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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10.2337/diabetes.51.2.271 | 123,192,602 | The hypothalamus and other regions within the central nervous system (CNS) link the sensing of nutrients to the control of metabolism and feeding behavior. Here, we report that intracerebroventricular (ICV) administration of the long-chain fatty acid oleic acid markedly inhibits glucose production and food intake. The ... | 10.1038/nrd2874 | In this work, the authors found that LCFAs serve as a signal to the CNS that leads to reduction of both hepatic glucose production and food intake. |
10.2337/db07-1824 | 59,914,663 | OBJECTIVE—Glucagon-like peptide-1 (GLP-1) promotes glucose homeostasis through regulation of islet hormone secretion, as well as hepatic and gastric function. Because GLP-1 is also synthesized in the brain, where it regulates food intake, we hypothesized that the central GLP-1 system regulates glucose tolerance as well... | 10.1038/nrd2874 | This article established that the incretin GLP1 acts on the CNS, specifically in the arcuate nucleus of the hypothalamus (as well as the periphery), to improve glucose homeostasis at the three major glucoregulatory organs (liver, skeletal muscle and pancreas). |
10.1126/science.1124147 | 107,158,894 | The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR ... | 10.1038/nrd2874 | This article established that hypothalamic mTOR also acts as a fuel sensor in the hypothalamus and is regulated by changes in leucine and leptin. |
10.1126/science.1093087 | 104,428,053 | Photosynthesis uses light energy to drive the oxidation of water at an oxygen-evolving catalytic site within photosystem II (PSII). We report the structure of PSII of the cyanobacterium Thermosynechococcus elongatus at 3.5 angstrom resolution. We have assigned most of the amino acid residues of this 650-kilodalton dime... | 10.1038/nrm1525 | Describes a high-resolution structure of PSII, which provides a more precise description of the manganese cluster and identifies the position of the calcium ion within the cluster. |
10.1126/science.286.5445.1700 | 107,240,748 | Adenosine triphosphate (ATP) synthase contains a rotary motor involved in biological energy conversion. Its membrane-embedded F 0 sector has a rotation generator fueled by the proton-motive force, which provides the energy required for the synthesis of ATP by the F 1 domain. An electron density map obtained from crysta... | 10.1038/nrm1525 | The structure of the c-ring of the F 0 -ATPase associated with the F 1 -ATPase from yeast showed that the c-ring contains contained ten c-subunits — a number that, contrary to predictions, is not divisible by three. |
10.1146/annurev.biophys.32.110601.142532 | 103,595,847 | ▪ Abstract Molecular docking is an invaluable tool in modern drug discovery. This review focuses on methodological developments relevant to the field of molecular docking. The forces important in molecular recognition are reviewed and followed by a discussion of how different scoring functions account for these forces.... | 10.1038/nrd1549 | Excellent review of research in the docking arena that contains an instructive section on the conceptually different processes involved in ligand–protein docking. |
10.1126/science.6879170 | 20,567,246 | A method is presented for analytically calculating a smooth, three-dimensional contour about a molecule. The molecular surface envelope may be drawn on either color raster computer displays or real-time vector computer graphics systems. Molecular areas and volumes may be computed analytically from this surface represen... | 10.1038/nrd1549 | References 16 and 17 outline the theoretical foundation of molecular surface calculations that have also become a crucial component of many shape-based docking algorithms. |
10.1101/gr.107524.110 | 125,319,007 | Next-generation DNA sequencing (NGS) projects, such as the 1000 Genomes Project, are already revolutionizing our understanding of genetic variation among individuals. However, the massive data sets generated by NGS—the 1000 Genome pilot alone includes nearly five terabases—make writing feature-rich, efficient, and robu... | 10.1038/nrg3767 | The GATK is a broad and widely used toolkit for variant discovery and data processing. |
10.1101/gr.129684.111 | 62,663,577 | Cancer is a disease driven by genetic variation and mutation. Exome sequencing can be utilized for discovering these variants and mutations across hundreds of tumors. Here we present an analysis tool, VarScan 2, for the detection of somatic mutations and copy number alterations (CNAs) in exome data from tumor–normal pa... | 10.1038/nrg3767 | VarScan (described in references 24 and 25) is one of the early programs for somatic SNV detection and has since added additional capability for germline, copy-number and indel events. |
10.1093/bioinformatics/btp352 | 20,853,394 | Abstract Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the for... | 10.1038/nrg3767 | SAMtools is a broad set of utilities for processing sequence data in the standardized SAM/BAM format, including variant calling. |
10.1093/bioinformatics/btp394 | 125,337,718 | Abstract Motivation: There is a strong demand in the genomic community to develop effective algorithms to reliably identify genomic variants. Indel detection using next-gen data is difficult and identification of long structural variations is extremely challenging. Results: We present Pindel, a pattern growth approach,... | 10.1038/nrg3767 | Pindel is focused on identifying breakpoints at single-base-resolution of indels, inversions and tandem duplications. |
10.1073/pnas.0710052104 | 19,298,276 | Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from r... | 10.1038/nrg3767 | GISTIC is one of the standard tools for finding genes that are affected by CNAs which have a bearing on cancer initiation or progression. |
