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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10.1146/annurev.immunol.19.1.523 | 40,441,823 | Helicobacter pylori is a gram negative, spiral, microaerophylic bacterium that infects the stomach of more than 50% of the human population worldwide. It is mostly acquired during childhood and, if not treated, persists chronically, causing chronic gastritis, peptic ulcer disease, and in some individuals, gastric adeno... | 10.1038/35073084 | A thorough and updated analysis of the current status of the effort to produce an anti H. pylori vaccine. |
10.1084/jem.191.9.1467 | 107,184,015 | Helicobacter pylori infection induces the appearance of inflammatory infiltrates, consisting mainly of neutrophils and monocytes, in the human gastric mucosa. A bacterial protein with neutrophil activating activity (HP-NAP) has been previously identified, but its role in infection and immune response is still largely u... | 10.1038/35073084 | An accurate characterization of the mode of activation and chemotaxis induced by HP-NAP, including the first demonstration that HP-NAP is a major antigen. |
10.1073/pnas.95.14.8075 | 61,637,494 | Loss-of-function mutations of the ClC-5 chloride channel lead to Dent’s disease, a syndrome characterized by low molecular weight proteinuria, hypercalciuria, and kidney stones. We show that ClC-5 is expressed in renal proximal tubule cells, which normally endocytose proteins passing the glomerular filter. Expression i... | 10.1038/35073084 | Identification of ClC-5 as the Cl − channel isoform that limits the rate of endosomal acidification by providing the counter-anion necessary for electric balance. |
10.1073/pnas.93.25.14648 | 83,484,028 | cagA , a gene that codes for an immunodominant antigen, is present only in Helicobacter pylori strains that are associated with severe forms of gastroduodenal disease (type I strains). We found that the genetic locus that contains cagA ( cag ) is part of a 40-kb DNA insertion that likely was acquired horizontally and i... | 10.1038/35073084 | The demonstration that virulent H. pylori contain a 40-kb foreign DNA (called pathogenicity island or PAI) coding for a type IV secretion system represented a milestone in the understanding of H. pylori pathogenesis and provided an explanation for the presence of the cagA gene only in a subset of strains. Also see refe... |
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... | 10.1038/35073084 | References 91 – 94 each independently reported this unique and novel finding in bacterial pathogenesis. A bacterial protein (CagA) is introduced by a specialized secretion system (type IV secretion) into the host cell, which tyrosine phosphorylates the bacterial protein and initiates a cascade of events, which ultimate... |
10.1083/jcb.139.7.1719 | 58,554,743 | Furin catalyzes the proteolytic maturation of many proproteins within the trans-Golgi network (TGN)/endosomal system. Furin's cytosolic domain (cd) directs both the compartmentalization to and transit between its manifold processing compartments (i.e., TGN/biosynthetic pathway, cell surface, and endosomes). Here we rep... | 10.1038/35052082 | Good example of the identification and functional workup of a filamin?partner relationship. |
10.1083/jcb.150.6.1271 | 109,159,598 | Tim23p (translocase of the inner membrane) is an essential import component located in the mitochondrial inner membrane. To determine how the Tim23 protein itself is transported into mitochondria, we used chemical cross-linking to identify proteins adjacent to Tim23p during its biogenesis. In the absence of an inner me... | 10.1038/35073006 | The precursor of the inner membrane protein Tim23 contains distinct internal import signals. Both intermembrane space complexes, Tim9–Tim10 and Tim8–Tim13, are involved in its import, but interact with different segments of the precursor. |
10.1073/pnas.95.5.2250 | 101,121,787 | A number of nuclear encoded inner membrane proteins of mitochondria span the membrane in such a manner that their N termini are located in the intermembrane space. Many of these proteins attain this membrane orientation by undergoing an export step from the matrix across the inner membrane. This export process, which r... | 10.1038/35073006 | References 96 and 97 show that the mitochondrial inner membrane protein Oxa1 is required for export of a protein from the matrix. This also has important implications for the function of Oxa1 homologues in bacteria. |
10.1242/dev.124.15.2923 | 62,597,883 | Analysis of mouse embryos homozygous for a loss-of-function allele of Gbx2 demonstrates that this homeobox gene is required for normal development of the mid/hindbrain region. Gbx2 function appears to be necessary at the neural plate stage for the correct specification and normal proliferation or survival of anterior h... | 10.1038/35053516 | Analysis of a Gbx2 knockout mouse indicates that Gbx2 is necessary for the development of rhombomeres 1–3. Otx2 expression, mesencephalic identity and the isthmic organizer are shifted caudally. |
10.1242/dev.125.16.3049 | 38,282,935 | Generation of cell diversity in the vertebrate central nervous system starts during gastrulation stages in the ectodermal germ layer and involves specialized cell groups, such as the organizer located at the midbrain-hindbrain boundary (MHB). Mutations in the zebrafish no isthmus (noi) gene alter development of the MHB... | 10.1038/35053516 | Analysis of Pax2.1 −/− mutant zebrafish highlights the molecular cascade of mid-hindbrain maintenance and indicates that Pax2.1 might be necessary for the induction of Engrailed. |
10.1242/dev.124.18.3639 | 104,179,743 | Understanding the genetic mechanisms that control patterning of the vertebrate brain represents a major challenge for developmental neurobiology. Previous data suggest that Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, might both contribute to brain morphogenesis. To gain insight into t... | 10.1038/35053516 | In Otx1 −/− Otx2 −/+ heterozygous mice, the isthmic organizer is shifted anteriorly, resulting in the replacement of midbrain structures by a giant cerebellum. Otx proteins are therefore necessary for the localization of isthmic organizer in a dose-dependent manner. |
10.1242/dev.127.1.177 | 41,558,964 | Current evidence suggests that the anterior segment of the vertebrate hindbrain, rhombomere 1, gives rise to the entire cerebellum. It is situated where two distinct developmental patterning mechanisms converge: graded signalling from an organising centre (the isthmus) located at the midbrain/hindbrain boundary confron... | 10.1038/35053516 | Using Fgf8 bead implantation, the authors show that Fgf8 expression downregulates Hox genes in the hindbrain. So, Fgf8 expressed at the IsO permits the development of rhombomere 1. |
