source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1126/science.1205405 | 83,307,251 | Phosphorylation of an autophagy receptor restricts pathogenic cytosolic bacterial growth. | 10.1038/nrm.2016.74 | Describes the role of TBK1-mediated phosphorylation of OPTN. This modification enhances the affinity of OPTN for LC3, showing the phosphoregulation of the LIR in OPTN. |
10.1126/science.1108190 | 82,938,903 | Transgenerational effects of environmental toxins require either a chromosomal or epigenetic alteration in the germ line. Transient exposure of a gestating female rat during the period of gonadal sex determination to the endocrine disruptors vinclozolin (an antiandrogenic compound) or methoxychlor (an estrogenic compou... | 10.1038/nmeth.4181 | First demonstration in rat that environmentally induced phenotypes can be passed across multiple generations and likely involve the germline epigenome. |
10.1182/blood-2007-01-069195 | 103,663,871 | Abstract The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Modulation of TREM-1–associated activation improves the outcome in rodent models for pneumonia and sepsis. However, the identity and occurrence of the nat... | 10.1038/nri2956 | In this article, the authors demonstrated that platelets express the ligand for TREM1, and showed that the binding of this molecule to neutrophil TREM1 augments LPS-induced neutrophil activation, and ultimately the innate inflammatory response. |
10.1126/science.1166296 | 101,031,479 | Platelets play a critical role in the pathogenesis of malarial infections by encouraging the sequestration of infected red blood cells within the cerebral vasculature. But platelets also have well-established roles in innate protection against microbial infections. We found that purified human platelets killed Plasmodi... | 10.1038/nri2956 | This elegant study demonstrated that platelets can kill parasites in vitro and in mice, and found that platelet-deficient mice are more likely to die from malaria than mice with normal platelet counts. In addition, it showed that a single dose of aspirin may interfere with platelets sufficiently to prevent their killin... |
10.1126/science.1181928 | 41,521,482 | Platelet Microparticles Drive Inflammatory Arthritis Platelets are best known for their critical role in blood clot formation during wound repair, but an appreciation for their role in inflammatory processes is growing. Platelet-derived cellular microparticles (MPs) are small membrane vesicles released from platelets i... | 10.1038/nri2956 | This interesting study described an essential role for platelet-derived microparticles in the development of the autoimmune disease rheumatoid arthritis, and identified the collagen receptor glycoprotein VI as a key stimulator of microparticle generation. |
10.2337/diab.40.11.1397 | 82,835,785 | Muscle and hepatic insulin resistance are two major defects of non-insulin-dependent diabetes mellitus. Dietary factors may be important in the etiology of insulin resistance. We studied progressive changes in the development of high-fat–diet–induced insulin resistance in tissues of the adult male Wistar rat. In vivo i... | 10.1038/nrendo.2017.56 | This seminal study demonstrated that hepatic steatosis and hepatic insulin resistance are early pathological features of high-fat feeding in rats. |
10.2337/diacare.29.04.06.dc05-1938 | 38,427,057 | OBJECTIVE—The α2-Heremans-Schmid glycoprotein (AHSG; fetuin-A in animals) impairs insulin signaling in vitro and in rodents. Whether AHSG is associated with insulin resistance in humans is under investigation. In an animal model of diet-induced obesity that is commonly associated with hepatic steatosis, an increase in ... | 10.1038/nrendo.2017.56 | This paper described the discovery of fetuin A as a liver-secreted protein that is increased with steatosis and diabetes mellitus, consistent with a potential role of fetuin A as a link between fatty liver and insulin resistance. |
10.1084/jem.193.1.1 | 20,705,077 | Thymic selection depends on positive and negative selective mechanisms based on the avidity of T cell interaction with antigen–major histocompatibility complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence ... | 10.1038/nri842 | Clear evidence for the deletion of self-reactive T cells that express high-affinity TCRs during an in vivo immune response. |
10.1084/jem.187.12.2055 | 106,921,416 | To study the contribution of endogenous myelin basic protein (MBP) to the positive and/or negative selection of the MBP-specific T cell repertoire, we studied the T cell response to MBP in MBP-deficient shiverer and MBP-expressing congenic C3H mice. Immunization with MBP induced a vigorous T cell response in shiverer m... | 10.1038/nri842 | References 24 and 25 show that high-avidity MBP-reactive T cells are present in MBP-deficient mice. |
10.1084/jem.191.5.761 | 121,831,116 | The autoreactive T cells that escape central tolerance and form the peripheral self-reactive repertoire determine both susceptibility to autoimmune disease and the epitope dominance of a specific autoantigen. SJL (H-2s) mice are highly susceptible to the induction of experimental autoimmune encephalomyelitis (EAE) with... | 10.1038/nri842 | Lack of autoantigen in the thymus allows a high frequency of PLP-reactive T cells to reach the periphery. |
10.4049/jimmunol.167.4.2030 | 17,575,962 | Abstract The in vivo T cell response to persistent Ag contains a hyporesponsive phase following an initial expansion and subsequent partial deletion of the responding cells. The mechanism(s) responsible for this tolerance process is poorly understood. In this study, we describe a new paired transgenic model (TCR and Ag... | 10.1038/nri842 | This study shows that encounter with self-antigen tunes T-cell-activation thresholds in the periphery. |
10.1084/jem.192.12.1719 | 106,934,883 | We recently described a novel way to isolate populations of antigen-reactive CD4+ T cells with a wide range of reactivity to a specific antigen, using immunization with a fixed dose of nominal antigen and FACS® sorting by CD4high expression. Phenotypic, FACS®, functional, antibody inhibition, and major histocompatibili... | 10.1038/nri842 | This paper describes the selection of moderate-affinity TCRs during an immune response. |