10.1158/0008-5472.can-09-1133 | 61,503,375 | Abstract Large-scale sequencing of cancer genomes has uncovered thousands of DNA alterations, but the functional relevance of the majority of these mutations to tumorigenesis is unknown. We have developed a computational method, called Cancer-specific High-throughput Annotation of Somatic Mutations (CHASM), to identify... | 10.1038/nrg3767 | CHASM (described in references 85 and 86) is a popular tool for assessing functional impact of somatic missense mutations on the basis of whether they confer selective advantage on cancerous cells. |
10.1084/jem.20101688 | 81,541,294 | Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1hi monocytes (MOs), Gr-1lo MOs, and ma... | 10.1038/nri3209 | This paper shows for the first time how macrophages, in cooperation with nestin-expressing MSCs, regulate HSC mobilization. |
10.1182/blood-2010-12-327353 | 20,246,083 | Abstract Human mesenchymal stem/progenitor cells (hMSCs) repair tissues and modulate immune systems but the mechanisms are not fully understood. We demonstrated that hMSCs are activated by inflammatory signals to secrete the anti-inflammatory protein, TNF-α–stimulated gene 6 protein (TSG-6) and thereby create a negativ... | 10.1038/nri3209 | In this study, the authors show that MSCs secrete the multifunctional protein TSG6 and thereby suppress inflammatory responses by macrophages. |
10.1634/stemcells.2007-0416 | 19,083,892 | Abstract Mesenchymal stem cells (MSC) establish close interactions with bone marrow sinusoids in a putative perivascular niche. These vessels contain a large storage pool of mature nonproliferating neutrophils. Here, we have investigated the effects of human bone marrow MSC on neutrophil survival and effector functions... | 10.1038/nri3209 | This study was the first to show that MSCs can have beneficial effects for neutrophils. |
10.1182/blood-2005-07-2775 | 62,070,889 | In recent years, mesenchymal stem cells (MSCs) have been shown to inhibit T-lymphocyte proliferation induced by alloantigens or mitogens. However, no substantial information is available regarding their effect on natural killer (NK) cells. Here we show that MSCs sharply inhibit IL-2-induced proliferation of resting NK ... | 10.1038/nri3209 | This paper showed how MSCs can inhibit NK cell function. |
10.1634/stemcells.2005-0156 | 67,445,657 | Abstract Interleukin-17A (IL-17A) is a proinflammatory cytokine expressed in activated T-cells. It is required for microbial host defense and is a potent stimulator of granulopoiesis. In a dose-dependent fashion, IL-17A expanded human mesenchymal stem cells (MSCs) and induced the proliferation of mature stroma cells in... | 10.1038/nri3209 | This study shows that IL-17A promotes the survival and proliferation of MSCs, thus forming a possible negative-feedback circuit. |
10.4049/jimmunol.0902007 | 60,857,173 | Abstract Mesenchymal stem cells (MSCs) exert immunomodulatory properties via the inhibition of T cell activation and proliferation. Because of the deleterious role of Th17 cells in the pathogenesis of inflammatory disease, we investigated whether proinflammatory cytokines could modify the expression of adhesion molecul... | 10.1038/nri3209 | This study demonstrates that MSCs favour the generation of FOXP3 + T Reg cells over that of T H 17 cells, and also shows that MSCs can reprogramme already differentiated pro-inflammatory T H 17 cells into suppressive T Reg cells. |
10.4049/jimmunol.0803055 | 67,486,170 | Abstract Mesenchymal stem cells (MSCs) have a great potential for tissue repair, especially if they can be delivered efficiently to sites of tissue injury. Since complement activation occurs whenever there is tissue damage, the effects of the complement activation products C3a and C5a on MSCs were examined. Both C3a an... | 10.1038/nri3209 | This was one of the first studies to establish a connection between the complement system and MSCs. |
10.1182/blood-2006-06-028704 | 19,931,916 | Abstract Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs... | 10.1038/nri3209 | This was one of the first broader studies of TLRs in MSCs. It investigated their expression and also their effect on several basic MSC functions. |
10.1146/annurev-immunol-032712-095956 | 83,512,758 | T cell activation leads to dramatic shifts in cell metabolism to protect against pathogens and to orchestrate the action of other immune cells. Quiescent T cells require predominantly ATP-generating processes, whereas proliferating effector T cells require high metabolic flux through growth-promoting pathways. Further,... | 10.1038/nri3701 | This is an outstanding and comprehensive review of metabolism in T cells. |
10.1242/jcs.125773 | 125,271,429 | The mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates key cellular functions linked to the promotion of cell growth and metabolism. This kinase, which is part of two protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), has a fundamental role in coordinating anabolic and catabo... | 10.1038/nri3701 | This is an outstanding and comprehensive review of mTOR signalling and function. |
10.4049/jimmunol.1003613 | 103,776,805 | Abstract Stimulated CD4+ T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, Th2, and Th17 cells expressed high surface levels of the g... | 10.1038/nri3701 | This is an early and important study in terms of defining the differences in metabolism between different T cell subsets. |
10.4049/jimmunol.174.8.4670 | 101,645,617 | Abstract Differentiation of CD8+ T cells from the naive to the effector state is accompanied by changes in basal gene expression profiles that parallel the acquisition of effector functions. Among these are metabolism genes, and we now show that 2C TCR transgenic effector CD8+ T cells express higher levels of glycolyti... | 10.1038/nri3701 | References 71 and 72 demonstrate the requirement of glycolysis for T cell effector function by using an inhibitor of glycolysis, 2-deoxy-d-glucose. Reference 71 indicates that inhibition of glycolysis in activated CD8 + T cells promotes the differentiation of long-lived memory cells. |