10.1242/dev.126.6.1189 | 41,649,627 | Beads containing recombinant FGF8 (FGF8-beads) were implanted in the prospective caudal diencephalon or midbrain of chick embryos at stages 9–12. This induced the neuroepithelium rostral and caudal to the FGF8-bead to form two ectopic, mirror-image midbrains. Furthermore, cells in direct contact with the bead formed an... | 10.1038/35053516 | Using Fgf8 bead implants into chick midbrain and diencephalon, the authors dissect the molecular cascade of IsO maintenance. |
10.1126/science.289.5476.85 | 41,663,901 | Domestication of many plants has correlated with dramatic increases in fruit size. In tomato, one quantitative trait locus (QTL), fw2.2 , was responsible for a large step in this process. When transformed into large-fruited cultivars, a cosmid derived from the fw2.2 region of a small-fruited wild species reduced fruit ... | 10.1038/35042049 | A landmark publication reporting the isolation of a quantitative trait locus gene by positional cloning. |
10.1083/jcb.57.2.315 | 41,383,229 | When the nerves of isolated frog sartorius muscles were stimulated at 10 Hz, synaptic vesicles in the motor nerve terminals became transiently depleted. This depletion apparently resulted from a redistribution rather than disappearance of synaptic vesicle membrane, since the total amount of membrane comprising these ne... | 10.1038/35044540 | A classical study worth reading by anybody interested in this field. It provides a first description of the clathrin-mediated recycling pathway of synaptic vesicles. |
10.1523/jneurosci.20-23-08667.2000 | 38,783,697 | Although clathrin assembly by adaptor proteins (APs) plays a major role in the recycling of synaptic vesicles, the molecular mechanism that allows APs to assemble clathrin is poorly understood. Here we demonstrate that AP180, like AP-2 and AP-3, binds to the N-terminal domain of clathrin. Sequence analysis reveals a mo... | 10.1038/35044540 | Identification of a novel motif in AP-180 with a putative function in coat assembly. |
10.1083/jcb.150.3.589 | 100,813,073 | Synaptojanin is a polyphosphoinositide phosphatase that is found at synapses and binds to proteins implicated in endocytosis. For these reasons, it has been proposed that synaptojanin is involved in the recycling of synaptic vesicles. Here, we demonstrate that the unc-26 gene encodes the Caenorhabditis elegans ortholog... | 10.1038/35044540 | Evidence that Caenorhabditis elegans synaptojanin has a function in the endocytic reactions. |
10.1083/jcb.148.5.1047 | 38,412,761 | Syndapin I (SdpI) interacts with proteins involved in endocytosis and actin dynamics and was therefore proposed to be a molecular link between the machineries for synaptic vesicle recycling and cytoskeletal organization. We here report the identification and characterization of SdpII, a ubiquitously expressed isoform o... | 10.1038/35044540 | Provides strong evidence for a link between an endocytic protein and actin. |
10.1242/dev.127.8.1727 | 20,348,189 | Fat facets is a deubiquitinating enzyme required in a cell communication pathway that limits to eight the number of photoreceptor cells in each facet of the Drososphila compound eye. Genetic data support a model whereby Faf removes ubiquitin, a polypeptide tag for protein degradation, from a specific ubiquitinated prot... | 10.1038/35044540 | The study reports the isolation of liquid facet as a dominant enhancer of the fat facet mutant eye phenotype of Drosophila melanogaster . It also reports that the liquid facet locus encodes epsin and links epsin both to endocytosis and to signalling during development. |
10.1083/jcb.144.6.1203 | 38,571,470 | Ark1p (actin regulating kinase 1) was identified as a yeast protein that binds to Sla2p, an evolutionarily conserved cortical actin cytoskeleton protein. Ark1p and a second yeast protein, Prk1p, contain NH2-terminal kinase domains that are 70% identical. Together with six other putative kinases from a number of organis... | 10.1038/35044540 | Characterization of a new family of protein kinases with a critical role in actin function. |
10.1146/annurev.biochem.66.1.717 | 83,486,695 | An X-ray structure of the F 1 portion of the mitochondrial ATP synthase shows asymmetry and differences in nucleotide binding of the catalytic β subunits that support the binding change mechanism with an internal rotation of the γ subunit. Other structural and mutational probes of the F 1 and F 0 portions of the ATP sy... | 10.1038/35089509 | Boyer's rotational catalysis and alternate-binding change model are concisely reviewed. |
10.1073/pnas.96.23.13438 | 82,963,167 | The function of dendritic spines, postsynaptic sites of excitatory input in the mammalian central nervous system (CNS), is still not well understood. Although changes in spine morphology may mediate synaptic plasticity, the extent of basal spine motility and its regulation and function remains controversial. We investi... | 10.1038/35104061 | Using time-lapse imaging, the authors observed high motility of spines and filopodia in slices from different brain areas. Spine motility declined with the maturation of neurons, but was not changed by the blockade or stimulation of neuronal activity. |
10.1126/science.283.5409.1923 | 19,490,294 | Activity shapes the structure of neurons and their circuits. Two-photon imaging of CA1 neurons expressing enhanced green fluorescent protein in developing hippocampal slices from rat brains was used to characterize dendritic morphogenesis in response to synaptic activity. High-frequency focal synaptic stimulation induc... | 10.1038/35104061 | References 43–45 were the first to report that spine-like protrusions formed in association with LTP-inducing stimuli. |
10.1083/jcb.144.3.575 | 82,318,356 | Dendritic spines are small protrusions that receive synapses, and changes in spine morphology are thought to be the structural basis for learning and memory. We demonstrate that the cell surface heparan sulfate proteoglycan syndecan-2 plays a critical role in spine development. Syndecan-2 is concentrated at the synapse... | 10.1038/35104061 | This paper showed that overexpression of syndecan 2, a synaptic heparan-sulphate proteoglycan, induced the maturation of mushroom-like spines. This effect was dependent on the cytoplasmic carboxyl terminus of syndecan 2. |
