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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10.1098/rspb.1958.0003 | 29,336,962 | An attempt has been made to correlate the dimensions of synapses as revealed by electron-microscopy with their functional operation. In particular the problems under consideration have concerned the synaptic cleft, which is the narrow space, 200 to 500 Å across, that separates the pre-synaptic from the sub-synaptic mem... | 10.1038/nrn.2017.101 | This study is a pioneering theoretical work predicting a substantial effect of electric fields on ion currents in small spaces such as the synaptic cleft. |
10.1126/science.1154330 | 81,279,890 | The synaptic response waveform, which determines signal integration properties in the brain, depends on the spatiotemporal profile of neurotransmitter in the synaptic cleft. Here, we show that electrophoretic interactions between AMPA receptor–mediated excitatory currents and negatively charged glutamate molecules acce... | 10.1038/nrn.2017.101 | This study provided the first experimental demonstration of electrodiffusion phenomena affecting glutamatergic transmission in the synaptic cleft. |
10.1038/s41598-017-11590-6 | 39,010,215 | Abstract Voltage and charge distributions in cellular microdomains regulate communications, excitability, and signal transduction. We report here new electrical laws in a biological cell, which follow from a nonlinear electro-diffusion model. These newly discovered laws derive from the geometrical cell-membrane propert... | 10.1038/nrn.2017.101 | This paper provides the most complete mathematical description to date of electrolyte electrodynamics in small cellular compartments. |
10.1242/jcs.00503 | 17,694,569 | In order to translate the findings from basic cellular research into clinical applications, cell-based models need to recapitulate both the 3D organization and multicellular complexity of an organ but at the same time accommodate systematic experimental intervention. Here we describe a hierarchy of tractable 3D models ... | 10.1038/nrmicro2423 | A definitive review on the relevance of using 3D tissue models as translational platforms to bridge the gap between basic cellular research and clinical applications. |
10.1186/1471-2180-13-131 | 27,961,054 | Abstract Background The global spread of bacterial resistance has given rise to a growing interest in new anti-bacterial agents with a new strategy of action. Pilicides are derivatives of ring-fused 2-pyridones which block the formation of the pili/fimbriae crucial to bacterial pathogenesis. They impair by means of a c... | 10.1038/nrmicro3432 | This paper provides a brief overview of two similar CUP pilus assembly pathways and shows that antivirulence compounds (pilicides) which were originally designed to specifically target one pathway have broad-spectrum activity against both CUP pilus pathways in E. coli |
10.1126/science.1084550 | 107,164,500 | Escherichia coli entry into the bladder is met with potent innate defenses, including neutrophil influx and epithelial exfoliation. Bacterial subversion of innate responses involves invasion into bladder superficial cells. We discovered that the intracellular bacteria matured into biofilms, creating pod-like bulges on ... | 10.1038/nrmicro3432 | This is the first paper to describe the intracellular cycle of a uropathogen and its importance for persistance. |
10.1126/scitranslmed.3009384 | 83,521,263 | Binding to host fibrinogen is a critical event in Enterococcus faecalis pathogenesis in catheter-associated urinary tract infections in mice. | 10.1038/nrmicro3432 | This is the first study to dissect the mechanism of E. faecalis infection during a CAUTI; this work led to the development of a vaccine that prevents infection in a mouse model of a CAUTI. |
10.1128/iai.00470-13 | 38,948,415 | ABSTRACT Urinary tract infections (UTI) are common and represent a substantial economic and public health burden. Roughly 80% of these infections are caused by a heterogeneous group of uropathogenic Escherichia coli (UPEC) strains. Antibiotics are standard therapy for UTI, but a rise in antibiotic resistance has compli... | 10.1038/nrmicro3432 | This investigation uses data from genomic, proteomic and metabolic screens to identify vaccine targets in E. coli ., all of which are involved in iron acquisition. Vaccination with several iron receptors during experimental UTIs in mice revealed that these factors were an effective target for the development of vaccine... |
10.1126/science.276.5312.607 | 20,816,519 | Virtually all uropathogenic strains of Escherichia coli , the primary cause of cystitis, assemble adhesive surface organelles called type 1 pili that contain the FimH adhesin. Sera from animals vaccinated with candidate FimH vaccines inhibited uropathogenic E. coli from binding to human bladder cells in vitro. Immuniza... | 10.1038/nrmicro3432 | This pivotal study shows that blocking the interaction between the bacterial adhesin and the host receptor through vaccination can prevent UTIs in mice. |
10.1126/scitranslmed.3003021 | 41,735,200 | Optimized mannoside compounds that block uropathogenic E. coli entry into bladder epithelium were effective in the treatment and prevention of urinary tract infections in mice. | 10.1038/nrmicro3432 | This key work uses compounds designed to prevent the E. coli type 1 pilus adhesin from binding the host receptor and demonstrates that these compounds are effective at preventing UTIs in mice. |
10.1128/mbio.02038-14 | 122,851,702 | ABSTRACT Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the l... | 10.1038/nrmicro3432 | This is the first paper to describe the role of pilicide in transcriptional and translational regulation in UPEC. |
10.1073/pnas.1315203110 | 2,696,962 | Significance The evolution of multidrug resistance in pathogenic bacteria, including uropathogenic Escherichia coli (UPEC), that cause most urinary tract infections is becoming a worldwide crisis. UPEC use a variety of virulence factors and adhesins, including the mannose-binding FimH adhesin, to colonize and invade bl... | 10.1038/nrmicro3432 | This study identifies the role of key FimH residues in protein conformation and virulence. |
