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10.1126/science.1128134 | 20,675,393 | Years of intensive investigation have yielded a sophisticated understanding of long-term potentiation (LTP) induced in hippocampal area CA1 by high-frequency stimulation (HFS). These efforts have been motivated by the belief that similar synaptic modifications occur during memory formation, but it has never been shown ... | 10.1038/nrn2055 | This study is of conceptual importance and shows that plasticity in hippocampal synapses of the brain is induced by hippocampal-dependent learning and is associated with the regulatory phosphorylation of AMPARs. |
10.1523/jneurosci.06-08-02117.1986 | 58,973,050 | Ocular dominance columns in the cat's visual cortex appear to develop out of an initially overlapping projection by a progressive segregation of the geniculocortical afferents serving the 2 eyes (reviewed in LeVay and Stryker, 1979). To determine whether electrical activity in the visual afferent pathway is involved in... | 10.1038/nrn703 | The first (and only) experiments to directly test the role of activity in the initial formation of ocular dominance columns. |
10.1002/cne.901790113 | 18,129,567 | Abstract The distribution of geniculocortical afferents serving the left and right eyes was studied in abult cats and in kittens of various ages. Methods used were autoradiography of transneuronally transported 3 H‐proline injected into one eye, and physiological recordings. In the adult cat, patches of label in layer ... | 10.1038/nrn703 | A seminal paper that provided the first ever view of the pattern of developing ocular dominance columns, and provided the experimental underpinning of most subsequent theories of column formation. |
10.1126/science.417397 | 15,746,848 | Autoradiographic representation of the local rates of cerebral glucose utilization and local cerebral functional activity by means of the [ 14 C]deoxyglucose technique reveals the existence of the ocular dominance columns in the striate cortex of the monkey in the first day of life. In contrast to the stability of thes... | 10.1038/nrn703 | Using improved autoradiographic techniques, this paper conclusively showed that ocular dominance columns can emerge fully without visual experience. |
10.1126/science.2035024 | 104,289,020 | The development of orderly connections in the mammalian visual system depends on action potentials in the optic nerve fibers, even before the retina receives visual input. In particular, it has been suggested that correlated firing of retinal ganglion cells in the same eye directs the segregation of their synaptic term... | 10.1038/nrn703 | Using a technically advanced microelectrode array, this paper revealed that spontaneous action potentials in the previsual retina are organized into wave-like patterns. These patterns could provide cues for competitive interactions in the thalamus and cortex. |
10.1126/science.279.5359.2108 | 62,268,913 | When contacts are first forming in the developing nervous system, many neurons generate spontaneous activity that has been hypothesized to shape appropriately patterned connections. In Mustela putorius furo , monocular intraocular blockade of spontaneous retinal waves of action potentials by cholinergic agents altered ... | 10.1038/nrn703 | Blocking retinal waves (see reference 35 ) in one retina leads to laminar rearrangements in the LGN that are reminiscent of the effects of activity imbalances in ocular dominance column formation. |
10.1126/science.285.5427.599 | 19,905,199 | The properties of spontaneous activity in the developing visual pathway beyond the retina are unknown. Multielectrode recordings in the lateral geniculate nucleus (LGN) of awake behaving ferrets, before eye opening, revealed patterns of spontaneous activity that reflect a reshaping of retinal drive within higher visual... | 10.1038/nrn703 | Recordings from multielectrode arrays in the LGN of awake ferrets revealed patterns of activity that were better correlated within than between eyes, consistent with the predictions of retinal recordings (see reference 35 ). However, significant differences were noted in the strength of ipsilateral and contralateral re... |
10.1126/science.279.5350.566 | 41,291,751 | The role of experience in the development of the cerebral cortex has long been controversial. Patterned visual experience in the cat begins when the eyes open about a week after birth. Cortical maps for orientation and ocular dominance in the primary visual cortex of cats were found to be present by 2 weeks. Early patt... | 10.1038/nrn703 | Using optical and single-unit recording techniques, the authors show that neurons in the developing cortex are initially activated almost exclusively by the contralateral eye, with ipsilateral eye responses developing much later and only with visual experience. They conclude that the intercalation of ipsilateral respon... |
10.1523/jneurosci.05-05-01132.1985 | 109,389,629 | The addition of a third eye primordium to the forebrain region of a Rana pipiens embryo invariably results in the development of a series of periodic, mutually exclusive eye-specific bands in tectal lobes dually innervated by the host and supernumerary fibers. A number of investigators have proposed that such source-sp... | 10.1038/nrn703 | The striking pattern of ocular dominance stripes in frog optic tectum, induced by transplanting a third eye, has served as a model for column development in the cortex. This paper shows that retinal activity is the crucial feature for inducing the segregation of eye-specific stripes. |
10.1126/science.290.5495.1321 | 41,293,014 | The segregation of lateral geniculate nucleus (LGN) axons into ocular dominance columns is believed to involve a prolonged, activity-dependent sorting process. However, visualization of early postnatal ferret LGN axons by direct LGN tracer injections revealed segregated ocular dominance columns <7 days after innerva... | 10.1038/nrn703 | By using direct injections of tracers into the developing LGN, the authors show that ocular dominance columns develop much earlier and much more rapidly than was previously believed, and with a surprising degree of specificity. |
10.1523/jneurosci.18-21-09020.1998 | 82,808,047 | Many neurons in the rat anterodorsal thalamus (ADN) and postsubiculum (PoS) fire selectively when the rat points its head in a specific direction in the horizontal plane, independent of the animal’s location and ongoing behavior. The lateral mammillary nuclei (LMN) are interconnected with both the ADN and PoS and, ther... | 10.1038/nrn1299 | Single neuron recordings in the lateral mammillary nucleus showed that most cells fired as a function of directional heading, head pitch or angular head velocity. Cells were found to anticipate the rat's future head direction by about 65 ms. |
