source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1126/science.290.5499.2144 | 45,485,826 | This report presents full-genome evidence that bacterial cells use discrete transcription patterns to control cell cycle progression. Global transcription analysis of synchronized Caulobacter crescentus cells was used to identify 553 genes (19% of the genome) whose messenger RNA levels varied as a function of the cell ... | 10.1038/nrmicro864 | First application of whole-genome DNA microarrays to the study of global gene expression patterns in wild-type and mutant Caulobacter |
10.1126/science.1072163 | 26,459,903 | Bacteria are often highly polarized, exhibiting specialized structures at or near the ends of the cell. Among such structures are actin-organizing centers, which mediate the movement of certain pathogenic bacteria within the cytoplasm of an animal host cell; organized arrays of membrane receptors, which govern chemosen... | 10.1038/nrmicro864 | An outstanding review of the molecular mechanisms used to produce, maintain and use asymmetry in bacteria. |
10.1073/pnas.95.4.1443 | 60,275,071 | Cell differentiation and division in Caulobacter crescentus are regulated by a signal transduction pathway mediated by the histidine kinase DivJ and the essential response regulator DivK. Here we report genetic and biochemical evidence that the DivJ and DivK proteins function to control the activity of CtrA, a response... | 10.1038/nrmicro864 | Another sophisticated genetic screen that identified the essential master regulator CtrA and placed it in the context of previously studied two-component signalling systems. |
10.1126/science.2683079 | 107,325,132 | The events of the cell cycle of most organisms are ordered into dependent pathways in which the initiation of late events is dependent on the completion of early events. In eukaryotes, for example, mitosis is dependent on the completion of DNA synthesis. Some dependencies can be relieved by mutation (mitosis may then o... | 10.1038/nrmicro864 | An authoritative discussion of checkpoints, from a definition to how they function in controlling cell-cycle progression. |
10.1126/science.1095191 | 45,561,678 | A newly identified cell-cycle master regulator protein, GcrA, together with the CtrA master regulator, are key components of a genetic circuit that drives cell-cycle progression and asymmetric polar morphogenesis in Caulobacter crescentus . The circuit drives out-of-phase temporal and spatial oscillation of GcrA and Ct... | 10.1038/nrmicro2612 | This paper identifies GcrA and provides a first outline of an oscillating genetic circuit, which is part of the cell cycle oscillator in C. crescentus |
10.1126/science.1108451 | 29,110,098 | Kai proteins globally regulate circadian gene expression of cyanobacteria. The KaiC phosphorylation cycle, which persists even without transcription or translation, is assumed to be a basic timing process of the circadian clock. We have reconstituted the self-sustainable oscillation of KaiC phosphorylation in vitro by ... | 10.1038/nrmicro2612 | This work is the first demonstration that the KaiABC system generates self-sustainable oscillations in KaiC phosphorylation in vitro |
10.1126/science.1197243 | 41,210,321 | Cyanobacterial circadian clock components are directly coupled to the metabolic status of the cell through interactions with adenine nucleotides. | 10.1038/nrmicro2612 | This study finds that light-induced changes which cause entrainment also induce a change in the ATP/ADP ratio, and that this directly affects KaiC phosphorylation in vitro |
10.1126/science.1148596 | 103,895,212 | The simple circadian oscillator found in cyanobacteria can be reconstituted in vitro using three proteins—KaiA, KaiB, and KaiC. The total phosphorylation level of KaiC oscillates with a circadian period, but the mechanism underlying its sustained oscillation remains unclear. We have shown that four forms of KaiC differ... | 10.1038/nrmicro2612 | This paper on the KaiABC system illustrates the strength of a combined theoretical and experimental approach. |
10.1126/science.1154413 | 82,943,559 | In the bacterium Escherichia coli , the Min proteins oscillate between the cell poles to select the cell center as division site. This dynamic pattern has been proposed to arise by self-organization of these proteins, and several models have suggested a reaction-diffusion type mechanism. Here, we found that the Min pro... | 10.1038/nrmicro2612 | This paper describes the reconstitution of the MinD–MinE oscillations on a membrane in vitro and provides evidence that MinD and MinE are the only components required for the oscillations. |
10.1073/pnas.0908347106 | 61,095,367 | Bacterial plasmids encode partitioning ( par ) loci that confer stable plasmid inheritance. We showed previously that, in the presence of ParB and parC encoded by the par2 locus of plasmid pB171, ParA formed cytoskeletal-like structures that dynamically relocated over the nucleoid. Simultaneously, the par2 locus distri... | 10.1038/nrmicro2612 | This report provides the first visualization of plasmid oscillations driven by the Par system and combines these observations with theoretical modelling to propose a mechanism for plasmid segregation. |
10.1126/science.1119052 | 56,446,463 | Little is known about directed motility of bacteria that move by type IV pilus–mediated (twitching) motility. Here, we found that during periodic cell reversals of Myxoccocus xanthus , type IV pili were disassembled at one pole and reassembled at the other pole. Accompanying these reversals, FrzS, a protein required fo... | 10.1038/nrmicro2612 | This study is the first to demonstrate how M. xanthus cellular reversals are accompanied by oscillations in protein localization. |
10.1073/pnas.0803124105 | 62,290,249 | We normally live in symbiosis with ∼10 13 bacteria present in the colon. Among the several mechanisms maintaining the bacteria/host balance, there is limited understanding of the structure, function, and properties of intestinal mucus. We now demonstrate that the mouse colonic mucus consists of two layers extending 150... | 10.1038/nrmicro2538 | Demonstration of the spatial relationship between the intestinal epithelium, the inner and outer mucus layers and the microbiota. |
10.1126/science.1099250 | 61,889,220 | Helicobacter pylori infects the stomachs of nearly a half the human population, yet most infected individuals remain asymptomatic, which suggests that there is a host defense against this bacterium. Because H. pylori is rarely found in deeper portions of the gastric mucosa, where O -glycans are expressed that have term... | 10.1038/nrmicro2538 | Evidence that a mucin carbohydrate can directly inhibit the growth of a mucus-residing pathogen. |