10.1189/jlb.0407214 | 40,317,480 | Abstract Polyclonal B cell activation is not a peculiar characteristic to a particular infection, as many viruses, bacteria, and parasites induce a strong polyclonal B cell response resulting in hyper-γ-globulinemia. Here, we discuss the different roles proposed for polyclonal B cell activation, which can be crucial fo... | 10.1038/nrmicro3415 | This review describes both positive and negative effects of polyclonal B cell activation on the protective immune response during infections. |
10.1084/jem.20130914 | 105,378,740 | Antibody-mediated immunity to Shigella, the causative agent of bacillary dysentery, requires several episodes of infection to get primed and is short-lasting, suggesting that the B cell response is functionally impaired. We show that upon ex vivo infection of human colonic tissue, invasive S. flexneri interacts with an... | 10.1038/nrmicro3415 | This paper describes how S. flexneri manipulates B cell function by characterizing the pathogenic virulence factor, as well as the intrinsic B cell signalling pathway involved. |
10.1523/jneurosci.3232-04.2005 | 19,234,029 | Connexin45 (Cx45) is known to be expressed in the retina, but its functional analysis was problematic because general deletion of Cx45 coding DNA resulted in cardiovascular defects and embryonic lethality at embryonic day 10.5. We generated mice with neuron-directed deletion of Cx45 and concomitant activation of the en... | 10.1038/nrn1627 | This study reports results that are similar to those obtained from CX36-deficient mice (see reference 35). Both CX36- and CX45-knockout studies indicate that CX36 and CX45 form heterotypic electrical synapses between AII amacrine and ON cone bipolar cells. |
10.1162/jocn.1989.1.1.12 | 123,869,632 | Physiological studies have demonstrated that inputs from different sensory modalities converge on, and are integrated by, individual superior colliculus neurons and that this integration is governed by specific spatial rules. The present experiments were an attempt to relate these neural processes to overt behavior by ... | 10.1038/nrn3742 | This paper showed that the physiological principles of multisensory integration that are evident in single superior colliculus neurons applies to overt orientation behaviour. |
10.1126/science.6867718 | 62,367,876 | The responses of superior colliculus cells to a given sensory stimulus were influenced by the presence or absence of other sensory cues. By pooling sensory inputs, many superior colliculus cells seem to amplify the effects of subtle environmental cues in certain conditions, whereas in others, responses to normally effe... | 10.1038/nrn3742 | This was the first paper to demonstrate the multisensory integration capability of single superior colliculus neurons. |
10.1152/jn.2001.85.2.506 | 18,507,749 | The majority of multisensory neurons in the cat superior colliculus (SC) are able to synthesize cross-modal cues (e.g., visual and auditory) and thereby produce responses greater than those elicited by the most effective single modality stimulus and, sometimes, greater than those predicted by the arithmetic sum of thei... | 10.1038/nrn3742 | Two areas of association cortical areas were shown to have crucial roles in superior colliculus multisensory integration. |
10.1111/ejn.12423 | 103,038,432 | Abstract It is commonly believed that the ability to integrate information from different senses develops according to associative learning principles as neurons acquire experience with co‐active cross‐modal inputs. However, previous studies have not distinguished between requirements for co‐activation versus co‐variat... | 10.1038/nrn3742 | This was the first study to demonstrate that superior colliculus neurons require experience with co-varying cross-modal signals to develop the circuitry needed to integrate the information they provide. |
10.1111/j.1467-7687.2006.00512.x | 29,249,375 | Abstract Previous studies have shown that adults respond faster and more reliably to bimodal compared to unimodal localization cues. The current study investigated for the first time the development of audiovisual (A‐V) integration in spatial localization behavior in infants between 1 and 10 months of age. We observed ... | 10.1038/nrn3742 | A description of the postnatal development of multisensory-processing capabilities in human subjects. |
10.1126/science.1085167 | 83,326,586 | The sorting of sodium channels to axons and the formation of clusters are of primary importance for neuronal electrogenesis. Here, we showed that the cytoplasmic loop connecting domains II and III of the Na v 1 subunit contains a determinant conferring compartmentalization in the axonal initial segment of rat hippocamp... | 10.1038/nrn1253 | Identified a motif in a Na + channel subunit that is necessary for its localization at the axon initial segment. |
10.1083/jcb.200203050 | 58,525,772 | An axonal complex of cell adhesion molecules consisting of Caspr and contactin has been found to be essential for the generation of the paranodal axo-glial junctions flanking the nodes of Ranvier. Here we report that although the extracellular region of Caspr was sufficient for directing it to the paranodes in transgen... | 10.1038/nrn1253 | Shows that the stabilization of the Caspr/contactin complex at the cell membrane requires the intracellular region, which includes the protein 4.1B-binding domain. |
10.1083/jcb.147.6.1145 | 38,558,192 | Mice incapable of synthesizing the abundant galactolipids of myelin exhibit disrupted paranodal axo-glial interactions in the central and peripheral nervous systems. Using these mutants, we have analyzed the role that axo-glial interactions play in the establishment of axonal protein distribution in the region of the n... | 10.1038/nrn1253 | The first demonstration that nodes can form independently of the paranodal junction and that the paranodal junction is necessary to separate juxtaparanodal K + channels from the nodes. |
10.1083/jcb.200305018 | 18,958,010 | In myelinated axons, K+ channels are concealed under the myelin sheath in the juxtaparanodal region, where they are associated with Caspr2, a member of the neurexin superfamily. Deletion of Caspr2 in mice by gene targeting revealed that it is required to maintain K+ channels at this location. Furthermore, we show that ... | 10.1038/nrn1253 | References 123 and 124 suggest the existence of an axonal Caspr2/Tag1 complex and interacts with glial Tag1 at the juxtaparanodes, complex that is necessary for the accumulation of shaker -like K + channels at this site. |
