marked with the histone H3 variant CenH3 (CENP-A in human), and CENP-C forms part of the inner k... | 10.1038/nrg.2016.157 | An important structural paper showing how CenH3 CENP-A interacts with CENP-C. |
10.1002/jbmr.2207 | 80,983,062 | ABSTRACT There is an increasing body of research suggesting that low body weight is associated with scoliosis, but this is based on case-control studies, which are prone to bias. No studies have investigated the components of body weight: fat and lean mass. We have therefore carried out the first population-based prosp... | 10.1038/nrdp.2015.30 | This is the first population-based large prospective study to show that a decrease in both lean and fat mass at 10 years of age is associated with an increased incidence of scoliosis at 15 years of age, providing important evidence of the link between endocrine metabolic abnormalities and the development of scoliosis. |
10.1083/jcb.201304051 | 41,440,517 | Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we ... | 10.1038/nrm3861 | This paper shows that lamellipodin directly interacts with the WAVE complex downstream of activated RAC, thereby controlling lamellipodium formation and the speed and persistence of cell migration in vitro , and both mesenchymal and epithelial collective cell migration in vivo |
10.1073/pnas.1107666108 | 79,665,763 | The WAVE regulatory complex (WRC) is a critical element in the control of actin polymerization at the eukaryotic cell membrane, but how WRC is activated remains uncertain. While Rho GTPase Rac1 can bind and activate WRC in vitro, this interaction is of low affinity, suggesting other factors may be important. By reconst... | 10.1038/nrm3861 | This paper describes the cooperativity of active ARF proteins and active RAC for efficient WAVE complex activation in cell extracts. ARF proteins are activated downstream of PtdIns(3,4,5)P 3 in cell extracts. The requirement for ARF proteins specifically refers to ARF1, ARF5 or ARL1. |
10.1073/pnas.1011271107 | 83,540,212 | Cells have an internal compass that enables them to move along shallow chemical gradients. As amoeboid cells migrate, signaling events such as Ras and PI3K activation occur spontaneously on pseudopodia. Uniform stimuli trigger a symmetric response, whereupon cells stop and round up; then localized patches of activity a... | 10.1038/nrm3861 | This paper reports the so-called LEGI-BEN model of cell migration, which is a major model accounting for chemotactic behaviour. It explains in particular how cells are intrinsically able to maintain a polarized state associated with directional persistence through the propagation of waves, which involves positive feedb... |
10.1093/bioinformatics/btg112 | 41,713,976 | Abstract Summary: R/qtl is an extensible, interactive environment for mapping quantitative trait loci (QTLs) in experimental populations derived from inbred lines. It is implemented as an add-on package for the freely-available statistical software, R, and includes functions for estimating genetic maps, identifying gen... | 10.1038/nrg1157 | This is a highly instructive and lucid review of the statistical rules of QTL mapping. |
10.1093/genetics/160.4.1609 | 41,693,211 | Abstract We describe a method to simultaneously detect and fine map quantitative trait loci (QTL) that is especially suited to the mapping of modifier loci in mouse mutant models. The method exploits the high level of historical recombination present in a heterogeneous stock (HS), an outbred population of mice derived ... | 10.1038/nrg1157 | An in-depth study of parameters of QTL mapping in heterogeneous crosses. |
10.1098/rstb.1998.0256 | 79,460,687 | The Min (multiple intestinal neoplasia) strain of the laboratory mouse and its derivatives permit the fundamental study of factors that regulate the transition between normal and neoplastic growth. A gene of central importance in mediating these alternative patterns of growth is Apc , the mouse homologue of the human a... | 10.1038/nrg1157 | An instructive review of the role of the APC Min and Mom1 genes in intestinal tumorigenesis. |
10.1126/science.1090100 | 103,897,782 | Alternative pre–messenger RNA (pre-mRNA) splicing plays important roles in development, physiology, and disease, and more than half of human genes are alternatively spliced. To understand the biological roles and regulation of alternative splicing across different tissues and stages of development, systematic methods a... | 10.1038/nrm1645 | Used a splice-sensitive microarray with probes for every known exon–exon junction in >10,000 human genes to reveal several global features of alternative splicing, as well as the discovery and validation of previously uncharacterized splicing events. |
10.1073/pnas.0136770100 | 123,883,256 | To better understand the role of alternative splicing, we conducted a large-scale analysis of reliable alternative isoforms of known human genes. Each isoform was classified according to its splice pattern and supporting evidence. We found that one-third of the alternative transcripts examined contain premature termina... | 10.1038/nrm1645 | A bioinformatics survey indicating that a large proportion of human alternative splicing leads to products that are degraded by nonsense-mediated decay. |
10.1101/gad.1195304 | 125,072,111 | We have searched for sequence motifs that contribute to the recognition of human pre-mRNA splice sites by comparing the frequency of 8-mers in internal noncoding exons versus unspliced pseudo exons and 5′ untranslated regions (5′ untranslated regions [UTRs]) of transcripts of intronless genes. This type of comparison a... | 10.1038/nrm1645 | A computational screen for ESSs and ESEs; the datasets produced by reference 28 and 29 allow pseudo-exons to be discriminated from authentic exons. |