10.1073/pnas.96.17.9781 | 83,184,135 | Multimeric peptide/class II MHC staining reagents were synthesized and shown to bind with appropriate specificity to T cell hybridomas. A small, expanded population of T cells detected with one of these reagents in peptide-immunized C57BL/10 mice persisted for several months. This population expanded further on seconda... | 10.1038/nri842 | The loss of high-affinity TCRs can be caused by high antigen doses in vivo and in vitro |
10.1126/science.1150473 | 102,315,334 | Online journals promise to serve more information to more dispersed audiences and are more efficiently searched and recalled. But because they are used differently than print—scientists and scholars tend to search electronically and follow hyperlinks rather than browse or peruse—electronically available journals may po... | 10.1038/nrd2973 | A much discussed study showing that online publishing, and the ease of following hyperlinks, tends to channel researchers towards a narrower and more recent set of publications, with a possible loss of diversity and historical perspective. |
10.1063/1.3524521 | 20,257,555 | We demonstrate over 1×1010 open-loop switching cycles from a simple memristive device stack of Pt/TaOx/Ta. We compare this system to a similar device stack based on titanium oxides to obtain insight into the solid-state thermodynamic and kinetic factors that influence endurance in metal-oxide memristors. | 10.1038/nnano.2012.240 | This article first proposed memristive material selection criteria for high endurance and low variability. |
10.1073/pnas.94.1.59 | 122,153,708 | The SELEX method and oligonucleotide combinatorial chemistry discovery process yields high-affinity/high-specificity ligands for virtually any molecular target. Typically, the enormous starting libraries used in the SELEX process contain 10 14 –10 15 sequences. We now ask if the smaller sequences, complexity of extant ... | 10.1038/nrm1403 | Although unpublished speculation that riboswitches might exist had been ongoing for several years, this is an early publication that briefly mentions the possibility. |
10.1261/rna.5090103 | 19,278,587 | Genetic control by metabolite-binding mRNAs is widespread in prokaryotes. These riboswitches are typically located in noncoding regions of mRNA, where they selectively bind their target compound and subsequently modulate gene expression. We have identified mRNA elements in fungi and in plants that match the consensus s... | 10.1038/nrm1403 | Demonstration that some eukaryotic mRNAs carry metabolite-binding domains that are probably components of riboswitches. |
10.1126/science.7510417 | 83,102,910 | Species of RNA that bind with high affinity and specificity to the bronchodilator theophylline were identified by selection from an oligonucleotide library. One RNA molecule binds to theophylline with a dissociation constant K d of 0.1 μM. This binding affinity is 10,000-fold greater than the RNA molecule's affinity fo... | 10.1038/nrm1403 | An early demonstration of the molecular recognition power of RNA aptamers. |
10.1084/jem.186.1.65 | 39,298,387 | Class I–restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be ... | 10.1038/nri.2015.10 | References 22 and 23 are the first reports to show that CD4 + T cell help during the primary response is mediated through CD40 signalling on the antigen-presenting cell. |
10.1126/science.1227049 | 123,324,230 | Treg-ulating Immune Responses There are many checks and balances to keep the immune system from running amok. One of the most critical is a specialized population of T cells, called regulatory T cells (T regs ). In their absence, a lethal autoimmune disease develops in both humans and mice. Although T regs are well kno... | 10.1038/nri.2015.10 | This was the first study to describe a role for T Reg cells in promoting CD8 + T cell memory. |
10.1126/science.1172815 | 27,019,526 | Controlling Chronic Viral Infections Chronic viral infections such as HIV and hepatitis B and C viruses are major public health concerns. T cell—mediated immune responses are critical for controlling viral infections. In contrast to acute infections, chronic viral infections are characterized by “exhausted” cytotoxic C... | 10.1038/nri.2015.10 | Collectively, references 100–102 are the first reports to show that IL-21 is crucial for maintaining CD8 + T cell functionality and mediating viral control during chronic infection. |
10.1126/science.1074192 | 4,697,166 | Transgenic mice expressing a stabilized β-catenin in neural precursors develop enlarged brains with increased cerebral cortical surface area and folds resembling sulci and gyri of higher mammals. Brains from transgenic animals have enlarged lateral ventricles lined with neuroepithelial precursor cells, reflecting an ex... | 10.1038/nrd4233 | This article highlights the importance of β-catenin in neuronal stem cells and neuronal development. |
10.1073/pnas.0504600102 | 83,081,425 | Wnt/β-catenin signaling has been shown to promote self-renewal in a variety of tissue stem cells, including neuronal stem cells and hematopoietic stem cells. However, activation of the Wnt/β-catenin pathway promoted and inhibition of the pathway prevented differentiation of neuronal precursor cells. A clear explanation... | 10.1038/nrd4233 | This is the first publication that describes the model for differential usage of coactivators in WNT–β-catenin signalling to explain the divergent outcomes — that is, proliferation versus differentiation via activation of the WNT signalling cascade. |
10.1073/pnas.1001520107 | 60,835,949 | Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a ravaging condition of progressive lung scarring and destruction. Anti-inflammatory therapies including corticosteroids have limited efficacy in this ultimately fatal disorder. An important unmet need is to identify new agents that interact with key m... | 10.1038/nrd4233 | This study first demonstrates that idiopathic pulmonary fibrosis may be pharmacologically reversible via modulation of WNT–β-catenin signalling. |
10.1126/science.1144090 | 83,352,175 | The regenerative potential of skeletal muscle declines with age, and this impairment is associated with an increase in tissue fibrosis. We show that muscle stem cells (satellite cells) from aged mice tend to convert from a myogenic to a fibrogenic lineage as they begin to proliferate and that this conversion is mediate... | 10.1038/nrd4233 | References 170–172 demonstrate that increased WNT signalling is associated with ageing. |