10.1073/pnas.0903438106 | 62,158,625 | The ulcer-causing gastric pathogen Helicobacter pylori is the only bacterium known to colonize the harsh acidic environment of the human stomach. H. pylori survives in acidic conditions by producing urease, which catalyzes hydrolysis of urea to yield ammonia thus elevating the pH of its environment. However, the manner... | 10.1038/nrmicro2538 | Demonstration that H. pylori reduces mucus visocosity in its microenvironment to promote bacterial motility. |
10.1073/pnas.0600623103 | 103,211,242 | In order for the protozoan parasite Entamoeba histolytica ( E.h. ) to cause invasive intestinal and extraintestinal infection, which leads to significant morbidity and mortality, it must disrupt the protective mucus layer by a previously unknown mechanism. We hypothesized that cysteine proteases secreted from the amoeb... | 10.1038/nrmicro2538 | Finding that there is specific enzymatic destruction of MUC2 polymers in mucus by an enteric amoebic parasite. |
10.1126/science.1109051 | 62,253,732 | Germ-free mice were maintained on polysaccharide-rich or simple-sugar diets and colonized for 10 days with an organism also found in human guts, Bacteroides thetaiotaomicron , followed by whole-genome transcriptional profiling of bacteria and mass spectrometry of cecal glycans. We found that these bacteria assembled on... | 10.1038/nrmicro2538 | Exploration of the altered utilization of mucin carbohydrates by an individual commensal bacterium under different host dietary conditions. |
10.1126/science.1127119 | 62,561,928 | The mammalian intestine harbors complex societies of beneficial bacteria that are maintained in the lumen with minimal penetration of mucosal surfaces. Microbial colonization of germ-free mice triggers epithelial expression of RegIIIγ, a secreted C-type lectin. RegIIIγ binds intestinal bacteria but lacks the complement... | 10.1038/nrmicro2538 | Finding that the production of specific antimicrobial molecules is regulated by the commensal microbiota. |
10.1038/ncomms5995 | 118,445,174 | Abstract Chronic stress is a risk factor for the development of psychopathologies characterized by cognitive dysfunction and deregulated social behaviours. Emerging evidence suggests a role for cell adhesion molecules, including nectin-3, in the mechanisms that underlie the behavioural effects of stress. We tested the ... | 10.1038/nrn3918 | This study implicates a new molecular cascade in the hippocampus that mediates the effects of chronic stress on sociability and cognition. |
10.1111/j.1460-9568.2006.05045.x | 104,325,304 | Abstract Early life stress in humans enhances the risk for psychopathologies, including excessive aggression and violence. In rodents, maternal separation is a potent early life stressor inducing long‐lasting changes in emotional and neuroendocrine responsiveness to stress, associated with depression‐ and anxiety‐like ... | 10.1038/nrn3918 | This study was the first to show that early life adversity in rodents can lead to increased aggression, and identified changes in social neuropeptides and serotonin as potential mediators. |
10.1146/annurev.neuro.27.070203.144148 | 38,216,360 | ▪ Abstract Because information about gender, kin, and social status are essential for reproduction and survival, it seems likely that specialized neural mechanisms have evolved to process social information. This review describes recent studies of four aspects of social information processing: (a) perception of social ... | 10.1038/nrn3918 | This is the first review to explicitly focus on the concept of the social brain. It analyses socially relevant neural systems from animals to humans, and encompasses all aspects of social behaviour from perception to action. |
10.1126/science.1072290 | 26,771,260 | We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A ( MAOA ) was found to moderate t... | 10.1038/nrn3918 | A landmark study showing that early life stress interacts with specific gene polymorphisms (in this case the MAOA gene), increasing the risk of developing violent behaviours. |
10.1126/science.1106477 | 41,594,871 | Dominance hierarchies occur in numerous social species, and rank within them can greatly influence the quality of life of an animal. In this review, I consider how rank can also influence physiology and health. I first consider whether it is high- or low-ranking animals that are most stressed in a dominance hierarchy; ... | 10.1038/nrn3918 | A pioneering work linking status in social hierarchy with different physiological outcomes. |
10.1073/pnas.0506735102 | 20,676,238 | Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for S... | 10.1038/nrmicro3143 | This is the first report of a SARS-related coronavirus in bats, and suggests that bats were a primary reservoir of the precursor to human SARS-CoV. |
10.1073/pnas.0808116105 | 20,611,924 | Defining prospective pathways by which zoonoses evolve and emerge as human pathogens is critical for anticipating and controlling both natural and deliberate pandemics. However, predicting tenable pathways of animal-to-human movement has been hindered by challenges in identifying reservoir species, cultivating zoonotic... | 10.1038/nrmicro3143 | This paper describes the reverse genetic design and recovery of bat SARS-related CoV with the epidemic and mouse-adapted SARS-CoV RBDs, including its capacity to infect mice and stimulate the production of cross-neutralizing antibodies. |
10.1073/pnas.1311542110 | 102,910,216 | Significance The identification of a novel, emerging human coronavirus with ∼50% mortality, designated Middle East respiratory syndrome coronavirus (MERS-CoV), emphasizes the importance of the rapid development of reagents that can be used to ( i ) characterize the replication and pathogenesis of emerging pathogens and... | 10.1038/nrmicro3143 | This paper describes the design and implementation of an infectious cDNA clone of MERS-CoV. |
10.1126/science.1116480 | 83,501,257 | The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 show... | 10.1038/nrmicro3143 | This paper reports the crystal structure of the SARS-CoV spike RBD in complex with the human ACE2 receptor molecule and identifies the key spike–ACE interaction residues. |
