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 |
|---|---|---|---|---|
10.1126/science.8016643 | 103,769,263 | Major histocompatibility complex (MHC) class II genes are expressed constitutively in only a few cell types, but they can be induced in the majority of them, in particular by interferon-γ (IFN-γ). The MHC class II transactivator gene CIITA is defective in a form of primary MHC class II deficiency. Here it is shown that... | 10.1038/nri1708 | This seminal paper was the first to show that IFN-γ-induced MHC class II expression is mediated by the induction of CIITA expression. |
10.4049/jimmunol.164.8.4143 | 99,473,470 | Abstract Inhibition of class II trans-activator (CIITA) expression prevents embryonic trophoblast cells from up-regulating MHC class II genes in response to IFN-γ. This is thought to be one mechanism of maternal tolerance to the fetal allograft. The CIITA gene is regulated by four distinct promoters; promoter III direc... | 10.1038/nri1708 | References 43 and 44 report that the gene encoding CIITA is irreversibly silenced in trophoblasts by DNA methylation of pIV. |
10.1128/mcb.19.1.431 | 2,578,282 | ABSTRACT The major histocompatibility complex (MHC) class II transactivator (CIITA) is the master regulatory factor required for appropriate expression of class II MHC genes. Understanding the expression of CIITA is key to understanding the regulation of class II MHC genes. This report describes the independent regulat... | 10.1038/nri1708 | This paper shows that pIII of the human CIITA gene can be induced by IFN-γ through a STAT1-dependent enhancer that is situated 5 kb upstream. |
10.4049/jimmunol.169.3.1326 | 122,745,993 | Abstract Class II transactivator (CIITA) is necessary for expression of class II MHC (MHC-II) molecules. In mice, CIITA expression is regulated by three promoters (pI, pIII, and pIV), producing types I, III, and IV CIITA. The relative roles of different CIITA types remain unclear. Unstimulated bone marrow-derived macro... | 10.1038/nri1708 | Together with reference 6, this detailed kinetic study of CIITA expression shows that transcription from pI is sustained in IFN-γ-stimulated macrophages, whereas pIV is induced only transiently. |
10.1128/mcb.22.13.4781-4791.2002 | 123,031,453 | ABSTRACT Chromatin immunoprecipitation assays were employed to assess the kinetics of transcription factor assembly and histone modifications that occur during gamma interferon (IFN-γ) induction of CIITA gene expression. CIITA is the master regulator of major histocompatibility complex class II transcription. Promoter ... | 10.1038/nri1708 | This paper reports a detailed time course of the events that lead to the activation of pIV by IFN-γ. |
10.4049/jimmunol.169.6.3112 | 28,999,363 | Abstract Although activated human T cells express MHC class II antigens, the regulation of these antigens in T cells is poorly understood. This study focuses on the control of the MHC2TA gene in these cells. MHC2TA encodes the transcriptional master regulator of MHC class II, the class II trans-activator (CIITA). It ha... | 10.1038/nri1708 | References 98 and 99 establish that pIII of the CIITA gene drives CIITA and MHC class II expression by human T cells. |
10.1182/blood-2004-03-0790 | 20,037,635 | Abstract In B cells, expression of CIITA and resulting major histocompatibility complex II (MHCII) is mediated exclusively by promoter III (CIITA-PIII) activation. Recent studies have established that CIITA-PIII also participates in the expression of CIITA in activated human T cells, dendritic cells, and monocytes. In ... | 10.1038/nri1708 | This paper shows that the B-cell-specific activity of pIII of the CIITA gene can be attributed to binding of the transcription factors E47, IRF4 and PU.1. |
10.1084/jem.188.3.597 | 38,558,188 | The requirement for major histocompatibility complex class II (MHC II) to initiate immune renal injury was studied in a murine model of CD4+ T cell–dependent crescentic glomerulonephritis (GN). C57BL/6 (MHC II+/+) mice developed crescentic GN with glomerular CD4+ T cell infiltration and renal injury, in response to a n... | 10.1038/nri1708 | This paper provides convincing evidence that MHC class II expression in renal tissues is required for the development of experimental glomerulonephritis in mice. |
10.1046/j.1365-2958.2003.03715.x | 125,215,042 | Summary Phenotypic heterogeneity describes non‐genetic variation that exists between individual cells within isogenic populations. The basis for such heterogeneity is not well understood, but it is evident in a wide range of cellular functions and phenotypes and may be fundamental to the fitness of microorganisms. Here... | 10.1038/nrmicro1460 | Showsthat heterogeneous copper resistance in S. cerevisiae is driven by cell cycle- and age-regulated activity of the Cu,Zn-superoxide dismutase. |
10.1128/jb.183.15.4614-4625.2001 | 17,609,697 | ABSTRACT Five histone deacetylase genes ( HDA1, RPD3, HOS1, HOS2, and HOS3 ) have been cloned from Candida albicans and characterized. Sequence analysis and comparison with 17 additional deacetylases resulted in a phylogenetic tree composed of three major groups. Transcription of the deacetylases HDA1 and RPD3 is down-... | 10.1038/nrmicro1460 | Establishes a link between histone deacetylation and the frequency of switches between colony morphologies in the pathogen C. albicans |
10.1128/jb.186.24.8172-8180.2004 | 62,643,827 | ABSTRACT Bacterial populations produce persisters, cells that neither grow nor die in the presence of bactericidal agents, and thus exhibit multidrug tolerance (MDT). The mechanisms of MDT and the nature of persisters have remained elusive. Our previous research has shown that persisters are largely responsible for the... | 10.1038/nrmicro1460 | Provides evidence indicating that variability in the activity of cellular functions that are normally corrupted by antibiotics could give rise to occasional persister cells, which might ensure survival of the population. |
10.1126/science.1080418 | 40,818,581 | Carbonylated proteins were visualized in single cells of the budding yeast Saccharomyces cerevisiae , revealing that they accumulate with replicative age. Furthermore, carbonylated proteins were not inherited by daughter cells during cytokinesis. Mother cells of a yeast strain lacking the sir2 gene, a life-span determi... | 10.1038/nrmicro1460 | Shows that oxidatively damaged proteins are preferentially retained in yeast mother cells during division, so creating cell-to-cell heterogeneity in oxidative burden. |