10.5966/sctm.2011-0033 | 60,206,781 | Abstract An optimal culture system for human pluripotent stem cells should be fully defined and free of animal components. To date, most xeno-free culture systems require human feeder cells and/or highly complicated culture media that contain activators of the fibroblast growth factor (FGF) and transforming growth fact... | 10.1038/nrd4233 | References 196 and 197 demonstrate that selective inhibition of WNT–β-catenin–p300 signalling maintains both mouse and human stem cell pluripotency. |
10.1073/pnas.1120068109 | 104,277,587 | The Wnt/β-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several coreceptors, has long been implicated in cancer. Here we demonstrate a therapeutic approach to targeting the Wnt pathway with a monoclonal antibody, OMP-18R5. This antibody, initially identified by binding to Frizzled 7, int... | 10.1038/nrd4233 | This manuscript describes preclinical studies utilizing the monoclonal antibody OMP-18R5, which is currently in Phase I clinical trials. |
10.1073/pnas.0404875101 | 62,247,509 | Inherited and somatic mutations in the adenomatous polyposis coli occur in most colon cancers, leading to activation of β-catenin-responsive genes. To identify small molecule antagonists of this pathway, we challenged transformed colorectal cells with a secondary structure-templated chemical library, looking for compou... | 10.1038/nrd4233 | This study and subsequent studies utilizing specific small-molecule CBP antagonists (including those detailed in references 252 and 253) provided the rationale for the clinical development of the second-generation CBP–catenin antagonist PRI-724, which is currently in Phase I/II clinical trials. |
10.4155/fmc.11.126 | 61,224,958 | The decision for a stem cell to undergo a symmetric versus an asymmetric differentiation is probably the most critical cellular decision process in adults, as it probably underlies a large array of diseases, is associated with a decrease in tissue maintenance/homeostasis and the ability to repair properly, may mediate ... | 10.1038/nrd4233 | This article outlines the mechanism whereby selective CBP–catenin antagonists can safely eliminate cancer stem cells via forced differentiation without having deleterious effects on the normal somatic stem cell populations. |
10.1073/pnas.1314239110 | 83,440,706 | Significance Targeting the Wnt pathway in cancer is an attractive therapeutic approach. However, success has been limited because of the lack of effective therapeutic agents and the lack of biomarkers to define the patient population that would benefit from such a therapy. Herein, we report the discovery of LGK974, a d... | 10.1038/nrd4233 | This study describes the discovery of the small-molecule Porcupine inhibitor LGK974, which is currently in Phase I clinical trials. |
10.1146/annurev.immunol.21.120601.141049 | 122,702,683 | Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleuk... | 10.1038/nrmicro1099 | Summarizes the known immunomodulator and host-range gene families found in poxviruses, and documents the members that can be encoded by different poxviruses. |
10.1128/jvi.62.4.1297-1304.1988 | 81,244,425 | Cowpox virus, in contrast to vaccinia virus, can multiply in Chinese hamster ovary cells. To study the genetic basis for this difference in host range, recombinants between vaccinia and cowpox viruses were isolated and their DNA restriction patterns were examined. The ability to multiply in Chinese hamster ovary cells ... | 10.1038/nrmicro1099 | Another classic paper showing that a specific gene, CHOhr (or CP77), is required for the replication of cowpox virus in CHO cells. |
10.1073/pnas.0402949101 | 103,803,924 | Ectromelia virus (ECTV), a natural mouse pathogen and an orthopoxvirus, has been used to investigate the correlation between polarized type 1 or type 2 immune responses and resistance to disease in poxvirus infections by using well defined resistant and susceptible mouse strains. Our data show that distinct differences... | 10.1038/nrmicro1099 | Provides a useful up-to-date summation of what is known about the importance of T H -polarized responses in determining whether a given poxvirus infection will cause pathology or resolve. |
10.4049/jimmunol.161.10.5133 | 139,034,847 | Abstract To evaluate tumor immunotherapies, we used transgenic mice that harbor a progressive liver tumor associated with the expression of the SV40 large tumor T oncoprotein (SV40-T). To induce “self” tumor Ag-specific CD8+ T cells, mice were injected with an immunodominant SV40-T CTL epitope mixed with a heterologous... | 10.1038/nri841 | A mouse model system that graphically illustrates the consequences of self-tolerance on tumour immunity and the effectiveness of adoptive therapies. |
10.1126/science.288.5466.669 | 83,484,463 | Severe combined immunodeficiency–X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the γc cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which particip... | 10.1038/nri841 | A description of the most successful human gene-therapy trial so far, which exemplifies the optimal conditions for gene therapy. |
10.1126/science.274.5284.94 | 104,308,349 | Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of... | 10.1038/nri841 | A landmark paper that describes how fluorescently labelled multivalent MHC molecules can be used to visualize antigen-specific T cells. |
10.1182/blood-2005-11-013458 | 29,333,078 | Abstract To better define the molecular basis of multiple myeloma (MM), we performed unsupervised hierarchic clustering of mRNA expression profiles in CD138-enriched plasma cells from 414 newly diagnosed patients who went on to receive high-dose therapy and tandem stem cell transplants. Seven disease subtypes were vali... | 10.1038/nrc2189 | This work provides a new classification of patients with multiple myeloma based on a comprehensive expression analysis of 414 newly diagnosed patients. |
10.1073/pnas.93.24.13931 | 80,097,515 | In multiple myeloma, karyotypic 14q32 translocations have been identified at a variable frequency (10–60% in different studies). In the majority of cases, the partner chromosome has not been identified (14q+), and in the remaining cases, a diverse array of chromosomal partners has been implicated, with 11q13 being the ... | 10.1038/nrc2189 | A landmark paper reporting the first description of frequent translocations into the IgH switch regions in multiple myeloma. |