10.1126/science.290.5495.1364 | 134,387,848 | PSD-95 is a neuronal PDZ protein that associates with receptors and cytoskeletal elements at synapses, but whose function is uncertain. We found that overexpression of PSD-95 in hippocampal neurons can drive maturation of glutamatergic synapses. PSD-95 expression enhanced postsynaptic clustering and activity of glutama... | 10.1038/35104061 | By the transfection of cultured neurons, this study showed that overexpression of PSD95 could stimulate the maturation of dendritic spines, which correlated with the recruitment of AMPA receptors to spines. |
10.1126/science.285.5434.1733 | 39,248,130 | Chemotherapy and radiation therapy for cancer often have severe side effects that limit their efficacy. Because these effects are in part determined by p53-mediated apoptosis, temporary suppression of p53 has been suggested as a therapeutic strategy to prevent damage of normal tissues during treatment of p53-deficient ... | 10.1038/35094077 | Traditional cancer therapies are invasive. DNA damage can occur in healthy cells and induce p53-dependent apoptosis. This paper describes an inhibitor of p53 that protects against these effects. |
10.1042/bj3520001 | 17,343,752 | Human cancer progression is driven in part by the mutation of oncogenes and tumour-suppressor genes which, under selective environmental pressures, give rise to evolving populations of biochemically altered cells with enhanced tumorigenic and metastatic potential. Given that human cancers are biologically and pathologi... | 10.1038/35094077 | A recent review highlighting the progress of new approaches to cancer therapy based on restoring the p53 tumour-suppressor pathway. |
10.1126/science.286.5449.2507 | 45,492,840 | Compounds that stabilize the DNA binding domain of p53 in the active conformation were identified. These small synthetic molecules not only promoted the stability of wild-type p53 but also allowed mutant p53 to maintain an active conformation. A prototype compound caused the accumulation of conformationally active p53 ... | 10.1038/35094077 | Reports the first screen for prototype pharmacological small molecules that stabilize the native structure of wild-type p53 conformation. |
10.1126/science.8023157 | 62,415,949 | Mutations in the p53 tumor suppressor are the most frequently observed genetic alterations in human cancer. The majority of the mutations occur in the core domain which contains the sequence-specific DNA binding activity of the p53 protein (residues 102-292), and they result in loss of DNA binding. The crystal structur... | 10.1038/35094077 | Presents the first crystal structure of p53 core domain. The location and structural consequences of hot-spot TP53 mutations are discussed. |
10.1242/dev.121.11.3651 | 41,633,487 | Mouse embryos homozygous for a null mutation in nodal arrest development at early gastrulation and contain little or no embryonic mesoderm. Here, two Xenopus nodal-related genes (Xnr-1 and Xnr-2) are identified and shown to be expressed transiently during embryogenesis, first within the vegetal region of late blastulae... | 10.1038/35042039 | The original demonstration that nodal –related genes induce mesoderm and completely rescue Xenopus embryos that have been ventralized by ultraviolet radiation. |
10.1083/jcb.136.5.1123 | 20,759,991 | Eggs of Xenopus laevis undergo a postfertilization cortical rotation that specifies the position of the dorso-ventral axis and activates a transplantable dorsal-determining activity in dorsal blastomeres by the 32-cell stage. There have heretofore been no reported dorso-ventral asymmetries in endogenous signaling prote... | 10.1038/35042039 | This paper describes the earliest asymmetries in the stability of the β-Catenin protein. |
10.1242/dev.127.9.1981 | 104,311,847 | We have isolated one member of the frizzled family of wnt receptors from Xenopus (Xfz7) to study the role of cell-cell communication in the establishment of the vertebrate axis. We demonstrate that this maternally encoded protein specifically synergizes with wnt proteins in ectopic axis induction. Embryos derived from ... | 10.1038/35042039 | This paper shows that Wnt receptors are required for dorsal–ventral patterning in Xenopus |
10.1242/dev.122.10.2987 | 104,247,467 | In previous work, we demonstrated that maternally encoded beta-catenin, the vertebrate homolog of armadillo, is required for formation of dorsal axial structures in early Xenopus embryos (Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., Kintner, C., Yoshida-Noro, C. and Wylie, C. (1994). Cell... | 10.1038/35042039 | Mesoderm induction takes place shortly after the midblastula stage of Xenopus development. |
10.1101/gad.14.4.435 | 133,907,521 | We have investigated the regulation of the activin-inducible distal element (DE) of the Xenopus goosecoid promoter. The results show that paired-like homeodomain transcription factors of the Mix family, Mixer and Milk, but not Mix.1, mediate activin/TGF-β-induced transcription through the DE by interacting with the eff... | 10.1038/35042039 | This paper shows that Smads are recruited to the goosecoid promoter through an interaction with the homeodomain protein, Mixer. |
10.1242/dev.127.4.821 | 125,326,588 | A number of genetic and molecular studies have implicated Chordin in the regulation of dorsoventral patterning during gastrulation. Chordin, a BMP antagonist of 120 kDa, contains four small (about 70 amino acids each) cysteine-rich domains (CRs) of unknown function. In this study, we show that the Chordin CRs define a ... | 10.1038/35042039 | The Chordin cysteine-rich domains are sufficient for BMP binding and procollagen II has anti-BMP activity. |
10.1242/dev.114.3.583 | 62,535,655 | Seven zygotically active genes are required for normal patterning of the dorsal 40% of the Drosophila embryo. Among these genes, decapentaplegic (dpp) has the strongest mutant phenotype: in the absence of dpp, all cells in the dorsal and dorsolateral regions of the embryo adopt fates characteristic of more ventrally de... | 10.1038/35042039 | This paper describes the original genetic analysis that revealed that tolloid and short-gastrulation interact with the BMP pathway. |
10.1242/dev.127.10.2143 | 83,468,308 | Structurally unrelated neural inducers in vertebrate and invertebrate embryos have been proposed to function by binding to BMP4 or Dpp, respectively, and preventing these homologous signals from activating their receptor(s). In this study, we investigate the functions of various forms of the Drosophila Sog protein usin... | 10.1038/35042039 | Proteolytic fragments of Short-gastrulation, called Supersogs, have BMP inhibitory activities. |