10.1523/jneurosci.23-31-10032.2003 | 95,450,416 | Molecular events involved in Na + channel clustering at the node of Ranvier have been investigated during early development. NrCAM, an ankyrin G -binding protein, precedes Na + channels at cluster sites adjacent to the tips of Schwann cell processes. Both Na + channel and ankyrin G sequestration at developing nodes are... | 10.1038/nrn1253 | References 151 and 152 provide in vitro and in vivo evidence for the role of nodal CAMs in Na + channels clustering. |
10.1083/jcb.200110003 | 100,813,339 | β-Spectrin and ankyrin are major components of the membrane cytoskeleton. We have generated mice carrying a null mutation in the βIV-spectrin gene using gene trapping in embryonic stem cells. Mice homozygous for the mutation exhibit tremors and contraction of hindlimbs. βIV-spectrin expression is mostly restricted to n... | 10.1038/nrn1253 | References 154 and 155 show the requirement of spectrin βIV for the clustering of Na + channels at the nodes of Ranvier and the axon initial segments. |
10.1083/jcb.200212054 | 82,951,852 | One essential function of epithelia is to form a barrier between the apical and basolateral surfaces of the epithelium. In vertebrate epithelia, the tight junction is the primary barrier to paracellular flow across epithelia, whereas in invertebrate epithelia, the septate junction (SJ) provides this function. In this s... | 10.1038/nrn1253 | The first evidence that generation of septate junctions in Drosophila requires neuroglian, the fly homologue of Nf155. |
10.1126/science.1111331 | 124,253,066 | Two distinct forms of consolidated associative memory are known in Drosophila : long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more s... | 10.1038/nrn3427 | An intriguing report documenting a trade-off between memory and lifespan under certain (stressful) conditions. |
10.1073/pnas.1100701108 | 45,500,829 | The physical properties of Arctic sea ice determine its habitability. Whether ice-dwelling organisms can change those properties has rarely been addressed. Following discovery that sea ice contains an abundance of gelatinous extracellular polymeric substances (EPS), we examined the effects of algal EPS on the microstru... | 10.1038/nrmicro3522 | Quantitative image and chemical analyses of natural and laboratory-grown sea ice shows that EPS produced by diatoms alters the physical complexity of ice pores, increasing the habitable liquid-filled space within the ice and the potential for primary productivity. |
10.1073/pnas.0504766102 | 81,255,705 | The completion of the 5,373,180-bp genome sequence of the marine psychrophilic bacterium Colwellia psychrerythraea 34H, a model for the study of life in permanently cold environments, reveals capabilities important to carbon and nutrient cycling, bioremediation, production of secondary metabolites, and cold-adapted enz... | 10.1038/nrmicro3522 | This paper provides comprehensive background information on cold adaptation in general and detailed insights into the numerous specific adaptations of the marine psychrophilic bacterium C. psychrerythraea 34H. |
10.1038/ismej.2012.107 | 80,269,241 | Abstract Darkening of parts of the Greenland ice sheet surface during the summer months leads to reduced albedo and increased melting. Here we show that heavily pigmented, actively photosynthesising microalgae and cyanobacteria are present on the bare ice. We demonstrate the widespread abundance of green algae in the Z... | 10.1038/nrmicro3522 | This study provides evidence for how the development of pigmentation in eukaryotic algae during the melting season promotes darkening of large areas of the Greenland Ice Sheet and thus influences its reflective properties. |
10.1038/ismej.2009.113 | 104,347,784 | Abstract Perennially cold habitats are diminishing as a result of climate change; however, little is known of the diversity or biogeography of microbes that thrive in such environments. Here we use targeted 16S rRNA gene surveys to evaluate the global affinities of cold-dwelling cyanobacteria from lake, stream and ice ... | 10.1038/nrmicro3522 | Using targeted sequencing of 16S rRNA of cyanobacteria, this study demonstrates a global distribution of low-temperature cyanobacterial ecotypes throughout the cold terrestrial biosphere. |
10.1126/science.1167350 | 20,681,929 | An active microbial assemblage cycles sulfur in a sulfate-rich, ancient marine brine beneath Taylor Glacier, an outlet glacier of the East Antarctic Ice Sheet, with Fe(III) serving as the terminal electron acceptor. Isotopic measurements of sulfate, water, carbonate, and ferrous iron and functional gene analyses of ade... | 10.1038/nrmicro3522 | This work provides important insight into the biogeochemistry of anoxic subglacial brine and microbial diversity in subglacial habitats and their role in global iron fluxes. |
10.1111/j.1471-4159.2006.03746.x | 45,403,052 | Abstract Peripheral nerve injury can induce spinal microglial/astrocyte activation. Substances released by activated glial cells excite spinal nociceptive neurons. Pharmacological disruption of glial activation or antagonism of substances released by activated glia prevent or reverse pain hypersensitivity. It is not kn... | 10.1038/nrn2533 | This study demonstrated that peripheral immune–CNS interactions lead to neuropathic pain through chemokine action. |
10.1073/pnas.0709250104 | 38,733,043 | Chemokines and chemokine receptors are widely expressed by cells of the immune and nervous systems. This review focuses on our current knowledge concerning the role of chemokines in the pathophysiology of chronic pain syndromes. Injury- or disease-induced changes in the expression of diverse chemokines and their recept... | 10.1038/nrn2533 | A comprehensive review that describes the role of chemokines in pain signalling. |
10.1002/prca.200780048 | 41,023,607 | Abstract Gram‐positive streptococci are non‐motile, chain‐forming bacteria commonly found in the normal oral and bowel flora of warm‐blooded animals. Over the past decade, a proteomic approach combining 2‐DE and MS has been used to systematically map the cellular, surface‐associated and secreted proteins of human patho... | 10.1038/nrmicro2648 | An overview of streptococcal proteomics and the selection of antigens as novel vaccine candidates. |