10.1162/jocn.1997.9.4.512 | 47,852,096 | Six monkeys were trained preoperatively in an automated object-in-place memory task in which they learned 20 new scenes in each daily session. Three of the six monkeys then received stereotaxically guided bilateral mamillary body lesions, leaving the fornix intact, while the other three received a control operation. Po... | 10.1038/nrn1299 | Preoperatively trained monkeys were impaired at learning new scenes in an object-in-place memory task after mammillary body lesions. This impairment was equal to that seen after fornix lesions or combined fornix and mammillary body lesions. |
10.1523/jneurosci.14-11-07040.1994 | 38,384,473 | We examined the activity of single cells of the supramammillary nucleus (SUM), the mammillary body (MB), and adjacent regions of the diencephalon with respect to the hippocampal electroencephalogram (EEG) in urethane-anesthetized rats. Twenty-nine of 170 cells were found to discharge synchronously with the theta rhythm... | 10.1038/nrn1299 | Theta-related neurons were found in the supramammillary nucleus and mammillary body of the rat. The theta-related cells in the mammillary body, but not the supramammillary nucleus, were correlated with the CA1 field of the hippocampus, consistent with the theta-related cells in the mammillary body being driven by the d... |
10.1128/iai.67.11.5699-5708.1999 | 122,926,534 | ABSTRACT The development of effective prophylactic agents against gonorrhea and the study of adaptation by Neisseria gonorrhoeae to the urogenital mucosa are hindered by the lack of a well-established animal model of gonococcal genital tract infection. Here, a murine model of long-term gonococcal genital tract infectio... | 10.1038/nrmicro2713 | This groundbreaking study describes the development of a genetically tractable model system for examining infection by the pathogenic Neisseria spp.: genital infection of female mice by N. gonorrhoeae |
10.1111/j.1365-2958.2005.04839.x | 104,329,536 | Summary Symptomatic gonococcal infection, caused by the pathogen Neisseria gonorrhoeae (Gc), is characterized by the influx of polymorphonuclear leukocytes (PMNs) to the site of infection. Although PMNs possess several mechanisms of oxidative killing, intact Gc can be found associated with PMNs, suggesting that gonococ... | 10.1038/nrmicro2713 | This article identifies the first N. gonorrhoeae gene products that protect the bacterium from killing by human neutrophils. |
10.1128/iai.21.2.575-584.1978 | 61,269,862 | Neisseria gonorrhoeae which exhibit high levels of leukocyte association have a surface protein which is considerably diminished in isogenic gonococci which exhibit low levels of leukocyte association (LA). The LA protein exhibits strain variation in molecular weight and immunogenicity. Membranes derived from LA+ and L... | 10.1038/nrmicro2713 | This study is the first to identify outer-membrane proteins — later found to be Opa proteins — that mediate interaction of N. gonorrhoeae with neutrophils. |
10.1128/iai.36.2.737-744.1982 | 61,271,182 | Serum-sensitive strains of Neisseria gonorrhoeae were incubated with suspensions of normal or chronic granulomatous disease human neutrophils in the absence or presence of fresh or heat-inactivated human serum; phagocytosis, gonococcal viability, and chemiluminescence were measured. Nonpiliated opaque or transparent go... | 10.1038/nrmicro2713 | The authors of this report use human neutrophils infected with N. gonorrhoeae expressing defined Opa proteins to correlate the Opa–neutrophil interaction with reduced bacterial survival and enhanced ROS production. |
10.1128/iai.65.6.2353-2361.1997 | 60,553,607 | Opacity (Opa) protein variation in Neisseria gonorrhoeae is implicated in the pathogenesis of gonorrhea, possibly by mediating adherence and entry of the bacteria into human tissues. One particular Opa protein mediates adherence to epithelial cells through cell surface proteoglycans. Recently, two other eukaryotic cell... | 10.1038/nrmicro2713 | References 77–81 identify members of the CEACAM family of receptors as the proteins (on neutrophils and other cells) that act as binding partners for a subset of neisserial Opa proteins. |
10.1128/iai.05702-11 | 28,039,341 | ABSTRACT Symptomatic infection of humans with Neisseria gonorrhoeae is characterized by a neutrophil-rich cervical or urethral exudate, suggesting that neutrophils are important both for the clearance of these bacteria and for the pathogenesis of gonorrhea. Neisseria interacts with neutrophils through ligation of human... | 10.1038/nrmicro2713 | The authors of this work express selected CEACAMs, alone or in combination, in mouse promyelocytic cells to show that each receptor initiates different signalling events in response to N. gonorrhoeae . CEACAM1 and CEACAM6 are found to enhance CEACAM3 signals in neutrophils, an unexpected finding given the inhibitory ro... |
10.1128/iai.52.2.384-389.1986 | 122,654,079 | The resistance of a piliated, transparent variant of Neisseria gonorrhoeae FA19 to intraleukocytic killing by human polymorphonuclear neutrophils (PMN) was examined. In both aerobic and anaerobic PMN monolayers, approximately 2% of the intracellular gonococci survived for as long as 165 min. Anaerobic PMN were as effec... | 10.1038/nrmicro2713 | References 95–97 provide the first evidence for N. gonorrhoeae replication inside human neutrophils. |
10.1128/iai.73.4.1971-1977.2005 | 123,526,299 | ABSTRACT Neisseria gonorrhoeae causes severe exudative urethritis. The exudates from infected individuals contain large numbers of polymorphonuclear leukocytes (PMN) with ingested gonococci. The fate of N. gonorrhoeae within PMN has been a topic of debate for years. In this study, we examined the interactions of N. gon... | 10.1038/nrmicro2713 | The authors of this article develop an in vitro infection assay with N. gonorrhoeae that yields evidence for bacterial survival and replication inside adherent primary human neutrophils. |
10.1111/j.1365-2958.2004.04315.x | 82,463,366 | Summary We have previously shown that in the human pathogen Neisseria meningitidis group B ( MenB ) more than 200 genes are regulated in response to growth with iron. Among the Fur‐dependent, upregulated genes identified by microarray analysis was a putative operon constituted by three genes, annotated as NMB1436, NMB1... | 10.1038/nrmicro2713 | This study identifies the first N. meningitidis gene products found to protect the bacterium from killing by primary human neutrophils. |
10.1128/iai.73.8.5269-5272.2005 | 101,104,110 | ABSTRACT Neisseria gonorrhoeae has well-characterized oxidative stress defense systems that protect against oxidative killing in in vitro assays. In contrast, mutant strains of N. gonorrhoeae lacking oxidative stress defenses are identical to the wild type when tested in an ex vivo survival assay using human polymorpho... | 10.1038/nrmicro2713 | This work uses N. gonorrhoeae carrying mutations in multiple antioxidant genes to show that neutrophil-mediated killing of gonococci is independent of ROS. |
