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10.1126/science.170.3959.758 | 56,823,688 | Recordings have been obtained simultaneously from several, individually selected neurons in the motor cortex of unanesthetized monkey as the animal performed simple arm movements. With the use of comparatively simple quantitative procedures, the activity of small sets of cells was found to be adequate for rather accura... | 10.1038/nrn3724 | This classic study was the first to make real-time predictions of movement-related parameters using single-unit recordings from multiple neurons in the motor cortex. |
10.1111/imj.13167 | 80,899,906 | Observational studies of the effectiveness of clinical interventions are proliferating as more ‘real‐world’ clinical data (so called ‘big data’) are gathered from clinical registries, administrative datasets and electronic health records. While well‐conducted randomised controlled trials ( RCT ) remain the scientific s... | 10.1038/nrneurol.2016.188 | This article proposes criteria for identifying high quality observational studies. |
10.1002/ana.24339 | 40,757,370 | Objective In patients suffering multiple sclerosis activity despite treatment with interferon β or glatiramer acetate, clinicians often switch therapy to either natalizumab or fingolimod. However, no studies have directly compared the outcomes of switching to either of these agents. Methods Using MSBase, a large intern... | 10.1038/nrneurol.2016.188 | The first comparative study evaluating the effectiveness of natalizumab and fingolimod after first-line treatment failure. |
10.1002/ana.21102 | 101,776,379 | Abstract Objective To investigate the impact of interferon‐beta (IFNβ) on disease progression in relapsing‐remitting multiple sclerosis patients. Methods A cohort of 1,504 relapsing‐remitting multiple sclerosis (1,103 IFNβ–treated and 401 untreated) patients was followed for up to 7 years. Cox proportional hazards regr... | 10.1038/nrneurol.2016.188 | The first study addressing the issue of long-term effectiveness of IFN-β treatment in MS by using propensity score technique. |
10.1073/pnas.0507044103 | 38,507,235 | The evolutionary conservation of the NF-κB transcription factors, from Drosophila to humans, underscores its pivotal role in immune response. Unexpectedly, the canonical NF-κB signaling pathway is not functional in the immune system of Caenorhabditis elegans . Therefore, the ancient origin of the NF-κB signaling pathwa... | 10.1038/nrmicro2539 | This study shows that the NF-κB signalling pathway is evolutionarily conserved and plays a part in pathogen infection and immunity |
10.1073/pnas.2237183100 | 81,276,400 | Epstein–Barr virus (EBV) latent infection membrane protein 1 (LMP1)-induced NF-κB activation is important for infected cell survival. LMP1 activates NF-κB, in part, by engaging tumor necrosis factor (TNF) receptor-associated factors (TRAFs), which also mediate NF-κB activation from LTβR and CD40. LTβR and CD40 activati... | 10.1038/nrmicro2539 | This study demonstrates that EBV LMP1 activates the alternative NF-κB signalling pathway. |
10.1073/pnas.0606019103 | 15,724,445 | Apoptosis is an innate immune response to viral infection that limits viral replication. However, the mechanisms by which cells detect viral infection and activate apoptosis are not completely understood. We now show that during Coxsackievirus infection, the viral protease 3C pro cleaves inhibitor of κBα (IκBα). A prot... | 10.1038/nrmicro2539 | This study shows that the coxsackievirus protease directly cleaves IκBα for inhibition of the NF-κB pathway. |
10.1073/pnas.0900452106 | 80,459,390 | Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. Here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cDN... | 10.1038/nrmicro2539 | This paper describes a class of poxvirus immunomodulatory proteins that inhibit the NF-κB pathway by targeting p105. |
10.1126/science.1126867 | 81,485,613 | Yersinia species use a variety of type III effector proteins to target eukaryotic signaling systems. The effector YopJ inhibits mitogen-activated protein kinase (MAPK) and the nuclear factor κB (NFκB) signaling pathways used in innate immune response by preventing activation of the family of MAPK kinases (MAPKK). We sh... | 10.1038/nrmicro2539 | This study shows that YopJ acts as an acetyltransferase for acetylation of IKKα and IKKβ and blocks activation of the IKK complex. |