10.1101/gad.1373905 | 123,208,219 | We have discovered that cells of Bacillus subtilis at the mid-exponential phase of growth are a mixed population of two strikingly different cell types. One type is single swimming cells (or cell doublets) in which the transcription factor for motility, σ D , is active (σ D ON). The other type is long chains of sessile... | 10.1038/nrmicro1460 | Characterizes part of the regulatory mechanism that determines whether individual cells of B. subtilis adopt a motile or sessile type. |
10.1111/j.1365-2958.2005.04488.x | 45,418,641 | Summary In Bacillus subtilis competence for genetic transformation develops only in a subpopulation of cells in an isogenic culture. The molecular mechanisms underlying this phenotypic heterogeneity are unknown. In this study, we stepwise simplify the signal transduction cascade leading to competence, yielding a strain... | 10.1038/nrmicro1460 | References 117 and 118 show that autostimulation of the ComK transcription factor is required for bistability of competence development in B. subtilis |
10.1126/science.2326648 | 59,388,090 | The mechanism by which erythropoietin controls mammalian erythrocyte production is unknown. Labeling experiments in vitro with [ 3 H]thymidine demonstrated DNA cleavage in erythroid progenitor cells that was accompanied by DNA repair and synthesis. Erythropoietin reduced DNA cleavage by a factor of 2.6. In the absence ... | 10.1038/nrc1648 | Erythropoietin is a survival factor for late erythroid progenitor cells. |
10.1084/jem.193.2.247 | 103,024,769 | The cysteine proteases known as caspases play a central role in most apoptotic pathways. Here, we show that caspase inhibitors arrest the maturation of human erythroid progenitors at early stages of differentiation, before nucleus and chromatin condensation. Effector caspases such as caspase-3 are transiently activated... | 10.1038/nrc1648 | Controlled activation of a death effector protease is essential for completion of erythroid differentiation. |
10.1182/blood.v93.3.796 | 81,513,029 | Abstract The possible involvement of Fas and Fas ligand (FasL) in the regulation of erythropoiesis was evaluated. Immunohistochemistry of normal bone marrow specimens revealed that several immature erythroblasts undergo apoptosis in vivo. Analysis of bone marrow erythroblasts and purified progenitors undergoing uniline... | 10.1038/nrc1648 | Differential regulation of FAS and its ligand during erythroid differentiation. |
10.1073/pnas.92.12.5258 | 38,227,220 | Epidemiological evidence indicates that avoidance of smoking, increased consumption of fruits and vegetables, and control of infections will have a major effect on reducing rates of cancer. Other factors include avoidance of intense sun exposure, increases in physical activity, and reduction of alcohol consumption and ... | 10.1038/nrc2090 | This paper describes the main environmental causes of cancer and the molecular mechanisms by which they function. |
10.1111/j.1349-7006.2004.tb03205.x | 125,091,825 | Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been ... | 10.1038/nrc2090 | This paper reviews the intriguing discovery of highly mutagenic and carcinogenic compounds formed during the high-temperature cooking of meats. |
10.1126/science.274.5291.1371 | 104,182,053 | Despite its high prevalence, very little is known regarding genetic predisposition to prostate cancer. A genome-wide scan performed in 66 high-risk prostate cancer families has provided evidence of linkage to the long arm of chromosome 1 (1q24-25). Analysis of an additional set of 25 North American and Swedish families... | 10.1038/nrc2090 | This is the first report in which, using a genome-wide scanning approach, a major prostate cancer-susceptibility gene was identified. |
10.1073/pnas.0506655103 | 41,707,441 | The microbiota of the human stomach and the influence of Helicobacter pylori colonization on its composition remain largely unknown. We characterized bacterial diversity within the human gastric mucosa by using a small subunit 16S rDNA clone library approach and analyzed 1,833 sequences generated by broad-range bacteri... | 10.1038/nrc2857 | A seminal study that used molecular techniques to define the gastric microbiome. |
10.1126/science.1086871 | 62,392,534 | Helicobacter pylori ( Hp ) vacuolating cytotoxin VacA induces cellular vacuolation in epithelial cells. We found that VacA could efficiently block proliferation of T cells by inducing a G 1 /S cell cycle arrest. It interfered with the T cell receptor/interleukin-2 (IL-2) signaling pathway at the level of the Ca 2 + -ca... | 10.1038/nrc2857 | This study demonstrated that a previously identified virulence factor could also suppress the immune response to H. pylori |
10.1126/science.287.5457.1497 | 82,918,880 | The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen ( cagA + ) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the... | 10.1038/nrc2857 | One of the first studies to demonstrate that H. pylori has the capacity to translocate a bacterial protein into host cells. |
10.1073/pnas.0711183105 | 38,415,965 | Infection with cagA -positive Helicobacter pylori is associated with gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma of B cell origin. The cagA -encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylat... | 10.1038/nrc2857 | A remarkable study demonstrating that transgenic expression of CagA in mice can lead to carcinoma, in the absence of co-existing gastritis. |
10.1126/science.1081919 | 17,559,733 | Helicobacter pylori translocates the protein CagA into gastric epithelial cells and has been linked to peptic ulcer disease and gastric carcinoma. We show that injected CagA associates with the epithelial tight-junction scaffolding protein ZO-1 and the transmembrane protein junctional adhesion molecule, causing an ecto... | 10.1038/nrc2857 | An insightful study demonstrating the ability of CagA to aberrantly disrupt apical-junctional complexes. |