10.1073/pnas.95.4.1829 | 18,733,323 | We have previously described the antibacterial capacity of protegrin-1 (PG-1), a cysteine-rich, cationic peptide from porcine leukocytes, against Neisseria gonorrhoeae . We now report genetic and biochemical evidence that gonococcal susceptibility to the lethal action of PG-1 and other structurally unrelated antibacter... | 10.1038/nrmicro2713 | This report describes the cloning and characterization of the gonococcal MtrCDE efflux pump and its crucial role in neisserial defence against cationic antimicrobial peptides. |
10.1128/iai.01280-08 | 19,466,262 | ABSTRACT The capacity of Neisseria gonorrhoeae to cause disseminated gonococcal infection requires that such strains resist the bactericidal action of normal human serum. The bactericidal action of normal human serum against N. gonorrhoeae is mediated by the classical complement pathway through an antibody-dependent me... | 10.1038/nrmicro2713 | In this investigation, different modifications of neisserial LOS, including the addition of phosphoethanolamine by LptA, were shown to differentially affect bacterial resistance to complement and cationic antimicrobial peptides. |
10.1146/annurev-marine-120709-142805 | 123,770,150 | Over the past two decades, marine virology has progressed from a curiosity to an intensely studied topic of critical importance to oceanography. At concentrations of approximately 10 million viruses per milliliter of surface seawater, viruses are the most abundant biological entities in the oceans. The majority of thes... | 10.1038/nrmicro3404 | This review provides an overview of marine viruses and the major challenges in the field, many of which are addressed by the technological advances described in this Review. |
10.1038/ismej.2012.121 | 122,985,393 | Abstract Viruses are abundant in the ocean and a major driving force in plankton ecology and evolution. It has been assumed that most of the viruses in seawater contain DNA and infect bacteria, but RNA-containing viruses in the ocean, which almost exclusively infect eukaryotes, have never been quantified. We compared t... | 10.1038/nrmicro3404 | This paper provides data from nucleic acid measurements and genome size extrapolations to suggest that RNA viruses may constitute half of the viral particles in the oceans; however, we currently lack accurate methods to measure their abundances. |
10.1038/ismej.2014.143 | 17,714,374 | Abstract Microbes drive myriad ecosystem processes, and their viruses modulate microbial-driven processes through mortality, horizontal gene transfer, and metabolic reprogramming by viral-encoded auxiliary metabolic genes (AMGs). However, our knowledge of viral roles in the oceans is primarily limited to surface waters... | 10.1038/nrmicro3404 | This paper uses protein clusters to identify core and flexible marine viral genes in the photic and aphotic zones of the water column, including a description of viral AMGs that are major contributors to niche differentiation. |
10.1073/pnas.1319778111 | 19,209,579 | Significance Microorganisms and their viruses are increasingly recognized as drivers of myriad ecosystem processes. However, our knowledge of their roles is limited by the inability of culture-dependent and culture-independent (e.g., metagenomics) methods to be fully implemented at scales relevant to the diversity foun... | 10.1038/nrmicro3404 | This paper describes the use of shared k-mer and social network analysis to evaluate differences between viral communities and the ecological drivers of those differences. |
10.1126/science.1200758 | 18,957,956 | Matching environmental phage with single, uncultured bacterial host cells reveals remarkable species specificity. | 10.1038/nrmicro3404 | This paper describes the use of microfluidic digital PCR to evaluate specific virus–host interactions in environmental samples. |
10.1111/1462-2920.12100 | 124,832,640 | Summary Microbes drive the biogeochemical cycles that fuel planet E arth, and their viruses (phages) alter microbial population structure, genome repertoire, and metabolic capacity. However, our ability to understand and quantify phage–host interactions is technique‐limited. Here, we introduce phage FISH – a markedly i... | 10.1038/nrmicro3404 | This paper describes the use of fluorescence in situ hybridization (FISH) to evaluate specific virus–host interactions during different stages of infection. |
10.1073/pnas.0705843104 | 38,408,541 | Human attentional control is unrivaled. We recently proposed that adults depend on distinct frontoparietal and cinguloopercular networks for adaptive online task control versus more stable set control, respectively. During development, both experience-dependent evoked activity and spontaneous waves of synchronized cort... | 10.1038/nrn3313 | A thoughtful analysis of the development of resting state networks from childhood through adolescence. |
10.1177/0956797610391102 | 82,417,233 | Adolescence is characterized by the emergence of advanced forms of social perspective taking and significant changes in social behavior. Yet little is known about how changes in social cognition are related to changes in brain function during adolescence. In this study, we investigated the neural correlates of social b... | 10.1038/nrn3313 | A social interaction study that shows, using a neuroeconomics approach, a transition from self-referential processing to other-referential processing in adolescence. |
10.1073/pnas.90.9.4171 | 82,963,205 | Simple methods are presented to estimate rates of spontaneous mutation from mutant frequencies and population parameters in RNA viruses. Published mutant frequencies yield a wide range of mutation rates per genome per replication, mainly because mutational targets have usually been small and, thus, poor samples of the ... | 10.1038/nrmicro863 | A key reference giving figures for the spontaneous rate of mutation in RNA viruses and the difficulties in making these measurements. |
10.1128/jvi.64.12.6278-6281.1990 | 101,182,126 | A variant clone of vesicular stomatitis virus recovered from a high-passage, evolving virus population replicated rapidly and produced remarkably high yields of virus, but these variants never dominated during further passages. We show that this clone is highly competitive, but it can overwhelm its progenitor populatio... | 10.1038/nrmicro863 | An important experimental study showing that a high-fitness variant was suppressed in a low-fitness population. Often interpreted as indicating that RNA viruses form quasispecies. |
10.1126/science.285.5434.1745 | 83,455,545 | In asexual populations, beneficial mutations that occur in different lineages compete with one another. This phenomenon, known as clonal interference, ensures that those beneficial mutations that do achieve fixation are of large effect. Clonal interference also increases the time between fixations, thereby slowing the ... | 10.1038/nrmicro863 | An important experimental demonstration that clonal interference slows down the rate of adaptive evolution in RNA viruses. |