10.1083/jcb.144.5.1069 | 124,504,862 | Type II procollagen is expressed as two splice forms. One form, type IIB, is synthesized by chondrocytes and is the major extracellular matrix component of cartilage. The other form, type IIA, contains an additional 69 amino acid cysteine-rich domain in the NH2-propeptide and is synthesized by chondrogenic mesenchyme a... | 10.1038/35042039 | The aminopropeptide of collagen II is retained in collagen fibres and binds BMP-4 and TGF-β1. |
10.1073/pnas.98.2.676 | 125,332,500 | A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baselin... | 10.1038/35094500 | This paper presents the PET data that support the use of the oxygen extraction fraction (OEF) in defining the baseline of the human brain. |
10.1046/j.1365-2869.2000.00214.x | 103,897,231 | Functional neuroimaging using positron emission tomography has recently yielded original data on the functional neuroanatomy of human sleep. This paper attempts to describe the possibilities and limitations of the technique and clarify its usefulness in sleep research. A short overview of the methods of acquisition and... | 10.1038/35094500 | A review of the small, but important, group of functional imaging studies detailing the regional changes in brain activity that are associated with stages of sleep. |
10.1126/science.275.5304.1293 | 62,618,241 | Deciding advantageously in a complex situation is thought to require overt reasoning on declarative knowledge, namely, on facts pertaining to premises, options for action, and outcomes of actions that embody the pertinent previous experience. An alternative possibility was investigated: that overt reasoning is preceded... | 10.1038/35094500 | An interesting experimental approach, which explores the functions of the ventral medial prefrontal cortex in social decision making. |
10.1126/science.286.5445.1692 | 62,213,101 | The ability to “mentalize,” that is to understand and manipulate other people's behavior in terms of their mental states, is a major ingredient in successful social interactions. A rudimentary form of this ability may be seen in great apes, but in humans it is developed to a high level. Specific impairments of mentaliz... | 10.1038/35094500 | An important synthesis of functional imaging experiments related to the topic of mentalizing, and the roles of the medial prefrontal cortex and STS in this process. |
10.1073/pnas.101129298 | 80,134,628 | Positron-emission tomography and functional MRS imaging signals can be analyzed to derive neurophysiological values of cerebral blood flow or volume and cerebral metabolic consumption rates of glucose (CMR Glc ) or oxygen (CMR O 2 ). Under basal physiological conditions in the adult mammalian brain, glucose oxidation i... | 10.1038/35094500 | References 87 and 88 provide an up-to-date synthesis of our current understanding of the cellular metabolic changes underlying the fMRI BOLD signal. |
10.1111/j.1600-0447.1999.tb00984.x | 100,630,806 | Objective: To study autism over time in order to ascertain whether there has been an increase in its prevalence in recent years. Method: All English language papers on the prevalence of autism were reviewed. Ten of the studies retrieved were not used in the final analysis because they did not meet full criteria for inc... | 10.1038/35103559 | A review of the literature about the effect of diagnostic criteria on autism prevalence. |
10.1111/j.1469-7610.1977.tb00443.x | 26,977,223 | Summary A systematic study was made of a representative group of 21 same‐sexed twin pairs (11 MZ and 10 DZ) in which at least one twin showed the syndrome of infantile autism. There was a 36 per cent pair‐wise concordance rate for autism in MZ pairs compared with o per cent concordance in DZ pairs. The concordance for ... | 10.1038/35103559 | The first published autism twin study, revealing significantly increased concordance for monozygotic twins and therefore establishing a genetic basis for autism; includes clinical summaries for each twin pair. |
10.1084/jem.194.6.733 | 45,024,736 | The E2A gene encodes the E47 and E12 basic helix-loop-helix (bHLH) transcription factors. T cell development in E2A-deficient mice is partially arrested before lineage commitment. Here we demonstrate that E47 expression becomes uniformly high at the point at which thymocytes begin to commit towards the T cell lineage. ... | 10.1038/35105060 | Describes the abrogation of the developmental block in Rag null or scid mutant thymocytes by a deficiency in E2A proteins, and shows that E-box binding activity is decreased and Id3 RNA transcripts accumulate in the thymocytes of Rag null mice injected with antibodies against CD3. It also presents flow cytometric analy... |
10.1084/jem.190.11.1605 | 100,813,088 | The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of... | 10.1038/35105060 | This paper shows that E2A-deficient mice exhibit increased thymocyte positive selection when bred into the HY or transgenic TCR backgrounds. |
10.1084/jem.192.12.1775 | 18,780,093 | We found previously that Id3, which inhibits transcriptional activities of many basic helix-loop-helix transcription factors, blocked T and B cell development but stimulated natural killer (NK) cell development. Here we report that ectopic expression of Id3 and another Id protein, Id2, strongly inhibited the developmen... | 10.1038/35105060 | This paper shows that enforced Id expression can block the development of lymphoid DCs. The data imply that there are other factors that act downstream of E-proteins to influence the T versus DC cell-fate decision. |
10.1126/science.6857250 | 38,410,628 | Nuclear transplantation in the mouse embryo was achieved by using a method that combines microsurgical removal of the zygote pronuclei with the introduction of a donor nucleus by a virus-mediated cell fusion technique. Survival of embryos was greater than 90 percent in tests of this procedure. The embryos developed to ... | 10.1038/35042066 | The first description of a workable nuclear-transfer technique in mammals. |
10.1073/pnas.97.3.1096 | 102,328,613 | The “WD40” domain is a widespread recognition module for linking partner proteins in intracellular networks of signaling and sorting. The clathrin amino-terminal domain, which directs incorporation of cargo into coated pits, is a β-propeller closely related in structure to WD40 modules. The crystallographically determi... | 10.1038/35043117 | Atomic model obtained by X-ray crystallography of complexes formed between clathrin and peptides of β-arrestin or of AP-2 adaptor that contain sequences known to be involved in the interaction with clathrin. |