10.1126/science.1099513 | 81,169,529 | Epithelial cancers are believed to originate from transformation of tissue stem cells. However, bone marrow–derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. We show that although acute injury, acute inflammation, or ... | 10.1038/nrc2857 | This article shifted the paradigm for understanding gastric carcinogenesis by demonstrating the ability of BMDCs to undergo malignant degeneration in the context of chronic gastric inflammation. |
10.1126/science.8465201 | 41,379,681 | The human BTF2 basic transcription factor (also called TFIIH), which is similar to the δ factor in rat and factor b in yeast, is required for class II gene transcription. A strand displacement assay was used to show that highly purified preparation of BTF2 had an adenosine triphosphate-dependent DNA helicase activity, ... | 10.1038/nrm3350 | Demonstrated that the helicase XPB, which is involved in NER, is closely associated with the TFIIH transcription complex, suggesting that DNA repair and transcription are functionally related. |
10.1073/pnas.86.19.7356 | 123,244,593 | A transcription factor required for synthesis of accurately initiated run-off transcripts by RNA polymerase II has been purified and shown to have an associated DNA-dependent ATPase (dATPase) activity that is strongly stimulated by the TATA region of promoters. This transcription factor, designated delta, was purified ... | 10.1038/nrm3350 | Reported the purification of a transcription factor from rat liver that was designated transcription factor-δ, which has an associated DNA-dependent ATPase activity. |
10.1126/science.1113329 | 62,604,554 | MicroRNAs are small RNA molecules that regulate messenger RNA (mRNA) expression. MicroRNA 122 (miR-122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs. A genetic interact... | 10.1038/ni.2537 | This is the first report showing that a host cellular miRNA is critical for viral replication |
10.1073/pnas.0506648102 | 83,369,373 | There is increasing concern regarding radiation-related second-cancer risks in long-term radiotherapy survivors and a corresponding need to be able to predict cancer risks at high radiation doses. Although cancer risks at moderately low radiation doses are reasonably understood from atomic bomb survivor studies, there ... | 10.1038/nrc3069 | An excellent model of risk at high doses, which is important for radiotherapy. |
10.1073/pnas.0804186105 | 58,602,378 | The central dogma of radiation biology, that biological effects of ionizing radiation are a direct consequence of DNA damage occurring in irradiated cells, has been challenged by observations that genetic/epigenetic changes occur in unexposed “bystander cells” neighboring directly-hit cells, due to cell-to-cell communi... | 10.1038/nrc3069 | Evidence from an animal model that cancer in distal organs can be caused by a non-targeted (bystander) effect and not low dose, stray radiation. |
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/nri2765 | This study shows that genetic deficiency of SYK or SLP76 leads to defective separation of blood and lymphatic vessels. |
10.1002/jcb.10694 | 29,139,853 | Abstract Osteoclasts are macrophage derived cells and as such are subject to regulation by molecules impacting other members of the immune system. Dap12 is an adaptor protein expressed by NK cells and B and T lymphocytes. Dap12 also mediates maturation of myeloid cells and is expressed by osteoclasts which are dysfunct... | 10.1038/nri2765 | This paper with references 5 and 132 show that SYK activation through DAP12 and FcRγ is required for osteoclast development and bone resorption. |
10.1182/blood-2009-04-216069 | 83,007,639 | Abstract During embryonic development, lymph sacs form from the cardinal vein, and sprout centrifugally to form mature lymphatic networks. Separation of the lymphatic from the blood circulation by a hitherto unknown mechanism is essential for the homeostatic function of the lymphatic system. O-glycans on the lymphatic ... | 10.1038/nri2765 | Together with references 138 and 139, this study describes a podoplanin–CLEC2–SLP76-mediated platelet signalling pathway required for separation of blood and lymphatic vessels. |
10.1002/art.27438 | 123,981,879 | Abstract Objective The Syk tyrosine kinase plays an important role in diverse functions in hematopoietic lineage cells. Although previous in vitro and pharmacologic analyses suggested Syk to be a possible player in the development of autoimmune arthritis, no in vivo genetic studies addressing that issue have yet been r... | 10.1038/nri2765 | This study provides the first genetic evidence for the role of SYK in an animal model of a major human disease (rheumatoid arthritis). |
10.1182/blood-2009-08-236471 | 62,331,491 | Abstract Certain malignant B cells rely on B-cell receptor (BCR)–mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fosta... | 10.1038/nri2765 | This paper and reference 151 report the results of the first human clinical trials with the SYK inhibitor fostamatinib, showing clinical benefit in rheumatoid arthritis (in reference 151) and B cell malignancies (in reference 166). |
10.1111/jcpp.12432 | 103,143,698 | Background Tourette syndrome ( TS ) is a common tic disorder in children and adolescents. There is preliminary evidence that herbal medicine may possess the potential to treat tics. The purpose of this study was to formally evaluate the efficacy and safety of 5‐Ling Granule (5‐ LG r), a proprietary polyherbal product, ... | 10.1038/nrdp.2016.97 | This is the largest randomized, double-blind, clinical trial ever completed for individuals 5–18 years of age with GTS ( n = 603). |
10.1111/j.1365-2958.2010.07218.x | 100,339,744 | Summary Drug resistance in Mycobacterium tuberculosis is a global problem, with major consequences for treatment and public health systems. As the emergence and spread of drug‐resistant tuberculosis epidemics is largely influenced by the impact of the resistance mechanism on bacterial fitness, we wished to investigate ... | 10.1038/nrg3922 | Reconstructed the resistance genotypes of clinical strains in an isogenic background, revealing a pathway for resistance development that suggests that compensatory evolution contributes to drug-resistant TB. |