10.1073/pnas.0504466102 | 102,681,295 | Bacteria of Shigella spp. are responsible for shigellosis in humans. They use a type III secretion system to inject effector proteins into host cells and induce their entry into epithelial cells or trigger apoptosis in macrophages. We present evidence that the effector OspG is a protein kinase that binds various ubiqui... | 10.1038/nrmicro2539 | This work finds that the S. flexneri T3SS effector protein OspG blocks degradation of phosphorylated IκBα by targeting the cellular ubiquitin machinery. |
10.1073/pnas.0907200106 | 60,458,676 | NF-κB is critical in innate immune defense responses against invading microbial pathogens. Legionella pneumophila infection of lung macrophages causes Legionnaire's disease with pneumonia symptoms. A set of NF-κB-controlled genes involved in inflammation and anti-apoptosis are up-regulated in macrophages upon L. pneumo... | 10.1038/nrmicro2539 | This study shows that the bacterial pathogen Legionella pneumophila activates NF-κB signalling by encoding a Ser/Thr kinase that directly phosphorylates IκBα |
10.1126/science.1075462 | 80,470,549 | Parasites have evolved a plethora of mechanisms to ensure their propagation and evade antagonistic host responses. The intracellular protozoan parasite Theileria is the only eukaryote known to induce uncontrolled host cell proliferation. Survival of Theileria -transformed leukocytes depends strictly on constitutive nuc... | 10.1038/nrmicro2539 | This work demonstrates that the intracellular protozoan parasites of the genus Theileria constitutively activate the NF-κB pathway by modulating the signalling of the cellular IKK complex. |
10.1111/1469-7610.00376 | 40,210,513 | Children with and without autism were compared on two visual search tasks in which a letter target appeared among two sets of letter distracters. In one task, the target shared colour with one set of distracters but was unique in shape‐the feature search task. In the other, the conjunctive search task, the target share... | 10.1038/nrn.2017.112 | This foundational study shows faster target detection during conjunctive visual search in autism — a finding now widely replicated. |
10.1007/s11689-009-9023-x | 125,167,908 | Abstract One unifying explanation for the complexity of Autism Spectrum Disorders (ASD) may lie in the disruption of excitatory/inhibitory (E/I) circuit balance during critical periods of development. We examined whether Parvalbumin (PV)-positive inhibitory neurons, which normally drive experience-dependent circuit ref... | 10.1038/nrn.2017.112 | This study provides insights into common circuit-level differences observed in multiple mouse models of autism with distinct genetic origins, by reporting a reduction in parvalbumin-expressing inhibitory neurons across parietal and occipital cortex. |
10.1126/science.1207313 | 20,586,786 | Chromosome tips seem to be maintained by an unusual mechanism in tumors that have mutations in chromatin remodeling genes. | 10.1038/nsmb.3106 | Pancreatic neuroendocrine tumors with characteristics of ALT have either mutations of the ATRX or DAXX genes or loss of nuclear expression of their encoded proteins (which are involved in chromatin remodeling at telomeres, among other functions) |
10.1083/jcb.201207189 | 18,458,787 | Telomeres in cells that use the recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length. We therefore investigated whether ALT telomeres contain structural abnormalities that contribute to ALT activity. Here we used next genera... | 10.1038/nsmb.3106 | ALT telomeres contain an increased content of noncanonical repeats, and one of these (TCAGGG) creates a high-affinity binding site for the nuclear receptors COUP-TF2 and TR4 |
10.1126/science.1257216 | 102,352,447 | Cancer's alternative means to an end To stay alive and proliferating, tumor cells must maintain their telomeres: the DNA sequences at the ends of chromosomes. The majority accomplish this by activating the enzyme telomerase. However, certain tumor types favor a different mechanism called alternative lengthening of telo... | 10.1038/nsmb.3106 | Inhibition of the protein kinase ATR, a regulator of recombination, inhibits ALT and selectively kills ALT cells, thus raising the possibility that ATR inhibitors may be a useful treatment for ALT cancers |