10.1126/science.285.5426.422 | 83,119,372 | The molecular basis of adaptation is a major focus of evolutionary biology, yet the dynamic process of adaptation has been explored only piecemeal. Experimental evolution of two bacteriophage lines under strong selection led to over a dozen nucleotide changes genomewide in each replicate. At least 96 percent of the ami... | 10.1038/nrmicro863 | A key experimental paper that provides evidence for both frequent adaptive and parallel evolution in RNA viruses. |
10.1093/genetics/148.3.929 | 104,386,016 | Abstract Several codon-based models for the evolution of protein-coding DNA sequences are developed that account for varying selection intensity among amino acid sites. The “neutral model” assumes two categories of sites at which amino acid replacements are either neutral or deleterious. The “positive-selection model” ... | 10.1038/nrmicro863 | Develops a rigorous, statistical methodology to determine selection pressures at individual amino acid sites. |
10.1126/science.1058321 | 107,219,907 | Hepatitis C virus (HCV) is a leading worldwide cause of liver disease. Here, we use a new model of HCV spread to investigate the epidemic behavior of the virus and to estimate its basic reproductive number from gene sequence data. We find significant differences in epidemic behavior among HCV subtypes and suggest that ... | 10.1038/nrmicro863 | Establishes the link between population genetics and mathematical epidemiology through the use of molecular phylogenies to study the population dynamics of infectious diseases. |
10.1126/science.2939560 | 122,740,966 | Variation in influenza A viruses was examined by comparison of nucleotide sequences of the NS gene (890 bases) of 15 human viruses isolated over 53 years (1933 to 1985). Changes in the genes accumulate with time, and an evolutionary tree based on the maximum parsimony method can be constructed. The evolutionary rate is... | 10.1038/nrmicro863 | A pioneering paper describing the molecular epidemiological analysis of RNA viruses. |
10.1126/science.1059128 | 16,748,487 | All retroviruses possess a highly error-prone reverse transcriptase, but the extent of the consequent sequence diversity and the rate of evolution differ greatly among retroviruses. Because of the high mutability of retroviruses, it is not the generation of new viral variants that limits the extent of diversity and the... | 10.1038/nrmicro863 | Illustrates some of the key factors that constrain the adaptability of RNA viruses. |
10.1073/pnas.1103764108 | 62,611,436 | The predominant mode of HIV-1 infection is heterosexual transmission, where a genetic bottleneck is imposed on the virus quasispecies. To probe whether limited genetic diversity in the genital tract (GT) of the transmitting partner drives this bottleneck, viral envelope sequences from the blood and genital fluids of ei... | 10.1038/nrmicro3471 | A study of transmission pairs suggesting that the transmission bottleneck is not just stochastic and may select for rare variants in the donor GT. |
10.1128/jvi.03577-12 | 19,106,153 | ABSTRACT Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and subjects with chronic infections in the context of sub... | 10.1038/nrmicro3471 | This study of a large number of heterosexually transmitted T/F env genes found that they are exclusively T cell-tropic. This study also observed that, relative to their controls, T/F viruses isolated from males have fewer glycosylation sites than T/F viruses isolated from females. This suggests that female-to-male tran... |
10.1128/jvi.00296-09 | 61,407,716 | ABSTRACT Human immunodeficiency virus type 1 transmission selects for virus variants with genetic characteristics distinct from those of donor quasispecies, but the biological factors favoring their transmission or establishment in new hosts are poorly understood. We compared primary target cell tropisms and entry core... | 10.1038/nrmicro3471 | The first study illustrating that T/F viruses are not macrophage-tropic and that transmission does not select for enhanced macrophage-tropism. |
10.1073/pnas.1304288110 | 104,201,143 | Defining the virus–host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) an... | 10.1038/nrmicro3471 | A Thorough analysis of T/F virus phenotypes, which observed that subtype B T/F viruses are more resistant to IFNα than controls. |
10.1126/science.166.3910.1303 | 88,231,109 | Neurons in inferotemporal cortex (area TE) of the monkey had visual receptive fields which were very large (greater than 10 by 10 degrees) and almost always included the fovea. Some extended well into both halves of the visual field, while others were confined to the ipsilateral or contralateral side. These neurons wer... | 10.1038/nrn2195 | The first report of a cell in the monkey inferior temporal cortex that responds most strongly to hands. |
10.1126/science.1063414 | 20,422,207 | Despite extensive evidence for regions of human visual cortex that respond selectively to faces, few studies have considered the cortical representation of the appearance of the rest of the human body. We present a series of functional magnetic resonance imaging (fMRI) studies revealing substantial evidence for a disti... | 10.1038/nrn2195 | Reports the discovery with fMRI of a body-selective area in the human extrastriate visual cortex: the EBA. |
10.1162/0898929055002481 | 27,974,145 | Most studies on visual perception of human beings have focused on perception of faces. However, bodies are another important visual element, which help us to identify a member of our species in the visual scene. In order to study whether similar configural information processing is used in body and face perception, we ... | 10.1038/nrn2195 | An ERP study investigating body and face processing that shows similar waveforms for static bodies and faces in both 3-month-old infants and adults. |
10.1152/jn.00513.2004 | 20,421,345 | Functional neuroimaging studies have revealed human brain regions, notably in the fusiform gyrus, that respond selectively to images of faces as opposed to other kinds of objects. Here we use fMRI to show that the mid-fusiform gyrus responds with nearly the same level of selectivity to images of human bodies without fa... | 10.1038/nrn2195 | Reports the discovery with fMRI of a body-selective area in the fusiform gyrus: the FBA. |
10.1162/0898929053467587 | 100,785,364 | Previous data from single-case and small group studies have suggested distinctions among structural, conceptual, and online sensorimotor representations of the human body. We developed a battery of tasks to further examine the prevalence and anatomic substrates of these body representations. The battery was administere... | 10.1038/nrn2195 | A large-scale neuropsychological investigation that suggests a triple dissociation among types of body representation. |