10.1126/science.285.5434.1745 | 83,455,545 | In asexual populations, beneficial mutations that occur in different lineages compete with one another. This phenomenon, known as clonal interference, ensures that those beneficial mutations that do achieve fixation are of large effect. Clonal interference also increases the time between fixations, thereby slowing the ... | 10.1038/nrg3922 | Measured the effects of clonal interference in an asexual RNA virus and quantified the rates and effects of beneficial mutations. |
10.1126/science.283.5400.404 | 82,679,392 | Mutator genotypes with increased mutation rates may be especially important in microbial evolution if genetic adaptation is generally limited by the supply of mutations. In experimental populations of the bacterium Escherichia coli , the rate of evolutionary adaptation was proportional to the mutation supply rate only ... | 10.1038/nrg3922 | Showed that the rate of evolutionary adaptation is proportional to mutation supply rate only in particular circumstances of small or well-adapted populations. |
10.1126/science.1123539 | 125,319,919 | Five point mutations in a particular β-lactamase allele jointly increase bacterial resistance to a clinically important antibiotic by a factor of ∼100,000. In principle, evolution to this high-resistance β-lactamase might follow any of the 120 mutational trajectories linking these alleles. However, we demonstrate that ... | 10.1038/nrg3922 | Analysis of the multistep evolution of high-level resistance to β-lactamases reveals that only a few evolutionary trajectories are accessible and consequently that much of evolution may be reproducible and even predictable. |
10.1128/aac.00410-06 | 60,203,184 | ABSTRACT Vancomycin resistance of Staphylococcus aureus NY-VRSA and VRSA-5 is due to acquisition of a vanA operon located in a Tn 1546 -like element. The vanA gene cluster of NY-VRSA contained one copy of insertion sequences IS 1251 and IS 1216V relative to that of VRSA-5. As evidenced by the nature of the late peptido... | 10.1038/nrg3922 | Revealed and explained the basis for an unexpected and potentially useful synergy between unrelated antibiotics against MRSA. |
10.1126/scitranslmed.3006609 | 81,388,328 | Elucidation of complex collateral sensitivity networks provides rationale for new sequential drug deployment strategies that restrain antibiotic resistance development. | 10.1038/nrg3922 | Combined experimental evolution and genome sequencing to map cross-resistance interactions between antibiotics in E. coli and derive common evolutionary principles. |
10.1038/ncomms5352 | 62,202,041 | Abstract Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli ... | 10.1038/nrg3922 | Experimentally showed the prevalence of collateral sensitivity, a potentially novel therapeutic paradigm for the cyclic use of drugs to treat infectious diseases and cancer. |
10.1073/pnas.111085598 | 20,817,149 | RNA viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in RNA virus populations. A high mutation frequency is a central tenet of the quasispecies theory. A corollary of the quasispecies theory postulates that, given their high mutation frequency, animal RNA vi... | 10.1038/nrg3922 | Show experimentally that RNA virus mutagens can effectively cause a loss of viral viability and may represent a promising class of antiviral drugs. |
10.1073/pnas.96.23.13180 | 39,600,180 | Members of the myc family of nuclear protooncogenes play roles in cell proliferation, differentiation, and apoptosis. Moreover, inappropriate expression of c- myc genes contributes to the development of many types of cancers, including B cell lymphomas in humans. Although Myc proteins have been shown to function as tra... | 10.1038/nrm1551 | Shows the ability of Myc to promote protein synthesis and increase the size of B cells. |
10.1128/mcb.18.8.4463 | 59,735,379 | ABSTRACT The macrolide antibiotic rapamycin inhibits cellular proliferation by interfering with the highly conserved TOR (for target of rapamycin) signaling pathway. Growth arrest of budding yeast cells treated with rapamycin is followed by the program of molecular events that characterizes entry into G 0 (stationary p... | 10.1038/nrm1551 | Shows that transcription by Pol I and Pol III is regulated by the TOR pathway. |
10.1073/pnas.230224097 | 58,490,476 | Most transformed cells display abnormally high levels of RNA polymerase (pol) III transcripts. Although the full significance of this is unclear, it may be fundamental because healthy cells use two key tumor suppressors to restrain pol III activity. We present the first evidence that a pol III transcription factor is o... | 10.1038/nrm1551 | First demonstration that a Pol-III-specific transcription factor is consistently overexpressed in tumours. |
10.1128/mcb.21.13.4246-4255.2001 | 125,071,140 | ABSTRACT Bop1 is a novel nucleolar protein involved in rRNA processing and ribosome assembly. We have previously shown that expression of Bop1Δ, an amino-terminally truncated Bop1 that acts as a dominant negative mutant in mouse cells, results in inhibition of 28S and 5.8S rRNA formation and deficiency of newly synthes... | 10.1038/nrm1551 | Shows that a defect in rRNA production can trigger a potent p53-mediated cell-cycle arrest. |
10.1084/jem.20050678 | 83,457,363 | Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and vertebrates. To test the requirement for Dicer in cell-lineage decisions in a mammalian organism, we have generated a conditio... | 10.1038/nri3494 | This study provides the first evidence that miRNAs are important regulators of T H cell differentiation. |
10.4049/jimmunol.1103171 | 60,321,537 | Abstract Th cell programming and function is tightly regulated by complex biological networks to prevent excessive inflammatory responses and autoimmune disease. The importance of microRNAs (miRNAs) in this process is highlighted by the preferential Th1 polarization of Dicer-deficient T cells that lack miRNAs. Using ge... | 10.1038/nri3494 | References 31, 34 and 35 show that miR-29 is an important regulator of IFNγ production in T H 1 cells. |
10.1126/science.1139253 | 19,011,092 | MicroRNAs are a class of small RNAs that are increasingly being recognized as important regulators of gene expression. Although hundreds of microRNAs are present in the mammalian genome, genetic studies addressing their physiological roles are at an early stage. We have shown that mice deficient for bic/microRNA-155 ar... | 10.1038/nri3494 | References 53 and 54 were the first to show that genetic disruption of a single miRNA in vivo can have adverse effects on immune cell homeostasis and function. |