10.2217/fmb.09.82 | 28,097,741 | The Gram-positive species Enterococcus faecium has long been thought of as a harmless commensal of the mammalian GI tract. In the last two decades, however, E. faecium has become an important cause of nosocomial bacteremias. These infections are often difficult to treat owing to the resistance of E. faecium to a large ... | 10.1038/nrmicro2761 | A review of the evolution and population genetics of E. faecium |
10.1126/science.1080613 | 62,129,689 | The complete genome sequence of Enterococcus faecalis V583, a vancomycin-resistant clinical isolate, revealed that more than a quarter of the genome consists of probable mobile or foreign DNA. One of the predicted mobile elements is a previously unknown vanB vancomycin-resistance conjugative transposon. Three plasmids ... | 10.1038/nrmicro2761 | The first report of closed whole-genome sequencing of an E. faecalis isolate. |
10.1073/pnas.1000139107 | 103,811,098 | The Enterococcus faecalis pathogenicity island (PAI) encodes known virulence traits and >100 additional genes with unknown roles in enterococcal biology. Phage-related integration and excision genes, and direct repeats flanking the island, suggest it moves as an integrative conjugative element (ICE). However, transf... | 10.1038/nrmicro2761 | A paper describing the mechanism by which large fragments of chromosomal DNA are transferred between enterococcal strains to produce 'hybrid' strains. |
10.1073/pnas.1006855107 | 124,231,234 | Inducible vancomycin resistance in enterococci is due to a sophisticated mechanism that combines synthesis of cell wall peptidoglycan precursors with low affinity for glycopeptides and elimination of the normal target precursors. Although this dual mechanism, which involves seven genes organized in two operons, is pred... | 10.1038/nrmicro2761 | An evaluation of the fitness costs of vancomycin resistance in enterococci. |
10.1111/j.1365-2958.2007.05744.x | 82,539,922 | Summary Linezolid, which targets the ribosome, is a new synthetic antibiotic that is used for treatment of infections caused by Gram‐positive pathogens. Clinical resistance to linezolid, so far, has been developing only slowly and has involved exclusively target site mutations. We have discovered that linezolid resista... | 10.1038/nrmicro2761 | The first description of the methyltransferase Cfr conferring resistance to linezolid in a human clinical isolate. |
10.1126/science.275.5297.213 | 125,310,102 | Activity-driven modifications in synaptic connections between neurons in the neocortex may occur during development and learning. In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found to indu... | 10.1038/nrn2774 | An important paper showing that modifications in synaptic connections between neurons in the neocortex are dependent on the precise temporal relation between postsynaptic action potentials and unitary excitatory postsynaptic potentials. |
10.1073/pnas.0900390106 | 102,278,269 | Brain development is characterized by maturational processes that span the period from childhood through adolescence to adulthood, but little is known whether and how developmental processes differ during these phases. We analyzed the development of functional networks by measuring neural synchrony in EEG recordings du... | 10.1038/nrn2774 | The first study to comprehensively examine the development of task-related neural synchrony in humans, highlighting the role of late brain maturation for the shaping and reorganization of functional networks. |
10.1073/pnas.1108561108 | 19,077,378 | We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on “hot” and “cool” versions of a go/nogo task to assess whether delay of gratification in childhood pred... | 10.1038/nrn.2017.8 | This article provides an astonishing demonstration of the predictive capability of behaviour in early life for subsequent adult outcomes. |
10.1126/science.1137073 | 19,367,838 | Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug ... | 10.1038/nrn.2017.8 | This article offers an experimental demonstration of how animal-based investigations of neurobehavioural syndromes may have relevance for understanding causal mechanisms in complex human disorders such as addiction. |
10.1126/science.1063736 | 82,868,626 | The functional architecture of the object vision pathway in the human brain was investigated using functional magnetic resonance imaging to measure patterns of response in ventral temporal cortex while subjects viewed faces, cats, five categories of man-made objects, and nonsense pictures. A distinct pattern of respons... | 10.1038/nrn1931 | One of the first studies using pattern-based analysis to investigate the nature of object representations in the human ventral visual cortex. |