10.1128/jvi.62.11.4407-4409.1988 | 62,395,514 | Suppression of host protein synthesis in cells infected by poliovirus and certain other picornaviruses involves inactivation of the cap-binding protein complex. Inactivation of this complex has been correlated with the proteolytic cleavage of p220, a component of the cap-binding protein complex. Since picornaviral RNA ... | 10.1038/nrmicro2452 | The finding that aphthovirus L pro can cleave a translation initiation factor. |
10.1126/science.1057499 | 41,569,170 | Familial advanced sleep phase syndrome (FASPS) is an autosomal dominant circadian rhythm variant; affected individuals are “morning larks” with a 4-hour advance of the sleep, temperature, and melatonin rhythms. Here we report localization of the FASPS gene near the telomere of chromosome 2q. A strong candidate gene (h ... | 10.1038/nsmb.3326 | A mutation at the phosphorylation site of human PER2 causes decreased transcription of PER2 protein with decreased stability, this leading to FASP |
10.1126/science.1141138 | 20,544,322 | By screening N -ethyl- N -nitrosourea–mutagenized animals for alterations in rhythms of wheel-running activity, we identified a mouse mutation, after hours ( Afh ). The mutation, a Cys 358 Ser substitution in Fbxl3, an F-box protein with leucine-rich repeats, results in long free-running rhythms of about 27 hours in ho... | 10.1038/nsmb.3326 | ENU mutagenesis screening identifies an Fbxl3 point mutation that causes an extremely long circadian period, thus indicating that Fbxl3 is a circadian gene |
10.1126/science.1141194 | 102,947,319 | One component of the circadian clock in mammals is the Clock-Bmal1 heterodimeric transcription factor. Among its downstream targets, two genes, Cry1 and Cry2 , encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop. We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded v... | 10.1038/nsmb.3326 | FBXL3 is shown to be responsible for CRY ubiquitination and proteasomal degradation, and to strongly affect the circadian clock |
10.1099/mic.0.26302-0 | 122,669,625 | A tip-high cytoplasmic calcium gradient has been identified as a requirement for hyphal growth in the fungus Neurospora crassa . The Ca 2+ gradient is less steep compared to wall vesicle, wall incorporation and vesicular Ca 2+ gradients, but this can be explained by Ca 2+ diffusion. Analysis of the relation between the... | 10.1038/nrmicro2591 | A description of the important role that intracellular Ca 2+ gradients have in fungal tip growth. |
10.1099/mic.0.27947-0 | 123,153,768 | Mass flow of cytoplasm in Neurospora crassa trunk hyphae was directly confirmed by injecting oil droplets into the hyphae. The droplets move in a manner similar to cytoplasmic particles and vacuoles within the hyphae. The direction of mass flow is towards the growing hyphal tips at the colony edge. Based on flow veloci... | 10.1038/nrmicro2591 | The direct verification of mass flow in hyphal networks, and details of the magnitude of pressure gradients that are required to cause mass flow in a low-Reynolds-number environment. |
10.1101/gad.1827009 | 41,713,625 | Gut homeostasis is controlled by both immune and developmental mechanisms, and its disruption can lead to inflammatory disorders or cancerous lesions of the intestine. While the impact of bacteria on the mucosal immune system is beginning to be precisely understood, little is known about the effects of bacteria on gut ... | 10.1038/nrmicro3074 | This study demonstrates that both the gut microbiota and pathogens alter epithelial renewal and stem cell activity in the gut of D. melanogaster |
10.1126/science.1149357 | 62,289,691 | Although commensalism with gut microbiota exists in all metazoans, the host factors that maintain this homeostatic relationship remain largely unknown. We show that the intestinal homeobox gene Caudal regulates the commensal-gut mutualism by repressing nuclear factor kappa B–dependent antimicrobial peptide genes. Inhib... | 10.1038/nrmicro3074 | In addition to describing the microbial diversity of the D. melanogaster midgut, this article shows how aberrant activation of the Imd pathway leads to dysbiosis and premature fly death. |
10.4049/jimmunol.1201022 | 39,315,597 | Abstract The Drosophila antimicrobial response is one of the best characterized systems of pattern recognition receptor-mediated defense in metazoans. Drosophila senses Gram-negative bacteria via two peptidoglycan recognition proteins (PGRPs), membrane-bound PGRP-LC and secreted/cytosolic PGRP-LE, which relay diaminopi... | 10.1038/nrmicro3074 | References 46 and 47 delineate how a combination of extracellular sensing by PGRP-LC isoforms and intracellular sensing through PGRP-LE provides a sophisticated mechanism to mediate Imd activation along the gut. |
10.1073/pnas.1009223107 | 67,523,704 | The signaling network of innate immunity in Drosophila is constructed by multiple evolutionarily conserved pathways, including the Toll- or Imd-regulated NF-κB and JNK pathways. The p38 MAPK pathway is evolutionarily conserved in stress responses, but its role in Drosophila host defense is not fully understood. Here we... | 10.1038/nrmicro3074 | A study that highlights the role of p38 stress pathways in host survival to intestinal pathogens. |
10.1046/j.0953-816x.2001.01806.x | 125,276,711 | Abstract It has been recently demonstrated that ubiquitin–proteasome‐mediated proteolysis is required for long‐term synaptic facilitation in Aplysia. Here we show that the hippocampal blockade of this proteolytic pathway is also required for the formation of long‐term memory in the rat. Bilateral infusion of lactacysti... | 10.1038/nrn2499 | This study demonstrated that the blockade of protein degradation can cause memory impairment in rodents. |
10.1073/pnas.90.16.7436 | 19,681,211 | In Aplysia, behavioral sensitization of defensive reflexes and the underlying presynaptic facilitation of sensory-to-motor neuron synapses lasts for several minutes (short term) or days to weeks (long term). Short-term sensitization has been explained by modulation of ion-channel function through cAMP-dependent protein... | 10.1038/nrn2499 | A pioneering study on the role of protein degradation in long-term synaptic plasticity in Aplysia , focusing on the cAMP–PKA–CREB pathway. |
10.1083/jcb.119.1.123 | 42,620,542 | The endocytic pathways from the axonal and dendritic surfaces of cultured polarized hippocampal neurons were examined. The dendrites and cell body contained extensive networks of tubular early endosomes which received endocytosed markers from the somatodendritic domain. In axons early endosomes were confined to presyna... | 10.1038/nrn2499 | An informative study on endocytic and lysosomal pathways in axons and dendrites that used multiple techniques, including real-time imaging and electron microscopy. |