10.1084/jem.20081062 | 80,874,417 | Regulatory T (T reg) cells are indispensable for preventing autoimmunity. Incumbent to this role is the ability of T reg cells to exert their suppressor function under inflammatory conditions. We found that T reg cell–mediated tolerance is critically dependent on the Dicer-controlled microRNA (miRNA) pathway. Depletion... | 10.1038/nri3494 | References 30, 117 and 118 describe that miRNA expression in T Reg cells is required to prevent autoimmunity. |
10.1186/1741-7015-6-6 | 88,059,943 | Abstract Background Based on a large, representative unscreened cohort from Malmö, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this associatio... | 10.1038/nrc2351 | This paper shows that a single PSA test taken at or before age 50 is a strong predictor of advanced prostate cancer diagnosed up to 25 years later, with advanced cancer defined as cancer that is locally advanced or metastatic at the time of diagnosis. |
10.1111/j.1541-0420.2007.00825.x | 100,635,770 | Summary The introduction of the prostate‐specific antigen (PSA) test has led to dramatic changes in the incidence of prostate cancer in the United States. In this article, we use information on the increase and subsequent decline in prostate cancer incidence following the adoption of PSA to estimate the lead time assoc... | 10.1038/nrc2351 | This study provides estimates of lead time and rates of overdiagnosis of prostate cancer resulting from PSA testing, based on trends in the incidence of prostate cancer. |
10.1126/science.1224820 | 41,757,817 | Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-s... | 10.1038/nrc3611 | This article shows the genotoxic and tumour-promoting potential of a pathobiont of the commensal microflora that blooms under inflammatory conditions. |
10.1126/science.aag0299 | 20,662,836 | Assessing smoke damage in cancer genomes We have known for over 60 years that smoking tobacco is one of the most avoidable risk factors for cancer. Yet the detailed mechanisms by which tobacco smoke damages the genome and creates the mutations that ultimately cause cancer are still not fully understood. Alexandrov et a... | 10.1038/nrc.2017.87 | This reference describes that smoking is associated with an increased mutation burden and with multiple distinct mutational signatures. |
10.1126/science.6274023 | 18,862,293 | A specific, acquired chromosomal abnormality (deletion 3p) has been found in at least one chromosome 3 in 100 percent of the metaphases in 12 of 12 cell lines cultured from human small-cell lung cancer tissue and in 2-day tumor culture specimens from three patients. Analysis of the shortest region of overlap shows the ... | 10.1038/nrc.2017.87 | The finding that most SCLC cells contain extensive deletions of the short arm of chromosome 3 is first reported in this article. |
10.1158/1535-7163.mct-16-0298 | 121,988,020 | Abstract Small-cell lung cancer (SCLC) cells have rapid proliferation, universal Rb inactivation, and high rates of MYC family amplification, making aurora kinase inhibition a natural target. Preclinical studies have demonstrated activity for Aurora A and pan-Aurora inhibitors with some relationship to MYC family expre... | 10.1038/nrc.2017.87 | This report finds that Aurora kinase inhibitors inhibit the growth of SCLC cell lines with MYC family amplification, offering a promising therapeutic approach. |
10.1126/science.285.5425.221 | 62,422,299 | The specialized junction between a T lymphocyte and an antigen-presenting cell, the immunological synapse, consists of a central cluster of T cell receptors surrounded by a ring of adhesion molecules. Immunological synapse formation is now shown to be an active and dynamic mechanism that allows T cells to distinguish p... | 10.1038/nri2688 | References 50 and 51 describe the first observations of the immunological synapse. |
10.1073/pnas.71.10.4135 | 62,296,148 | The specificity with which the genetic code is read in protein synthesis, and with which other highly specific biosynthetic reactions take place, can be increased above the level available from free energy differences in intermediates or kinetic barriers by a process defined here as kinetic proofreading. A simple kinet... | 10.1038/nri2688 | References 54 and 55 pioneered the concept of kinetic proofreading and its application to TCR signalling. |
10.1126/science.1086507 | 81,538,970 | The immunological synapse is a specialized cell-cell junction between T cell and antigen-presenting cell surfaces. It is characterized by a central cluster of antigen receptors, a ring of integrin family adhesion molecules, and temporal stability over hours. The role of this specific organization in signaling for T cel... | 10.1038/nri2688 | In this report, complementary computational and experimental approaches were used to dissect signalling in the immunological synapse. |
10.1111/j.1471-4159.1990.tb01236.x | 20,787,815 | Abstract: To provide an “in vitro” system for studying brain capillary function, we have developed a process ofcoculture that closely mimics the “in vivo” situation by culturing brain capillary endothelial cells on one side of a filter and astrocytes on the other. Under these conditions, endothelial cells retain all th... | 10.1038/nrd2368 | One of the earliest papers describing a reproducible method for developing a BBB co-culture model with brain endothelial and glial cells that could be used in the pharmaceutical industry. Besides its use as BBB permeability and transport screen, the model has also been used in mechanistic studies in physiological and p... |
10.1083/jcb.138.4.877 | 103,897,571 | Lipoprotein transport across the blood–brain barrier (BBB) is of critical importance for the delivery of essential lipids to the brain cells. The occurrence of a low density lipoprotein (LDL) receptor on the BBB has recently been demonstrated. To examine further the function of this receptor, we have shown using an in ... | 10.1038/nrd2368 | One of the first papers describing trancytosis of LDL across the BBB in vitro |