10.1046/j.1365-2958.2003.03797.x | 26,721,237 | Summary A globally disseminated strain of M1T1 group A Streptococcus (GAS) has been associated with severe infections in humans including necrotizing fasciitis and toxic shock syndrome. Recent clinicoepidemiologic data showed a striking inverse relationship between disease severity and the degree to which M1T1 GAS expr... | 10.1038/nrmicro2648 | Proteomic analyses showing that covRS mutations results in the downregulation of SpeB protease activity and the upregulation of multiple GAS serotype M1T1 virulence factors. |
10.1159/000203645 | 125,188,098 | M1 protein contributes to Group A <i>Streptococcus</i> (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation... | 10.1038/nrmicro2648 | A report describing the finding that M1 protein enhances bacterial survival of neutrophil-mediated killing through inhibition of human antimicrobial peptides. |
10.1126/science.1101245 | 60,834,472 | Group A streptococci, a common human pathogen, secrete streptokinase, which activates the host's blood clot–dissolving protein, plasminogen. Streptokinase is highly specific for human plasminogen, exhibiting little or no activity against other mammalian species, including mouse. Here, a transgene expressing human plasm... | 10.1038/nrmicro2648 | A report showing that human plasminogen is activated to plasmin on the GAS cell surface, allowing the destruction of host tissue barriers and triggering systemic spread. |
10.1159/000317640 | 64,454,857 | Group A <i>Streptococcus</i> (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (<i>covRS)</i> operon correlat... | 10.1038/nrmicro2648 | The first report of non-M1 GAS undergoing covRS mutations in vivo , but at a reduced frequency compared with GAS serotype M1T1. |
10.1099/mic.0.042614-0 | 36,195,167 | Expression of the extensive arsenal of virulence factors by Streptococcus pyogenes is controlled by many regulators, of which CovRS is one of the best characterized and can influence ∼15 % of the genome. Animal models have established that mutants of covRS arise spontaneously in vivo resulting in highly invasive organi... | 10.1038/nrmicro2648 | The first report to document the covRS mutations of GAS serotype M81.0 in humans. |
10.1126/science.1254426 | 104,387,229 | HIV's shape-shifting envelope protein HIV's envelope protein (Env) coats virus particles and allows HIV to enter host cells. HIV entry is highly dynamic. Env proteins work in groups of three (called trimers), which bind to the viral receptor and co-receptor, both expressed by host cells. Viral receptor binding causes a... | 10.1038/nsmb.3119 | The authors labeled a small fraction of fusion proteins on the surface of HIV particles with FRET probes and visualized conformational changes of the individual fusion trimers |
10.1126/science.1078973 | 18,937,592 | After transport across the cytoplasmic membrane, bacterial outer membrane proteins are assembled into the outer membrane. Meningococcal Omp85 is a highly conserved protein in Gram-negative bacteria, and its homolog Toc75 is a component of the chloroplast protein-import machinery. Omp85 appeared to be essential for viab... | 10.1038/nrmicro2733 | This elegant study demonstrates the essential nature of BamA and its role in the biogenesis of OMPs. |
10.1111/j.1365-2958.2009.06607.x | 27,074,505 | Summary Autotransporter (AT) proteins are a large and diverse family of extracellular virulence proteins from Gram‐negative bacteria, characterized by a central β‐helix domain within the mature virulence protein. It is not clear how these proteins cross the outer membrane (OM) quickly and efficiently, without assistanc... | 10.1038/nrmicro2733 | This report documents vectorial transport and folding of pertactin, showing (through disulphide bond-mediated passenger domain stalling) that the carboxyl terminus of the passenger domain is presented on the bacterial cell surface first and folds into a stable protease-resistant structure. |
10.1073/pnas.0507923103 | 122,643,412 | Many virulence factors secreted from pathogenic Gram-negative bacteria are autotransporter proteins. The final step of autotransporter secretion is C → N-terminal threading of the passenger domain through the outer membrane (OM), mediated by a cotranslated C-terminal porin domain. The native structure is formed only af... | 10.1038/nrmicro2733 | This study reveals the folding of pertactin, demonstrating that the carboxyl terminus of the β-helix is more stable than the amino-terminal rungs. The authors suggest a general mechanism for AT secretion, in which the carboxy-terminal core serves as a scaffold that allows stacking of the β-helix to initiate vectorial f... |
10.1046/j.1365-2958.2003.03377.x | 18,597,354 | Summary Autotransporter secretion represents a unique mechanism that Gram‐negative bacteria employ to deliver proteins to their cell surface. BrkA is a Bordetella pertussis autotransporter protein that mediates serum resistance and contributes to adherence of the bacterium to host cells. BrkA is a 103 kDa protein that ... | 10.1038/nrmicro2733 | This paper provides genetic, biochemical and structural evidence that the AC domain of BrkA is required for folding and stability of the passenger domain concurrent with or after outer-membrane translocation. |
10.1126/science.1188919 | 107,326,954 | Bring Out the β-Barrel The assembly of β-barrel membrane proteins, which are found in the outer membrane of Gram-negative bacteria and in the mitochondria and chloroplasts of eukaryotes, is poorly understood. Now Hagan et al. (p. 890 , published online 8 April; see the Perspective by Stroud et al. ) describe the develo... | 10.1038/nrmicro2733 | This work shows, for the first time, that components of the Bam complex can be purified and functionally reconstituted in proteoliposomes. This study finds that the assembly of a β-barrel substrate requires a soluble chaperone in addition to the Bam complex and occurs without an input of energy. |
10.1111/j.1460-9568.2010.07253.x | 29,259,571 | Abstract In higher vertebrates, the extracellular matrix (ECM) wrapping cells of the adult brain differs significantly from that of the developing and juvenile brain. The mature ECM is established at the end of critical periods for wiring and it restricts the regenerative potential and constrains the plasticity of the ... | 10.1038/nrn3320 | This is a comprehensive review of current information about how the ECM regulates synaptic plasticity. |