10.1073/pnas.0600244103 | 62,216,539 | The development of high-resolution neuroimaging and multielectrode electrophysiological recording provides neuroscientists with huge amounts of multivariate data. The complexity of the data creates a need for statistical summary, but the local averaging standardly applied to this end may obscure the effects of greatest... | 10.1038/nrn1931 | This study introduces the 'searchlight' approach that searches across the entire brain for specific local patterns that encode information about a cognitive or perceptual state. |
10.1126/science.1214935 | 125,167,861 | Enduring Tolerance During an infection, the host organism deploys multiple defense strategies. Disease resistance, the process by which the immune system decreases pathogen burden is perhaps the most well-known, and certainly the mechanism that is best studied and understood. Other defense strategies range from pathoge... | 10.1038/nrneph.2016.186 | This review summarizes the host defence against infection and discusses the integral role of tolerance in this response. |
10.1126/scitranslmed.3001118 | 125,239,188 | Heme from red blood cells released in septic shock worsens organ dysfunction and increases the risk of death, but can be overcome by a scavenger of free heme. | 10.1038/nrneph.2016.186 | This experimental study demonstrates that free haemoglobin induces substantial organ injury during murine sepsis, and that activation of haem-oxygenase-1 or administration of haemopexin confers protection against organ injury and a survival advantage by increasing tolerance. |
10.1126/science.1148526 | 62,036,967 | Hosts can in principle employ two different strategies to defend themselves against parasites: resistance and tolerance. Animals typically exhibit considerable genetic variation for resistance (the ability to limit parasite burden). However, little is known about whether animals can evolve tolerance (the ability to lim... | 10.1038/nrneph.2016.186 | The first study to demonstrate tolerance mechanisms in mammals using a model of murine malaria and a statistical framework developed by plant ecologists. |
10.1126/science.1250684 | 20,656,203 | A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into the many components of our immune system, the BLUEPRINT consortium examined the regulation of DNA and RNA transcription to dissect the molecular traits that govern blood cell differentiation. By inducin... | 10.1038/nrneph.2016.186 | This study demonstrates that a shift of central glucose metabolism from oxidative phosphorylation to aerobic glycolysis is the metabolic basis for trained immunity. |
10.1126/science.290.5497.1782 | 107,146,691 | Area 5 in the parietal lobe of the primate brain is thought to be involved in monitoring the posture and movement of the body. In this study, neurons in monkey area 5 were found to encode the position of the monkey's arm while it was covered from view. The same neurons also responded to the position of a visible, reali... | 10.1038/nrn3292 | Important research in macaque monkeys on the neurophysiology of area 5 neurons and the integration of visual, proprioceptive and tactile cues. These findings are of relevance for self-attribution of an individual's hand. |
10.1152/jn.1998.79.1.126 | 61,386,850 | Duhamel, Jean-René, Carol L. Colby, and Michael E. Goldberg. Ventral intraparietal area of the macaque: congruent visual and somatic response properties. J. Neurophysiol. 79: 126–136, 1998. In a previous report, we described the visual response properties in the ventral intraparietal area (area VIP) of the awake macaqu... | 10.1038/nrn3292 | Pioneering work on the neurophysiology of VIP neurons and the integration of visual and tactile cues that are likely to be of relevance for self-identification. |
10.1113/jphysiol.1990.sp018306 | 124,941,716 | 1. In four Java monkeys (Macaca fascicularis) 152 vestibular neurones were recorded in the parietal cortex located in the upper bank of the lateral sulcus near the posterior end of the insula. We called this region parieto‐insular vestibular cortex (PIVC). PIVC extends about 6‐8 mm in the anterior‐posterior direction f... | 10.1038/nrn3292 | Pioneering work on the neurophysiology of PIVC neurons and the integration of visual, vestibular and somatosensory cues that are likely to be of relevance for self-location and the first-person perspective. |