10.1126/science.1346729 | 80,281,622 | Long-term potentiation (LTP) is an extensively studied model of synaptic plasticity, in part because it is a plausible biological correlate for the Hebbian synaptic modification that forms the basis for theoretical models of neural development, learning, and memory. Although these models must incorporate algorithms tha... | 10.1038/nrn2356 | This key paper provided the first clear demonstration that prior activation of NMDARs can inhibit the induction of subsequent LTP. |
10.1046/j.1460-9568.2002.02008.x | 1,365,107 | Abstract Metaplasticity refers to the activity‐dependent modification of the ability of synapses to undergo subsequent synaptic plasticity. Here, we have addressed the question of whether metaplasticity contributes to the induction of long‐term depression (LTD) by low‐frequency stimulation (LFS). The experiments were c... | 10.1038/nrn2356 | This paper provided the first demonstration that the induction of LTD by LFS involves an initial NMDAR-induced reduction in the threshold for LTD by pulses early in the LFS, so that pulses later in the LFS can induce the LTD. |
10.1242/dev.129.3.787 | 62,105,483 | The disabled 1 (Dab1) p80 protein is essential for reelin signaling during brain development. p80 has an N-terminal domain for association with reelin receptors, followed by reelin-dependent tyrosine phosphorylation sites and about 310 C-terminal residues of unknown function. We have generated mutant mice that express ... | 10.1038/nrn1113 | This paper shows that a Dab1 null mutation can be rescued fully by a knock-in of the normal Dab1 cDNA, and partially by a partial cDNA that contains the PI/PTB domain and the adjacent region that encodes key Tyr residues, but not by a cDNA in which five Tyr residues are replaced by Phe. |
10.1152/jn.1996.76.1.255 | 82,331,317 | 1. The role of gamma-aminobutyric acid (GABA) on the pattern generation properties of neuronal ensembles in the olivocerebellar system was studied utilizing multiple electrode recordings of complex spikes (CSs) from rat crus 2a Purkinje cells (PCs). Initially multiple electrode experiments were combined with microinjec... | 10.1038/nrn3011 | This study showed that the spatiotemporal patterns of complex-spike activity can be dynamically regulated by the GABAergic inputs to the inferior olive that are derived from the cerebellar nuclei. |
10.1152/jn.2002.87.6.3059 | 50,890,633 | The cells of the inferior olivary (IO) nucleus generate a large repertoire of electrical signals, among them subthreshold oscillations of the membrane potential (STO). To date, subthreshold oscillations have been studied at the level of single-cell recordings, from which network properties were inferred. In this study ... | 10.1038/nrn3011 | One of the first optical imaging studies of the inferior olive, which demonstrated that olivary neurons can show phase-shifted activity in the form of propagating waves of activity within an oscillating region. |
10.1152/jn.00974.2006 | 123,519,114 | The deep cerebellar nuclei (DCN) integrate inputs from the brain stem, the inferior olive, and the spinal cord with Purkinje cell output from cerebellar cortex and provide the major output of the cerebellum. Despite their crucial function in motor control and learning, the various populations of neurons in the DCN are ... | 10.1038/nrn3011 | One of the first demonstrations that the GABAergic and non-GABAergic neurons in the cerebellar nuclei show distinct electrophysiological features, which has major implications for the way in which the nuclei can differentially influence activity of neurons in the inferior olive and motor related brainstem nulcei downst... |
10.1073/pnas.94.9.4273 | 38,242,455 | We have isolated and characterized a cDNA for a novel Per-Arnt/AhR-Sim basic helix–loop–helix (bHLH-PAS) factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence exhibits significant similarity to the hypoxia-inducible factor 1α (HIF1α) and Drosophila trachealess ( d... | 10.1038/nrn1408 | References 9 and 10 provided the first evidence of the HIF1α-related protein HIF2α. |
10.1126/science.1066373 | 20,683,576 | Mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of HIF is targeted for degradation under normoxic conditions by a ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. We identified... | 10.1038/nrn1408 | The same year as reference 58, these authors also revealed a family of HIF1 prolyl-hydroxylases named HPHs, which seemed to be identical to the PHD class of HIF1 prolyl-hydroxylase described by Epstein et al |
10.1101/gad.924501 | 103,678,182 | Hypoxia-inducible factor 1 (HIF-1) is a master regulator of oxygen homeostasis that controls angiogenesis, erythropoiesis, and glycolysis via transcriptional activation of target genes under hypoxic conditions. O 2 -dependent binding of the von Hippel-Lindau (VHL) tumor suppressor protein targets the HIF-1α subunit for... | 10.1038/nrn1408 | The identification and characterization of FIH1 (factor inhibiting HIF1), a negative regulator of HIF1 transactivation-domain function. The authors demonstrate that FIH1 interacts with HIF1, as well as with VHL, and that both FIH1 and VHL inhibit HIF1 transactivation-domain function, establishing a unifying mechanism f... |
10.1046/j.1460-9568.1999.00845.x | 62,433,959 | Abstract HIF‐1 is a heterodimeric transcription factor, induced by hypoxia, that is composed of HIF‐1α and HIF‐1β protein subunits. It binds to promoter/enhancer elements and stimulates the transcription of hypoxia‐inducible target genes, including glucose transporter‐1 and the glycolytic enzymes. Because HIF‐1 activat... | 10.1038/nrn1408 | The first study reporting HIF1 upregulation in the brain after focal cerebral ischaemia. |
10.1101/gad.184481.111 | 7,513,918 | Photoreceptor cell death is the hallmark of a group of human inherited retinal degeneration. Although the causative genetic mutations are often known, the mechanisms leading to photoreceptor degeneration remain poorly defined. Here, we show that Semaphorin 4A (Sema4A), a member of axonal guidance molecule semaphorin, p... | 10.1038/nrn3302 | Elegant work showing that endosomal sorting by SEMA4A in retinal pigment epithelium supports photoreceptor survival. |