10.1152/jn.00202.2007 | 19,973,395 | Extracellular proteolysis is an important regulatory nexus for coordinating synaptic functional and structural plasticity, but the identity of such proteases is incompletely understood. Matrix metalloproteinases (MMPs) have well-known, mostly deleterious roles in remodeling after injury or stroke, but their role in non... | 10.1038/nrn3320 | This study demonstrates loss- and gain-of-function effects of MMP9 in adult rat hippocampal synaptic physiology in vivo , which validates the relevance of slice studies and introduces a new modification of in vivo zymography. |
10.1073/pnas.0807248105 | 40,396,069 | Persistent dendritic spine enlargement is associated with stable long-term potentiation (LTP), and the latter is thought to underlie long-lasting memories. Extracellular proteolytic remodeling of the synaptic microenvironment could be important for such plasticity, but whether or how proteolytic remodeling contributes ... | 10.1038/nrn3320 | This study combines whole-cell recording with simultaneous two-photon imaging to demonstrate that MMP9 acts through integrins to coordinate both synaptic potentiation and spine enlargement. |
10.1073/pnas.0601354103 | 20,363,561 | Long-term potentiation (LTP), like memory, becomes progressively more resistant to disruption with time after its formation. Here we show that threshold conditions for inducing LTP cause a rapid, long-lasting increase in polymerized filamentous actin in dendritic spines of adult hippocampus. Two independent manipulatio... | 10.1038/nrn3320 | This is one of a series of papers from the Lynch and Gall laboratories that define the role of integrins in consolidation of hippocampal LTP. |
10.1046/j.1460-9568.2000.00035.x | 109,154,576 | Abstract We found that neuropsin, an extracellular matrix serine protease, has a regulatory effect on Schaffer‐collateral long‐term potentiation (LTP) in the mouse hippocampus. Bath application of 1–170 n m recombinant neuropsin modulated early phase LTP in the Schaffer‐collateral pathway with a ‘bell‐shape’ dose–respo... | 10.1038/nrn3320 | This is one of a series of studies from the Shiosaka laboratory on the role, regulation and targets of the serine protease neuropsin in LTP. |
10.1101/lm.476207 | 121,838,261 | Persistent drug seeking/taking behavior involves the consolidation of memory. With each drug use, the memory may be reactivated and reconsolidated to maintain the original memory. During reactivation, the memory may become labile and susceptible to disruption; thus, molecules involved in plasticity should influence acq... | 10.1038/nrn3320 | This and the preceding study make the important link between maladaptive plasticity of drug addiction and aberrant MMP regulation and activity. |
10.1002/glia.20927 | 100,428,812 | Abstract Astrocytes play an active role in the central nervous system and are critically involved in astrogliosis, a homotypic response of these cells to disease, injury, and associated neuroinflammation. Among the numerous molecules involved in these processes are the matrix metalloproteinases (MMPs), a family of zinc... | 10.1038/nrn3320 | This and reference 147 provide detailed information on cellular trafficking and vesicular release of MMPs and TIMPs in neurons and glia. |
10.1126/science.1925601 | 102,720,379 | To better understand the basis for human immunodeficiency virus type 1 (HIV-1) persistence and latency, the form in which viral DNA exists in the peripheral T lymphocyte reservoir of infected individuals was investigated. In asymptomatic individuals, HIV-1 was harbored predominantly as full-length, unintegrated complem... | 10.1038/nrmicro3352 | This paper identifies resting T lymphocytes as a major reservoir of HIV-1 infection in which the virus can be reactivated following cell stimulation. |
10.1126/science.1256304 | 123,024,880 | A not-so-random integration for HIV Even in the face of a cocktail of antiretroviral drugs, HIV manages to hang on. It does so by integrating its own genome into those of host cells, where it persists in a latent state. To better understand this process, Wagner et al. determined the sites where HIV integrated into thre... | 10.1038/nrmicro3352 | References 35 and 38 show that HIV-1 integrates into genes associated with cellular proliferation, which may contribute to aberrant proliferation of silenced HIV-1 genomes. |
10.1126/science.1242974 | 41,615,552 | Background Many mature cells of the body are continuously replaced, particularly in tissues that are most exposed to the environment such as cells of the immune system. The need for new cells is driven by cellular turnover during normal tissue homeostasis and is further increased upon infection. Because differentiated ... | 10.1038/nrmicro3352 | This article reviews recent evidence indicating that, like stem cells, macrophages have self-renewing capabilities. |
10.1111/j.1749-6632.2001.tb05829.x | 82,578,817 | A bstract : Nitric oxide (NO) is an unstable gas that plays important roles in the brain in general and in neuroendocrine functions in particular. We have shown that NO exerts opposite effects within the median eminence‐pituitary axis, where it inhibits ACTH responses to blood‐borne signals [such as the systemic inject... | 10.1038/nrn2214 | A useful paper for understanding the controversial action of NO in the regulation of the stress axis. |
10.1046/j.1471-4159.2003.01786.x | 87,105,803 | Abstract Nitration of tyrosine in biological conditions represents a pathological event that is associated with several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease (AD). Increased levels of nitrated proteins have been reported in AD brain and CSF, demon... | 10.1038/nrn2214 | This was the first proteomics study to identify nitrated proteins in the brain of patients with Alzheimer's disease. |
10.1523/jneurosci.14-09-05147.1994 | 82,475,690 | In a remarkably brief period of time, NO and CO have been recognized as putative neurotransmitters. These two novel messenger molecules have greatly expanded the criteria for candidacy of a chemical for the status of neurotransmitter and our notions about how synaptic transmission takes place. The involvement of NO and... | 10.1038/nrn2214 | This paper provides details on the distribution of nNOS in the CNS and PNS. |
10.1073/pnas.74.8.3203 | 20,508,504 | Nitric oxide gas (NO) increased guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue preparations examined. The extent of activation was variable among different tissue pr... | 10.1038/nrn2214 | A milestone paper about the ability of NO to activate sGC. |