10.1126/science.282.5392.1327 | 104,354,791 | Many cell surface proteins are marked for endocytosis by a cytoplasmic sequence motif, tyrosine-X-X-(hydrophobic residue), that is recognized by the μ2 subunit of AP2 adaptors. Crystal structures of the internalization signal binding domain of μ2 complexed with the internalization signal peptides of epidermal growth fa... | 10.1038/35043117 | First atomic structure of a complex between a peptide containing a tyrosine-based endocytic sorting signal of the type YppØ and the μ2 subunit of the clathrin adaptor complex AP-2. |
10.1126/science.287.5457.1433 | 29,285,982 | Neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian organisms, including humans. Neural stem cells can also be derived from more primitive embryonic stem cells. The location of the adult stem cells and the brain regions to which their progeny... | 10.1038/35052535 | Review of cell lineage specification in the central nervous system during development and in adulthood. |
10.1126/science.273.5277.974 | 18,162,649 | Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypot... | 10.1038/35086018 | The first demonstration of a complementary DNA that encodes the GHS receptor by the use of an expression cloning technique. |
10.1126/science.272.5263.886 | 38,522,478 | The development of the thymus depends initially on epithelial-mesenchymal and subsequently on reciprocal lympho-stromal interactions. The genetic steps governing development and differentiation of the thymic microenvironment are unknown. With the use of a targeted disruption of the whn gene, which recapitulates the phe... | 10.1038/35095500 | Shows that Whn is the product of the nude gene locus, and indicates that Whn is dispensible for the initial formation of the thymic epithelial primordium, but not for the later development into cortical and medullary epithelial cells. |
10.1073/pnas.93.12.5742 | 100,819,412 | The nude mutation (nu) causes athymia and hairlessness, but the molecular mechanisms by which it acts have not been determined. To address the role of nu in thymogenesis, we investigated whether all or part of the nude thymic epithelium could be rescued by the presence of wild-type cells in nude <--> wild-type ch... | 10.1038/35095500 | Uses mouse embryo fusion chimaeras to show that Whn functions in a cell-autonomous fashion, with only a small proportion of thymic epithelial cells in mouse chimaeras being derived from the nude donor. |
10.1073/pnas.95.20.11822 | 79,469,678 | Thymocyte and thymic epithelial cell (TEC) development are interdependent processes. Although lineage relationships among progressively maturing thymocyte subsets have been characterized, the developmental relationships among TEC subsets are obscure. Because epithelial cells express distinct keratin (K) species as a fu... | 10.1038/35095500 | Identifies a keratin (K) 8 + K5 + 'double-positive' epithelial subset, abundant in CD3ɛ transgenic mice, in which thymic cortical epithelial development is perturbed (Reference 28 ). Introduction of Rag1 −/− thymocytes into CD3ɛ transgenic thymi induces cortical organization and appearance of K8 + K5 − cortical epithel... |
10.1002/eji.1830270522 | 59,908,976 | Abstract We have investigated the role of specific components of the thymic stroma during development of CD4 − 8 − T cell precursors by separating and reaggregating precursor subsets with individual or combinations of stromal cells. We show that while the development of CD25 + 44 + precursors is dependent upon a combin... | 10.1038/35095500 | Reaggregate thymus organ cultures were used to show that the requirement for mesenchymal cells during maturation of T-cell precursors maps to the CD4 − 8 − 25 + 44 + stage. Treatment of mesenchymal cells with hyaluronidase was found to abrogate the ability of these cells to influence thymocyte development, indicating a... |
10.1073/pnas.96.16.8873 | 16,985,443 | The Holliday junction is an essential intermediate of homologous recombination. RecA of Bacteria, Rad51 of Eukarya, and RadA of Archaea are structural and functional homologs. These proteins play a pivotal role in the formation of Holliday junctions from two homologous DNA duplexes. RuvC is a specific endonuclease that... | 10.1038/35073057x | First identification of an archaeal Holliday-junction-resolving enzyme, using random expression of Pyrococcus furiosus genes in Escherichia coli |
10.1073/pnas.150238697 | 40,517,442 | Homologous DNA recombination promotes genetic diversity and the maintenance of genome integrity, yet no enzymes with specificity for the Holliday junction (HJ)—a key DNA recombination intermediate—have been purified and characterized from metazoa or their viruses. Here we identify critical structural elements of RuvC, ... | 10.1038/35073057x | Identification of the pox viral Holliday junction-resolving enzyme, and its relationship with RuvC and Cce1. |
10.1073/pnas.091613398 | 1,634,910 | The 2.15-Å structure of Hjc, a Holliday junction-resolving enzyme from the archaeon Sulfolobus solfataricus , reveals extensive structural homology with a superfamily of nucleases that includes type II restriction enzymes. Hjc is a dimer with a large DNA-binding surface consisting of numerous basic residues surrounding... | 10.1038/35073057x | The crystal structure of the archaeal Hjc enzyme confirms its close relationship with the type II restriction enzymes and allows prediction of a model for junction binding and cleavage. |
10.1073/pnas.97.8.3971 | 16,753,642 | Holliday junctions are important structural intermediates in recombination, viral integration, and DNA repair. We present here the single-crystal structure of the inverted repeat sequence d(CCGGTACCGG) as a Holliday junction at the nominal resolution of 2.1 Å. Unlike the previous crystal structures, this DNA junction h... | 10.1038/35073057x | The crystal structure of a four-way DNA junction in the stacked X-shape conformation. This is the first structure that is completely free of base mismatches. |
10.1083/jcb.141.4.929 | 82,956,129 | Lateral assemblies of glycolipids and cholesterol, “rafts,” have been implicated to play a role in cellular processes like membrane sorting, signal transduction, and cell adhesion. We studied the structure of raft domains in the plasma membrane of non-polarized cells. Overexpressed plasma membrane markers were evenly d... | 10.1038/35036052 | The first demonstration that clusters of rafts segregate away from non-raft proteins. |