10.1083/jcb.149.2.307 | 41,126,958 | Individual members of the serine-arginine (SR) and heterogeneous nuclear ribonucleoprotein (hnRNP) A/B families of proteins have antagonistic effects in regulating alternative splicing. Although hnRNP A1 accumulates predominantly in the nucleus, it shuttles continuously between the nucleus and the cytoplasm. Some but n... | 10.1038/nrm1645 | An important demonstration of a signalling pathway that alters alternative splicing patterns by relocalizing hnRNP A1 to the cytoplasm, thereby altering the nuclear ratio of hnRNP A1 and SF2/ASF. |
10.1126/science.1090095 | 103,743,774 | Nova proteins are neuron-specific antigens targeted in paraneoplastic opsoclonus myoclonus ataxia (POMA), an autoimmune neurologic disease characterized by abnormal motor inhibition.Nova proteins regulate neuronal pre-messenger RNA splicing by directly binding to RNA.To identify Nova RNA targets, we developed a method ... | 10.1038/nrm1645 | Reports a novel technique that allowed the identification of cellular targets of Nova proteins in mouse brain, many of which were subsequently validated by analysing their splicing patterns in Nova-knockout mice. |
10.1101/gad.12.13.1998 | 80,293,480 | Using an in vitro randomization and functional selection procedure, we have identified three novel classes of exonic splicing enhancers (ESEs) recognized by human SF2/ASF, SRp40, and SRp55, respectively. These ESEs are functional in splicing and are highly specific. For SF2/ASF and SRp55, in most cases, only the cognat... | 10.1038/nrm1645 | References 112 and 113 describe a functional SELEX approach in which ESEs were selected in cytoplasmic S100 extract in the presence of individual SR proteins, allowing the identification of ESEs specific for each protein. This allowed the development of the ESEfinder web resource. |
10.1126/science.1073774 | 61,475,990 | Specific short oligonucleotide sequences that enhance pre-mRNA splicing when present in exons, termed exonic splicing enhancers (ESEs), play important roles in constitutive and alternative splicing. A computational method, RESCUE-ESE, was developed that predicts which sequences have ESE activity by statistical analysis... | 10.1038/nrm1645 | A computational survey for ESEs, based on the enrichment in exons versus introns, and in exons with weak splice sites versus exons with strong splice sites; led to the development of the RESCUE-ESE web resource. |
10.1073/pnas.0407004101 | 102,427,936 | Alternative splicing is thought to be regulated by nonspliceosomal RNA binding proteins that modulate the association of core components of the spliceosome with the pre-mRNA. Although the majority of metazoan genes encode pre-mRNAs that are alternatively spliced, remarkably few splicing regulators are currently known. ... | 10.1038/nrm1645 | An RNAi screen allowed the identification of a large number of splicing regulators, including a number of constitutive splicing factors. |
10.1073/pnas.91.23.10809 | 102,706,641 | The cDNA for a member of the nuclear receptor family was cloned and named ubiquitous receptor (UR), since UR protein and mRNA are detected in many cell types. Rat UR/human retinoid X receptor alpha (hRXR alpha) heterodimers bound preferentially to double-stranded oligonucleotide direct repeats having the consensus half... | 10.1038/nrc3912 | This is the earliest report of the discovery of LXRβ, which was the first LXR to be cloned. |
10.1101/gad.850400 | 62,328,305 | The discovery of oxysterols as the endogenous liver X receptor (LXR) ligands and subsequent gene targeting studies in mice provided strong evidence that LXR plays a central role in cholesterol metabolism. The identification here of a synthetic, nonsteroidal LXR-selective agonist series represented by T0314407 and T0901... | 10.1038/nrc3912 | This paper describes the identification of T0901317 as a synthetic LXR agonist and provides the first evidence that hyperlipidaemia and liver steatosis are potential adverse effects of LXR agonists. |
10.1073/pnas.112059299 | 17,688,322 | The nuclear receptors LXRα and LXRβ have been implicated in the control of cholesterol and fatty acid metabolism in multiple cell types. Activation of these receptors stimulates cholesterol efflux in macrophages, promotes bile acid synthesis in liver, and inhibits intestinal cholesterol absorption, actions that would c... | 10.1038/nrc3912 | This study demonstrated the effects of GW3965 on reducing atherosclerotic lesions. |
10.1073/pnas.172510899 | 45,539,340 | Liver X receptors (LXRα and -β) are nuclear receptors abundant in the liver where they are regulators of lipid homeostasis. Both LXRs are also expressed in the brain, but their roles in this tissue remain to be clarified. We examined the brains of mice in which the genes of both LXRα and -β have been disrupted and foun... | 10.1038/nrc3912 | This is the first report showing that the LXRs are important for CNS function. |
10.1177/0091270009335768 | 39,334,000 | Liver X‐receptor (LXR) agonists have been postulated to enhance reverse cholesterol transport (RCT), a process believed to shuttle cholesterol from the periphery back to the liver. Enhancing RCT via the upregulation of cholesterol transporters such as the adenosine triphosphate—binding cassettes ABCA1 and ABCG1 could t... | 10.1038/nrc3912 | These are the only published clinical trial results of a LXR agonist to show adverse effects on the CNS. |
10.1093/bioinformatics/bti504 | 27,732,859 | Abstract Summary: Efficient RNA sequence manipulations (such as multiple alignments) need to be constrained by rules of RNA structure folding. The structural knowledge has increased dramatically in the last years with the accumulation of several large RNA structures similar to those of the bacterial ribosome subunits. ... | 10.1038/nmeth.1427 | Offers the most complete set of features for viewing RNA structures. Recommended for advanced users. Also available by web services |