10.1182/blood-2005-01-0034 | 19,990,940 | Two oncogenic pathways have been hypothesized for multiple myeloma (MM) and premalignant monoclonal gammopathy of undetermined significance (MGUS) tumors: a nonhyperdiploid pathway associated with a high prevalence of IgH translocations and a hyperdiploid pathway associated with multiple trisomies of 8 chromosomes. Cyc... | 10.1038/nrc2189 | This work provides a comprehensive analysis of the role of cyclin dysregulation in multiple myeloma, and proposes a multiple myeloma classification, the TC (translocation/cyclin D) classification, based on translocations and associated dysregulation of specific cyclins. |
10.1182/blood.v93.5.1658.405a19_1658_1667 | 100,072,020 | Integrin-mediated adhesion influences cell survival and may prevent programmed cell death. Little is known about how drug-sensitive tumor cell lines survive initial exposures to cytotoxic drugs and eventually select for drug-resistant populations. Factors that allow for cell survival following acute cytotoxic drug expo... | 10.1038/nrc2189 | This work demonstrates the concept of CAMDR, which overcomes conventional treatment in multiple myeloma. |
10.1182/blood.v87.3.1104.bloodjournal8731104 | 41,301,681 | Adhesion of multiple myeloma (MM) cells to bone marrow stromal cells (BMSCs) not only localizes MM cells in the marrow microenvironment, but also triggers interleukin-6 (IL-6) secretion by BMSCs and related MM cell proliferation. In the present study, we characterized the regulation of IL-6 gene expression in BMSCs dur... | 10.1038/nrc2189 | This is the first study to demonstrate that transcription and secretion of IL6 from BMSCs are modulated by NFκB. |
10.1242/dev.126.16.3617 | 62,560,505 | In situ immunolocalization of tubulin revealed that important rearrangements occur during all the early symbiotic steps in the Medicago/R. meliloti symbiotic interaction. Microtubular cytoskeleton (MtC) reorganizations were observed in inner tissues, first in the pericycle and then in the inner cortex where the nodule ... | 10.1038/nrmicro1705 | The definitive microscopy study of plant cytological changes during infection thread formation. |
10.1104/pp.103.021634 | 41,364,427 | Abstract A critical step in establishing a successful nitrogen-fixing symbiosis between rhizobia and legume plants is the entrapment of the bacteria between root hair cell walls, usually in characteristic 180° to 360° curls, shepherd's crooks, which are formed by the host's root hairs. Purified bacterial signal molecul... | 10.1038/nrmicro1705 | Demonstrated that Nod factor has a directional effect on root hair polar tip growth. |
10.1104/pp.106.084657 | 29,299,793 | Abstract Rhizobial Nod factors are key symbiotic signals responsible for starting the nodulation process in host legume plants. Of the six Medicago truncatula genes controlling a Nod factor signaling pathway, Nod Factor Perception (NFP) was reported as a candidate Nod factor receptor gene. Here, we provide further evid... | 10.1038/nrmicro1705 | Cloned the NFP -encoded Nod factor receptor and demonstrated that it has a role in infection thread formation. |
10.1126/science.1090074 | 104,248,234 | The rhizobial infection of legumes has the most stringent demand toward Nod factor structure of all host responses, and therefore a specific Nod factor entry receptor has been proposed. The SYM2 gene identified in certain ecotypes of pea ( Pisum sativum ) is a good candidate for such an entry receptor. We exploited the... | 10.1038/nrmicro1705 | Identified and cloned the MtLYK3 and MtLYK4 Nod factor receptors. |
10.1101/gad.2.6.677 | 17,708,430 | To help dissect the molecular basis of the Rhizobium-legume symbiosis, we used in vitro translation and Northern blot analysis of nodule RNA to examine alfalfa-specific genes (nodulins) expressed in two types of developmentally defective root nodules elicited by Rhizobium meliloti. Fix- nodules were elicited by R. meli... | 10.1038/nrmicro1705 | First demonstrated that cyclic- β -glucan mutants and exopolysaccharide mutants of S. meliloti lack infection threads. |
10.1128/jb.180.19.5183-5191.1998 | 84,497,134 | ABSTRACT Rhizobium meliloti Rm1021 must be able to synthesize succinoglycan in order to invade successfully the nodules which it elicits on alfalfa and to establish an effective nitrogen-fixing symbiosis. Using R. meliloti cells that express green fluorescent protein (GFP), we have examined the nature of the symbiotic ... | 10.1038/nrmicro1705 | Showed that succinoglycan must be succinylated and acetylated to efficiently facilitate infection thread formation. |
10.1104/pp.103.031518 | 17,679,977 | Abstract In the Medicago truncatula/Sinorhizobium meliloti symbiosis, the plant undergoes a series of developmental changes simultaneously, creating a root nodule and allowing bacterial entry and differentiation. Our studies of plant genes reveal novel transcriptional regulation during the establishment of the symbiosi... | 10.1038/nrmicro1705 | Plant and rhizobial mutants arrested at different morphologically defined stages of symbiotic development are also arrested in the ability to undergo symbiosis-specific transcriptional changes. |
10.1073/pnas.0600912103 | 19,848,890 | Symbiosis between legumes and Rhizobium bacteria leads to the formation of root nodules where bacteria in the infected plant cells are converted into nitrogen-fixing bacteroids. Nodules with a persistent meristem are indeterminate, whereas nodules without meristem are determinate. The symbiotic plant cells in both nodu... | 10.1038/nrmicro1705 | Showed that plants that form indeterminate nodules impose a programme of genomic endoreduplication on the bacteria, whereas plants that form determinate nodules do not. |
10.1073/pnas.0504284102 | 101,821,519 | In most legume nodules, the N 2 -fixing rhizobia are present as organelle-like structures inside their host cells. These structures, named symbiosomes, contain one or a few rhizobia surrounded by a plant membrane. Symbiosome formation requires the release of bacteria from cell-wall-bound infection threads. In primitive... | 10.1038/nrmicro1705 | Demonstrated that a Nod factor signalling intermediate DMI2 is required for symbiosome formation as well as early events in Nod factor signalling. |