10.1046/j.1460-9568.2002.02206.x | 103,933,379 | Abstract Self‐motion detection requires the interaction of a number of sensory systems for correct perceptual interpretation of a given movement and an eventual motor response. Parietal cortical areas are thought to play an important role in this function, and we have thus studied the encoding of multimodal signals and... | 10.1038/nrn3292 | Important work on the neurophysiology of VIP neurons and the integration of visual, vestibular and somatosensory cues that are likely to be of relevance for self-identification, self-location and the first-person perspective. |
10.1073/pnas.1605635113 | 38,260,154 | Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there ... | 10.1038/nrneph.2017.132 | Pilot study demonstrating that VNS inhibited TNF production and improved disease severity in patients with rheumatoid arthritis. |
10.1111/nmo.12792 | 122,982,936 | Abstract The vagus nerve ( VN ) is a link between the brain and the gut. The VN is a mixed nerve with anti‐inflammatory properties through the activation of the hypothalamic–pituitary–adrenal axis by its afferents and by activating the cholinergic anti‐inflammatory pathway through its efferents. We have previously show... | 10.1038/nrneph.2017.132 | Pilot study demonstratating the potential efficacy and safety of chronic VNS in patients with Crohn disease. |
10.1126/science.1209985 | 41,661,804 | A neural circuit that involves a specialized population of memory T cells regulates the immune response. | 10.1038/nrneph.2017.132 | Landmark study demonstrating that an acetylcholine-producing, memory T cell population is integral to the inflammatory reflex following VNS in mice. |
10.1152/physrev.1997.77.1.75 | 125,314,645 | The renal nerves are the communication link between the central nervous system and the kidney. In response to multiple peripheral and central inputs, efferent renal sympathetic nerve activity is altered so as to convey information to the major structural and functional components of the kidney, the vessels, glomeruli, ... | 10.1038/nrneph.2017.132 | Comprehensive review of the role of the neural system in controlling renal function. |
10.1084/jem.20070657 | 103,780,449 | Hypertension promotes atherosclerosis and is a major source of morbidity and mortality. We show that mice lacking T and B cells (RAG-1−/− mice) have blunted hypertension and do not develop abnormalities of vascular function during angiotensin II infusion or desoxycorticosterone acetate (DOCA)–salt. Adoptive transfer of... | 10.1038/nrneph.2017.132 | Study demonstrating a role of T cells in the genesis of hypertension. This finding supports a role of inflammation in the pathogenesis of hypertension. |
10.1073/pnas.0500729102 | 79,418,917 | Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function. Here, we compare recombination of the distantly related β-lactamases PSE-4 and TEM-1 to mutation of PSE-4. We show that, am... | 10.1038/nrmicro2614 | An important paper exploring the relative impact of mutation and recombination on the functionality of proteins. |
10.1099/vir.0.19277-0 | 20,406,347 | Recombination is increasingly seen as an important means of shaping genetic diversity in RNA viruses. However, observed recombination frequencies vary widely among those viruses studied to date, with only sporadic occurrences reported in RNA viruses with negative-sense genomes. To determine the extent of homologous rec... | 10.1038/nrmicro2614 | A study that uses a comparative phylogenetic analysis to show the low rate of recombination in (−)ssRNA viruses. |
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/nrmicro2614 | An important experimental demonstration of clonal interference in RNA viruses. |
10.1126/science.1101786 | 17,759,803 | Reproductive strategies such as sexual reproduction and recombination that involve the shuffling of parental genomes for the production of offspring are ubiquitous in nature. However, their evolutionary benefit remains unclear. Many theories have identified potential benefits, but progress is hampered by the scarcity o... | 10.1038/nrmicro2614 | An important study showing that positive (antagonistic) epistasis occurs in HIV and, hence, that recombination is unlikely to be selected as a way of purging deleterious mutations. |