10.1073/pnas.92.19.8813 | 60,477,613 | Calcium-dependent homotypic cell-cell adhesion, mediated by molecules such as E-cadherin, guides the establishment of classical epithelial cell polarity and contributes to the control of migration, growth, and differentiation. These actions involve additional proteins, including alpha- and beta-catenin (or plakoglobin)... | 10.1038/nrm1433 | Shows αE-catenin to be a new actin-binding and -bundling protein, and supports a model in which αE-catenin is responsible for organizing and tethering actin filaments at the zones of E-cadherin-mediated cell–cell contact. |
10.4049/jimmunol.176.3.1517 | 124,014,159 | Abstract Lineage differentiation and the formation of heterogeneous mature subsets are crucial for immune cells to maintain a breadth of responsiveness to pathogens while controlling reactivity to self. In this study, we report that CD27 is a key marker of the NK cell lineage, dissecting the mature Mac-1high NK cell po... | 10.1038/nri2154 | An interesting paper describing functional subsets of mature NK cells in mice that differ in their expression of CD27. |
10.4049/jimmunol.136.12.4480 | 139,047,538 | Abstract We examined the antigenic and functional characteristics of human peripheral blood lymphocytes that differentially express the CD16 (Leu-11) and Leu-19 (NKH-1) antigens. Leu-19 is a approximately 220,000 daltons protein expressed on approximately 15% of freshly isolated peripheral blood lymphocytes. Within the... | 10.1038/nri2154 | The first report of differential expression of CD16 by human NK cells and the functional characterization of NK-cell subsets. |
10.1182/blood-2004-02-0656 | 80,507,465 | Abstract Tumor suppressor p53 plays an important role in regulating cell cycle progression and apoptosis. Here we applied RNA interference to study the role of p53 in human hematopoietic development in vivo. An siRNA construct specifically targeting the human tumor-suppressor gene p53 was introduced into human CD34+ pr... | 10.1038/nri2154 | References 98 and 99 describe novel humanized mice that develop a complete immune system including B, T and NK cells. |
10.1073/pnas.0507719102 | 38,395,085 | Current techniques in high-speed cell sorting are limited by the inherent coupling among three competing parameters of performance: throughput, purity, and rare cell recovery. Microfluidics provides an alternate strategy to decouple these parameters through the use of arrayed devices that operate in parallel. To effici... | 10.1038/nrmicro1715 | This article describes the first successful screening of a bacterial library by the μFACS system. |
10.1073/pnas.0605422103 | 81,813,738 | A quantitative methodology was developed to identify protein interactions in a broad range of cell types by using FRET between fluorescent proteins. Genetic fusions of a target receptor to a FRET acceptor and a large library of candidate peptide ligands to a FRET donor enabled high-throughput optical screening for opti... | 10.1038/nrmicro1715 | This article demonstrated the first quantitative analysis of the protein–protein interaction in the E. coli cytoplasm and the screening of interacting proteins by the use of new FRET probes. |
10.1073/pnas.170297297 | 38,405,509 | Single-chain antibody mutants have been evolved in vitro with antigen-binding equilibrium dissociation constant K d = 48 fM and slower dissociation kinetics (half-time > 5 days) than those for the streptavidin–biotin complex. These mutants possess the highest monovalent ligand-binding affinity yet reported for an en... | 10.1038/nrmicro1715 | An extraordinary example of affinity maturation of an immunological molecule by cell-surface display on yeast. Antibodies with femtomolar binding affinity to the small molecule fluorescein were isolated. |
10.1111/j.2517-6161.1972.tb00899.x | 62,624,504 | Summary The analysis of censored failure times is considered. It is assumed that on each individual are available values of one or more explanatory variables. The hazard function (age-specific failure rate) is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbit... | 10.1038/nrg.2016.27 | The author proposes the proportional hazard regression model and partial-likelihood method for statistical inference. In the discussion following the paper, N.E. Breslow proposes an estimator for baseline hazard function that is required for absolute risk estimation. |
10.1126/science.1140579 | 97,828,222 | Primate genomes contain a large number of endogenous retroviruses and encode evolutionarily dynamic proteins that provide intrinsic immunity to retroviral infections. We report here the resurrection of the core protein of a 4-million-year-old endogenous virus from the chimpanzee genome and show that the human variant o... | 10.1038/nrg3905 | This landmark paper was the first to demonstrate that past infections contribute to shaping susceptibility to novel pathogens in extant species. |
10.1073/pnas.1201193109 | 62,210,294 | Lipopolysaccharide (LPS), also known as endotoxin, activates the innate immune response through toll-like receptor 4 (TLR4) and its coreceptor, MD-2. MD-2 has a unique hydrophobic cavity that directly binds to lipid A, the active center of LPS. Tetraacylated lipid IVa, a synthetic lipid A precursor, acts as a weak agon... | 10.1038/nrg3905 | This paper presents the crystal structure of the mouse TLR4–LY96–lipid IVa complex and compares it to the human counterpart, elucidating elements that may account for different responsiveness in the two species. |
10.1128/jvi.00311-12 | 62,229,528 | ABSTRACT In 2002, severe acute respiratory syndrome (SARS)-coronavirus (CoV) appeared as a novel human virus with high similarity to bat coronaviruses. However, while SARS-CoV uses the human angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry, no coronavirus isolated from bats appears to use ACE2. Here w... | 10.1038/nrg3905 | A good example of how evolutionary studies can provide insight into host range and disease emergence. |