10.1128/jb.172.8.4295-4306.1990 | 17,679,008 | Bacteroid differentiation was examined in developing and mature alfalfa nodules elicited by wild-type or Fix- mutant strains of Rhizobium meliloti. Ultrastructural studies of wild-type nodules distinguished five steps in bacteroid differentiation (types 1 to 5), each being restricted to a well-defined histological regi... | 10.1038/nrmicro1705 | The first observation of a plant defence response associated with failed infection threads. |
10.1111/j.1365-2958.1993.tb01177.x | 82,540,700 | Summary DEAE‐cellulose chromatography of extracts of free‐living Rhizobium meliloti cells revealed separate NAD + ‐dependent and NADP + ‐dependent malic enzyme activities. The NAD + malic enzyme exhibited more activity with NAD + as cofactor, but also showed some activity with NADP + . The NADP + malic enzyme only show... | 10.1038/nrmicro1705 | Showed that rhizobial malic enzyme is required for nitrogen fixation and proposed a model for carbon assimilation by bacteroids. |
10.1104/pp.106.090985 | 42,511,149 | Abstract In the establishment of symbiosis between Medicago truncatula and the nitrogen-fixing bacterium Sinorhizobium meliloti, the lipopolysaccharide (LPS) of the microsymbiont plays an important role as a signal molecule. It has been shown in cell cultures that the LPS is able to suppress an elicitor-induced oxidati... | 10.1038/nrmicro1705 | Showed that the S. meliloti LPS suppresses short-term M. truncatula defence responses such as oxidative burst and longer-term defence responses requiring transcriptional changes. |
10.1073/pnas.82.18.6231 | 17,706,151 | By screening with the fluorescent stain Calcofluor, we have isolated 26 independent transposon Tn5 insertion mutants of Rhizobium meliloti that are deficient in the production of a known extracellular polysaccharide (Exo-). The mutants belonged to six distinct genetic groups based on the ability of their Exo- phenotype... | 10.1038/nrmicro1705 | Demonstrated that succinoglycan is critical for successful infection thread formation. |
10.1126/science.287.5462.2492 | 28,141,531 | Brucella abortus , a mammalian pathogen, and Rhizobium meliloti , a phylogenetically related plant symbiont, establish chronic infections in their respective hosts. Here a highly conserved B. abortus homolog of the R. meliloti bacA gene, which encodes a putative cytoplasmic membrane transport protein required for symbi... | 10.1038/nrmicro1705 | Established that the bacA gene is required for survival of B. abortus within mammalian cells, as well as for survival of S. meliloti within plant cells. |
10.1073/pnas.0530291100 | 104,385,636 | Breast cancer is the most common malignancy in United States women, accounting for >40,000 deaths each year. These breast tumors are comprised of phenotypically diverse populations of breast cancer cells. Using a model in which human breast cancer cells were grown in immunocompromised mice, we found that only a mino... | 10.1038/nrc1232 | Not all human breast cancer cells are equal in terms of their ability to form tumours in immunocompromised mice, and the tumorigenic subset of cells exhibits properties of cancer stem cells. The tumorigenic cell population represents a minority of cells within the tumours, but can be isolated from most of the patients ... |
10.1073/pnas.252462599 | 40,044,343 | Acute myelogenous leukemia (AML) is typically a disease of stem/progenitor cell origin. Interestingly, the leukemic stem cell (LSC) shares many characteristics with normal hematopoietic stem cells (HSCs) including the ability to self-renew and a predominantly G 0 cell-cycle status. Thus, although conventional chemother... | 10.1038/nrc1232 | Shows that it is possible to identify therapeutic agents that kill leukaemic stem cells but not normal haematopoietic stem cells. |
10.1126/science.1071489 | 123,158,111 | Pharmacological inactivation of oncogenes is being investigated as a possible therapeutic strategy for cancer. One potential drawback is that cessation of such therapy may allow reactivation of the oncogene and tumor regrowth. We used a conditional transgenic mouse model for MYC -induced tumorigenesis to demonstrate th... | 10.1038/nrc1232 | Even a transient loss of MYC function can lead to an irreversible loss of neoplastic cells. This is consistent with the idea that MYC is required to maintain the state of cancer stem cells, much as it would be expected to be required for normal stem-cell self-renewal. So, targeting pathways that are required for mainte... |
10.2307/1941034 | 102,451,616 | The effects of both genotype and spatial position of host plants on density, proportion, and total community structure of herbivore species were experimentally tested for a guild of gall—forming sawflies on their host plant, the arroyo willow, Salix lasiolepis. Genetic differences among individually potted stem cutting... | 10.1038/nrg1877 | One of the first studies to examine how plant genotypes affect an arthropod herbivore community. |
10.1073/pnas.150237597 | 83,306,093 | Artificial selection has been practiced for centuries to shape the properties of individual organisms, providing Darwin with a powerful argument for his theory of natural selection. We show that the properties of whole ecosystems can also be shaped by artificial selection procedures. Ecosystems initiated in the laborat... | 10.1038/nrg1877 | The first study to demonstrate selection at the level of the ecosystem. |
10.1126/science.2953071 | 20,678,540 | Neoplastic transformation has been associated with a variety of structural changes in cell surface carbohydrates, most notably increased sialylation and β1-6-linked branching of complex-type asparagine (Asn)-linked oligosaccharides (that is, -GlcNAcβ1-6Manα1-6Manβ1-). However, little is known about the relevant glycopr... | 10.1038/nrc3982 | This study reported that increased expression of β1–6-linked branching oligosaccharide structures is directly related to the metastatic potential of the cells. |
10.1073/pnas.92.19.8754 | 63,359,617 | The beta 1-6 structure of N-linked oligosaccharides, formed by beta-1,6-N-acetylglucosaminyltransferase (GnT-V), is associated with metastatic potential. We established a highly metastatic subclone, B16-hm, from low metastatic B16-F1 murine melanoma cells. The gene encoding beta-1,4-N-acetylglucosaminyltransferase (GnT... | 10.1038/nrc3982 | This article provides the first demonstration of the tumour-suppressive role of GnT-III. |