10.1126/science.1067568 | 125,254,979 | The deposition of amyloid-β (Aβ) peptides into amyloid plaques precedes the cognitive dysfunction of Alzheimer's disease (AD) by years. Biomarkers indicative of brain amyloid burden could be useful for identifying individuals at high risk for developing AD. As in AD in humans, baseline plasma Aβ levels in a transgenic ... | 10.1038/nrd2368 | References 111–114 demonstrate transport of Aβ across the blood–brain barrier from blood-to-brain and from brain-to-blood indicating the importance of kinetic and dynamic considerations in the study of Aβ accumulation in brain. |
10.1182/blood.v106.11.1575.1575 | 94,775,923 | Abstract Proteasome inhibitors are a new class of drugs that have shown to be cytotoxic and induce apoptosis in tumor cells, particularly, multiple myeloma (MM). This led to the clinical evaluation and subsequent FDA approval of the proteasome inhibitor, bortezomib, for the treatment of refractory and relapsed multiple... | 10.1038/nrc3139 | This study showed that the proteasome inhibitor PS-341 directly inhibits proliferation and induces apoptosis of human multiple myeloma cell lines and multiple myeloma cells from isolated patients, indicating the possibility of the use of PS-341 as a drug for targeting multiple myeloma. |
10.1073/pnas.1101544108 | 16,791,030 | TRIM24 (TIF1α), TRIM28 (TIF1β), and TRIM33 (TIF1γ) are three related cofactors belonging to the tripartite motif superfamily that interact with distinct transcription factors. TRIM24 interacts with the liganded retinoic acid (RA) receptor to repress its transcriptional activity. Germ line inactivation of TRIM24 in mice... | 10.1038/nrc3139 | The paper showed that hepatocellular carcinoma induced by TRIM24 inactivation is enhanced by further loss of TRIM33, suggesting that TRIM33 functions as a tumour suppressor in collaboration with TRIM24. |
10.1083/jcb.147.2.221 | 19,692,081 | Nuclear domain 10 (ND10), also referred to as nuclear bodies, are discrete interchromosomal accumulations of several proteins including promyelocytic leukemia protein (PML) and Sp100. In this study, we investigated the mechanism of ND10 assembly by identifying proteins that are essential for this process using cells li... | 10.1038/nrc3139 | This study demonstrated that as NBs are dispersed in PML −/− cells, PML is responsible for the proper localization of all other NB-associated proteins and that a dynamic mechanism for protein recruitment to NBs is controlled by the SUMO1 modification state of PML. |
10.1073/pnas.0813177106 | 104,263,012 | Numerous studies focus on the tumor suppressor p53 as a protector of genomic stability, mediator of cell cycle arrest and apoptosis, and target of mutation in 50% of all human cancers. The vast majority of information on p53, its protein-interaction partners and regulation, comes from studies of tumor-derived, cultured... | 10.1038/nrc3139 | Mass spectrometric analysis of a p53 complex showed that TRIM24 interacts with p53 and mediates ubiquitylation of p53, followed by negative regulation of p53 level. |
10.1002/gcc.20046 | 40,838,774 | Abstract Our group previously identified two novel genes, RFP2/LEU5 and DLEU2 , within a 13q14.3 genomic region of loss seen in various malignancies. However, no specific inactivating mutations were found in these or other genes in the vicinity of the deletion, suggesting that a nonclassical tumor‐suppressor mechanism ... | 10.1038/nrc3139 | This paper showed that DLEU2 encodes a putative non-classical antisense RNA with one exon directly overlapping the first exon of TRIM13 in the opposite orientation, suggesting that antisense RNA from DLEU2 regulates the expression level of TRIM13. |
10.1002/art.24567 | 102,881,896 | Abstract Objective To determine the efficacy, safety, and tolerability of 3 different dosages of CP‐690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response. Methods Patients (n = ... | 10.1038/nrd3264 | References 89–92 describe a series of randomized, double-blind Phase II studies demonstrating remarkable activity of the potent JAK inhibitor tasocitinib (CP 690550) in patients with rheumatoid arthritis. |
10.1182/blood-2009-04-215848 | 39,153,834 | Abstract A somatic point mutation (V617F) in the JAK2 tyrosine kinase was found in a majority of patients with polycythemia vera (PV), essential thrombocythemia, and primary myelofibrosis. However, contribution of the JAK2V617F mutation in these 3 clinically distinct myeloproliferative neoplasms (MPNs) remained unclear... | 10.1038/nrd3264 | References 152 and 153 describe mouse models of JAK2V617F-positive MPNs in which the mutant JAK2V617F is expressed from its endogenous promoter, and the authors suggest that JAK2 inhibitor therapy does not eradicate the disease-initiating cells. |
10.1083/jcb.200901145 | 104,425,184 | The trans-Golgi network (TGN) is the major sorting station in the secretory pathway of all eukaryotic cells. How the TGN sorts proteins and lipids to generate the enrichment of sphingolipids and sterols at the plasma membrane is poorly understood. To address this fundamental question in membrane trafficking, we devised... | 10.1038/nrm2977 | The first direct experimental support for a post-Golgi raft pathway that transports proteins towards the plasma membrane. |
10.1073/pnas.0611357104 | 83,329,858 | The membrane raft hypothesis postulates the existence of lipid bilayer membrane heterogeneities, or domains, supposed to be important for cellular function, including lateral sorting, signaling, and trafficking. Characterization of membrane lipid heterogeneities in live cells has been challenging in part because inhomo... | 10.1038/nrm2977 | Shows the presence of liquid-ordered-like and liquid-disordered-like phases in plasma membrane vesicles containing native lipids and proteins. |
10.1073/pnas.0804374105 | 123,984,879 | Cell membranes are not randomly organized, but rather are populated by fluctuating nanoassemblies of increased translational order termed lipid rafts. This lateral heterogeneity can be biophysically extended because cooling formaldehyde-isolated plasma membrane preparations results in separation into phases similar to ... | 10.1038/nrm2977 | Shows that inflated plasma membranes can separate into large-scale domains at 37°C following cholera toxin cross-linking. |