10.1073/pnas.84.24.9265 | 125,130,627 | The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and vein that mediates the action of endothelium-dependent vasodilators. NO i... | 10.1038/nrn2214 | A milestone paper that reveals the identity of EDRF as NO. |
10.1073/pnas.0511321103 | 865,494 | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) participates in a cell death cascade wherein a variety of stimuli activate nitric oxide (NO) synthases with NO nitrosylating GAPDH, conferring on it the ability to bind to Siah, an E3-ubiquitin-ligase, whose nuclear localization signal enables the GAPDH/Siah protein comp... | 10.1038/nrn2214 | This paper describes a GAPDH–SIAH1-mediated pathway for cell death and unravels a new mechanism of action for selegiline, a drug used in the treatment of Parkinson's disease. |
10.1073/pnas.90.6.2394 | 102,802,081 | Brief learning experience (classical conditioning) induces frequency-specific receptive-field (RF) plasticity in the auditory cortex, characterized as increased response to the frequency of the conditioned stimulus and decreased responses to most other frequencies, including the pretraining best frequency. This experim... | 10.1038/nrn1366 | This paper showed that CS-specific plasticity in A1 exhibits long-term retention, tested to eight weeks post-training. |
10.1126/science.287.5451.248 | 38,447,845 | The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mec... | 10.1038/nrn1366 | An outstanding overview of theory and findings in brain and memory consolidation. |
10.1046/j.0953-816x.2001.01568.x | 4,214,926 | Abstract Long‐term modification of cortical receptive field maps follows learning of sensory discriminations and conditioned associations. In the process of determining whether appetitive – as opposed to aversive – conditioning is effective in causing such plastic changes, it was discovered that multineuron receptive f... | 10.1038/nrn1366 | This is the first report of appetitive suprathreshold tuning shifts and includes an extended pre-training baseline period, showing that RF plasticity is associative rather than reflective of spontaneous tuning changes. |
10.1073/pnas.93.20.11219 | 102,406,927 | Auditory cortical receptive field plasticity produced during behavioral learning may be considered to constitute "physiological memory" because it has major characteristics of behavioral memory: associativity, specificity, rapid acquisition, and long-term retention. To investigate basal forebrain mechanisms in receptiv... | 10.1038/nrn1366 | This paper initiated inquiries into the role of the NB in associative mechanisms in auditory cortical plasticity and memory by showing that pairing a tone with NB stimulation induced associative CS-specific RF plasticity in the auditory cortex. |
10.1073/pnas.062057099 | 65,346,037 | The nucleus basalis (NB) has been implicated in memory formation indirectly, by lesions, pharmacological manipulations, and neural correlates of learning. Prior findings imply that engagement of the NB during learning promotes memory storage. We directly tested this NB-memory hypothesis by determining whether stimulati... | 10.1038/nrn1366 | This is the only known demonstration that pairing a tone with non-motivational stimulation of the brain induces a highly specific behavioural memory, directly implicating the NB. |
10.1126/science.1193692 | 103,731,678 | MicroRNA-16 and Depression Signal transmission between neurons is effected by neurotransmitters such as serotonin. Membrane-bound transporters remove excess neurotransmitters. Disruption of the delicate balance between neurotransmitter release and removal can lead to larger disruptions in neuronal circuitry. Depression... | 10.1038/nrn3879 | In this comprehensive study, a specific miRNA was strongly linked to the mode of action of SSRIs using animal and cellular models. |
10.1523/jneurosci.0914-13.2013 | 62,537,729 | Neuropsychiatric disease frequently presents with an underlying hyporeactivity or hyperreactivity of the HPA stress axis, suggesting an exceptional vulnerability of this circuitry to external perturbations. Parental lifetime exposures to environmental challenges are associated with increased offspring neuropsychiatric ... | 10.1038/nrn3879 | In this paper, it is implied that sperm miRNAs are mediators of the transgenerational effects of stress. |
10.1073/pnas.0905959106 | 64,372,940 | In biology, rapid oxidation and evolution of H 2 is catalyzed by metalloenzymes known as hydrogenases. These enzymes have unusual active sites, consisting of iron complexed by carbonyl, cyanide, and thiolate ligands, often together with nickel, and are typically inhibited or irreversibly damaged by O 2 . The Knallgas b... | 10.1038/nrmicro2940 | In this study, the reaction behaviour of R. eutropha MBH is examined over a range of potentials, pH values and temperatures, revealing that O 2 tolerance correlates with the reactivation kinetics rather than with H 2 affinity or the kinetics of O 2 attack. |
10.1073/pnas.1001703107 | 16,262,335 | Many Gram-negative bacteria secrete specific proteins via the type II secretion systems (T2SS). These complex machineries share with the related archaeal flagella and type IV pilus (T4P) biogenesis systems the ability to assemble thin, flexible filaments composed of small, initially inner membrane-localized proteins ca... | 10.1038/nrmicro2762 | A description of a pseudopilus model that combines experimental data and modelling methods. |
10.1073/pnas.84.21.7418 | 79,681,391 | The secretion of enterotoxin by Vibrio cholerae is punctuated by the transient entry of the toxin subunits into the periplasm. In this paper, we show that the subunits oligomerize into an assembled holotoxin within the periplasm prior to their secretion across the outer membrane. The rate of toxin assembly was studied ... | 10.1038/nrmicro2762 | The first study to show that proteins to be secreted via the T2SS have already folded into tertiary and even quaternary conformations. |
10.1126/science.1166112 | 82,998,424 | During fixation, the eyes are not still but often exhibit microsaccadic movements. The function of microsaccades is controversial, largely because the neural mechanisms responsible for their generation are unknown. Here, we show that the superior colliculus (SC), a retinotopically organized structure involved in volunt... | 10.1038/nrn3405 | This research established a causal role of the SC in microsaccade production. |