10.1073/pnas.0802982105 | 4,631,878 | The growing resistance to current first-line antimalarial drugs represents a major health challenge. To facilitate the discovery of new antimalarials, we have implemented an efficient and robust high-throughput cell-based screen (1,536-well format) based on proliferation of Plasmodium falciparum (Pf) in erythrocytes. F... | 10.1038/nrmicro3138 | This paper contains a description of the first ultra-high-throughput cellular screen for antimalarial drugs and is the source of methods for one of the publicly available antimalarial data sets, the chEMBL Neglected Tropical Disease archive. |
10.1126/science.1193225 | 104,227,912 | Antimalarial Drug Candidate Spiroindolones were discovered as promising antimalarial drug candidates through a high-throughput screening approach that should be applicable to a range of neglected infectious diseases. Rottmann et al. (p. 1175 ; see the Perspective by Wells ) present the preclinical profile for an optimi... | 10.1038/nrmicro3138 | This paper is a description of the target discovery for the first new class of antimalarial drugs to enter clinical trials. |
10.1126/science.1211936 | 123,266,405 | Imidazolopiperazine compounds inhibit liver-stage malaria parasites with one oral dose in mice. | 10.1038/nrmicro3138 | This paper describes a medium-throughput screen that further delineates blood-stage antimalarial drugs into those with probable causal prophylactic activity and those without. |
10.1073/pnas.1204556109 | 82,954,351 | Malarial dihydrofolate reductase (DHFR) is the target of antifolate antimalarial drugs such as pyrimethamine and cycloguanil, the clinical efficacy of which have been compromised by resistance arising through mutations at various sites on the enzyme. Here, we describe the use of cocrystal structures with inhibitors and... | 10.1038/nrmicro3138 | This paper gives beautiful examples of how target-based drug discovery can work. |
10.1126/science.1236192 | 62,286,052 | Infections Against Infection In the same way that infection with the bacteria Wolbachia spp. can make Aedes mosquitoes resistant to dengue virus, there have been hints that these bacteria can interfere with the reproduction of malaria parasites. Bian et al. (p. 748 ) established a heritable Wolbachia infection in anoph... | 10.1038/nrmicro3138 | In this paper. the authors show a novel, alternative approach to using drugs to control malaria. |
10.1152/physrev.00028.2005 | 103,768,572 | Locomotion results from intricate dynamic interactions between a central program and feedback mechanisms. The central program relies fundamentally on a genetically determined spinal circuitry (central pattern generator) capable of generating the basic locomotor pattern and on various descending pathways that can trigge... | 10.1038/nrn2608 | An important review that comprehensively covers the role of sensory feedback in locomotion. |
10.1073/pnas.0907039106 | 122,688,251 | Cell-cell communication is essential for coordinating physiological responses in multicellular organisms and is required for various developmental processes, including cell migration, differentiation, and fusion. To facilitate communication, functional differences are usually required between interacting cells, which c... | 10.1038/nrmicro2580 | This paper describes signalling that occurs prior to cell fusion between N. crassa germlings, and forms the basis for the model of how genetically identical individuals undergo bidirectional communication without responding to their own signals. |
10.1098/rspb.1977.0085 | 20,601,874 | Of the many possible functions of the macaque monkey primary visual cortex (striate cortex, area 17) two are now fairly well understood. First, the incoming information from the lateral geniculate bodies is rearranged so that most cells in the striate cortex respond to specifically oriented line segments, and, second, ... | 10.1038/nrn1536 | Summary of the early seminal work of Hubel and Wiesel on the primary visual cortex. |
10.1111/j.1751-1097.1976.tb06810.x | 45,453,209 | Abstract— With a view toward elucidating the physiocochemical properties of the nerve membrane, the behavior of various dye molecules incorporated into the membrane was investigated. By measuring the difference between the absorption spectra of dyes in the membrane at rest and those during nerve excitation, the nature ... | 10.1038/nrn1536 | The first optical recording of electrical activity based on extrinsic probes using extensive signal averaging. |
10.1152/jn.1977.40.6.1281 | 38,993,839 | 1. Using an optical method for measuring membrane potential, we have been able to monitor action-potential activity simultaneously in 14 neurons of the supraesophageal ganglion of the barnacle. 2. Under favorable conditions, 4-mV synaptic potentials could also be detected optically. | 10.1038/nrn1536 | This shows the first optical recording of action potentials from 14 neurons simultaneously, including optical recordings of excitatory and inhibitory synaptic potential without averaging (also shown in Ref. 18). |
10.1113/jphysiol.1982.sp014453 | 100,708,506 | 1. Voltage‐sensitive membrane‐bound dyes and a matrix of 100 photodetectors were used to detect the spread of evoked electrical activity at the CA1 region of rat hippocampus slices. A display processor was designed in order to visualize the spread of electrical activity in slow motion. 2. The stimulation of the Schaffe... | 10.1038/nrn1536 | Describing the shift from optical recording of single sells to VSDI of heterogeneous population activity from mixed neuronal compartments viewed by a given detector, as well as detection of fast intrinsic signals from mammalian brain slice. |
10.1073/pnas.87.16.6082 | 81,162,802 | We have shown previously the existence of small, activity-dependent changes in intrinsic optical properties of cortex that are useful for optical imaging of cortical functional architecture. In this study we introduce a higher resolution optical imaging system that offers spatial and temporal resolution exceeding that ... | 10.1038/nrn1536 | High-resolution optical imaging based on intrinsic signals rather than VSDI reveals the functional architecture in cat and monkey visual cortex. These maps can be obtained by relying on signals originating from oxygen consumption, blood volume or light scattering changes. |
10.1152/jn.00234.2004 | 45,482,913 | One of the major limitations in the current set of techniques available to neuroscientists is a dearth of methods for imaging individual cells deep within the brains of live animals. To overcome this limitation, we developed two forms of minimally invasive fluorescence microendoscopy and tested their abilities to image... | 10.1038/nrn1536 | Evidence that microendoscopy can provide imaging of deep brain structures. |