10.1126/science.1173596 | 41,173,013 | Sensory information detected by the peripheral nervous system is represented as a topographic map in the brain. It has long been thought that the topography of the map is determined by graded positional cues that are expressed by the target. Here, we analyzed the pre-target axon sorting for olfactory map formation in m... | 10.1038/nrn3302 | An elegant study showing that SEMA3A and NRP1 regulate the sorting of axons of olfactory sensory neurons as they progress towards their synaptic target: the olfactory bulb. This mechanism is necessary for the establishment of A–P topographical olfactory connections. |
10.1126/science.1211956 | 20,428,146 | A protein involved in redox signaling disassembles actin filaments and alters their reassembly. | 10.1038/nrn3302 | References 169 and 170 demonstrate that the plexin-interacting protein Mical can regulate actin dynamics downstream of Sema-1a and PlexA in D. melanogaster. The Mical flavoprotein monooxygenase domain binds filamentous actin and induces the disassembly of actin filaments through the oxidation of filamentous actin subun... |
10.4319/lo.2003.48.5.1721 | 62,043,717 | The elemental composition of marine cyanobacteria is an important determinant of the ecological stoichiometry in low‐latitude marine biomes. We analyzed the cellular carbon (C), nitrogen (N), and phosphorus (P) contents of Prochlorococcus (MED4) and Synechococcus (WH8103 and WH8012) under nutrient‐replete and P‐starved... | 10.1038/nrmicro3289 | This paper describes how phosphorus limitation shifts the subsequent elemental composition of marine cyanobacteria grown in culture. |
10.1111/j.1365-2427.2006.01677.x | 59,861,798 | Summary 1. We used the freshwater alga Chlorella NC64A (Division Chlorophyta) and its virus Paramecium bursaria Chlorella virus‐1 (PBCV‐1) as a model system to test for potential stoichiometric constraints on a virus–host interaction. 2. Media phosphorus concentrations were manipulated to create Chlorella NC64A host ce... | 10.1038/nrmicro3289 | This study shows how virus productivity during infections decreases with decreasing host quality, and tabulates the total elemental content of a single algal virus. |
10.1038/ismej.2013.67 | 122,238,258 | Abstract Viruses influence oceanic ecosystems by causing mortality of microorganisms, altering nutrient and organic matter flux via lysis and auxiliary metabolic gene expression and changing the trajectory of microbial evolution through horizontal gene transfer. Limited host range and differing genetic potential of ind... | 10.1038/nrmicro3289 | This study provides quantitative estimates of the size and morphology of virus particles in seawater and provides constraints on the probable ranges of marine virus sizes. |
10.5194/bg-7-695-2010 | 122,976,073 | Abstract. Inorganic phosphorus (SRP) concentrations in the subtropical North Atlantic are some of the lowest in the global ocean and have been hypothesized to constrain primary production. Based upon data from several transect cruises in this region, it has been hypothesized that dissolved organic phosphorus (DOP) supp... | 10.1038/nrmicro3289 | This study shows the importance of organic, rather than inorganic, forms of phosphorus in supporting primary production in some oceanic realms (for example, in the Sargasso Sea). |
10.1126/science.283.5401.541 | 81,580,872 | Neuronal rhythmic activities within thalamocortical circuits range from partially synchronous oscillations during normal sleep to hypersynchrony associated with absence epilepsy. It has been proposed that recurrent inhibition within the thalamic reticular nucleus serves to reduce synchrony and thus prevents seizures. I... | 10.1038/nrn811 | Using knockout mice, the authors show for the first time that removal of a GABA A receptor subunit in NRT neurons leads to decreased intra-NRT GABA A -receptor-mediated inhibition and hypersynchronous activity in an isolated thalamic network. |
10.1126/science.289.5479.619 | 61,288,134 | The path of the nucleic acids through a transcription elongation complex was tracked by mapping cross-links between bacterial RNA polymerase (RNAP) and transcript RNA or template DNA onto the x-ray crystal structure. In the resulting model, the downstream duplex DNA is nestled in a trough formed by the β′ subunit and e... | 10.1038/nrmicro787 | A masterful article that explains how to apply intelligent chemistry to supplement structural data to produce a model for the bacterial transcription elongation complex. |
10.1046/j.1365-2958.2000.01972.x | 61,153,813 | In recent years, it has become clear that promoter recognition by bacterial RNA polymerase involves interactions not only between core promoter elements and the σ subunit, but also between a DNA element upstream of the core promoter and the α subunit. DNA binding by α can increase transcription dramatically. Here we re... | 10.1038/nrmicro787 | A nicely written micro-review that summarizes our current understanding about the RNA polymerase α-subunit C-terminal domain. |
10.1126/science.1069595 | 60,050,555 | The crystal structure of Thermus aquaticus RNA polymerase holoenzyme (α 2 ββ′ωσ A ) complexed with a fork-junction promoter DNA fragment has been determined by fitting high-resolution x-ray structures of individual components into a 6.5-angstrom resolution map. The DNA lies across one face of the holoenzyme, completely... | 10.1038/nrmicro787 | References 12 and 13 represent a quantum leap in our understanding of RNA polymerase and its interactions with promoters |
10.1101/gad.870001 | 122,815,389 | The α subunit of E. coli RNAP plays an important role in the recognition of many promoters by binding to the A+T-rich UP element, a DNA sequence located upstream of the recognition elements for the ς subunit, the −35 and −10 hexamers. We examined DNA–RNAP interactions using high resolution interference and protection f... | 10.1038/nrmicro787 | A great illustration of how clever biochemistry can be used to discover basic information about the ways in which a protein recognizes its DNA target. |
10.1046/j.1365-2958.2001.02416.x | 18,633,041 | Negative superhelical tension can drive local transitions to alternative DNA structures. Long regions of DNA may contain several sites that are susceptible to forming alternative structures. Their relative propensities to undergo transition are ordered according to the energies required for their formation. These energ... | 10.1038/nrmicro787 | Rightly or wrongly, it is said that it is the exception that proves the rule — this article advocates the exceptional cases. |