10.1084/jem.20112607 | 103,891,098 | mTORC1 (mammalian target of rapamycin complex 1) controls transcriptional programs that determine CD8+ cytolytic T cell (CTL) fate. In some cell systems, mTORC1 couples phosphatidylinositol-3 kinase (PI3K) and Akt to the control of glucose uptake and glycolysis. However, PI3K–Akt-independent mechanisms control glucose ... | 10.1038/nri3701 | This study demonstrates that mTORC1 activity controls glucose uptake and glycolysis by regulating the expression of HIF1α. |
10.1084/jem.20112583 | 103,611,061 | Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive ... | 10.1038/nri3646 | This study identifies a key regulatory DC population in human skin that is characterized by the production of IL-10. |
10.1126/science.1225152 | 41,754,539 | Skin Specifics Much of the recent attention paid to the trillions of bacteria that colonize our bodies has been given to the bacteria that reside in the gut. Naik et al. (p. 1115 , published online 26 July) report that colonization of the skin with commensal bacteria is important for tuning effector T cell responses in... | 10.1038/nri3646 | This study shows that a commensal skin bacterium, S. epidermidis , controls dermis-resident T cell function and immunity to L. major by activating an IL-1-dependent immune response. |
10.1126/science.1071884 | 107,208,239 | Estrogen regulates a plethora of functionally dissimilar processes in a broad range of tissues. Recent progress in the study of the molecular mechanism of action of estrogen(s) has revealed why different cells can respond to the same hormone in a different manner. Three of these findings are of particular importance: (... | 10.1038/nrc1879 | An excellent review that provides an extensive overview of the mechanistic actions of ERs. |
10.1126/science.1099993 | 125,295,630 | Autophagy, the process by which cells recycle cytoplasm and dispose of excess or defective organelles, has entered the research spotlight largely owing to the discovery of the protein components that drive this process. Identifying the autophagy genes in yeast and finding orthologs in other organisms reveals the conser... | 10.1038/nri2161 | References 1–4 provide excellent general reviews on autophagy and its molecular mechanisms, physiological functions and roles in disease. |
10.1084/jem.20061318 | 61,235,296 | Apicomplexan protozoan pathogens avoid destruction and establish a replicative niche within host cells by forming a nonfusogenic parasitophorous vacuole (PV). Here we present evidence for lysosome-mediated degradation of Toxoplasma gondii after invasion of macrophages activated in vivo. Pathogen elimination was depende... | 10.1038/nri2161 | References 8–9 provide the first demonstrations that autophagy has a role in the elimination of parasites. |
10.1126/science.1136880 | 20,587,005 | Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytos... | 10.1038/nri2161 | This is a landmark paper describing a new function of autophagy in innate immunity; this paper provides the first evidence that the autophagic machinery delivers viral genetic material to endosomal TLRs. |
10.1126/science.1103966 | 41,644,611 | We found that the autophagic machinery could effectively eliminate pathogenic group A Streptococcus (GAS) within nonphagocytic cells. After escaping from endosomes into the cytoplasm, GAS became enveloped by autophagosome-like compartments and were killed upon fusion of these compartments with lysosomes. In autophagy-d... | 10.1038/nri2161 | References 42–44 are landmark papers that formed the foundation for the principle that autophagy is important in defence against intracellular bacterial pathogens (such as M. tuberculosis and Shigella spp.) and extracellular bacterial pathogens that invade the cytosol (such as group A Streptococcus |
10.1126/science.1129577 | 82,777,795 | Immunity-related p47 guanosine triphosphatases (IRG) play a role in defense against intracellular pathogens. We found that the murine Irgm1 (LRG-47) guanosine triphosphatase induced autophagy and generated large autolysosomal organelles as a mechanism for the elimination of intracellular Mycobacterium tuberculosis . We... | 10.1038/nri2161 | This paper identified an important signalling mechanism (involving IRGM) that activates autophagy-dependent control of mycobacteria. |
10.1128/jvi.72.11.8586-8596.1998 | 81,637,451 | ABSTRACT bcl-2 , the prototypic cellular antiapoptotic gene, decreases Sindbis virus replication and Sindbis virus-induced apoptosis in mouse brains, resulting in protection against lethal encephalitis. To investigate potential mechanisms by which Bcl-2 protects against central nervous system Sindbis virus infection, w... | 10.1038/nri2161 | This paper provided the first demonstration of an antimicrobial effect of an autophagy gene. |
10.1126/science.1104904 | 19,037,328 | CD4 + T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acid... | 10.1038/nri2161 | This paper provided the first genetic evidence that autophagy components can be required for efficient MHC class II presentation of an endogenous antigen. |
10.1091/mbc.e03-09-0704 | 62,537,830 | Macroautophagy mediates the bulk degradation of cytoplasmic components. It accounts for the degradation of most long-lived proteins: cytoplasmic constituents, including organelles, are sequestered into autophagosomes, which subsequently fuse with lysosomes, where degradation occurs. Although the possible involvement of... | 10.1038/nri2161 | This paper describes the characterization of transgenic autophagy reporter mice (a tool that has greatly facilitated the study of autophagy in vivo ) and the presence of high levels of autophagy in neonatal thymic epithelial cells. |
10.1073/pnas.012485299 | 104,000,941 | The eIF2α kinases are a family of evolutionarily conserved serine/threonine kinases that regulate stress-induced translational arrest. Here, we demonstrate that the yeast eIF2α kinase, GCN2 , the target phosphorylation site of Gcn2p, Ser-51 of eIF2α, and the eIF2α-regulated transcriptional transactivator, GCN4 , are es... | 10.1038/nri2161 | This paper demonstrated that the IFN-inducible, antiviral signalling molecule PKR is required for virus-induced autophagy. |