10.1126/science.1191046 | 59,646,189 | Complex I Under Scrutiny Mitochondrial complex I is a large macromolecular membrane complex that couples electron transfer to proton pumping across the mitochondrial membrane and helps to drive adenosine 5′-triphosphate synthesis. Hunte et al. (p. 448 , published online 1 July) now describe the structure of complex 1 f... | 10.1038/nrm3997 | First study of mitochondrial complex I by X-ray crystallography, at 6.3 Å resolution, showing the arrangement of functional modules. |
10.1126/science.1259859 | 41,543,094 | Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complicated membrane protein complexes. The enzyme contributes substantially to oxidative energy conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. We report the x-ra... | 10.1038/nrm3997 | X-ray crystallography study of mitochondrial complex I from Y. lipolytica at 3.8 Å resolution, revealing the structure of the large parts of the core subunits. |
10.1126/science.1123809 | 41,470,344 | Respiratory complex I plays a central role in cellular energy production in bacteria and mitochondria. Its dysfunction is implicated in many human neurodegenerative diseases, as well as in aging. The crystal structure of the hydrophilic domain (peripheral arm) of complex I from Thermus thermophilus has been solved at 3... | 10.1038/nrm3997 | First atomic structure of the peripheral arm of complex I, showing the arrangement of subunits and redox cofactors, including uniquely long chain of Fe–S clusters. |
10.1128/jb.176.6.1729-1737.1994 | 61,256,657 | Escherichia coli K-12 strains and Shigella flexneri grown to stationary phase can survive several hours at pH 2 to 3, which is considerably lower than the acid limit for growth (about pH 4.5). A 1.3-kb fragment cloned from S. flexneri conferred acid resistance on acid-sensitive E. coli HB101; sequence data identified t... | 10.1038/nrmicro1021 | First study to demonstrate the inducible nature of acid resistance in both E. coli and S. flexneri |
10.1128/jb.177.14.4097-4104.1995 | 81,916,322 | Several members of the family Enterobacteriaceae were examined for differences in extreme acid survival strategies. A surprising degree of variety was found between three related genera. The minimum growth pH of Salmonella typhimurium was shown to be significantly lower (pH 4.0) than that of either Escherichia coli (pH... | 10.1038/nrmicro1021 | First description of the three basic systems of acid resistance in E. coli — the glutamate-dependent, arginine-dependent and glucose-repressed or oxidative system. It also identified adiA , which encodes arginine decarboxylase, as an important part of arginine-dependent acid resistance |
10.1046/j.1365-2958.1999.01430.x | 18,561,462 | Inducible bacterial amino acid decarboxylases are expressed at the end of active cell division to counteract acidification of the extracellular environment during fermentative growth. It has been proposed that acid resistance in some enteric bacteria strictly relies on a glutamic acid‐dependent system. The Escherichia ... | 10.1038/nrmicro1021 | Described the transcriptional organization of the gadBC operon and revealed that it is regulated by acid, osmolarity and stationary phase. |
10.1128/jb.178.13.3978-3981.1996 | 40,673,236 | Stationary-phase cultures of Escherichia coli can survive several hours or exposure to extreme acid (pH 2 to 3), a level well below the pH range for growth (pH 4.5 to 9). To identify the genes needed for survival in extreme acid, a microliter screening procedure was devised. Colonies from a Tn10 transposon pool in E. c... | 10.1038/nrmicro1021 | Identified the first component of the glutamate-dependent acid-resistance system, which proved to be the glutamate/GABA antiporter. |
10.1046/j.1365-2958.2003.03633.x | 84,444,248 | Summary Commensal and pathogenic strains of Escherichia coli possess three inducible acid resistance systems that collaboratively protect cells against acid stress to pH 2 or below. The most effective system requires glutamate in the acid challenge media and relies on two glutamate decarboxylases (GadA and B) combined ... | 10.1038/nrmicro1021 | First study to identify GadE as the direct activator of the gadA and gadBC genes. |
10.1046/j.1365-2958.2003.03477.x | 122,799,867 | Summary Overexpression of the response regulator EvgA confers an acid‐resistant phenotype to exponentially growing Escherichia coli . This acid resistance is partially abolished by deletion of ydeP , yhiE or ydeO , genes induced by EvgA overexpression. Microarray analysis identified two classes of operons (genes). The ... | 10.1038/nrmicro1021 | Describes a brilliant approach used to define regulatory circuits in acid resistance. The first report to describe a connection between EvgA and acid resistance. |
10.1046/j.1365-2958.2001.02570.x | 103,501,167 | Enteropathogenic Escherichia coli (EPEC) is a major cause of infantile diarrhoea in a number of developing countries and is the prototype of pathogenic bacteria that cause attaching and effacing (A/E) intestinal lesions. A chromosomal pathogenicity island, termed the locus of enterocyte effacement (LEE), contains all t... | 10.1038/nrmicro1021 | The first report to demonstrate a role for GadX in regulating glutamate-dependent acid resistance and to link acid resistance to the regulation of genes in the LEE pathogenicity island of enteropathogenic E. coli |
10.1002/chin.200215266 | 124,518,272 | Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” opti... | 10.1038/nrd1280 | Explains the regulatory issues related to the polymorphism of pharmaceuticals. |