10.1126/science.287.5454.864 | 62,191,077 | Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation between selected neurons. Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmit... | 10.1038/nsmb.1450 | This paper shows that neurotransmitter secretion from synaptic vesicles is completely abrogated in Munc18-1 knockout mice and that the brain can still assemble in the absence of neurotransmitter release. |
10.1083/jcb.146.2.333 | 80,624,081 | Proteins of the Sec1 family have been shown to interact with target-membrane t-SNAREs that are homologous to the neuronal protein syntaxin. We demonstrate that yeast Sec1p coprecipitates not only the syntaxin homologue Ssop, but also the other two exocytic SNAREs (Sec9p and Sncp) in amounts and in proportions character... | 10.1038/nsmb.1450 | Sec1p is shown to bind to its cognate SNARE complex, providing the first evidence for formation of the SM protein–SNARE complex assemblies that may form the core of intracellular membrane fusion machineries. |
10.1083/jcb.200109021 | 83,444,853 | In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mi... | 10.1038/nrn1196 | Conditional deletion of β1 integrin in Schwann cells causes a severe neuropathy with missorted axons. |
10.1073/pnas.152621799 | 60,455,773 | Schwann cell-derived peripheral myelin protein-22 (PMP-22) when mutated or overexpressed causes heritable neuropathies with a previously unexplained “gain-of-function” endoplasmic reticulum (ER) retention phenotype. In wild-type sciatic nerves, PMP-22 associates in a specific, transient ( t 1/2 ≈ 11 min), and oligosacc... | 10.1038/nrn1196 | PMP22 mutants have a prolonged association with the endoplasmic reticulum chaperone protein calnexin, possibly depleting the pool of calnexin and causing neuropathy. |
10.1083/jcb.200107114 | 100,813,337 | Mutations in P0 (MPZ), the major myelin protein of the peripheral nervous system, cause the inherited demyelinating neuropathy Charcot-Marie-Tooth disease type 1B. P0 is a member of the immunoglobulin superfamily and functions as a homophilic adhesion molecule. We now show that point mutations in the cytoplasmic domain... | 10.1038/nrn1196 | A CMT1B mutation that abolishes the protein kinase C phosphorylation of P0 causes loss of P0-mediated adhesion, providing an important clue towards signal transduction mediated by P0. |
10.1083/jcb.142.4.1095 | 29,222,133 | The Schwann cell myelin sheath is a multilamellar structure with distinct structural domains in which different proteins are localized. Intracellular dye injection and video microscopy were used to show that functional gap junctions are present within the myelin sheath that allow small molecules to diffuse between the ... | 10.1038/nrn1196 | Dye transfer studies demonstrate that incisures contain 'reflexive' gap junctions that provide a radial pathway for diffusion of small molecules across the myelin sheath. The correct functioning of this system might be crucial for maintaining myelin sheaths. |
10.1242/jcs.00148 | 102,776,036 | Neurofilaments (NFs) are the major intermediate filaments (IFs) of mature neurons. They play important roles in the structure and function of axons. Recently, two mutations in the neurofilament light (NFL) subunit have been identified in families affected by Charcot-Marie-Tooth (CMT) neuropathy type 2. We have characte... | 10.1038/nrn1196 | Together, references 120 and 121 show that mutant NEFL proteins do not properly form intermediate filaments, have dominant effects on the assembly of wild-type neurofilaments and disrupt the axonal transport of neurofilaments. |
10.1083/jcb.200301026 | 125,061,271 | To test the hypothesis that fast anterograde molecular motor proteins power the slow axonal transport of neurofilaments (NFs), we used homologous recombination to generate mice lacking the neuronal-specific conventional kinesin heavy chain, KIF5A. Because null KIF5A mutants die immediately after birth, a synapsin-promo... | 10.1038/nrn1196 | Mice lacking neuronal KIF5A have greatly diminished transport of neurofilaments. |
10.1152/jappl.1963.18.3.523 | 74,108,439 | We have demonstrated respiratory chemosensitivity to changes in (H + ) and Pco 2 of the cerebrospinal fluid (CSF) in the subarachnoid space on the ventrolateral surface of the medulla. Respiratory stimulation was elicited from this region by increased Pco 2 and (H + ), nicotine, and acetylcholine; and respiratory depre... | 10.1038/nrn1409 | The authors applied acidic solution to the ventrolateral surface of the cat medulla and observed an increase in ventilation. This early work, and other papers by these authors, led to the widespread acceptance that the ventrolateral medulla was the sole location of central respiratory chemoreceptors, and that these neu... |
10.1152/jn.1995.73.3.933 | 62,167,521 | 1. It has been hypothesized that CO2-sensitive neurons are located in the rostral ventral medulla. To demonstrate this at the cellular level, perforated patch-clamp recordings were made from rat medullary slices in vitro. The effect of respiratory acidosis/alkalosis on the electrophysiologic properties of neurons was s... | 10.1038/nrn1409 | Using patch-clamp recordings from in vitro brain slices, it was shown, for the first time, that there are neurons within the medullary raphé nuclei that are intrinsically sensitive to an increase in carbon dioxide. This was the foundation for further work on the mechanisms of central chemoreception by serotonergic neur... |
10.1152/jappl.1996.80.1.108 | 113,584,812 | We injected acetazolamide (AZ; 5 x 10(-6) M; 1 nl; n = 14), its inactive analogue 2-acetylamino-1,3,4-thiadiazole-5-sulfon-t-butylamide (5 x 10(-5) M; n = 6), or mock cerebrospinal fluid (n = 5) into the caudal raphe in the midline brain stem of anesthetized paralyzed ventilated rats. These AZ injections have been show... | 10.1038/nrn1409 | The authors showed that microinjection of acetazolamide into the medullary raphé leads to an increase in ventilation. This effect was thought to result from focal acidosis, and was taken as evidence for central respiratory chemoreceptors in this region. |
10.1126/science.3925552 | 88,221,138 | The nucleus tractus solitarius (NTS) contains neurons that are part of the central neuronal network controlling rhythmic breathing movements in mammals. Nerve terminals within the NTS show immunoreactivity to thyrotropin-releasing hormone (TRH), a neuropeptide that has potent stimulatory effects on respiration. By mean... | 10.1038/nrn1409 | Application of thyrotropin-releasing hormone to guinea pig brain slices converted neurons in the ventrolateral nucleus tractus solitarius from random firing to bursting. The bursting was similar to that seen in this region in vivo in inspiratory neurons that project to the phrenic motor nucleus. The bursting was furthe... |