10.1126/science.7690989 | 29,326,328 | Interferon-γ (IFN-γ) stimulates transcription of specific genes by inducing tyrosine phosphorylation of a 91-kilodalton cytoplasmic protein (termed STAT for signal transducer and activator of transcription). Stat91 was phosphorylated on a single site (Tyr 701 ), and phosphorylation of this site was required for nuclear... | 10.1038/nri2958 | One of the first reports to define the importance of STAT1 in interferon signalling. |
10.1146/annurev.genom.9.081307.164359 | 41,510,410 | Recent scientific discoveries that resulted from the application of next-generation DNA sequencing technologies highlight the striking impact of these massively parallel platforms on genetics. These new methods have expanded previously focused readouts from a variety of DNA preparation protocols to a genome-wide scale ... | 10.1038/nri2958 | This review compares and discusses the basic chemistries used by currently available next-generation sequencing platforms. |
10.1093/eurjhf/hfq198 | 16,460,203 | Aims Calcium channel plays an important role in the autoimmune pathogenesis of idiopathic dilated cardiomyopathy (DCM). Autoantibodies have emerged as a new upstream target of sudden death in DCM. We sought to validate the hypothesis that autoantibodies against L ‐type calcium channel (CC‐AAbs) are arrhythmogenic and l... | 10.1038/nrcardio.2017.61 | This study shows that in patients with idiopathic dilated cardiomyopathy, agonist-like autoantibodies against L-type calcium channels are frequently detected and independently predict ventricular tachycardia and sudden cardiac death. |
10.1111/ene.12234 | 103,047,881 | Background and purpose There is no general consensus as to whether autoimmune myasthenia gravis ( MG ) is associated with heart diseases, despite the fact that myocarditis, a serious cardiac involvement treatable by immunotherapy, is a complication of MG . It has been observed previously that MG patients with clinicall... | 10.1038/nrcardio.2017.61 | This paper shows that circulating anti-K v 1.4 channel autoantibodies are present in a substantial percentage of patients with myasthenia gravis who frequently have corrected QT interval prolongation and in some cases died from lethal QT-associated arrhythmias. |
10.1128/jb.155.2.768-775.1983 | 104,412,647 | Except for a small fraction of persisters, 10(-6) to 10(-5), Escherichia coli K-12 is killed by prolonged inhibition of murein synthesis. The progeny of persisters are neither more resistant to inhibition of murein synthesis nor more likely to persist than normal cells. Mutants have been isolated in which a larger frac... | 10.1038/nrmicro1557 | A paper describing the first approach to identify persister genes. |
10.1126/science.1099390 | 104,375,088 | A fraction of a genetically homogeneous microbial population may survive exposure to stress such as antibiotic treatment. Unlike resistant mutants, cells regrown from such persistent bacteria remain sensitive to the antibiotic. We investigated the persistence of single cells of Escherichia coli with the use of microflu... | 10.1038/nrmicro1557 | The paper demonstrates that persisters pre-exist in the population and are slow-growing cells. |
10.1186/1471-2180-6-53 | 18,859,787 | Abstract Background Bacterial populations contain persisters, phenotypic variants that constitute approximately 1% of cells in stationary phase and biofilm cultures. Multidrug tolerance of persisters is largely responsible for the inability of antibiotics to completely eradicate infections. Recent progress in understan... | 10.1038/nrmicro1557 | A method to isolate persisters by cell sorting demonstrates that persisters are dormant cells. |
10.1126/science.1128242 | 103,714,865 | Resistance to the limited number of available antifungal drugs is a serious problem in the treatment of Candida albicans . We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of chromosome 5, were associated with azole resistance. The iso... | 10.1038/nrmicro1835 | Established a novel mechanism of fungal drug resistance that involves aneuploidy and isochromosome formation; also showcased the genomic plasticity that underpins phenotypic variability. |
10.1126/science.1118370 | 103,714,907 | Hsp90 is a molecular chaperone for many signal transducers and may influence evolution by releasing previously silent genetic variation in response to environmental change. In fungi separated by ∼800 million years of evolution, Hsp90 potentiated the evolution of drug resistance in a different way, by enabling new mutat... | 10.1038/nrmicro1835 | Describes a new mechanism by which Hsp90 can enable the evolution of fungal drug resistance and modulate the relationship between genotype and phenotype. |
10.1073/pnas.95.15.8420 | 82,523,820 | Evolvability is an organism’s capacity to generate heritable phenotypic variation. Metazoan evolution is marked by great morphological and physiological diversification, although the core genetic, cell biological, and developmental processes are largely conserved. Metazoan diversification has entailed the evolution of ... | 10.1038/nrmicro1835 | An insightful perspective on evolvability 2014 the capacity to generate heritable phenotypic variation. |
10.1126/science.1070532 | 83,402,306 | Schizophrenia is a debilitating mental illness that affects 1% of the population. Despite intensive study, its molecular etiology remains enigmatic. Like many common diseases, schizophrenia is multifactorial in origin, with both genetic and environmental contributions likely playing an important role in the manifestati... | 10.1038/nrg910 | An in-depth review of approaches to studying the pathogenesis of schizophrenia. |
10.1126/science.8202715 | 123,105,888 | In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM1 and peripherin/ RDS , in which only double heterozygotes develop retinitis... | 10.1038/nrg910 | Shows that heterozygous mutations in two distinct genes are necessary and sufficient to cause RP in some patients. Probably the first example of digenic mutations in humans. |