10.1093/oso/9780198500728.001.0001 | 149,177,161 | Abstract Direct methods are, at present, applied to a large variety of cases: X-ray, neutron or electron data; single crystal and powder data; small molecules and macromolecules. While direct methods solved in practice the phase problem for small molecules, their application to macromolecules is recent and still underg... | 10.1038/nrd1280 | Explains the most common technique for solving crystal structures from single crystal X-ray diffraction patterns. |
10.1126/science.220.4598.671 | 83,534,307 | There is a deep and useful connection between statistical mechanics (the behavior of systems with many degrees of freedom in thermal equilibrium at a finite temperature) and multivariate or combinatorial optimization (finding the minimum of a given function depending on many parameters). A detailed analogy with anneali... | 10.1038/nrd1280 | This seminal paper explains the value and the process of simulated annealing. |
10.1126/science.284.5414.641 | 81,282,694 | Primary effusion lymphoma (PEL) cells harbor Kaposi's sarcoma–associated herpesvirus (KSHV) episomes and express a KSHV-encoded latency-associated nuclear antigen (LANA). In PEL cells, LANA and KSHV DNA colocalized in dots in interphase nuclei and along mitotic chromosomes. In the absence of KSHV DNA, LANA was diffusel... | 10.1038/nri2076 | This report is the first to show that primary effusion lymphoma cells harbour latent KSHV genomes and that LANA tether these genomes to the host DNA during cellular division. For a long period of time, PEL cells were the only cell type in which KSHV replication could be studied. |
10.1126/science.1088902 | 123,895,521 | The glycine-alanine repeat domain (GAr) of Epstein-Barr virus–encoded nuclear antigen 1 (EBNA1) prevents major histocompatibility complex (MHC) class I–restricted presentation of EBNA1 epitopes to cytotoxic T cells. This effect has previously been attributed to the ability of GAr to inhibit its own proteasomal degradat... | 10.1038/nri2076 | This report is the first to show that EBNA1, in addition to preventing its degradation (reference 7), also regulates its translation presumably to lower the amount of viral peptides that can be presented to T cells. |
10.1261/rna.2326106 | 79,412,953 | We have developed an approach to identify microRNAs (miRNAs) that is based on bioinformatics and array-based technologies, without the use of cDNA cloning. The approach, designed for use on genomes of small size (<2 Mb), was tested on cells infected by either of two lymphotropic herpesviruses, KSHV and EBV. The vira... | 10.1038/nri2076 | References 20–25 describe the identification of miRNAs in KSHV. These miRNAs are expressed during latency and might allow the virus to modify its host environment without increasing recognition by CTLs. |
10.1126/science.277.5332.1656 | 123,507,172 | Kaposi's sarcoma–associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed a broader spectrum of receptor activities than any mammalian chemokine as it bound with high affinity to a number of both CC and CXC chemokine receptors. Binding of vMIP-II, however, was not associated with the normal, ra... | 10.1038/nri2076 | This report is the first to show that KSHV-encoded chemokines were effective at binding a broad spectrum of chemokine receptors. This led to the idea that KSHV might regulate the balance between T H 1 and T H 2 cells. |
10.1126/science.1110340 | 19,686,740 | Ubiquitination controls a broad range of cellular functions. The last step of the ubiquitination pathway is regulated by enzyme type 3 (E3) ubiquitin ligases. E3 enzymes are responsible for substrate specificity and catalyze the formation of an isopeptide bond between a lysine residue of the substrate (or the N terminu... | 10.1038/nri2076 | This report is the first to show that E3 ubiquitin ligases, such as the KSHV-encoded MIR1, can ubiquitylate their substrate on cysteine residues. This observation broadens the number of potential substrates that can be targeted by ubiquitylation. |
10.4049/jimmunol.162.1.263 | 139,039,867 | Abstract Hashimoto’s thyroiditis (HT) is a chronic autoimmune disease resulting from Fas-mediated thyrocyte destruction. Although autocrine/paracrine Fas-Fas ligand (FasL) interaction is responsible for thyrocyte cell death during the active phases of HT, the role of infiltrating T lymphocytes (ITL) in this process is ... | 10.1038/nri750 | Unexpected findings indicating that thyrocytes kill infiltrating T cells in Hashimoto's thyroiditis. |
10.1177/030098588302000503 | 57,768,030 | Spontaneous lymphocytic thyroiditis was observed at necropsy in 36 BB Wistar diabetic rats (63.2%) and in eight of their nondiabetic siblings (42.1%). The incidence of thyroiditis decreased both with age and with longer duration of diabetes. All rats with pancreatic insulitis (a manifestation of the onset of diabetes) ... | 10.1038/nri750 | Description of a spontaneous model of autoimmune thyroiditis in mammals. |
10.1084/jem.186.8.1193 | 86,307,686 | Fas is an apoptosis-inducing surface receptor involved in controlling tissue homeostasis and function at multiple sites. Here we show that β cells from the pancreata of newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients express Fas and show extensive apoptosis among those cells located in proximity to ... | 10.1038/nri750 | Describes a new pathway that is responsible for autoimmune β-cell destruction in human diabetes. |
10.1002/eji.1830271228 | 81,006,234 | Abstract Most human organ‐specific autoimmune diseases such as Hashimoto's thyroiditis (HT) are considered to be Th1 mediated, and a quantitative dominance of Th1 cells in thyroid infiltrates from both Graves' disease (GD) and HT affected glands has been reported. However, Th2 dominance would be expected in GD, where t... | 10.1038/nri750 | The first analysis of cytokine production at a single-cell level in activated T cells that infiltrate the thyroid. |