10.1073/pnas.212500599 | 109,136,906 | When images are stabilized on the retina, visual perception fades. During voluntary visual fixation, however, constantly occurring small eye movements, including microsaccades, prevent this fading. We previously showed that microsaccades generated bursty firing in the primary visual cortex (area V-1) in the presence of... | 10.1038/nrn3405 | The parameters of microsaccade-triggered bursts of spikes in the lateral geniculate nucleus and area V1 varied depending on whether the stationary stimuli presented were optimal or non-optimal. |
10.1126/science.1099745 | 41,749,409 | Clocks tick, bridges and skyscrapers vibrate, neuronal networks oscillate. Are neuronal oscillations an inevitable by-product, similar to bridge vibrations, or an essential part of the brain's design? Mammalian cortical neurons form behavior-dependent oscillating networks of various sizes, which span five orders of mag... | 10.1038/nrn2201 | An excellent introduction to the role of oscillations over a wide frequency range in supporting cortical network structure. |
10.1146/annurev.neuro.29.051605.112819 | 103,733,804 | Functional brain imaging with positron emission tomography and magnetic resonance imaging has been used extensively to map regional changes in brain activity. The signal used by both techniques is based on changes in local circulation and metabolism (brain work). Our understanding of the cell biology of these changes h... | 10.1038/nrn2201 | A comprehensive review of brain circulation and metabolism, its relationship to neurophysiology and functional brain imaging signals. |
10.1002/mrm.1910340409 | 125,327,842 | Abstract An MRI time course of 512 echo‐planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodolo... | 10.1038/nrn2201 | The first paper to note the presence of spontaneous, spatially coherent activity in the fMRI BOLD signal. |
10.1073/pnas.1831638100 | 62,545,847 | We assessed the relation between hemodynamic and electrical indices of brain function by performing simultaneous functional MRI (fMRI) and electroencephalography (EEG) in awake subjects at rest with eyes closed. Spontaneous power fluctuations of electrical rhythms were determined for multiple discrete frequency bands, ... | 10.1038/nrn2201 | A simultaneous BOLD/EEG study relating changes in the power of different EEG frequency bands to spontaneous BOLD fluctuations in distinct systems. |
10.1073/pnas.0305375101 | 62,619,953 | Human cortical activity has been intensively examined at frequencies ranging from 0.5 Hz to several hundred Hz. Recent studies have, however, reported also infraslow fluctuations in neuronal population activity, magnitude of electroencephalographic oscillations, discrete sleep events, as well as in the occurrence of in... | 10.1038/nrn2201 | An important paper addressing the role of infra-slow brain oscillations as seen from the EEG perspective. |
10.1126/science.3059497 | 81,580,704 | This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between th... | 10.1038/nrn2201 | An early paper by one of the long term advocates of the importance of intrinsic activity for brain function. |
10.1073/pnas.0809467105 | 125,231,112 | In contrast to the cell division machineries of bacteria, euryarchaea, and eukaryotes, no division components have been identified in the second main archaeal phylum, Crenarchaeota. Here, we demonstrate that a three-gene operon, cdv , in the crenarchaeon Sulfolobus acidocaldarius , forms part of a unique cell division ... | 10.1038/nrmicro2406 | This study and that described in reference 16 provide evidence that Sulfolobus spp. homologues of ESCRT-III and VPS4 are involved in cell division. |
10.1186/1745-6150-4-9 | 122,684,136 | Abstract Background Phagocytosis, that is, engulfment of large particles by eukaryotic cells, is found in diverse organisms and is often thought to be central to the very origin of the eukaryotic cell, in particular, for the acquisition of bacterial endosymbionts including the ancestor of the mitochondrion. Results Com... | 10.1038/nrmicro2406 | This study describes archaeal actin-like proteins and suggests a hypothetical scenario of eukaryogenesis. In this scenario, the archaeal ancestor of eukaryotes possessed an actin-based cytoskeleton, including branched filaments, that allowed this organism to produce actin-supported membrane protrusions, and these protr... |
10.1126/science.3749894 | 38,918,467 | Cholinergic agonists rapidly and transiently induced transcription of the c- fos protooncogene and one or more actin genes in neuronally differentiated PC12 cells. Transcription was activated within minutes after stimulation of the nicotinic acetylcholine receptor and required an influx of extracellular Ca 2+ ions thro... | 10.1038/nrn987 | The first demonstration that neurotransmitters can rapidly induce gene transcription. |
10.1126/science.1063395 | 80,154,923 | Increases in the intracellular concentration of calcium ([Ca 2+ ] i ) activate various signaling pathways that lead to the expression of genes that are essential for dendritic development, neuronal survival, and synaptic plasticity. The mode of Ca 2+ entry into a neuron plays a key role in determining which signaling p... | 10.1038/nrn987 | This paper shows that the association of the signalling molecule calmodulin with the L-VGCC is required for calcium entry through the L-VGCC to activate CREB-dependent transcription. |
10.1073/pnas.79.24.7929 | 62,310,262 | A panel of 148 monoclonal antibodies directed against Drosophila neural antigens has been prepared by using mice immunized with homogenates of Drosophila tissue. Antibodies were screened immunohistochemically on cryostat sections of fly heads. A large diversity of staining patterns was observed. Some antigens were broa... | 10.1038/nrn1243 | The first paper to identify markers that recognize individual neurons. This paper greatly aided the description of the neuronal architecture and enabled the accurate description of mutant phenotypes. |
10.1242/dev.125.6.1049 | 62,622,716 | A modular misexpression system was used to carry out systematic gain-of-function genetic screens in Drosophila. The system is based on inducible expression of genes tagged by insertion of a P-element vector carrying a GAL4-regulated promoter oriented to transcribe flanking genomic sequences. To identify genes involved ... | 10.1038/nrn1243 | Application of a modular misexpression system of Drosophila to allow gain-of-function screens. The system involves the creation of modified P-elements containing GAL4 binding sequences (EP-elements) that can be mobilized to allow over- or misexpression of random genes in identified cells. |