10.1073/pnas.262438199 | 20,678,682 | Human core 1 β3-galactosyltransferase (C1β3Gal-T) generates the core 1 O-glycan Galβ1-3GalNAcα1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in animal glycoproteins. We report here that C1β3Gal-T activity requires expression of a molecular chaperone designated Cosmc ( co re 1 β3-Gal-T- s pecifi... | 10.1038/nrc3982 | This study describes the role of the molecular chaperone C1GALT1C1 for activity of the core 1 β3-GalT. |
10.1073/pnas.96.6.2805 | 83,422,063 | The assembly of focal adhesions and actin stress fibers by cells plated on fibronectin depends on adhesion-mediated signals involving both integrins and cell-surface heparan sulfate proteoglycans. These two cell-surface receptors interact with different domains of fibronectin. To attempt to identify the heparan sulfate... | 10.1038/nrc3982 | This article describes how a proteoglycan cooperates with integrins interfering with focal adhesions and actin stress fibres. |
10.1126/science.1235681 | 81,085,181 | Glycosylation plays a key role in a wide range of biological processes. Specific modification to a glycan’s structure can directly modulate its biological function. Glycans are not only essential to glycoprotein folding, cellular homeostasis, and immune regulation but are involved in multiple disease conditions. An inc... | 10.1038/nrc3982 | Addresses the potential of glycans to be an important source for the development of novel targeted therapeutic strategies. |
10.1073/pnas.95.20.12022 | 103,230,673 | A class of high-affinity inhibitors is disclosed that selectively target and irreversibly inactivate the epidermal growth factor receptor tyrosine kinase through specific, covalent modification of a cysteine residue present in the ATP binding pocket. A series of experiments employing MS, molecular modeling, site-direct... | 10.1038/nrd3410 | This was the first example of targeted covalent inhibition of a kinase with detailed in vitro and in vivo characterization. |
10.1083/jcb.200502053 | 83,250,455 | Yeast actin patches are dynamic structures that form at the sites of cell growth and are thought to play a role in endocytosis. We used biochemical analysis and live cell imaging to investigate actin patch assembly in fission yeast Schizosaccharomyces pombe. Patch assembly proceeds via two parallel pathways: one depend... | 10.1038/nrm1940 | An important study of regulators of actin polymerization at endocytic sites in S. pombe |
10.1091/mbc.e04-09-0774 | 83,395,408 | Clathrin-mediated endocytosis in mammalian cells is critical for a variety of cellular processes including nutrient uptake and cell surface receptor down-regulation. Despite the findings that numerous endocytic accessory proteins directly or indirectly regulate actin dynamics and that actin assembly is spatially and te... | 10.1038/nrm1940 | This work showed a functional requirement for dynamic actin at endocytic sites in mammalian cells. |
10.1083/jcb.200404173 | 62,278,454 | Using FM4-64 to label endosomes and Abp1p-GFP or Sac6p-GFP to label actin patches, we find that (1) endosomes colocalize with actin patches as they assemble at the bud cortex; (2) endosomes colocalize with actin patches as they undergo linear, retrograde movement from buds toward mother cells; and (3) actin patches int... | 10.1038/nrm1940 | The visualization of endocytic vesicles in actin patches and their movement along actin cables using a lipid dye in S. cerevisiae |
10.1242/jcs.02444 | 123,057,001 | WASP and WAVE family proteins promote actin polymerization by stimulating Arp2/3-complex-dependent filament nucleation. Unlike WAVE proteins, which are known to drive the formation of protrusions such as lamellipodia and membrane ruffles, vertebrate cell functions of WASP or N-WASP are less well established. Recent wor... | 10.1038/nrm1940 | Showed a functional requirement for N-WASP in endocytic internalization in mammalian cells. |
10.1126/science.1150255 | 20,809,315 | Dietary vitamin A deficiency causes eye disease in 40 million children each year and places 140 to 250 million at risk for health disorders. Many children in sub-Saharan Africa subsist on maize-based diets. Maize displays considerable natural variation for carotenoid composition, including vitamin A precursors α-carote... | 10.1038/nrg2342 | This paper is an example of a successful study using combinational approaches, with association analysis, QTL mapping and chemical mutagenesis revealing that the variation at the lycE locus has major effects on carotenoid and provitamin A composition in maize grain. |
10.1126/science.1113373 | 38,397,761 | Most agriculturally important traits are regulated by genes known as quantitative trait loci (QTLs) derived from natural allelic variations. We here show that a QTL that increases grain productivity in rice, Gn1a , is a gene for cytokinin oxidase/dehydrogenase (OsCKX2), an enzyme that degrades the phytohormone cytokini... | 10.1038/nrg2342 | This paper provides evidence that levels of the phytohormone cytokinin in the inflorescence affect the branching pattern of the panicle, and thus the grain yield, of rice. A QTL pyramiding method in rice is also demonstrated. |
10.1073/pnas.0707193104 | 80,330,814 | Commercially improved crop performance under drought conditions has been challenging because of the complexity of the trait and the multitude of factors that influence yield. Here we report the results of a functional genomics approach that identified a transcription factor from the nuclear factor Y (NF-Y) family, AtNF... | 10.1038/nrg2342 | This paper reports a good example to show that the identification of a transcription factor in model plants can be applied for crop improvement in the field. |
10.1104/pp.107.095992 | 17,747,361 | Abstract The modification of an endogenous gene into a designed sequence by homologous recombination, termed gene targeting (GT), has broad implications for basic and applied research. Rice (Oryza sativa), with a sequenced genome of 389 Mb, is one of the most important crops and a model plant for cereals, and the singl... | 10.1038/nrg2342 | This report and previous studies by the same group have showed the advance in homologous recombination in rice. |
10.1126/scisignal.aaa1796 | 29,313,986 | The human pathogen Salmonella senses ʟ-arginine and responds by increasing c-di-GMP and cellulose synthesis. | 10.1038/nrmicro.2016.190 | This study applies a fluorescence resonance energy transfer (FRET) sensor for c-di-GMP to identify l-arginine as a signal that activates a DGC and leads to biofilm formation. |