10.1126/science.270.5235.484 | 123,111,153 | The characteristics of an organism are determined by the genes expressed within it. A method was developed, called serial analysis of gene expression (SAGE), that allows the quantitative and simultaneous analysis of a large number of transcripts. To demonstrate this strategy, short diagnostic sequence tags were isolate... | 10.1038/nrg.2016.10 | This paper provides an early description of multiplexed RNA detection that helped set the stage for use of microarray and spotted arrays within diagnostics. |
10.1126/science.1259657 | 103,749,897 | Evolution of Ebola virus over time The high rate of mortality in the current Ebola epidemic has made it difficult for researchers to collect samples of the virus and study its evolution. Gire et al. describe Ebola epidemiology on the basis of 99 whole-genome sequences, including samples from 78 affected individuals. Th... | 10.1038/nrg.2016.10 | This paper describes the use of RNA-seq for viral detection and measurement for epidemic emergence and tracking. |
10.1101/gr.189621.115 | 103,600,663 | RNA-seq by poly(A) selection is currently the most common protocol for whole transcriptome sequencing as it provides a broad, detailed, and accurate view of the RNA landscape. Unfortunately, the utility of poly(A) libraries is greatly limited when the input RNA is degraded, which is the norm for research tissues and cl... | 10.1038/nrg.2016.10 | This paper describes the application of exome- capture transcriptome sequencing to FFPE samples in the clinical setting. |
10.1101/gr.121095.111 | 83,008,899 | High-throughput sequencing of cDNA (RNA-seq) is a widely deployed transcriptome profiling and annotation technique, but questions about the performance of different protocols and platforms remain. We used a newly developed pool of 96 synthetic RNAs with various lengths, and GC content covering a 2 20 concentration rang... | 10.1038/nrg.2016.10 | This article discusses the development of widely adopted synthetic RNA spike-ins providing sensitivity, accuracy and biases in RNA-seq experiments; this work also provides an early characterization of the limits for discovery of rare transcripts in RNA-seq. |
10.1200/jco.2007.14.3222 | 36,894,652 | The 70-gene profile is a new prognostic tool that has the potential to greatly improve risk assessment and treatment decision making for early breast cancer. Its prospective validation is currently ongoing through the MINDACT (Microarray in Node-Negative Disease May Avoid Chemotherapy) trial, a 6,000-patient randomized... | 10.1038/nrg.2016.10 | This paper describes the development and clinical validation trial for the Mammaprint gene expression based breast cancer recurrence test. |
10.1091/mbc.e07-06-0537 | 40,275,875 | Cilia and basal bodies are essential organelles for a broad spectrum of functions, including the development of left-right asymmetry, kidney function, cerebrospinal fluid transport, generation of photoreceptor outer segments, and hedgehog signaling. Zebrafish fleer (flr) mutants exhibit kidney cysts, randomized left-ri... | 10.1038/nrm3085 | Demonstrates that a protein required for tubulin modification also plays a part in building the outer doublet microtubule structure. |
10.1242/jcs.3.2.207 | 20,739,446 | This study presents reconstructions of the processes of centriolar formation and ciliogenesis based on evidence found in electron micrographs of tissues and organ cultures obtained chiefly from the lungs of foetal rats. A few observations on living cultures supplement the major findings. In this material, centrioles ar... | 10.1038/nrm3085 | Classic ultrastructural description of the individual steps that lead to the production of cilia from basal bodies. |
10.1091/mbc.8.11.2187 | 59,150,950 | When ciliogenesis first occurs in sea urchin embryos, the major building block proteins, tubulin and dynein, exist in substantial pools, but most 9+2 architectural proteins must be synthesized de novo. Pulse-chase labeling with [ 3 H]leucine demonstrates that these proteins are coordinately up-regulated in response to ... | 10.1038/nrm3085 | A dramatic demonstration that microtubules in the ciliary axoneme are not static but undergo continuous turnover. |
10.1073/pnas.90.12.5519 | 82,226,618 | We report a motility in the flagella of the green alga Chlamydomonas that is unrelated to dynein-based flagellar beating. This motility, referred to as intraflagellar transport, was observed as the rapid bidirectional movement of granule-like particles along the length of the flagella. Intraflagellar transport could be... | 10.1038/nrm3085 | The first reported observation of intraflagellar transport detected by differential interference contrast microscopy analysis of C. reinhardtii flagella. |
10.1083/jcb.141.4.993 | 20,061,536 | We previously described a kinesin-dependent movement of particles in the flagella of Chlamydomonas reinhardtii called intraflagellar transport (IFT) (Kozminski, K.G., K.A. Johnson, P. Forscher, and J.L. Rosenbaum. 1993. Proc. Natl. Acad. Sci. USA. 90:5519–5523). When IFT is inhibited by inactivation of a kinesin, FLA10... | 10.1038/nrm3085 | The first biochemical analysis of IFT components, exploiting the advantages of C. reinhardtii for both biochemistry and genetics, and leading to the realization that proteins involved in IFT are related to polycystic kidney disease gene products. |
10.1242/dev.01240 | 80,296,015 | Polycystic kidney disease (PKD) is a common human genetic illness. It is characterized by the formation of multiple kidney cysts that are thought to result from over-proliferation of epithelial cells. Zebrafish larvae can also develop kidney cysts. In an insertional mutagenesis screen in zebrafish, we identified 12 gen... | 10.1038/nrm3085 | Describes the use of a forward genetic screen in zebrafish to find candidate cystic kidney disease genes, which revealed a number of IFT protein-encoding genes. |