10.1126/science.1063525 | 45,372,375 | Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by multiple clinical features that include pigmentary retinal dystrophy, polydactyly, obesity, developmental delay, and renal defects. BBS is considered an autosomal recessive disorder, and recent positional cloning efforts have identifie... | 10.1038/nrg910 | First example of triallelic inheritance in humans, in a disease considered historically to be an autosomal-recessive trait. |
10.1073/pnas.97.1.268 | 125,221,926 | Reduced penetrance in genetic disorders may be either dependent or independent of the genetic background of gene carriers. Hirschsprung disease (HSCR) demonstrates a complex pattern of inheritance with ≈50% of familial cases being heterozygous for mutations in the receptor tyrosine kinase RET . Even when identified, th... | 10.1038/nrg910 | References 59 and 60 establish statistical methods to analyse the documented oligogenicity of Hirschsprung disease. |
10.1073/pnas.93.24.13726 | 61,030,771 | Retinitis pigmentosa (RP) is a group of progressive retinal dystrophies that include the most common hereditary degenerative diseases affecting the retina. Although most disease phenotypes appear to result from defects at single genetic loci (monogenic), at least one instance of RP appears to require a coinheritance of... | 10.1038/nrg910 | References 82 and 83 illustrate the molecular basis of digenic inheritance involving ROM1 and RDS in human RP. |
10.1242/dev.129.4.1075 | 83,526,434 | Alagille syndrome is a human autosomal dominant developmental disorder characterized by liver, heart, eye, skeletal, craniofacial and kidney abnormalities. Alagille syndrome is caused by mutations in the Jagged 1 (JAG1) gene, which encodes a ligand for Notch family receptors. The majority of JAG1 mutations seen in Alag... | 10.1038/nrg910 | Describes the molecular basis of phenotypic modification of the Jag1 mutation. |
10.1093/genetics/158.1.209 | 59,266,659 | Abstract Nonallelic noncomplementation occurs when recessive mutations in two different loci fail to complement one another, in other words, the double heterozygote exhibits a phenotype. We observed that mutations in the genes encoding the physically interacting synaptic proteins UNC-13 and syntaxin/UNC-64 failed to co... | 10.1038/nrg910 | A comprehensive analysis of non-allelic non-complementation and establishment of its parameters of action in the worm synapse. |
10.1093/genetics/119.2.249 | 83,543,227 | Abstract Mutations in genes of Saccharomyces cerevisiae that code for proteins that interact with beta-tubulin were sought by screening for unlinked mutations that fail to complement mutations in the single beta-tubulin-encoding gene (TUB2). Among the first three noncomplementing mutations examined, two are linked to T... | 10.1038/nrg910 | A classic paper on the use of non-allelic non-complementation to study specific signalling pathways. |
10.4049/jimmunol.167.9.5420 | 103,734,220 | Abstract Human papillomavirus (HPV) infection, particularly type 16, is causally associated with the development of cervical cancer. The E6 and E7 proteins of HPV are constitutively expressed in cervical carcinoma cells making them attractive targets for CTL-based immunotherapy. However, few studies have addressed whet... | 10.1038/nri1260 | This paper provides evidence that cervical cancer cells are selected for poor presentation of HPV-encoded antigens to the immune system. |
10.1073/pnas.162488599 | 38,333,540 | A fundamental feature of the architecture and functional design of vertebrate animals is a stroma, composed of extracellular matrix and mesenchymal cells, which provides a structural scaffold and conduit for blood and lymphatic vessels, nerves, and leukocytes. Reciprocal interactions between mesenchymal and epithelial ... | 10.1038/nrc1877 | This study compares primary fibroblasts that were isolated from various sites and sheds new light on the vast diversity of fibroblasts. |
10.1073/pnas.0401064101 | 40,767,404 | The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an ortho... | 10.1038/nrc1877 | Demonstrates that fibroblasts aid mammary epithelia in forming functional breast tissue, and carcinogenesis. |
10.1126/science.1090922 | 62,257,157 | Stromal cells can have a significant impact on the carcinogenic process in adjacent epithelia. The role of transforming growth factor–β (TGF-β) signaling in such epithelial-mesenchymal interactions was determined by conditional inactivation of the TGF-β type II receptor gene in mouse fibroblasts ( Tgfbr2 fspKO ). The l... | 10.1038/nrc1877 | Indicates that deletion of TGFβ type II receptor in FSP1-positive cells leads to the emergence of epithelial tumours. |
10.1073/pnas.1233687100 | 84,567,524 | There has been much recent speculation that global warming may allow the reestablishment of malaria transmission in previously endemic areas such as Europe and the United States. In this report we analyze temporal trends in malaria in Britain between 1840 and 1910, to assess the potential for reemergence of the disease... | 10.1038/nrmicro2336 | A quantitative assessment of the various factors that drove malaria from Britain in the past century. |
10.1073/pnas.0508391103 | 20,232,780 | The expansion of global air travel and seaborne trade overcomes geographic barriers to insect disease vectors, enabling them to move great distances in short periods of time. Here we apply a coupled human–environment framework to describe the historical spread of Aedes albopictus , a competent mosquito vector of 22 arb... | 10.1038/nrmicro2336 | Combination of satellite-derived environmental data and human activities (shipping traffic), analysed with methods borrowed from molecular phylogenists. |