10.1126/science.286.5439.509 | 83,557,230 | Systems as diverse as genetic networks or the World Wide Web are best described as networks with complex topology. A common property of many large networks is that the vertex connectivities follow a scale-free power-law distribution. This feature was found to be a consequence of two generic mechanisms: (i) networks exp... | 10.1038/nrn3801 | A classic study that introduces a model of scale-free networks that arise from growth by preferential attachment. |
10.1523/jneurosci.5062-08.2009 | 125,269,039 | Recent evidence suggests that some brain areas act as hubs interconnecting distinct, functionally specialized systems. These nexuses are intriguing because of their potential role in integration and also because they may augment metabolic cascades relevant to brain disease. To identify regions of high connectivity in t... | 10.1038/nrn3801 | Demonstration of the correlation between topological properties, in particular node degree, and spatial patterns of amyloid deposition in AD. |
10.1073/pnas.1208933109 | 103,670,394 | Human brain networks have topological properties in common with many other complex systems, prompting the following question: what aspects of brain network organization are critical for distinctive functional properties of the brain, such as consciousness? To address this question, we used graph theoretical methods to ... | 10.1038/nrn3801 | This study shows that hub reorganization may be the most salient feature of brain networks that are in states of impaired consciousness. |
10.1073/pnas.0801372105 | 20,075,796 | Many complex neuronal circuits have been shown to display nonrandom features in their connectivity. However, the functional impact of nonrandom network topologies in neurological diseases is not well understood. The dentate gyrus is an excellent circuit in which to study such functional implications because proepilepti... | 10.1038/nrn3801 | A detailed simulation of seizures in neural networks that demonstrates the importance of network topology, and in particular the presence of hubs, for the spreading of epileptic activity. |
10.1126/science.1090674 | 41,516,282 | During mammalian cerebral corticogenesis, progenitor cells become progressively restricted in the types of neurons they can produce. The molecular mechanism that determines earlier versus later born neuron fate is unknown. We demonstrate here that the generation of the earliest born neurons, the Cajal-Retzius cells, is... | 10.1038/nrn2151 | The authors find that the absence of Foxg1 results in the generation of increased numbers of Cajal–Retzius cells instead of neocortical projection neurons. Remarkably, inactivation of Foxg1 midway through the generation of projection neurons results in the production of additional Cajal–Retzius cells. |
10.1126/science.1067132 | 20,438,843 | The identification of pathways mediated by the kinase Cdk5 and the ligand reelin has provided a conceptual framework for exploring the molecular mechanisms underlying proper lamination of the developing mammalian cerebral cortex. In this report, we identify a component of the regulation of Cdk5-mediated cortical lamina... | 10.1038/nrn2151 | The authors show that Brn1 and Brn2 are necessary for proper cortical lamination, such that in the absence of both these genes neurons of upper layers II/III and layer V fail to migrate and position below the subplate, whereas layer VI neurons are unaffected, resulting in an inverted cortex. |
10.1073/pnas.0508732102 | 62,288,685 | During the development of the cerebral cortex, progenitor cells produce neurons that migrate to laminar positions appropriate for their birth dates, adopt specific neuronal identities, and form appropriate local and long-distance axonal connections. Here, we report that forebrain embryonic zinc-finger-like protein ( Fe... | 10.1038/nrn2151 | Similarly to reference 29, this reports that Fez2f regulates the differentiation of layer V neurons and their subcerebral projections. |
10.1073/pnas.0509032102 | 20,042,333 | Pyramidal neurons of the cerebral cortex display marked layer- and subtype-specific differences in their axonal projections and dendritic morphologies. Here we show that transcription factor Zfp312 is selectively expressed by layer V and VI subcortical projection pyramidal neurons and their progenitor cells. Knocking d... | 10.1038/nrn2151 | The authors knocked down Fez2f expression in cortical neurons via small interfering RNA and showed that reduced levels of this transcription factor results in abnormal connectivity by layer V and VI neurons to subcortical targets and in abnormal neuronal subtype-specific dendritic differentiation. |