10.1038/ncomms12481 | 103,788,317 | Abstract C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c... | 10.1038/nrmicro.2016.190 | By elucidating the structure of the N-terminal domain of the MshE ATPase bound to c-di-GMP, this study defines a large and widespread new family of c-di-GMP-binding proteins. |
10.1101/gad.222679.113 | 124,216,523 | Eukaryotic morphogenesis is seeded with the establishment and subsequent amplification of polarity cues at key times during the cell cycle, often using (cyclic) nucleotide signals. We discovered that flagellum de- and repolarization in the model prokaryote Caulobacter crescentus is precisely orchestrated through at lea... | 10.1038/nrmicro.2016.190 | This study demonstrates how oscillations of c-di-GMP contribute to flagellar polarity in a simple polarized bacterium. |
10.1111/j.1399-0004.2006.00708.x | 45,453,531 | Evidence from many sources suggests that similar phenotypes are begotten by functionally related genes. This is most obvious in the case of genetically heterogeneous diseases such as Fanconi anemia, Bardet‐Biedl or Usher syndrome, where the various genes work together in a single biological module. Such modules can be ... | 10.1038/nrg3253 | This paper provides a motivation to use the guilt by association principle to identify novel disease causing genes |
10.1111/j.1742-4658.2012.08471.x | 82,799,582 | The identification of genes involved in human hereditary diseases often requires the time‐consuming and expensive examination of a great number of possible candidate genes, since genome‐wide techniques such as linkage analysis and association studies frequently select many hundreds of ‘positional’ candidates. Even cons... | 10.1038/nrg3253 | This review focuses on the different data sources and the algorithms underlying the prioritization methods. |
10.1093/bioinformatics/btq076 | 28,139,187 | Abstract Motivation: Understanding the association between genetic diseases and their causal genes is an important problem concerning human health. With the recent influx of high-throughput data describing interactions between gene products, scientists have been provided a new avenue through which these associations ca... | 10.1038/nrg3253 | This is a recent review about predicting disease–gene associations using gene–protein networks and network-based algorithms. |
10.1101/gr.117143.110 | 58,445,122 | Whole exome sequencing has become a pivotal methodology for rapid and cost-effective detection of pathogenic variations in Mendelian disorders. A major challenge of this approach is determining the causative mutation from a substantial number of bystander variations that do not play any role in the disease etiology. Cu... | 10.1038/nrg3253 | This is a study in which traditional mapping methods, new sequencing tools and network analysis are combined to identify the causal mutation for a rare monogenic disease. |
10.3762/bjnano.3.14 | 123,870,719 | Contact electrochemical transfer of silver from a metal-film stamp (parallel process) or a metal-coated scanning probe (serial process) is demonstrated to allow site-selective metallization of monolayer template patterns of any desired shape and size created by constructive nanolithography. The precise nanoscale contro... | 10.1038/nnano.2014.157 | Comprehensive study of the use of oxidation scanning probe lithography to pattern organic monolayers and their use as templates for the deposition of metallic nanoparticles. |
10.1126/science.270.5242.1639 | 63,224,083 | Metal wires and metal-oxide-metal junctions were fabricated by anodic oxidation with the conducting tip of an atomic force microscope (AFM). The width of the wires and resistance of the junctions were controlled by real-time, in situ measurement of the device resistance during fabrication. Because the properties of nan... | 10.1038/nnano.2014.157 | One of the earliest applications of oxidation scanning probe lithography to fabricate nanoscale transistors. |
10.1126/science.270.5240.1354 | 42,588,809 | A yeast two-hybrid system was used to identify a protein that interacts with and enhances the human progesterone receptor (hPR) transcriptional activity without altering the basal activity of the promoter. Because the protein stimulated transactivation of all the steroid receptors tested, it has been termed steroid rec... | 10.1038/nrc2695 | This article identified SRC1 as the first steroid receptor co-activator. |
10.1126/science.277.5328.965 | 82,807,486 | Members of the recently recognized SRC-1 family of transcriptional coactivators interact with steroid hormone receptors to enhance ligand-dependent transcription. AIB1, a member of the SRC-1 family, was cloned during a search on the long arm of chromosome 20 for genes whose expression and copy number were elevated in h... | 10.1038/nrc2695 | This article first reported that SRC3 was amplified and overexpressed in breast cancer. |
10.1073/pnas.0808703105 | 103,672,292 | Steroid receptor coactivator-1 (SRC-1) is a coactivator for nuclear hormone receptors such as estrogen and progesterone receptors and certain other transcription factors such as Ets-2 and PEA3. SRC-1 expression in breast cancer is associated with HER2 and c-Myc expression and with reduced disease-free survival. In this... | 10.1038/nrc2695 | This article first reported that SRC1 deficiency strongly suppressed breast cancer metastasis in MMTV-PyMT mice by inhibiting ERBB2 and CSF1 expression. |
10.1158/0008-5472.can-03-3745 | 38,590,762 | Abstract Although the amplified in breast cancer 1 (AIB1) coactivator is amplified and overexpressed in breast cancers, its role in mammary carcinogenesis remains unknown. We demonstrate that during mammary development and tumorigenesis, the elevation of AIB1 level and its nuclear localization correlate with normal and... | 10.1038/nrc2695 | This article first demonstrated that SRC3 deficiency suppressed oncogene-induced mammary tumour initiation, growth and metastasis and inhibited the IGF1 signalling pathways by downregulating IGF1, IRS1 and IRS2. |
10.1158/0008-5472.can-05-1179 | 109,414,523 | Abstract Amplified in breast cancer 1 (AIB1; steroid receptor coactivator-3, p/CIP, RAC3, ACTR, TRAM-1, or NCoA-3) is a transcriptional coactivator for nuclear receptors and certain other transcription factors and is a newly defined oncogene overexpressed in human breast cancer. Although the role and molecular mechanis... | 10.1038/nrc2695 | This article demonstrated that SRC3 deficiency specifically protected mouse mammary gland from chemical carcinogen-induced tumorigenesis. |