10.1146/annurev.ento.53.103106.093258 | 26,956,035 | West Nile virus (WNV) (Flavivirus: Flaviviridae) is the most widespread arbovirus in the world. A significant range expansion occurred beginning in 1999 when the virus was introduced into New York City. This review highlights recent research into WNV epizootiology and epidemiology, including recent advances in understa... | 10.1038/nrmicro2336 | Comprehensive review of genetic, biological and environmental factors behind the emergence of WNV in North America within its global context. |
10.1002/rmv.566 | 40,129,995 | Abstract Tick‐borne encephalitis (TBE), the most serious widespread vector‐borne disease of humans in Europe, increased from 2‐ to 30‐fold in many Central and Eastern European countries from 1992 to 1993, coinciding with independence from Soviet rule. Unemployment and low income have been shown in Latvia to be statisti... | 10.1038/nrmicro2336 | Extensive detailed data making a compelling case for the role of human activities, driven by socioeconomic consequences of political reform, in tick-borne disease emergence in Europe. |
10.1111/j.2006.0906-7590.04596.x | 20,796,383 | Prediction of species’ distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approache... | 10.1038/nrmicro2336 | Comparative review to help make sense of the burgeoning range of statistical methods increasingly used for species distribution modelling. |
10.1084/jem.192.5.761 | 102,955,993 | The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC ... | 10.1038/nri1869 | This paper was the first to highlight potential mechanistic differences in T-cell trafficking to the small intestine and colon, and to suggest a role for CCR9 specifically in small-intestinal immunity. |
10.1084/jem.20011502 | 109,159,555 | Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of ‘tissue-specific’ adhesion and chemoattractant receptors. However, little is known about the development of these selecti... | 10.1038/nri1869 | This paper, together with reference 34, shows that T cells rapidly acquire intestinal- and skin-homing receptors in vivo following their activation in intestinal- and skin-draining lymph nodes, respectively. |
10.4049/jimmunol.172.2.857 | 80,673,349 | Abstract The effector/memory T cell pool branches in homing subsets selectively trafficking to organs such as gut or skin. Little is known about the critical factors in the generation of skin-homing CD8+ T cells, although they are crucial effectors in skin-restricted immune responses such as contact hypersensitivity an... | 10.1038/nri1869 | This paper shows that antigen-pulsed DCs isolated from the skin or skin-draining lymph nodes induce T cells to express skin-homing receptors. |
10.1084/jem.20041035 | 84,426,977 | Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease characterized by progressive bile duct destruction, develops as an extra-intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991. Gut. 32:1433–1435). However, the liver and bowel inflammation are rarely concomitant, and P... | 10.1038/nri1869 | This paper provides an intriguing example of how tissue-tropic T-cell populations can be redirected under certain inflammatory conditions by the aberrant expression of tissue-homing ligands. |
10.1084/jem.20032177 | 107,205,696 | Effective immune surveillance is essential for maintaining protection and homeostasis of peripheral tissues. However, mechanisms controlling memory T cell migration to peripheral tissues such as the skin are poorly understood. Here, we show that the majority of human T cells in healthy skin express the chemokine recept... | 10.1038/nri1869 | This paper highlights a potential role for CCR8 in the immunosurveillance of cutaneous tissues by memory T cells. |
10.1126/science.290.5491.486 | 61,367,140 | With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus–1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-el... | 10.1038/nri776 | The first report of the control of SHIV-89.6P challenge by a predominantly T-cell response. |
10.1083/jcb.200203043 | 27,022,314 | Tcell antigen receptor (TCR) ligation initiates tyrosine kinase activation, signaling complex assembly, and immune synapse formation. Here, we studied the kinetics and mechanics of signaling complex formation in live Jurkat leukemic T cells using signaling proteins fluorescently tagged with variants of enhanced GFP (EG... | 10.1038/nri1750 | In this study, the authors investigate the temporal and spatial localization of proximal signalling molecules and highlight the potential of use of microscopy for investigation of these important aspects of signalling. |
10.1126/science.1079477 | 41,418,028 | Lymphatic vessels develop from specialized endothelial cells in preexisting blood vessels, but the molecular signals that regulate this separation are unknown. Here we identify a failure to separate emerging lymphatic vessels from blood vessels in mice lacking the hematopoietic signaling protein SLP-76 or Syk. Blood-ly... | 10.1038/nri1750 | This study reports the intriguing finding that points to a newly discovered role for SLP76 and SYK in regulating lymphatic vessel separation from blood vasculature. |
10.1126/scisignal.2000568 | 20,625,410 | Gas5 is a noncoding RNA that acts as a decoy glucocorticoid response element to inhibit glucocorticoid-mediated transcription. | 10.1038/nrm3884 | This paper shows that a widely expressed lncRNA was able to accumulate during stress and act as a decoy RNA to prevent steroid receptors from binding to their target DNA. |
10.4049/jimmunol.1001794 | 120,579,543 | Abstract Posttranscriptional regulation is emerging as a key factor in glucocorticoid (GC)-mediated gene regulation. We investigated the role of the human GC receptor (GR) as an RNA-binding protein and its effect on mRNA turnover in human airway epithelial cells. Cell treatment with the potent GC budesonide accelerated... | 10.1038/nrm3884 | This study shows that the GCR binds to mRNAs involved in inflammation to accelerate their degradation. |
10.7554/elife.00762 | 103,892,996 | Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of mouse lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds of lncRNAs, including 54 pseudogene ... | 10.1038/nrm3884 | This study shows that the expression of pseudogene lncRNAs is actively regulated and that these lncRNAs may interact directly with proteins to modulate cell signalling. |