10.1242/dev.127.4.851 | 62,582,706 | During development of the adult Drosophila visual system, axons of the eight photoreceptors in each ommatidium fasciculate together and project as a single bundle towards the optic lobes of the brain. Within the brain, individual photoreceptor axons from each bundle then seek specific targets in distinct layers of the ... | 10.1038/nrn1243 | Reports the generation of mosaic animals in a tissue-specific manner. This strategy was used here to perform a large-scale mutagenesis screen for mosaic larvae with visual system defects. |
10.1523/jneurosci.03-01-00031.1983 | 102,228,787 | In the previous paper (Raper, J.A., M. Bastiani, and C.S. Goodman (1983) J. Neurosci. 3:20–30) we showed that the growth cones of two sibling neurons, the G and C cells, follow the same route in the developing grasshopper neuropil until they reach a stereotypic choice point. Here their growth cones diverge from each ot... | 10.1038/nrn1243 | In this paper, it is proposed that growth cones of later differentiating neurons are programmed to choose between and elongate on the axons of specifically labelled pioneer axons, leading to the labelled pathway hypothesis. |
10.1002/ana.24646 | 81,998,930 | We assessed loss of dorsolateral nigral hyperintensity (DNH) on high‐field susceptibility‐weighted imaging (SWI), a novel magnetic resonance imaging marker for Parkinson's disease (PD), in 15 subjects with idiopathic rapid eye movement sleep behavior disorder (iRBD) and compared findings to 42 healthy controls (HCs) an... | 10.1038/nrneurol.2017.157 | This MRI study shows that at least two-thirds of patients with idiopathic RBD present with loss of dorsolateral nigral hyperintensity, similarly to that in patients with degenerative parkinsonism, and introduces a novel potential biomarker of prodromal PD. |
10.1002/ana.25026 | 17,594,476 | Objective To determine the usefulness of dopamine transporter (DAT) imaging to identify idiopathic rapid eye movement sleep behavior disorder (IRBD) patients at risk for short‐term development of clinically defined synucleinopathy. Methods Eighty‐seven patients with polysomnography‐confirmed IRBD underwent 123 I‐FP‐CIT... | 10.1038/nrneurol.2017.157 | This study shows that DAT imaging deficits identify patients with idiopathic RBD at an increased risk of early development of clinically defined α-synucleinopathy. |
10.1002/ana.22282 | 124,220,810 | Abstract Objective: For development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. However, current means of identifying “preclinical” neurodegeneration are limited. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) are at >50% risk of syn... | 10.1038/nrneurol.2017.157 | This longitudinal study of patients with idiopathic RBD shows that individuals with olfactory dysfunction or impaired colour vision at baseline were more likely than those without these features to develop overt neurodegeneration during 5 years of follow-up. |
10.1038/ncomms14967 | 6,972,588 | Abstract Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood–brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). H... | 10.1038/nrn.2018.7 | This study reports the development of a novel tool allowing chemical genetic ablation of genes of interest strictly in peripheral tissues. |
10.1152/physrev.00015.2003 | 125,083,480 | Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic e... | 10.1038/nrn.2018.7 | This is a comprehensive and detailed review of BAT biology. |
10.1152/ajpregu.00344.2016 | 18,181,450 | White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their function. We injected two isogenic strains of pseudorabies virus, a retro... | 10.1038/nrn.2018.7 | This paper provides neuroanatomical and functional evidence of the existence of SNS crosstalk for thermoregulation and BeAT development. |
10.1002/cne.10643 | 82,246,684 | Abstract The thermogenic activity of interscapular brown adipose tissue (IBAT) in response to physiologic stimuli, such as cold exposure, is controlled by its sympathetic innervation. To determine which brain regions might be involved in the regulation of cold‐evoked increases in sympathetic outflow to IBAT, the presen... | 10.1038/nrn.2018.7 | This study demonstrates the central circuitry responsible for cold-induced increase in sympathetic outflow to interscapular BAT. |
10.1016/j.febslet.2009.10.071 | 101,014,478 | In the budding yeast, a large fraction of genes is coordinately regulated with growth rate. We argue that this correlation does not reflect a direct feedback from growth rate to gene expression. Rather, what appears to be a response to growth rate is dominated by environmental sensing. External parameters, such as nutr... | 10.1038/nrmicro3238 | This paper brings forwards the distinction between feedforward and feedback strategies of growth regulation. |
10.1073/pnas.1202582110 | 60,523,140 | Regulation of metabolic operation in response to extracellular cues is crucial for cells’ survival. Next to the canonical nutrient sensors, which measure the concentration of nutrients, recently intracellular “metabolic flux” was proposed as a novel impetus for metabolic regulation. According to this concept, cells wou... | 10.1038/nrmicro3238 | This study experimentally demonstrates the potential of FBP to report glycolytic flux in E. coli |
10.1038/msb.2013.14 | 107,366,212 | Gene expression is regulated by specific transcriptional circuits but also by the global expression machinery as a function of growth. Simultaneous specific and global regulation thus constitutes an additional—but often neglected—layer of complexity in gene expression. Here, we develop an experimental‐computational app... | 10.1038/nrmicro3238 | This paper unravels the regulatory logic of the arginine biosynthesis pathway in E. coli by combining experimental and computational efforts. |
10.1073/pnas.132285199 | 80,892,905 | We showed previously that rrn P1 promoters require unusually high concentrations of the initiating nucleoside triphosphates (ATP or GTP, depending on the promoter) for maximal transcription in vitro . We proposed that this requirement for high initiating NTP concentrations contributes to control of the rrn P1 promoters... | 10.1038/nrmicro3238 | This paper demonstrates the regulation of rRNA expression by nucleotide triphosphates in E. coli |
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