10.1152/physrev.00038.2014 | 107,180,674 | TOR (target of rapamycin) and its mammalian ortholog mTOR have been discovered in an effort to understand the mechanisms of action of the immunosuppressant drug rapamycin extracted from a bacterium of the Easter Island (Rapa Nui) soil. mTOR is a serine/threonine kinase found in two functionally distinct complexes, mTOR... | 10.1038/nrneurol.2016.81 | A comprehensive review of cellular and molecular biology of mTOR and its contributions to brain function. |
10.1152/physrev.00030.2009 | 41,470,144 | (Macro)autophagy is a bulk degradation process that mediates the clearance of long-lived proteins and organelles. Autophagy is initiated by double-membraned structures, which engulf portions of cytoplasm. The resulting autophagosomes ultimately fuse with lysosomes, where their contents are degraded. Although the term a... | 10.1038/nrneurol.2016.81 | This comprehensive review discusses molecular and cellular mechanisms of autophagy. |
10.1002/ana.20211 | 18,418,525 | Abstract Balloon cells (BCs) in focal cortical dysplasia (FCD) and giant cells (GCs) in tubers of the tuberous sclerosis complex (TSC) share phenotypic similarities. TSC1 or TSC2 gene mutations in TSC lead to mTOR pathway activation and p70S6kinase (phospho‐S6K) and ribosomal S6 (phospho‐S6) protein phosphorylation. Ph... | 10.1038/nrneurol.2016.81 | The first article reporting overactive mTOR signalling in brain malformations. |
10.1002/ana.21331 | 4,621,269 | Abstract Objective Tuberous sclerosis complex (TSC) represents one of the most common genetic causes of epilepsy. TSC gene inactivation leads to hyperactivation of the mammalian target of rapamycin signaling pathway, raising the intriguing possibility that mammalian target of rapamycin inhibitors might be effective in ... | 10.1038/nrneurol.2016.81 | This important study was the first to show a benefit of mTOR inhibitors in a mouse model of tuberous sclerosis complex. |
10.1111/gbb.12106 | 83,253,388 | Abstract In a research environment dominated by reductionist approaches to brain disease mechanisms, gene network analysis provides a complementary framework in which to tackle the complex dysregulations that occur in neuropsychiatric and other neurological disorders. Gene–gene expression correlations are a common sour... | 10.1038/nrneurol.2016.84 | This article summarizes the origin of coexpression networks — one of the most common types of molecular network studied in the context of AD. |
10.1002/ana.23964 | 83,469,274 | Objective The pathologic indices of Alzheimer disease, cerebrovascular disease, and Lewy body disease accumulate in the brains of older persons with and without dementia, but the extent to which they account for late life cognitive decline remains unknown. We tested the hypothesis that these pathologic indices account ... | 10.1038/nrneurol.2016.84 | This article shows that AD and age-related neuropathologies do not fully account for cognitive decline observed with ageing. |
10.1073/pnas.0701361104 | 125,102,070 | A network of disorders and disease genes linked by known disorder–gene associations offers a platform to explore in a single graph-theoretic framework all known phenotype and disease gene associations, indicating the common genetic origin of many diseases. Genes associated with similar disorders show both higher likeli... | 10.1038/nrneurol.2016.84 | This study found widespread coherence in disease organization through the use of phenotypic similarity or gene signature overlap. |
10.1073/pnas.0712231105 | 62,411,091 | The understanding of the structural and dynamic complexity of mammalian brains is greatly facilitated by computer simulations. We present here a detailed large-scale thalamocortical model based on experimental measures in several mammalian species. The model spans three anatomical scales. ( i ) It is based on global (w... | 10.1038/nrneurol.2016.84 | This work showed that a highly simplified neuronal model could be connected realistically with other models to reproduce large-scale patterns of brain activation. |
10.1073/pnas.1509757112 | 62,606,908 | A scientist’s choice of research problem affects his or her personal career trajectory. Scientists’ combined choices affect the direction and efficiency of scientific discovery as a whole. In this paper, we infer preferences that shape problem selection from patterns of published findings and then quantify their effici... | 10.1038/nrneurol.2016.84 | This work demonstrates that exploration of high risk, interdisciplinary research brings personal benefits and increases efficiency of scientific discovery. |
10.1002/glia.22375 | 59,959,344 | Abstract Type I interferons (IFNα/β) provide a primary defense against infection. Nevertheless, the dynamics of IFNα/β induction and responsiveness by central nervous system (CNS) resident cells in vivo in response to viral infections are poorly understood. Mice were infected with a neurotropic coronavirus with tropism... | 10.1038/nrn.2016.140 | The authors show that oligodendrocytes are poor sensors of viral infection and require exogenous IFNα and IFNβ to establish an antiviral state. |
10.4049/jimmunol.0800596 | 103,774,767 | Abstract Several neurotropic viruses such as vesicular stomatitis virus (VSV) induce peripheral neutralizing Ab responses and still can infect cells within the CNS. To address whether local type I IFN receptor (IFNAR) triggering plays a role in controlling virus replication within the brain, we generated mice with a ce... | 10.1038/nrn.2016.140 | The authors illustrate the crucial role of neuron specific IFN signalling in controlling vesicular stomatitis virus infection within the brain. |
10.1126/science.7624779 | 38,196,862 | Whether neurons express major histocompatibility complex (MHC) class I genes has not been firmly established. The techniques of confocal laser microscopy, patch clamp electrophysiology, and reverse transcriptase-polymerase chain reaction were combined here to directly examine the inducibility of MHC class I genes in in... | 10.1038/nrn.2016.140 | This article demonstrates that transcription of MHC class I genes is rare in healthy neurons but detected in electrically silent neurons, suggesting that immunosurveillance by cytotoxic T cells may be focused on functionally impaired neurons. |