10.1083/jcb.200308132 | 62,213,367 | Intraflagellar transport (IFT) is the bidirectional movement of multisubunit protein particles along axonemal microtubules and is required for assembly and maintenance of eukaryotic flagella and cilia. One posited role of IFT is to transport flagellar precursors to the flagellar tip for assembly. Here, we examine radia... | 10.1038/nrm3085 | Presents the first direct evidence that IFT particles can actually bind cargo, by showing that many flagellar proteins co-immunoprecipitate with IFT particles isolated from C. reinhardtii flagella. |
10.1091/mbc.e04-07-0586 | 18,476,268 | Flagellar length regulation provides a simple model system for addressing the general problem of organelle size control. Based on a systems-level analysis of flagellar dynamics, we have proposed a mechanism for flagellar length control in which length is set by the balance of continuous flagellar assembly and disassemb... | 10.1038/nrm3085 | Describes several experiments to test the balance-point model for length control, including testing predictions concerning the variation of flagellar length with number. |
10.1083/jcb.200802025 | 19,224,817 | Formation of flagellar outer dynein arms in Chlamydomonas reinhardtii requires the ODA16 protein at a previously uncharacterized assembly step. Here, we show that dynein extracted from wild-type axonemes can rebind to oda16 axonemes in vitro, and dynein in oda16 cytoplasmic extracts can bind to docking sites on pf28 (o... | 10.1038/nrm3085 | Provides the first evidence that IFT particles may use adaptor proteins to carry specific subsets of cargo. |
10.1083/jcb.201006105 | 19,875,058 | Mutations in human CEP290 cause cilia-related disorders that range in severity from isolated blindness to perinatal lethality. Here, we describe a Chlamydomonas reinhardtii mutant in which most of the CEP290 gene is deleted. Immunoelectron microscopy indicated that CEP290 is located in the flagellar transition zone in ... | 10.1038/nrm3085 | Identifies a key regulator of protein entry through the ciliary transition zone. |
10.1126/science.1191054 | 82,391,947 | Staying in Place The primary cilium is found on nearly all mammalian cells and is a key regulatory organelle for proper signal transduction throughout development and in adults. Extracellular signal transduction, such as that promoted by Sonic hedgehog (Shh), requires the enrichment of receptors and downstream signalin... | 10.1038/nrm3085 | Presents evidence that septins, which form barriers to the lateral diffusion of proteins through the cell membrane during cell division, perform a similar function at the base of cilia. |
10.1083/jcb.201004003 | 124,150,773 | In most lineages, cell cycle exit is correlated with the growth of a primary cilium. We analyzed cell cycle exit and ciliogenesis in human retinal cells and found that, contrary to the classical view, not all cells exiting the cell division cycle generate a primary cilium. Using adhesive micropatterns to control indivi... | 10.1038/nrm3085 | By growing cells on micropatterned substrates, the authors provide evidence that cell shape and spreading influences ciliogenesis. |
10.1073/pnas.0408358102 | 4,695,582 | The important role that cilia and flagella play in human disease creates an urgent need to identify genes involved in ciliary assembly and function. The strong and specific induction of flagellar-coding genes during flagellar regeneration in Chlamydomonas reinhardtii suggests that transcriptional profiling of such cell... | 10.1038/nrm3085 | The first transcriptomic analysis of the genomic programme that is activated during cilia assembly. |
10.1073/pnas.1209119109 | 104,089,749 | Archaebacterial halophiles (Haloarchaea) are oxygen-respiring heterotrophs that derive from methanogens—strictly anaerobic, hydrogen-dependent autotrophs. Haloarchaeal genomes are known to have acquired, via lateral gene transfer (LGT), several genes from eubacteria, but it is yet unknown how many genes the Haloarchaea... | 10.1038/nrmicro.2017.41 | This paper suggests that a single gene transfer event transformed a methanogen in the last haloarchaeal common ancestor. |
10.1128/jb.177.15.4417-4426.1995 | 81,339,874 | A plasmid of 45 kb, designated pNOB8, was found in high copy number in a new heterotrophic Sulfolobus isolate, NOB8H2, from Japan. Dissemination of the plasmid occurred in six cultures of nine different Sulfolobus strains when small amounts of the donor were added. These mixed cultures exhibited a high average copy num... | 10.1038/nrmicro.2017.41 | This study describes the first observation of an archaeal conjugative plasmid. |
10.1073/pnas.1513740113 | 6,363,709 | The intercellular transfer of DNA is a phenomenon that occurs in all domains of life and is a major driving force of evolution. Upon UV-light treatment, cells of the crenarchaeal genus Sulfolobus express Ups pili, which initiate cell aggregate formation. Within these aggregates, chromosomal DNA, which is used for the r... | 10.1038/nrmicro.2017.41 | This study, for the first time, describes proteins that are involved in DNA transport machinery in archaea. |
10.1111/j.1758-2229.2012.00348.x | 38,221,790 | Summary Thermococcales are hyperthermophilic archaea found in deep‐sea hydrothermal vents. They have been recently reported to produce membrane vesicles (MVs) into their culture medium. Here, we have characterized the mode of production and determined the biochemical composition of MVs from two species of Thermococcale... | 10.1038/nrmicro.2017.41 | This paper describes, for the first time, the transfer of archaeal plasmids through vesicles. |
10.1128/jb.162.1.461-462.1985 | 20,443,051 | Auxotrophic mutants of Halobacterium volcanii generated by chemical mutagenesis were used to demonstrate a native genetic transfer system in this extremely halophilic member of the class Archaeobacteria. | 10.1038/nrmicro.2017.41 | This study is the first to show gene transfer in archaea using auxotrophic mutants of H. volcanii |