10.1126/science.8420004 | 60,487,183 | A transfer RNA (tRNA) binding protein present in HeLa cell nuclear extracts was purified and identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Studies with mutant tRNAs indicated that GAPDH recognizes both sequence and structural features in the RNA. GAPDH discriminated between wild-... | 10.1038/nrm3884 | This study identifies GAPDH as a tRNA-binding protein, demonstrating in principle how tRNA levels may control metabolism and how metabolites may influence protein synthesis. |
10.1126/science.1120976 | 104,315,756 | The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases. A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid tr... | 10.1038/nrm3884 | This study shows that the DNA methylase DNMT2 evolved the ability to methylate tRNA. |
10.1126/science.1079490 | 20,880,943 | Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3 , which encodes a transcription factor that is genetically defective in an autoimmune and ... | 10.1038/nri.2015.1 | This is a landmark paper that shows that FOXP3 is the master transcription factor driving development of T Reg cells. |
10.4049/jimmunol.1301777 | 59,139,862 | Abstract Immune homeostasis in peripheral tissues is achieved by maintaining a balance between pathogenic effector T cells (Teffs) and protective Foxp3+ regulatory T cells (Tregs). Using a mouse model of an inducible tissue Ag, we demonstrate that Ag persistence is a major determinant of the relative frequencies of Tef... | 10.1038/nri.2015.1 | This paper shows that persistent self antigen expression in tissues leads to the preferential accumulation of T Reg cells instead of effector T cells. It also shows that memory T Reg cells can be generated from peripherally derived T Reg cells. |
10.4049/jimmunol.1200645 | 17,368,417 | Abstract Natural CD4+CD25+Foxp3+ regulatory T cells (Tregs) are critical for the control of immune responses to pathogens. However, most studies have focused on chronic infections, in which pathogen-specific Tregs contribute to pathogen persistence and, in some cases, concomitant immunity. How Tregs behave and function... | 10.1038/nri.2015.1 | References 14 and 15 phenotypically and functionally define memory T Reg cells in a mouse model of infection. |
10.4049/jimmunol.1300212 | 58,620,414 | Abstract Thymic Foxp3-expressing regulatory T cells are activated by peripheral self-antigen to increase their suppressive function, and a fraction of these cells survive as memory regulatory T cells (mTregs). mTregs persist in nonlymphoid tissue after cessation of Ag expression and have enhanced capacity to suppress t... | 10.1038/nri.2015.1 | This work shows that memory T Reg cells in mouse skin are dependent on IL-7 and not on IL-2. |
10.1084/jem.20131142 | 84,471,766 | Immune tolerance and activation depend on precise control over the number and function of immunosuppressive Foxp3+ regulatory T (T reg) cells, and the importance of IL-2 in maintaining tolerance and preventing autoimmunity is clear. However, the homeostatic requirement for IL-2 among specific populations of peripheral ... | 10.1038/nri.2015.1 | This work phenotypically and functionally defines resting and effector T Reg cell subsets in mice. The authors show that resting T Reg cells are highly dependent on IL-2 for survival, whereas effector T Reg cells are dependent on signalling through ICOS. |
10.1073/pnas.0605127103 | 104,393,044 | The evolution of marine microbes over billions of years predicts that the composition of microbial communities should be much greater than the published estimates of a few thousand distinct kinds of microbes per liter of seawater. By adopting a massively parallel tag sequencing strategy, we show that bacterial communit... | 10.1038/nrmicro1888 | Showed that microbial diversity can be studied by high-throughput sequencing of rRNA tags. |
10.1111/j.1462-2920.2007.01352.x | 82,374,746 | Summary We have coupled fluorescence in situ hybridization (FISH) with Raman microscopy for simultaneous cultivation‐independent identification and determination of 13 C incorporation into microbial cells. Highly resolved Raman confocal spectra were generated for individual cells which were grown in minimal medium wher... | 10.1038/nrmicro1888 | Showed that single microbial cells can be analysed for identity and function by a combination of stable-isotope Raman spectroscopy and FISH. |
10.1111/j.1462-2920.2007.01246.x | 27,047,031 | Summary Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus are major contributors to oceanic primary production. The genera are genetically diverse, comprising several known ecotypes or lineages. However, little is known of the distribution of these lineages over large geographic areas. Here, we a... | 10.1038/nrmicro1888 | Reported the basin-scale distribution patterns of cyanobacteria in the Atlantic Ocean. |
10.1126/science.1083529 | 102,382,625 | Plant cells create highly structured microtubule arrays at the cell cortex without a central organizing center to anchor the microtubule ends. In vivo imaging of individual microtubules in Arabidopsis plants revealed that new microtubules are initiated at the cell cortex and exhibit dynamics at both ends. Polymerizatio... | 10.1038/nrm1277 | Evidence that cortical microtubules translocate using a modified form of treadmilling. |
10.1105/tpc.014977 | 28,234,717 | Abstract A phospholipase D (PLD) was shown recently to decorate microtubules in plant cells. Therefore, we used tobacco BY-2 cells expressing the microtubule reporter GFP-MAP4 to test whether PLD activation affects the organization of plant microtubules. Within 30 min of adding n-butanol, a potent activator of PLD, cor... | 10.1038/nrm1277 | References 44–47 show that a phospholipase D links cortical microtubules to the plasma membrane and suggest how signalling chains might alter cell morphology. |