10.1083/jcb.200609174 | 17,778,419 | The signaling mechanisms for glycosylphosphatidylinositol-anchored receptors (GPI-ARs) have been investigated by tracking single molecules in living cells. Upon the engagement or colloidal gold–induced cross-linking of CD59 (and other GPI-ARs) at physiological levels, CD59 clusters containing three to nine CD59 molecul... | 10.1038/nrm2977 | This paper introduced the STALL concept of GPI-anchored protein signalling, which shows that clusters undergoing STALL generate short-lived, digital-like signalling bursts. |
10.1126/science.1062245 | 121,959,963 | The transthyretin (TTR) amyloid diseases, representative of numerous misfolding disorders, are of considerable interest because there are mutations that cause or suppress disease. The Val 30 → Met 30 (V30M) TTR mutation is the most prevalent cause of familial amyloid polyneuropathy in heterozygotes, whereas a Thr 119 →... | 10.1038/nrd769 | This manuscript shows the molecular basis of interallelic trans-suppression of misfolding. Incorporation of T119M subunits into a tetramer also composed of disease-associated subunits stabilizes the tetramer and slows rate-limiting dissociation. |
10.1073/pnas.241406698 | 100,904,463 | The amyloidoses are a large group of protein misfolding diseases. Genetic and biochemical evidence support the hypothesis that amyloid formation from wild-type or 1 of 80 sequence variants of transthyretin causes the human amyloid diseases senile systemic amyloidosis or familial amyloid polyneuropathy, respectively. Th... | 10.1038/nrd769 | This publication shows that ligands that bind to amyloidogenic proteins can have a dramatic influence on amyloidogenicity. More than seventy gene products control the two ligands that bind to TTR. |
10.1002/cncr.11671 | 60,702,650 | Abstract BACKGROUND Mucositis is a common but poorly studied problem among patients with solid tumors. The authors examined the clinical and economic outcomes of oral and gastrointestinal (GI) mucositis among patients receiving myelosuppressive chemotherapy. METHODS A retrospective, random sample of 599 patients who de... | 10.1038/nrc1318 | The clinical and economic impact of mucositis following myeloablative chemotherapy is significant among patients who are treated for common solid tumours. |
10.1126/science.1060191 | 61,470,174 | Gastrointestinal (GI) tract damage by chemotherapy or radiation limits their efficacy in cancer treatment. Radiation has been postulated to target epithelial stem cells within the crypts of Lieberkühn to initiate the lethal GI syndrome. Here, we show in mouse models that microvascular endothelial apoptosis is the prim... | 10.1038/nrc1318 | The endothelium, not the epithelium, is the primary initiator of radiation-induced mucosal injury. |
10.1126/science.1130563 | 41,075,782 | The evolutionarily conserved actin-related protein (Arp2/3) complex is a key component of actin filament networks that is dynamically regulated by nucleation-promoting and inhibitory factors. Although much is known about actin assembly, the physiologic functions of inhibitory proteins are unclear. We generated coronin ... | 10.1038/nri3465 | This paper shows that deletion of coronin 1 in mice results in peripheral T cell deficiency. |
10.1084/jem.20100876 | 123,430,780 | Cyclin-dependent kinase 5 (Cdk5) is a ubiquitously expressed serine/threonine kinase. However, a requirement for Cdk5 has been demonstrated only in postmitotic neurons where there is abundant expression of its activating partners p35 and/or p39. Although hyperactivation of the Cdk5–p35 complex has been found in a varie... | 10.1038/nri3465 | References 83, 85 and 86 characterize the role of coronin 1 in the development of EAE. |
10.1038/embor.2009.197 | 38,820,925 | Nuclear factor (NF)‐κB is a positive regulator of tumour development and progression, but how it functions in normal cells leading to oncogenesis is not clear. As cellular senescence has proven to be an intrinsic tumour suppressor mechanism that cells must overcome to establish deregulated growth, we used primary fibro... | 10.1038/nrc3204 | This paper demonstrates that loss of RELA results in genomic instability and reduced DNA repair after damage, adding to the number of potentially tumour-suppressing characteristics of NF-κB. |
10.1101/gad.17620611 | 122,288,959 | In malignancies, enhanced nuclear factor-κB (NF-κB) activity is largely viewed as an oncogenic property that also confers resistance to chemotherapy. Recently, NF-κB has been postulated to participate in a senescence-associated and possibly senescence-reinforcing cytokine response, thereby suggesting a tumor-restrainin... | 10.1038/nrc3204 | References 100 and 101 both identify tumour suppressor-like characteristics of RELA and NF-κB associated with the induction of senescence. |
10.4049/jimmunol.176.4.2079 | 122,526,460 | Abstract Whether tissue microenvironment influences memory CD8 T cell differentiation is unclear. We demonstrate that virus-specific intraepithelial lymphocytes in gut resemble neither central nor effector memory CD8 T cells isolated from spleen or blood. This unique phenotype arises in situ within the gut, suggesting ... | 10.1038/nri3442 | This study showed that the tissue microenvironment influences T cell differentiation in situ |
10.4049/jimmunol.1102243 | 40,758,064 | Abstract We identify in this article a new class of lung tissue-resident memory CD4 T cells that exhibit tissue tropism and retention independent of Ag or inflammation. Tissue-resident memory CD4 T cells in the lung did not circulate or emigrate from the lung in parabiosis experiments, were protected from in vivo Ab la... | 10.1038/nri3442 | References 104, 105 and 107 show that resident T EM cells positioned within non-lymphoid tissues accelerate pathogen control upon local re-infection. |
10.1084/jem.187.10.1721 | 16,745,313 | Itk, a Tec family tyrosine kinase, plays an important but as yet undefined role in T cell receptor (TCR) signaling. Here we show that T cells from Itk-deficient mice have a TCR-proximal signaling defect, resulting in defective interleukin 2 secretion. Upon TCR stimulation, Itk−/− T cells release normal amounts of calci... | 10.1038/nri1591 | This paper was the first to describe the Ca 2+ -mobilization defect after TCR stimulation of T cells from Itk −/− mice. |