10.1158/0008-5472.can-06-3168 | 58,357,844 | Abstract Although the amplified-in-breast cancer 1 (AIB1; SRC-3, ACTR, or NCoA3) was defined as a coactivator for androgen receptor (AR) by in vitro studies, its role in AR-mediated prostate development and prostate cancer remained unexplored. We report here that AIB1 is expressed in the basal and stromal cells but not... | 10.1038/nrc2695 | This article first reported that SRC3 deficiency in mice arrested spontaneous prostate cancer progression at a well-differentiated stage. |
10.1126/science.279.5358.1922 | 101,890,845 | The in vivo biological function of a steroid receptor coactivator was assessed in mice in which the SRC-1 gene was inactivated by gene targeting. Although in both sexes the homozygous mutants were viable and fertile, target organs such as uterus, prostate, testis, and mammary gland exhibited decreased growth and develo... | 10.1038/nrc2695 | This article first reported the phenotype of SRC1-knockout mice and demonstrated an important physiological role of the co-activator in vivo |
10.1073/pnas.120166297 | 83,316,698 | Steroid receptor coactivator-3 (SRC-3) is a coactivator of nuclear receptors in the SRC family as assayed in vitro . Here, we show that mouse SRC-3 is expressed in a tissue-specific fashion and distributed mainly in the oocytes, mammary glands, hippocampus, olfactory bulb, smooth muscle, hepatocytes, and vaginal epithe... | 10.1038/nrc2695 | This article first reported the phenotype of SRC3-knockout mice and demonstrated that SRC3 has an important role in growth and mammary gland development. |
10.1189/jlb.0502261 | 44,907,381 | Abstract Over most of the 20th century, immunotherapy for cancer was based on empiricism. Interesting phenomena were observed in the areas of cancer, infectious diseases, or transplantation. Inferences were made and extrapolated into new approaches for the treatment of cancer. If tumors regressed, the treatment approac... | 10.1038/nri1592 | A comprehensive and excellent review of the development of immunotherapy for cancer, including DC-based vaccination trials. |
10.1146/annurev.immunol.21.120601.141040 | 123,169,333 | ▪ Abstract Dendritic cells (DCs) have several functions in innate and adaptive immunity. In addition, there is increasing evidence that DCs in situ induce antigen-specific unresponsiveness or tolerance in central lymphoid organs and in the periphery. In the thymus DCs generate tolerance by deleting self-reactive T cell... | 10.1038/nri1592 | An outstanding review that summarizes studies on tolerogenic DCs, written by the researchers who were the first to propose and show that DCs can induce immune tolerance. |
10.2337/diab.14.10.619 | 20,705,586 | 1. Quantitative study of insular tissue has revealed that the number of B cells is greatly diminished in Patients with acute juvenile diabetes from the time of clinical onset of the disease. The number of these cells is as a rule less than 10 per cent of normal. Such B cells as are still present show the cytological si... | 10.1038/nrdp.2017.16 | This paper represents the hallmark investigation and rediscovery of insulitis in individuals who died shortly after the clinical diagnosis of T1DM. |
10.2337/db13-0300 | 103,896,263 | We analyzed demographic and genetic differences between children with various diabetes-associated autoantibodies reflecting the autoimmune process. In a prospective birth cohort comprising children with HLA-conferred susceptibility to type 1 diabetes (T1D), the pattern of autoantibody appearance was analyzed in 520 chi... | 10.1038/nrdp.2017.16 | This is the first investigation to dissect the temporal pattern of the first-appearing β-cell-targeting autoantibody as a biomarker of T1DM. |
10.1111/apm.12023 | 60,656,265 | Autoimmune and allergic diseases have become a major health problem in the Western world during past decades. The hygiene hypothesis suggests that decreased microbial exposure in childhood leads to increasing prevalence of these diseases. This review summarizes epidemiological evidence and current immunological knowled... | 10.1038/nrdp.2017.16 | Along with other studies by the same authors, this study demonstrates the importance of gene–environment interactions in the risk of developing both allergies and cell-specific autoimmune diseases such as T1DM. |
10.2337/diabetes.51.5.1346 | 20,528,657 | Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0–34 years. GADAs were associated... | 10.1038/nrdp.2017.16 | This major investigation of patients with newly diagnosed T1DM (1–34 years of age) demonstrates that the age-dependent onset of T1DM is strongly related to the presence of β-cell-targeting autoantibodies, which is associated with specific HLA-DR-DQ genotypes. |
10.1084/jem.194.4.393 | 19,718,473 | MHC class II (MHCII) molecules play a pivotal role in the induction and regulation of immune responses. The transcriptional coactivator class II transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice. These mice e... | 10.1038/nri1708 | This paper describes the generation of mice that lack pIV of the C2ta gene. It shows that this promoter is essential for driving IFN-γ-induced CIITA and MHC class II expression by non-haematopoietic cells but is dispensable for this function in macrophages. |
10.1101/gad.14.9.1156 | 133,915,560 | By virtue of its control over major histocompatibility complex class II (MHC-II) gene expression, CIITA represents a key molecule in the regulation of adaptive immune responses. It was first identified as a factor that is defective in MHC-II deficiency, a hereditary disease characterized by the absence of MHC-II expres... | 10.1038/nri1708 | This paper was the first to show that CIITA is physically recruited to the promoters of its target genes in vivo and in vitro through multiple protein–protein interactions with an enhanceosome complex formed by DNA-bound transcription factors. |
10.1182/blood-2002-06-1855 | 84,454,429 | Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4+ T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated ... | 10.1038/nri1708 | This paper shows that pIV of the C2ta gene is essential for driving positive selection of CD4 + T cells, because it is required for the induction of CIITA and MHC class II expression in TECs. |
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