10.1152/jappl.2001.90.1.269 | 102,029,060 | Nucleus raphéobscurus (NRo) modulates hypoglossal (XII) nerve motor output in the in vitro transverse brain stem slice of neonatal rats (1–5 days old); chemical ablation of NRo and its focal CO 2 acidification modulated the bursting rhythm of XII nerves. We microinjected a 4.5 mM solution of kainic acid into the NRo to... | 10.1038/nrn1409 | The authors used slices of the rat medulla and showed that the frequency of bursts generated by the pre-BötC was increased by application of acidic solution into the midline raphé. They further showed that rhythm generation was abolished by ablation of midline raphé neurons. |
10.1126/science.282.5392.1321 | 38,582,068 | Glycine receptors are anchored at inhibitory chemical synapses by a cytoplasmic protein, gephyrin. Molecular cloning revealed the similarity of gephyrin to prokaryotic and invertebrate proteins essential for synthesizing a cofactor required for activity of molybdoenzymes. Gene targeting in mice showed that gephyrin is ... | 10.1038/nrn3670 | This paper describes the effects of targeted deletion of Gphn in mice, revealing gephyrin's dual function in molybdenum cofactor biosynthesis and postsynaptic clustering of GlyRs and GABA A Rs at inhibitory synapses. |
10.1073/pnas.1011824108 | 80,691,400 | Postsynaptic scaffolding proteins ensure efficient neurotransmission by anchoring receptors and signaling molecules in synapse-specific subcellular domains. In turn, posttranslational modifications of scaffolding proteins contribute to synaptic plasticity by remodeling the postsynaptic apparatus. Though these mechanism... | 10.1038/nrn3670 | This paper reports the identification of gephyrin residue Ser270 as a target for GSK3β-mediated phosphorylation to regulate the density of GABAergic synapses and the frequency of miniature inhibitory postsynaptic currents in vitro , which also requires activation of the calcium-dependent protein calpain. |
10.1515/bc.2009.071 | 64,343,200 | Abstract Carbohydrate chains of glycoproteins, glycolipids, proteoglycans, and polysaccharides mediate processes of biological and medical importance through their interactions with complementary proteins. The unraveling of these interactions is therefore a priority in biomedical sciences. Carbohydrate microarray techn... | 10.1038/nrmicro3346 | This review provides a comprehensive description of glycan array technology. |
10.1128/jvi.03518-12 | 19,077,524 | ABSTRACT Naturally occurring bovine-human reassortant rotaviruses with a P[11] VP4 genotype exhibit a tropism for neonates. Interaction of the VP8* domain of the spike protein VP4 with sialic acid was thought to be the key mediator for rotavirus infectivity. However, recent studies have indicated a role for nonsialylat... | 10.1038/nrmicro3346 | This study defines the glycan receptor specificity of neonatal rotavirus infections. |
10.1128/jvi.01822-12 | 110,832,359 | ABSTRACT Mammalian reoviruses display serotype-specific patterns of tropism and disease in the murine central nervous system (CNS) attributable to polymorphisms in viral attachment protein σ1. While all reovirus serotypes use junctional adhesion molecule-A as a cellular receptor, they differ in their utilization of car... | 10.1038/nrmicro3346 | This work shows that sialic acid-binding capacity increases reovirus-induced neurovirulence in mice. |
10.1073/pnas.1323162111 | 38,255,770 | Significance Studies using novel “shotgun glycan microarray” technology identify, for the first time to our knowledge, the endogenous receptors for influenza viruses from a natural host, the pig. Libraries of total N-glycans from pig lung were probed for binding properties using a panel of influenza viruses isolated fr... | 10.1038/nrmicro3346 | This study demonstrates how shotgun glycomics can be used to identify influenza virus receptors. |
10.1111/cdep.12079 | 80,949,893 | Abstract Distributing learning events in time promotes memory to a greater degree than massing learning together in immediate succession, a phenomenon known as the spacing effect. In this article, I review research on the spacing effect in children's acquisition and generalization of conceptual knowledge. For decades, ... | 10.1038/nrn.2015.18 | This study found that, in children's education, spacing of learning sessions promoted not only better fact retention but also generalization of currently learned items to bind with and extend previously established conceptual categories. |
10.1523/jneurosci.5561-12.2013 | 123,199,550 | Although the importance of spaced training trials in the formation of long-term memory (LTM) is widely appreciated, surprisingly little is known about the molecular mechanisms that support interactions between individual trials. The intertrial dynamics of ERK/MAPK activation have recently been correlated with effective... | 10.1038/nrn.2015.18 | This work characterized the dynamics of MAPK and its activation of C/EBP, a transcription factor that is important for long-term memory formation, identifying the response of MAPK within a specific time window as essential for generating an optimal inter-trial interval. |
10.1002/cne.23646 | 82,784,616 | ABSTRACT Nascent zones and active zones are adjacent synaptic regions that share a postsynaptic density, but nascent zones lack the presynaptic vesicles found at active zones. Here dendritic spine synapses were reconstructed through serial section electron microscopy (3DEM) and EM tomography to investigate nascent zone... | 10.1038/nrn.2015.18 | This work, one of a group of related studies by the Harris laboratory, characterized in detail pre- and postsynaptic structural changes that are necessary for the consolidation of LTP. |
10.1073/pnas.1120700109 | 58,385,232 | The superiority of spaced vs. massed training is a fundamental feature of learning. Here, we describe unanticipated timing rules for the production of long-term potentiation (LTP) in adult rat hippocampal slices that can account for one temporal segment of the spaced trials phenomenon. Successive bouts of naturalistic ... | 10.1038/nrn.2015.18 | This study, together with reference 48, substantiates the key hypothesis that spaced stimuli first prime and then strengthen upon repetition successive groups of dendritic spines, creating a morphological correlate of the memory trace that spaced, but not massed, protocols effectively consolidate. |
10.1523/jneurosci.0324-14.2014 | 103,241,491 | Little is known about the temporal progression and regulation of the mechanisms underlying memory consolidation. Brain-derived-neurotrophic-factor (BDNF) has been shown to mediate the maintenance of memory consolidation, but the mechanisms of this regulation remain unclear. Using inhibitory avoidance (IA) in rats, here... | 10.1038/nrn.2015.18 | This study characterizes the dynamics of a molecular positive feedback loop demonstrated to be important for the consolidation of long-term (24 hours or more) memory, as well as the late repression of Bdnf that terminates the feedback. |