10.1083/jcb.145.4.877 | 109,156,783 | Tyrosine phosphorylation of the high affinity immunoglobulin (Ig)E receptor (FcεRI) by the Src family kinase Lyn is the first known biochemical step that occurs during activation of mast cells and basophils after cross-linking of FcεRI by antigen. The hypothesis that specialized regions in the plasma membrane, enriched... | 10.1038/35036052 | This paper is the culmination of a series of studies showing the role of rafts in IgE receptor signalling. |
10.1126/science.283.5402.680 | 45,532,108 | Although dispensable, costimulation through CD28 facilitates activation of naı̈ve T lymphocytes. CD28 engagement led to the redistribution and clustering of membrane and intracellular kinase-rich raft microdomains at the site of T cell receptor (TCR) engagements. Although not affecting TCR down-regulation, this process... | 10.1038/35036052 | Antibody-coated beads are used to activate clustering of raft components in T-cell signalling. |
10.1083/jcb.149.5.1131 | 58,554,681 | We have determined the membrane topography of the high-affinity IgE receptor, FcεRI, and its associated tyrosine kinases, Lyn and Syk, by immunogold labeling and transmission electron microscopic (TEM) analysis of membrane sheets prepared from RBL-2H3 mast cells. The method of Sanan and Anderson (Sanan, D.A., and R.G.W... | 10.1038/35036052 | Clear visualization of raft clustering during IgE signalling by immuno-electron microscopy. |
10.1073/pnas.97.7.3376 | 123,591,566 | Although Drosophila possesses potent immune responses, little is known about the microbial pathogens that infect Drosophila . We have identified members of the bacterial genus Erwinia that induce the systemic expression of genes encoding antimicrobial peptides in Drosophila larvae after ingestion. These Erwinia strains... | 10.1038/35042080 | This paper describes the Erwinia carotovora – Drosophila pathogen–host system, which will provide a simple method for doing genetic screens in the future. |
10.1126/science.288.5475.2376 | 122,101,481 | Malaria is a devastating public health menace, killing over one million people every year and infecting about half a billion. Here it is shown that the protozoan Plasmodium gallinaceum , a close relative of the human malaria parasite Plasmodium falciparum , can develop in the fruit fly Drosophila melanogaster . Plasmod... | 10.1038/35042080 | A Plasmodium– Drosophila parasite–host model permits the identification of flies that have altered abilities to support plasmodia growth. |
10.1073/pnas.93.20.11173 | 61,567,970 | Although cyclin-dependent kinase 5 (Cdk5) is closely related to other cyclin-dependent kinases, its kinase activity is detected only in the postmitotic neurons. Cdk5 expression and kinase activity are correlated with the extent of differentiation of neuronal cells in developing brain. Cdk5 purified from nervous tissue ... | 10.1038/35096019 | Cdk5 -deficient mice uncovered the role of Cdk5 in CNS development, particularly neuronal positioning. |
10.1146/annurev.neuro.24.1.167 | 83,551,177 | ▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of pat... | 10.1038/35097575 | An authoritative recent review and theoretical synthesis of physiological and cognitive work on prefrontal function. |
10.1126/science.291.5502.312 | 83,338,729 | The ability to group stimuli into meaningful categories is a fundamental cognitive process. To explore its neural basis, we trained monkeys to categorize computer-generated stimuli as “cats” and “dogs.” A morphing system was used to systematically vary stimulus shape and precisely define the category boundary. Neural a... | 10.1038/35097575 | A key experiment showing that neurons in a wide region of the lateral prefrontal cortex adapt to task context, coding just those stimulus distinctions or categorizations of current behavioural significance. |
10.1073/pnas.95.24.14529 | 38,405,834 | A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluati... | 10.1038/35097575 | A computational model sharing many central aspects with the adaptive coding model. |
10.1046/j.1365-2958.2000.01759.x | 102,607,370 | We describe here 20 families of secondary (pmf‐driven) carriers which, in addition to nine families within the ATP‐dependent ABC superfamily, and seven families of Gram‐negative bacterial outer membrane porins, largely account for the stereospecific transport of sugars and their derivatives into and out of all living c... | 10.1038/35085077 | Thorough classification of the diversity and relationship between membrane transport proteins that catalyse translocation of various molecules across cell and organellar membranes. |
10.1073/pnas.91.12.5421 | 16,765,150 | An engineered fusion protein containing two tandem lactose permease molecules (permease dimer) exhibits high transport activity and is used to test the phenomenon of negative dominance. Introduction of the mutation Glu-325-->Cys into either the first or the second half of the dimer results in a 50% decrease in activ... | 10.1038/35085077 | This study uses fused tandem lacY genes to show that the lactose permease does not show the phenomenon of negative dominance, thereby confirming other observations indicating that the permease is functional as a monomer. |
10.1073/pnas.96.19.10695 | 123,235,362 | Genes encoding membrane proteins comprise a substantial proportion of genomes sequenced to date, but ability to perform structural studies on this portion of the proteome is limited. Electrospray ionization-MS (ESI-MS) of an intact protein generates a profile defining the native covalent state of the gene product and i... | 10.1038/35085077 | Electrospray ionization–mass spectrometry of intact lactose permease generates a profile defining the native covalent state of the gene product and its homogeneity, thereby allowing studies on chemical modification and post-translational modification. |
10.1073/pnas.200351797 | 40,565,352 | We studied the effect of pH on ligand binding in wild-type lactose permease or mutants in the four residues—Glu-269, Arg-302, His-322, and Glu-325—that are the key participants in H + translocation and coupling between sugar and H + translocation. Although wild-type permease or mutants in Glu-325 and Arg-302 exhibit ma... | 10.1038/35085077 | Using a novel binding assay, the p K a of mutants in the six irreplaceable residues with respect to ligand binding is measured. The findings led to a detailed mechanistic model for lactose/H + symport. |