10.1105/tpc.011593 | 59,301,588 | Abstract As critical determinants of growth anisotropy in plants, cortical microtubules are thought to constrain the movement of cellulose synthase complexes and thus align newly deposited cellulose microfibrils. We tested this cellulose synthase constraint model using the temperature-sensitive mor1-1 mutant of Arabido... | 10.1038/nrm1277 | This work shows that the relationship between microtubules and cellulose alignment is far from simple. |
10.1002/0471141755.ph0121s11 | 103,576,783 | Abstract Studies of the behavior of many ligand‐gated ion channels have long provided evidence that more than one molecule of ligand was able to bind to each receptor complex, a phenomenon termed cooperativity. The conclusion that some receptors possessed more than one binding site for ligands thus invoked another phen... | 10.1038/nrd746 | A detailed step-by-step protocol for studying allosterism at G-protein-coupled receptors. |
10.1073/pnas.251541198 | 83,324,648 | Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and fo... | 10.1038/nrc927 | References 47 and 48 provide evidence that ubiquitin-protein ligases (E3) might be rate-limiting for proteasome proteolysis in skeletal muscle. |
10.1073/pnas.0915068107 | 4,627,455 | Centromere-associated protein-E (CENP-E) is a kinetochore-associated mitotic kinesin that is thought to function as the key receptor responsible for mitotic checkpoint signal transduction after interaction with spindle microtubules. We have identified GSK923295, an allosteric inhibitor of CENP-E kinesin motor ATPase ac... | 10.1038/nrc3310 | This work describes the mechanism of action of the first CENPE inhibitor that displayed in vivo efficacy. |
10.1091/mbc.e05-02-0167 | 103,915,668 | Microtubule (MT)-based motor proteins, kinesins and dyneins, play important roles in multiple cellular processes including cell division. In this study, we describe the generation and use of an Escherichia coli RNase III-prepared human kinesin/dynein esiRNA library to systematically analyze the functions of all human k... | 10.1038/nrc3310 | This work describes a detailed study identifying 12 members of the kinesin superfamily involved in mitosis and cytokinesis using RNAi and high-resolution imaging. |
10.1101/gad.1700908 | 20,879,058 | Multiple centrosomes in tumor cells create the potential for multipolar divisions that can lead to aneuploidy and cell death. Nevertheless, many cancer cells successfully divide because of mechanisms that suppress multipolar mitoses. A genome-wide RNAi screen in Drosophila S2 cells and a secondary analysis in cancer ce... | 10.1038/nrc3310 | This work identified the role of KIFC1 in the chromosome clustering phenomenon that allows cancer cells to divide and evade cell death despite the presence of extra centrosomes. |
10.1126/science.1146711 | 100,988,450 | The most ecologically successful and destructive termite species are those with both a nymph caste and an irreversibly wingless worker caste. The early developmental bifurcation separating these castes is widely accepted to be strictly environmentally determined. We present evidence that genotype also influences this p... | 10.1038/nrg2429 | The first study to extend genetic caste determination to a non-hymenopteran (non-haplodiploid) social insect. |
10.1073/pnas.0508866103 | 102,259,169 | Lower termites express a unique form of eusocial polyphenism in that totipotent workers can differentiate into either soldier or reproductive caste phenotypes. In this initial effort using RNA interference in termites, we found that two hexamerin genes, Hex-1 and Hex-2 , participate in the regulation of caste polypheni... | 10.1038/nrg2429 | Prominent example of the use of RNAi to manipulate caste determination in termites. |
10.1126/science.1146647 | 41,277,939 | The presence of workers that forgo reproduction and care for their siblings is a defining feature of eusociality and a major challenge for evolutionary theory. It has been proposed that worker behavior evolved from maternal care behavior. We explored this idea by studying gene expression in the primitively eusocial was... | 10.1038/nrg2429 | Outlines ideas from W. M. Wheeler, H. E. Evans, M. J. West-Eberhard and J. H. Hunt on the evolution of eusociality from maternal behaviour, and provides the first supporting molecular evidence. Also demonstrates the benefits of combining 'next-generation' sequencing with an important model social species that had been ... |
10.1126/science.1069911 | 62,049,550 | Genes can affect natural behavioral variation in different ways. Allelic variation causes alternative behavioral phenotypes, whereas changes in gene expression can influence the initiation of behavior at different ages. We show that the age-related transition by honey bees from hive work to foraging is associated with ... | 10.1038/nrg2429 | Reports on the first gene found to have a causal effect on worker–worker division of labour. |
10.1126/science.1153069 | 83,432,703 | Fertile queens and sterile workers are alternative forms of the adult female honeybee that develop from genetically identical larvae following differential feeding with royal jelly. We show that silencing the expression of DNA methyltransferase Dnmt3, a key driver of epigenetic global reprogramming, in newly hatched la... | 10.1038/nrg2429 | First demonstration of a function for DNA methylation in a social insect. |
10.1101/gr.5012006 | 62,051,418 | The genomic architecture underlying the evolution of insect social behavior is largely a mystery. Eusociality, defined by overlapping generations, parental brood care, and reproductive division of labor, has most commonly evolved in the Hymenopteran insects, including the honey bee Apis mellifera . In this species, the... | 10.1038/nrg2429 | A prominent example of a gene involved in worker–worker division of labour, but not through direct effects on the brain. Royal jelly is fed to larvae by 'nurse' honeybees, who produce it in their hypopharyngeal glands. |
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