10.1126/science.146.3649.1325 | 58,475,163 | Under conditions of ocular rivalry, changes in the rhythmic brain response to flicker stimulation of one eye correspond closely to the subject's report of changes in the perceptual dominance of that eye. | 10.1038/nrn1055 | The first study to identify a neural correlate of awareness during binocular rivalry by using EEG to measure occipital responses. |
10.1126/science.2772635 | 16,676,625 | Neuronal activity in the superior temporal sulcus of monkeys, a cortical region that plays an important role in analyzing visual motion, was related to the subjective perception of movement during a visual task. Single neurons were recorded while monkeys ( Macaca mulatta ) discriminated the direction of motion of stimu... | 10.1038/nrn1055 | The first of a series of influential studies recording single-unit activity in monkeys that reported their perceptions during rivalry (see also references 65 and 66). |
10.1126/science.1057099 | 61,783,007 | Much is known about the pathways from photoreceptors to higher visual areas in the brain. However, how we become aware of what we see or of having seen at all is a problem that has eluded neuroscience. Recordings from macaque V1 during deactivation of MT+/V5 and psychophysical studies of perceptual integration suggest ... | 10.1038/nrn1055 | An innovative TMS study that tested whether feedback projections from MT to V1 might be necessary for awareness of motion phosphenes. |
10.1242/jeb.199.3.731 | 121,880,517 | The accuracy with which the visuomotor system of Empoasca vitis can prescribe a jump trajectory towards a bright, uniformly illuminated target shape was investigated. The targets consisted of discs, rings or bars cut out of black card and mounted in front of a source of stroboscopic light diffused through translucent p... | 10.1038/nrn872 | This paper, which deserves to be better known, shows that insects can aim at the centre of gravity of a target. |
10.1242/jeb.199.1.155 | 41,625,786 | Honeybees are widely believed to assess feeder distances by the energy spent on foraging flights. However, a critical review of this 'energy hypothesis' reveals many inconsistencies in the experiments from which it was derived. In fact, new evidence shows that the energy hypothesis cannot be correct. Foragers loaded wi... | 10.1038/nrn872 | This paper and reference 50 were the first to report that insects measure the distance of a flight path in terms of the amount of translational retinal image motion (optic flow) that is experienced during flight. Bees flying to a food source on the ground experience more optic flow than do bees flying to a food source ... |
10.1073/pnas.91.10.4471 | 58,477,030 | Honeybees and some other insects, in learning the sun's course, behave as if they can estimate the sun's position at times of day when they have never seen it, but there are competing ideas about the computational mechanisms underlying this ability. In an approach to this problem, we provided incubator-reared bees with... | 10.1038/nrn872 | This paper shows that bees have an innate ephemeris function: they expect the sun to rise in one direction, to set in the opposite direction, and to switch abruptly between the two around midday, as in the tropics. Over the first few days of flight experience, this initial expectation is modified to match the sun's act... |
10.1242/jeb.202.12.1655 | 104,294,118 | Honeybees have long served as a model organism for investigating insect navigation. Bees, like many other nesting animals, primarily use learned visual features of the environment to guide their movement between the nest and foraging sites. Although much is known about the spatial information encoded in memory by exper... | 10.1038/nrn872 | Shows that, during a single orientation flight, bees can learn enough about landmarks near the hive that they will home directly if displaced to a site from which the hive is visible. |
10.1046/j.1365-2664.1999.00428.x | 38,355,698 | Summary 1. Bumble bees play a vital role in the pollination of many crops and wild flowers, and plans for their conservation require a knowledge of the dynamics and spatial scale of their foraging flights, which are, at present, poorly understood. 2. We investigated the foraging range and constancy of two colonies of b... | 10.1038/nrn872 | The first study to illustrate multiple foraging trips of a single bee. |