10.1126/science.1384130 | 60,380,087 | In order to understand the structural bases of ion conduction, ion selectivity, and gating in the nicotinic acetylcholine receptor, mutagenesis and covalent modification were combined to identify the amino acid residues that line the channel. The side chains of alternate residues—Ser248, Leu250, Ser252, and Thr254—in M... | 10.1038/35085077 | First studies describing scanning cysteine accessibility mutagenesis (SCAM), using methyl thiosulphonate derivatives to study the ion-conduction pathway in the nicotinic acetylcholine receptor. |
10.1073/pnas.95.17.9802 | 80,496,581 | Site-directed N -ethylmaleimide labeling was studied with Glu-126 and/or Arg-144 mutants in lactose permease containing a single, native Cys residue at position 148 in the substrate-binding site. Replacement of either Glu-126 or Arg-144 with Ala markedly decreases Cys-148 reactivity, whereas interchanging the residues,... | 10.1038/35085077 | Provides evidence that Glu126 (helix IV) and Arg144 (helix V) are charge paired and crucial for substrate binding. A model of the binding site is presented. |
10.1073/pnas.87.11.4325 | 81,643,661 | The lacY gene of Escherichia coli was cut into two approximately equal-size fragments with Afl II and subcloned individually or together under separate lac operator/promoters in plasmid pT7-5. Under these conditions, lac permease is expressed in two portions: (i) the N-terminal portion (the N terminus, the first six pu... | 10.1038/35085077 | Demonstrates that functional lactose permease can be expressed in two contiguous, non-overlapping polypeptides that correspond to the amino- and carboxy-terminal six helices. The finding has been exploited for crosslinking studies. |
10.1242/dev.123.1.1 | 41,770,172 | In a large-scale screen, we isolated mutants displaying a specific visible phenotype in embryos or early larvae of the zebrafish, Danio rerio. Males were mutagenized with ethylnitrosourea (ENU) and F2 families of single pair matings between sibling F1 fish, heterozygous for a mutagenized genome, were raised. Egg lays w... | 10.1038/35103567 | Together, references 5 and 6 are the first to report large-scale genetic screening in a vertebrate organism. |
10.1126/science.1060418 | 26,721,575 | Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleava... | 10.1038/35103567 | Zebrafish mutants with non-morphological defects of the digestive tract are identified using a fluorescent reporter to visualize enzymatic activity in live embryos. |
10.1073/pnas.97.24.12965 | 81,390,485 | Much has been learned about vertebrate development by random mutagenesis followed by phenotypic screening and by targeted gene disruption followed by phenotypic analysis in model organisms. Because the timing of many developmental events is critical, it would be useful to have temporal control over modulation of gene f... | 10.1038/35103567 | A screen for small molecules that can modulate embryonic development in a conditional manner reveals the potential of a 'chemical-genetic' approach to studying zebrafish developmental processes. |
10.1083/jcb.125.1.67 | 19,867,485 | Classically, the polymeric immunoglobulin receptor and its ligand, IgA, are thought to be sorted from basolateral early endosomes into transcytotic vesicles that directly fuse with the apical plasma membrane. In contrast, we have found that in MDCK cells IgA is delivered from basolateral endosomes to apical endosomes a... | 10.1038/35096054 | Together with reference 95 and studies from the Kai Simons group, this paper shows the organization of the apical and basolateral endocytic pathways in epithelial cells along the degradation, recycling and transcytotic routes. |
10.1083/jcb.127.5.1199 | 81,716,566 | Caveolae are specialized invaginations of the plasma membrane which have been proposed to play a role in diverse cellular processes such as endocytosis and signal transduction. We have developed an assay to determine the fraction of internal versus plasma membrane caveolae. The GPI-anchored protein, alkaline phosphatas... | 10.1038/35096054 | Provides the first evidence that caveolae can be endocytosed in non-endothelial cells. |
10.1083/jcb.144.6.1271 | 39,462,457 | To understand the mechanisms for endocytic sorting of lipids, we investigated the trafficking of three lipid-mimetic dialkylindocarbocyanine (DiI) derivatives, DiIC16(3) (1,1′-dihexadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate), DiIC12(3) (1,1′- didodecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate), a... | 10.1038/35096054 | Shows that hydrophobic tails are important for lipid sorting in early endosomes. |
10.1083/jcb.133.1.29 | 81,774,047 | In this paper, we show that beta COP is present on endosomes and is required for the formation of vesicles which mediate transport from early to late endosomes. Both the association of beta COP to endosomal membranes as well as transport vesicle formation depend on the lumenal pH. We find that epsilon COP, but not gamm... | 10.1038/35096054 | References 53 and 54 show that an endosomal version of the COPI coat — which regulates retrograde transport in the early biosynthetic pathway — functions in the early endocytic pathway. |
10.4049/jimmunol.165.3.1259 | 123,049,623 | Abstract Follicular dendritic cells (FDCs) present in lymphoid follicles play a critical role in germinal center reactions. They trap native Ags in the form of immune complexes providing a source for continuous stimulation of specific B lymphocytes. FDCs have been reported to express MHC class II molecules, suggesting ... | 10.1038/35096054 | Together with previous studies from Hans Geuze's group, this paper shows that exosomes are microvesicles derived from late endocytic membrane invaginations, which are secreted through a novel pathway. |
10.1034/j.1600-0854.2000.011104.x | 20,242,704 | As sequencing of the human genome nears completion, the genes that cause many human diseases are being identified and functionally described. This has revealed that many human diseases are due to defects of intracellular trafficking. This ‘Toolbox’ catalogs and briefly describes these diseases. | 10.1038/35096054 | Offers a complete list — at the time of publication — of human diseases that are linked to transport defects. |
10.1146/annurev.arplant.48.1.575 | 103,676,437 | ▪ Abstract In “gene-for-gene” interactions between plants and their pathogens, incompatibility (no disease) requires a dominant or semidominant resistance (R) gene in the plant, and a corresponding avirulence (Avr) gene in the pathogen. Many plant/pathogen interactions are of this type. R genes are presumed to (a) enab... | 10.1038/35080508 | This chapter from a graduate-level textbook provides an excellent summary with many helpful illustrations of disease resistance in plants. |