10.1126/science.1086909 | 83,479,501 | Barriers to dispersal between populations allow them to diverge through local adaptation or random genetic drift. High-resolution multilocus sequence analysis revealed that, on a global scale, populations of hyperthermophilic microorganisms are isolated from one another by geographic barriers and have diverged over the... | 10.1038/nrmicro.2017.41 | This paper describes the role and importance of geographical barriers in the evolution of hyperthermophilic archaea. |
10.1126/science.1072221 | 20,855,366 | Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. PARP-1 is also a mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. We show that PARP-1 activation is required for translocation of apopt... | 10.1038/nrm1963 | Demonstration that PARP-1 activation signals AIF release from mitochondria, resulting in a caspase-independent cell death. |
10.1073/pnas.79.11.3423 | 123,163,789 | When rat pancreatic polynucleosomes were poly(ADP-ribosyl)ated with purified calf thymus poly(ADP-ribose) polymerase and examined by electron microscopy, a relaxation of their native zigzag structure was observed. At high ionic strengths control nucleosomes condensed into 250-A-thick fibers, but poly(ADP-ribosyl)ated p... | 10.1038/nrm1963 | The first demonstration of the relaxation of chromatin superstructure that is induced by poly(ADP-ribosyl)ation of histone H1. |
10.1128/mcb.23.11.3974-3981.2003 | 122,391,893 | ABSTRACT DNA single-strand breaks (SSB) are one of the most frequent DNA lesions produced by reactive oxygen species and during DNA metabolism, but the analysis of cellular responses to SSB remains difficult due to the lack of an experimental method to produce SSB alone in cells. By using human cells expressing a forei... | 10.1038/nrm1963 | Elegantly demonstrates the PAR-dependent recruitment of XRCC1 to a locally induced damaged site. |
10.1126/science.1078764 | 83,113,429 | Steroid response and stress-activated genes such as hsp70 undergo puffing in Drosophila larval salivary glands, a local loosening of polytene chromatin structure associated with gene induction. We find that puffs acquire elevated levels of adenosine diphosphate (ADP)-ribose modified proteins and that poly(ADP)-ribose p... | 10.1038/nrm1963 | Shows the requirement for PAR to loosen polytene-chromatin structure, which is associated with high gene expression. |
10.1126/science.1096775 | 27,963,502 | PolyADP-ribose-polymerase 1 is activated in neurons that mediate several forms of long-term memory in Aplysia . Because polyADP-ribosylation of nuclear proteins is a response to DNA damage in virtually all eukaryotic cells, it is surprising that activation of the polymerase occurs during learning and is required for lo... | 10.1038/nrm1963 | Describes the necessity for PARP-1 activation during learning and the establishment of long-term memory in Aplysia |
10.1017/s146239940500904x | 56,314,065 | Poly(ADP-ribose) polymerase 1 (PARP-1) is a zinc-finger DNA-binding enzyme that is activated by binding to DNA breaks. Poly(ADP-ribosyl)ation of nuclear proteins by PARP-1 converts DNA damage into intracellular signals that activate either DNA repair by the base-excision pathway or cell death. A family of 18 PARPs has ... | 10.1038/nrm1963 | Together with reference 15, excellent reviews describing the therapeutic promise of PARP inhibitors in cancer treatment or in inflammatory diseases. |
10.1126/science.1065199 | 100,832,707 | The recently released human genome sequences provide us with reference data to conduct comparative genomic research on primates, which will be important to understand what genetic information makes us human. Here we present a first-generation human-chimpanzee comparative genome map and its initial analysis. The map was... | 10.1038/nrg981 | Analysis of the first large set of genomic DNA sequences from the chimpanzee. |
10.1073/pnas.182257399 | 84,480,935 | Humans are genetically deficient in the common mammalian sialic acid N -glycolylneuraminic acid (Neu5Gc) because of an Alu -mediated inactivating mutation of the gene encoding the enzyme CMP- N -acetylneuraminic acid (CMP-Neu5Ac) hydroxylase (CMAH). This mutation occurred after our last common ancestor with bonobos and... | 10.1038/nrg981 | Reviews the discovery that humans are unable to synthesize a sialic acid found in great apes and other primates due to an inactivating mutation in the gene for an enzyme that modifies a precursor; also, estimates the timing of this mutation relative to other steps in human evolution. |
10.1126/science.1249240 | 39,339,444 | Resilient Hyperpolarization Despite constant exposure to all sorts of stressors, most people are resilient and do not develop depression, but we do not understand the neurophysiological underpinnings of stress resilience. Friedman et al. (p. 313 ) studied this phenomenon in a mouse model of social-defeat stress depress... | 10.1038/nn.4114 | This paper showed that enhancing VTA dopamine neuron activity in mice susceptible to social-defeat stress reversed depression-like behaviors. This effect was considered to be somewhat paradoxical, as the susceptible mice already exhibited hyperactivity in dopamine neurons |
10.1113/jphysiol.2007.150078 | 20,849,426 | Stress induces the release of the peptide corticotropin‐releasing factor (CRF) into the ventral tegmental area (VTA), and also increases dopamine levels in brain regions receiving dense VTA input. Therefore, stress may activate the mesolimbic dopamine system in part through the actions of CRF in the VTA. Here, we explo... | 10.1038/nn.4114 | This study identified the cellular mechanism by which CRF increases the basal firing rate of VTA dopamine neurons |
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