10.1084/jem.191.9.1459 | 40,379,449 | Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent virus in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 in a latent state in sensory neurons may provide new approaches to reducing susceptibility to recurrent ... | 10.1038/nrn.2016.140 | The authors demonstrate that CD8 + T cells residing alongside trigeminal ganglionic neurons infected with HSV are essential in preventing viral reactivation in the absence of neuronal death. |
10.1126/science.1164164 | 26,881,953 | Reactivation of herpes simplex virus type 1 (HSV-1) from neuronal latency is a common and potentially devastating cause of disease worldwide. CD8 + T cells can completely inhibit HSV reactivation in mice, with interferon-γ affording a portion of this protection. We found that CD8 + T cell lytic granules are also requir... | 10.1038/nrn.2016.140 | This paper shows that non-cytotoxic CD8 + T cells mediate prevention of HSV reactivation from latency that is triggered by granzyme B-mediated cleavage of an essential early HSV protein. |
10.1126/scitranslmed.aac8201 | 83,022,648 | Human endogenous retrovirus-K is activated in the cortical neurons of patients with amyotrophic lateral sclerosis, and expression of the viral envelope protein in mouse brain reproduces the clinical and pathological phenotype of this disease. | 10.1038/nrn.2016.140 | The authors identify a human endogenous retrovirus as a causative agent in neurodegenerative disease, positing an aetiology of amyotrophic lateral sclerosis. |
10.1126/science.287.5453.664 | 38,444,163 | Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1 α −/− fibroblasts were impaired in JNK activation by ER stress. T... | 10.1038/nrmicro3393 | This paper shows that IRE1 links ER stress to JNK, which is an activator of AP-1. |
10.1084/jem.20030088 | 81,786,633 | The intracellular pathogen Brucella is the causative agent of brucellosis, a worldwide zoonosis that affects mammals, including humans. Essential to Brucella virulence is its ability to survive and replicate inside host macrophages, yet the underlying mechanisms and the nature of the replicative compartment remain uncl... | 10.1038/nrmicro3393 | This paper provides evidence that Brucella spp. exploits the ER via its VirB T4SS to evade killing by macrophages. |
10.1073/pnas.0406873102 | 124,583,999 | The pathogen Brucella abortus resides inside macrophages within a unique, replication-permissive organelle that is derived from the endoplasmic reticulum (ER). Although dependent on the Brucella type IV secretion system VirB, the mechanisms governing the biogenesis of this compartment remain elusive. Here, we investiga... | 10.1038/nrmicro3393 | This paper provides evidence that B. abortus intercepts traffic from ERESs to promote its intracellular replication. |
10.1128/mbio.00418-12 | 81,901,752 | ABSTRACT Host cytokine responses to Brucella abortus infection are elicited predominantly by the deployment of a type IV secretion system (T4SS). However, the mechanism by which the T4SS elicits inflammation remains unknown. Here we show that translocation of the T4SS substrate VceC into host cells induces proinflammat... | 10.1038/nrmicro3393 | This paper shows that elements of the UPR sense localization of a Brucella spp. effector protein to the ER. |
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/nrn2148 | Seminal review/manifesto by a pioneer of CNS cellular electrophysiology, surveying the wide variety of intrinsic excitability of central neurons and emphasizing the intrinsic oscillatory behaviour of cells and circuits. |
10.1152/jn.1985.54.4.782 | 104,316,561 | Slices of sensorimotor and anterior cingulate cortex from guinea pigs were maintained in vitro and bathed in a normal physiological medium. Electrophysiological properties of neurons were assessed with intracellular recording techniques. Some neurons were identified morphologically by intracellular injection of the flu... | 10.1038/nrn2148 | Introduces 'regular-spiking', 'bursting' and 'fast-spiking' classifications of firing patterns of neocortical neurons, correlates firing patterns with spike shape, and identifies fast-spiking neocortical neurons as GABA-mediated interneurons. |
10.1523/jneurosci.23-06-02058.2003 | 123,167,076 | Kv3 channels are thought to be essential for the fast-spiking (FS) phenotype in GABAergic interneurons, but how these channels confer the ability to generate action potentials (APs) at high frequency is unknown. To address this question, we developed a fast dynamic-clamp system (≈50 kHz) that allowed us to add a Kv3 mo... | 10.1038/nrn2148 | Uses the dynamic clamp technique to demonstrate that the Kv3-mediated potassium current speeds up firing and that deactivation kinetics are a crucial parameter for this effect. |
10.1152/jn.1982.48.6.1302 | 103,775,614 | 1. Intracellular recordings were obtained from neurons of the guinea pig sensorimotor cortical slice maintained in vitro. Under control recording conditions input resistances, time constants, and spiking characteristics of slice neurons were well within the ranges reported by other investigators for neocortical neurons... | 10.1038/nrn2148 | Classic description of all-or-none bursting, and of afterdepolarizations and action potential broadening, in neocortical pyramidal neurons. |
10.1111/j.1469-7793.1997.617ba.x | 104,281,014 | Initiation and propagation of action potentials evoked by extracellular synaptic stimulation was studied using simultaneous dual and triple patch pipette recordings from different locations on neocortical layer 5 pyramidal neurons in brain slices from 4‐week‐old rats (P26–30) at physiological temperatures. Simultaneous... | 10.1038/nrn2148 | Uses double (and triple) patch pipette recordings in layer 5 pyramidal neurons to directly demonstrate that spikes are initiated in the axon before the soma — even with strong synaptic stimulation that first elicits regenerative potentials in dendrites. Also demonstrates back-propagation of axonal spikes into the dendr... |
10.1113/jphysiol.2006.106682 | 4,624,758 | Cerebellar neurones show complex and differentiated mechanisms of action potential generation that have been proposed to depend on peculiar properties of their voltage‐dependent Na + currents. In this study we analysed voltage‐dependent Na + currents of rat cerebellar granule cells (GCs) by performing whole‐cell, patch... | 10.1038/nrn2148 | State-of-the-art combination of voltage-clamp analysis of currents and modelling of firing, using a model with nine distinct conductances including an allosteric sodium channel model. |