10.1126/science.7732374 | 59,306,890 | Plant breeders have used disease resistance genes ( R genes) to control plant disease since the turn of the century. Molecular cloning of R genes that enable plants to resist a diverse range of pathogens has revealed that the proteins encoded by these genes have several features in common. These findings suggest that p... | 10.1038/35080508 | Although numerous reviews of R genes have followed, this paper is historically important for being the first to describe the common structural features in R genes, which was surprising news at the time. |
10.1146/annurev.phyto.35.1.271 | 121,802,928 | ▪ Abstract The L6 and M rust-resistance genes, representing two of the five rust-resistance gene loci in flax (Linum usitatissimum), have been cloned. The molecular data are fully consistent with earlier genetic data: the L locus is a single gene with multiple alleles expressing different rust resistance specificities,... | 10.1038/35080508 | Another historically important review that updates Flor's classic 'gene for gene' description of disease resistance in flax with advances in molecular characterization of R genes. |
10.1101/gr.8.11.1113 | 20,249,918 | Classical genetic and molecular data show that genes determining disease resistance in plants are frequently clustered in the genome. Genes for resistance ( R genes) to diverse pathogens cloned from several species encode proteins that have motifs in common. These motifs indicate that R genes are part of signal-transdu... | 10.1038/35080508 | An ambitious review that provides a useful conceptual framework for explaining how disease resistance genes have proliferated and diversified in plants. |
10.1126/science.8235595 | 38,399,490 | Microdomains of high intracellular calcium ion concentration, [Ca 2+ ] i , have been hypothesized to occur in living cells exposed to stimuli that generate inositol 1,4,5-trisphosphate (IP 3 ). Mitochondrially targeted recombinant aequorin was used to show that IP 3 -induced Ca 2+ mobilization from intracellular stores... | 10.1038/35036035 | The first demonstration that mitochondria sense the high concentrations of Ca 2+ that build up in the vicinity of intracellular channels such as the inositol-1,4,5-trisphosphate receptor. |
10.1126/science.8235594 | 82,772,006 | Spontaneous local increases in the concentration of intracellular calcium, called "calcium sparks," were detected in quiescent rat heart cells with a laser scanning confocal microscope and the fluorescent calcium indicator fluo-3. Estimates of calcium flux associated with the sparks suggest that calcium sparks result f... | 10.1038/35036035 | One of the first visualizations of the localized Ca 2+ signal emerging from small groups of ryanodine receptors. Such elementary events are the basic building blocks of Ca 2+ signals. |
10.1126/science.278.5345.1940 | 122,101,296 | The inositol 1,4,5-trisphosphate (IP 3 ) receptor is a calcium ion channel involved in the release of free Ca 2+ from intracellular stores. For analysis of the role of IP 3 -induced Ca 2+ release (IICR) on patterning of the embryonic body, monoclonal antibodies that inhibit IICR were produced. Injection of these blocki... | 10.1038/35036035 | A role for Ca 2+ in setting up the dorsoventral axis in Xenopus oocytes was demonstrated by showing that the axis was modified by inhibiting the activity of the inositol-1,4,5-trisphosphate receptor. |
10.1126/science.286.5443.1358 | 17,625,766 | A mechanism by which the Ras–mitogen-activated protein kinase (MAPK) signaling pathway mediates growth factor–dependent cell survival was characterized. The MAPK-activated kinases, the Rsks, catalyzed the phosphorylation of the pro-apoptotic protein BAD at serine 112 both in vitro and in vivo. The Rsk-induced phosphory... | 10.1038/35085068 | References 33 and 34 show a role of CREB in growth-factor-dependent cell survival and demonstrate an alternative non-cAMP pathway for CREB action. |
10.1126/science.282.5397.2275 | 61,431,816 | cAMP (3′,5′ cyclic adenosine monophosphate) is a second messenger that in eukaryotic cells induces physiological responses ranging from growth, differentiation, and gene expression to secretion and neurotransmission. Most of these effects have been attributed to the binding of cAMP to cAMP-dependent protein kinase A (P... | 10.1038/35073073 | References 13 and 14 were the first papers to show that a Rap1GEF is a genuine target for cAMP. |
10.1083/jcb.148.6.1151 | 38,196,292 | Integrin-mediated leukocyte adhesion is a critical aspect of leukocyte function that is tightly regulated by diverse stimuli, including chemokines, antigen receptors, and adhesion receptors. How cellular signals from CD31 and other adhesion amplifiers are integrated with those from classical mitogenic stimuli to regula... | 10.1038/35073073 | Together with references 67 and 72 , the first paper to show that Rap1 functions in the regulation of integrin activation. |
10.1073/pnas.96.26.14967 | 18,183,595 | Studies into posttranslational modifications of histones, notably acetylation, have yielded important insights into the dynamic nature of chromatin structure and its fundamental role in gene expression. The roles of other covalent histone modifications remain poorly understood. To gain further insight into histone meth... | 10.1038/35073047 | Indicates that histone methylation can be correlated with gene activation. |
10.1126/science.6239375 | 19,849,837 | Breaks were observed at 51 sites in homologous chromosomes in lymphocytes from ten humans and two great apes when cells were deprived of thymidine. The incidence of breaks was enhanced by caffeine, a substance that inhibits DNA repair in replicating cells. The locations of 20 sites were correlated with breakpoints that... | 10.1038/35106058 | Notes that locations of about half of the common fragile sites seem cytogenetically to coincide with locations of specific chromosome translocations that are associated with human cancers and might be near proto-oncogenes. |
10.1073/pnas.94.25.13771 | 102,902,118 | The candidate tumor suppressor gene, FHIT , encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal cancer translocation breakpoint, and cancer cell homozygous deletions. Fhit hydrolyzes dinucleotide 5′,5‴-P 1 ,P 3 -triphosphate in vitro and mutation of a central histidine abolishes hydrol... | 10.1038/35106058 | The first report of suppression of cancer-cell tumorigenicity by overexpression of exogenous Fhit |
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