10.1146/annurev-clinpsy-050212-185538 | 17,714,580 | Translational research on emotion in schizophrenia has revealed deficits in emotion perception and expression, as well as intact areas, including emotional experience and brain activation in the presence of emotionally evocative material. Yet, a closer look at emotional experience reveals that all is not well in the ex... | 10.1038/nrn4005 | This article comprehensively reviews the literature on emotion experience in schizophrenia across self-reporting, physiological and neuroimaging methods. |
10.1017/s0033291711000614 | 40,481,749 | Background Empathy is crucial for successful social relationships. Despite its importance for social interactions, little is known about empathy in schizophrenia. This study investigated the degree to which schizophrenia patients can accurately infer the affective state of another person (i.e. empathic accuracy). Metho... | 10.1038/nrn4005 | This study demonstrates that people with schizophrenia show impaired empathic accuracy and benefit less than healthy controls from social cues when making empathic judgments. |
10.1161/hs0202.102328 | 107,180,350 | Background and Purpose — Because infections subsequent to influenza may play a role in promoting the complications of atherosclerotic disease and may also induce hypercoagulation, we hypothesized that influenza vaccination may protect against brain infarction. Methods — During the influenza epidemic period we studied 2... | 10.1038/nrneurol.2016.125 | This article recommends influenza vaccination to prevent secondary cardiovascular risk, and reviews the evidence for this recommendation. |
10.1126/science.1143839 | 20,172,793 | Do learning and retrieval of a memory activate the same neurons? Does the number of reactivated neurons correlate with memory strength? We developed a transgenic mouse that enables the long-lasting genetic tagging of c- fos –active neurons. We found neurons in the basolateral amygdala that are activated during Pavlovia... | 10.1038/nrn4000 | This study introduced the influential TetTag approach that allows permanent labelling of neuronal ensembles that are activated during fear memory encoding. These authors showed that tagged neurons were reactivated at above chance levels when the corresponding memory is later recalled. |
10.1126/science.1139438 | 80,126,619 | Competition between neurons is necessary for refining neural circuits during development and may be important for selecting the neurons that participate in encoding memories in the adult brain. To examine neuronal competition during memory formation, we conducted experiments with mice in which we manipulated the functi... | 10.1038/nrn4000 | This study shows that neurons with higher CREB activity in the LA are more likely than their neighbours with lower CREB activity to be allocated to a fear memory engram. |
10.1126/science.1164139 | 102,282,266 | Memories are thought to be encoded by sparsely distributed groups of neurons. However, identifying the precise neurons supporting a given memory (the memory trace) has been a long-standing challenge. We have shown previously that lateral amygdala (LA) neurons with increased cyclic adenosine monophosphate response eleme... | 10.1038/nrn4000 | Using an allocate-and-manipulate approach, this paper is the first to show that fear memories may be 'erased' by ablating engram neurons in the LA. |
10.1126/science.1239073 | 103,773,118 | Can You Trust Your Memory? Being highly imaginative animals, humans constantly recall past experiences. These internally generated stimuli sometimes get associated with concurrent external stimuli, which can lead to the formation of false memories. Ramirez et al. (p. 387 ; see the cover) identified a population of cell... | 10.1038/nrn4000 | In this study, a 'false' memory was generated by pairing artificial activation of engram neurons coding for a safe (non-shocked) context with a footshock. |
10.1126/science.287.5461.2262 | 38,401,141 | To elucidate mechanisms that control and execute activity-dependent synaptic plasticity, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPA-Rs) with an electrophysiological tag were expressed in rat hippocampal neurons. Long-term potentiation (LTP) or increased activity of the calcium/calmodulin-dependen... | 10.1038/nrn1556 | The first direct electrophysiological evidence that AMPARs are incorporated into synapses during LTP. |
10.1126/science.1096615 | 123,054,544 | Activation of N -methyl- d -aspartate subtype glutamate receptors (NMDARs) is required for long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission at hippocampal CA1 synapses, the proposed cellular substrates of learning and memory. However, little is known about how activation o... | 10.1038/nrn1556 | This study showed that activation of NR2A- and NR2B-containing NMDAR subpopulations is required for hippocampal homosynaptic LTP and LTD, respectively. Therefore, this paper provides strong evidence that NR2 subunit composition might be a crucial molecular determinant that dictates the polarity of synaptic plasticity. |
10.1126/science.1086909 | 83,479,501 | Barriers to dispersal between populations allow them to diverge through local adaptation or random genetic drift. High-resolution multilocus sequence analysis revealed that, on a global scale, populations of hyperthermophilic microorganisms are isolated from one another by geographic barriers and have diverged over the... | 10.1038/nrmicro819 | Describes the intra-species diversity that is found in different geographical locations. |
10.1126/science.289.5486.1902 | 41,744,670 | Extremely halophilic archaea contain retinal-binding integral membrane proteins called bacteriorhodopsins that function as light-driven proton pumps. So far, bacteriorhodopsins capable of generating a chemiosmotic membrane potential in response to light have been demonstrated only in halophilic archaea. We describe her... | 10.1038/nrmicro819 | The first attempt by recombinant techniques to link phylogeny to function. |
10.1073/pnas.252630999 | 107,226,687 | The recent application of molecular phylogeny to environmental samples has resulted in the discovery of an abundance of unique and previously unrecognized microorganisms. The vast majority of this microbial diversity has proved refractory to cultivation. Here, we describe a universal method that provides access to this... | 10.1038/nrmicro819 | Describes a new high-throughput cultivation method based on microencapsulation and flow cytometry. |
10.1002/ana.22479 | 101,702,601 | Abstract Objective: Enduring, abnormal expression and function of the ion channel hyperpolarization‐activated cyclic adenosine monophosphate gated channel type 1 (HCN1) occurs in temporal lobe epilepsy (TLE). We examined the underlying mechanisms, and investigated whether interfering with these mechanisms could modify ... | 10.1038/nrn3482 | In the kainate model of acquired chronic TLE in rodents, interference with the interaction between REST and target genes using antisense oligodeoxynucleotides prevented status epilepticus-induced REST-mediated repression of HCN1 and led to a decrease in spontaneous seizure frequency. |
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