10.1523/jneurosci.20-22-08493.2000 | 20,263,079 | Neostriatal cholinergic interneurons produce spontaneous tonic firing in the absence of synaptic input. Perforated patch recording and whole-cell recording combined with calcium imaging were used in vitro to identify the intrinsic membrane properties underlying endogenous excitability. Spontaneous firing was driven by ... | 10.1038/nrn2148 | A combination of current-clamp, voltage-clamp and calcium imaging to determine the ionic mechanism of pacemaking in tonically active cholinergic neurons of the striatum. |
10.1098/rstb.1999.0386 | 16,748,133 | We studied the relation between the size of presynaptic calcium influx and transmitter release by making simultaneous voltage clamp recordings from presynaptic terminals, the calyces of Held and postsynaptic cells, the principal cells of the medial nucleus of the trapezoid body, in slices of the rat brainstem. Calyces ... | 10.1038/nrn2148 | Action potential clamp experiments on presynaptic terminals (calyx of Held) showing that calcium channels are activated with high efficacy by action potentials. |
10.1113/jphysiol.1987.sp016517 | 124,941,785 | 1. The repolarization of the action potential, and a fast after‐hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28‐37 degrees C). Single spikes were elicited by brief (1‐3 ms) current pulses, at membrane potentials close to rest (‐60 to ‐70 mV). 2. Each action potentia... | 10.1038/nrn2148 | Analysis using pharmacology and ionic substitution of the potassium currents underlying spike repolarization, fast, medium and slow afterhyperpolarizations in CA1 pyramidal neurons. |
10.1523/jneurosci.16-13-04089.1996 | 18,958,331 | The R20 neurons of Aplysia exhibit frequency-dependent spike broadening. Previously, we had used two-electrode voltage clamp to examine the mechanisms of this spike broadening (Ma and Koester, 1995). We identified three K + currents that mediate action-potential repolarization: a transient A-type K + current ( I Adepol... | 10.1038/nrn2148 | Combines the use of action potential clamp and dynamic clamp to analyse the changes in ionic currents underlying frequency-dependent spike broadening in an Aplysia neuron. |
10.1113/jphysiol.1971.sp009366 | 107,327,562 | 1. Membrane parameters of an isolated neural cell body have been determined by voltage clamp analysis. Data are expressed as membrane ion‐specific conductances, leak conductance, and capacitance. 2. Three ionic currents are present: Inward, I I ; and two operationally distinct outward currents, I K and I A . Both outwa... | 10.1038/nrn2148 | Classic pair of papers describing I A in a snail neuron and using a computer model to analyse how it enables steady low-frequency firing. |
10.1523/jneurosci.2155-04.2004 | 17,696,820 | Striatal cholinergic interneurons are critical elements of the striatal circuitry controlling motor planning, movement, and associative learning. Intrastriatal release of dopamine and inhibition of interneuron activity is thought to be a critical link between behaviorally relevant events, such as reward, and alteration... | 10.1038/nrn2148 | Combines current clamp, voltage clamp, and modelling to show that modest changes in sodium channel gating produced by dopamine can produce surprisingly large effects on the frequency of spontaneous firing. |
10.1523/jneurosci.21-14-05229.2001 | 29,088,447 | The electrical characteristics of many neurons are remarkably robust in the face of changing internal and external conditions. At the same time, neurons can be highly sensitive to neuromodulators. We find correlates of this dual robustness and sensitivity in a global analysis of the structure of a conductance-based mod... | 10.1038/nrn2148 | Remarkable demonstration — using modelling together with dynamic clamp experiments — that nearly identical bursting behaviour can be produced by highly variable combinations of levels of five conductances, even when small changes in a given conductance can modulate firing. |
10.1091/mbc.e07-12-1292 | 82,980,678 | Autophagy is a potent intracellular degradation process with pivotal roles in health and disease. Atg8, a lipid-conjugated ubiquitin-like protein, is required for the formation of autophagosomes, double-membrane vesicles responsible for the delivery of cytoplasmic material to lysosomes. How and when Atg8 functions in t... | 10.1038/nsmb.2787 | Shows that Atg8 levels correlate with the size of autophagosomes |
10.1111/j.1365-2443.2008.01238.x | 60,142,001 | Autophagy is a non‐selective bulk degradation process in which isolation membranes enclose a portion of cytoplasm to form double‐membrane vesicles, called autophagosomes, and deliver their inner constituents to the lytic compartments. Recent studies have also shed light on another mode of autophagy that selectively deg... | 10.1038/nsmb.2787 | Refs. 22 and 44 identify the structural basis for AIM or LIR binding to Atg8 (LC3) UBLs |
10.1126/science.1205405 | 83,307,251 | Phosphorylation of an autophagy receptor restricts pathogenic cytosolic bacterial growth. | 10.1038/nsmb.2787 | Refs. 50 and 51 demonstrated phosphorylation-dependent recruitment of cargo to Atg8 (LC3) family members |
10.1038/embor.2012.208 | 18,957,513 | Atg12 is conjugated to Atg5 through enzymatic reactions similar to ubiquitination. The Atg12–Atg5 conjugate functions as an E3‐like enzyme to promote lipidation of Atg8, whereas lipidated Atg8 has essential roles in both autophagosome formation and selective cargo recognition during autophagy. However, the molecular ro... | 10.1038/nsmb.2787 | Refs. 65 and 79 revealed the structure of the Atg12–Atg5 conjugate |
10.1038/embor.2009.256 | 62,147,366 | Autophagy is the cellular homeostatic pathway that delivers large cytosolic materials for degradation in the lysosome. Recent evidence indicates that autophagy mediates selective removal of protein aggregates, organelles and microbes in cells. Yet, the specificity in targeting a particular substrate to the autophagy pa... | 10.1038/nsmb.2787 | Refs. 102 and 103 show that BNIP3L (Nix) is a mitophagy receptor that binds LC3 |
10.1523/jneurosci.18-18-07336.1998 | 42,632,139 | Recent studies have suggested a role for neurotrophins in the growth and refinement of neural connections, in dendritic growth, and in activity-dependent adult plasticity. To unravel the role of endogenous neurotrophins in the development of neural connections in the CNS, we studied the ontogeny of hippocampal afferent... | 10.1038/nrn988 | The first results to indicate a role for neurotrophin signalling in the regulation of synapse number in the CNS. |
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