10.1126/science.284.5414.638 | 122,101,226 | T cell receptor (TCR) signaling requires activation of Zap-70 and Src family tyrosine kinases, but requirements for other tyrosine kinases are less clear. Combined deletion in mice of two Tec kinases, Rlk and Itk, caused marked defects in TCR responses including proliferation, cytokine production, and apoptosis in vitr... | 10.1038/nri1591 | This study shows that T cells from mice that are deficient in both RLK and ITK have more severe cellular defects than do ITK-deficient T cells, indicating that there is genetic redundancy between the TEC-family kinases. |
10.4049/jimmunol.170.10.5056 | 57,942,617 | Abstract Allergic asthma patients manifest airway inflammation and some show increases in eosinophils, TH2 cells, and cytokines, increased mucous production in the lung, and elevated serum IgE. This TH2-type response suggests a prominent role for TH2 cells and their cytokines in the pathology of this disease. The Tec f... | 10.1038/nri1591 | This study shows that ITK is important for the pathology of allergic asthma, a T H 2-cell-mediated response. |
10.1034/j.1600-065x.2003.00032.x | 103,272,632 | Summary: Vav1 is a 95‐kDa protein expressed in all hemopoietic cells that becomes rapidly tyrosine phosphorylated following T cell antigen receptor (TCR) stimulation. Vav1 contains multiple domains characteristic of signal transducing proteins, including a Dbl homology domain, a hallmark of a guanine nucleotide exchang... | 10.1038/nri1591 | This paper provides an excellent review of the phenotypes of Vav1 −/− mice. |
10.1111/j.0105-2896.2004.00209.x | 80,906,438 | Summary: In order for an immune response to be successful, it must be of the appropriate type and magnitude. Intracellular residing pathogens require a cell‐mediated immune response, whereas extracellular pathogens evoke a humoral immune response. T‐helper (Th) cells orchestrate the immune response and are divided into... | 10.1038/nri1591 | This paper provides a comprehensive review of the effects of signalling molecules and transcription factors on T H -cell differentiation, including a description of the phenotypes of the various NFAT-deficient mice. |
10.4049/jimmunol.173.10.6440 | 103,637,910 | Abstract In vitro and recent in vivo studies have identified protein kinase Cθ (PKCθ) as an important intermediate in signaling pathways leading to T cell activation, proliferation, and cytokine production. However, the importance of PKCθ to many T cell-driven inflammatory responses has not been demonstrated. In this s... | 10.1038/nri1591 | This paper, together with reference 77, shows T H 2-cell defects in Pkc-θ −/− mice. |
10.1111/j.1474-9726.2006.00262.x | 20,622,330 | Summary In multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic c... | 10.1038/nrg3728 | This is the first analysis of telomerase activity across species in relation to lifespan and body mass. |
10.1111/j.1474-9726.2008.00431.x | 104,063,872 | Summary Large, long‐lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short‐lived species. Large, long‐lived species are thus expected to evolve more elaborate tumor suppressor systems. In previous work, we showed that telomerase activity coevolv... | 10.1038/nrg3728 | This paper identifies rules that control evolution of tumour suppressors depending on lifespan and body mass. |
10.1126/science.2173145 | 20,032,863 | The Wilms tumor locus on chromosome 11p13 has been mapped to a region defined by overlapping, tumor-specific deletions. Complementary DNA clones representing transcripts of 2.5 (WIT-1) and 3.5 kb (WIT-2) mapping to this region were isolated from a kidney complementary DNA library. Expression of WIT-1 and WIT-2 was rest... | 10.1038/nrc1696 | This study and references 11–14 identified WT1 as a candidate tumour-suppressor gene for Wilms' tumour |
10.1242/dev.126.9.1845 | 20,832,700 | The Wilms' Tumour gene WT1 has important functions during development. Knock-out mice were shown to have defects in the urogenital system and to die at embryonic day E13.5, probably due to heart failure. Using a lacZ reporter gene inserted into a YAC construct, we demonstrate that WT1 is expressed in the early proepica... | 10.1038/nrc1696 | Used YAC complementation to reveal a role for WT1 in later stages of kidney development |
10.1126/science.1163885 | 125,151,041 | The protein modifier ubiquitin is a signal for proteasome-mediated degradation in eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin-like protein, Pup (Rv2111c), which was specifically conjugated to proteasome ... | 10.1038/nrd3846 | This study provides the first evidence of a ubiquitin-like pathway in a prokaryotic organism. |
10.1046/j.1365-2958.2000.01773.x | 83,021,592 | We identified the stress‐induced ClpP of Listeria monocytogenes and demonstrated its crucial role in intracellular survival of this pathogen. ClpP is a 21.6 kDa protein belonging to a family of proteases highly conserved in prokaryotes and eukaryotes. A clpP ‐deleted mutant enabled us to demonstrate that ClpP is involv... | 10.1038/nrd3846 | This is one of the first studies to explore why proteolytic complexes are essential for virulence in a pathogenic organism. |
10.1073/pnas.0808807105 | 15,504,267 | Dynamic protein localization is an integral component of the regulatory circuit that drives the Caulobacter cell cycle. The ClpXP protease is localized to the Caulobacter cell pole, where it catalyzes the degradation of the CtrA master regulator at specific times in the cell cycle. Clearance of active CtrA at the G1/S ... | 10.1038/nrd3846 | This is a key study that elucidates the mechanism of cell cycle regulation by the ClpXP protease, which is essential for normal growth in C. crescentus |
10.1038/embor.2010.114 | 59,403,198 | Mammalian and prokaryotic high‐temperature requirement A (HtrA) proteins are chaperones and serine proteases with important roles in protein quality control. Here, we describe an entirely new function of HtrA and identify it as a new secreted virulence factor from Helicobacter pylori , which cleaves the ectodomain of t... | 10.1038/nrd3846 | This study identifies the first HtrA-specific inhibitor that is able to prevent the spread of H. pylori in an ex vivo culture of gastric epithelial cells. |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.