10.1242/jeb.202.11.1481 | 103,683,769 | The motion of the thorax of the blowfly Calliphora vicina was measured during cruising flight inside a cage measuring 40 cmx40 cmx40 cm. Sensor coils mounted on the thorax picked up externally generated magnetic fields and yielded measurements of the position and orientation of the thorax with a resolution of 1 ms, 0.3... | 10.1038/nrn872 | This paper reports a technical tour de force in which the three-dimensional rotational and translational movements of both the head and the body of a fly are monitored during free flight. |
10.1152/jn.2001.85.5.1969 | 20,393,455 | In this first intracellular study of neocortical activities during waking and sleep states, we hypothesized that synaptic activities during natural states of vigilance have a decisive impact on the observed electrophysiological properties of neurons that were previously studied under anesthesia or in brain slices. We i... | 10.1038/nrn1198 | First intracellular recordings during different behavioural states. The same neurons are shown to experience consistent changes of membrane parameters across periods of waking, slow-wave sleep and rapid eye movement sleep. |
10.1152/jn.1998.79.3.1450 | 10,314,856 | Paré, Denis, Eric Shink, Hélène Gaudreau, Alain Destexhe, and Eric J. Lang. Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons in vivo. J. Neurophysiol. 79: 1450–1460, 1998. The frequency of spontaneous synaptic events in vitro is probably lower than in vivo because o... | 10.1038/nrn1198 | First characterization of synaptic background activity in vivo ; the first study in which the same neurons were compared between active network states and after total suppression of network activity. |
10.1152/jn.2000.84.3.1488 | 80,532,033 | Neocortical pyramidal neurons in vivo are subject to an intense synaptic background activity but little is known of how this activity affects cellular responsiveness and what function it may serve. These issues were examined in morphologically reconstructed neocortical pyramidal neurons in which synaptic background act... | 10.1038/nrn1198 | Theoretical study investigating the effect of synaptic noise on neuronal responsiveness. This was the first demonstration of the contrasting effects of conductance and noise with a suggested link to an attentional mechanism. |
10.1152/jn.2001.86.3.1104 | 32,841,137 | Stochastic resonance (SR) is a phenomenon whereby the detection of a low-level signal is enhanced in a nonlinear system by the introduction of noise. Studies of the effects of SR in neurons have suggested that noise could play a prominent role in improving detection of small signals. Most experimental SR research has f... | 10.1038/nrn1198 | First experimental evidence that synaptic noise can improve signal detection in central neurons. |
10.1152/jn.00919.2005 | 107,326,256 | Response variability is often correlated across populations of neurons, and these noise correlations may play a role in information coding. In previous studies, this possibility has been examined from the encoding and decoding perspectives. Here we used d prime and related information measures to examine how studies of... | 10.1038/nrn1888 | Combines a theoretical and empirical examination of the way in which studies of information encoding and decoding are related, as well as investigating the role of stimulus-modulated correlations. |
10.1162/089976699300016827 | 45,560,682 | We study the impact of correlated neuronal firing rate variability on the accuracy with which an encoded quantity can be extracted from a population of neurons. Contrary to widespread belief, correlations in the variabilities of neuronal firing rates do not, in general, limit the increase in coding accuracy provided by... | 10.1038/nrn1888 | One of the most influential theoretical studies of the effect of noise correlations on information encoding. |
10.1162/089976601300014349 | 1,428,407 | This study investigates a population decoding paradigm in which the maximum likelihood inference is based on an unfaithful decoding model (UMLI). This is usually the case for neural population decoding because the encoding process of the brain is not exactly known or because a simplified decoding model is preferred for... | 10.1038/nrn1888 | The first study to theoretically investigate the effects of ignoring correlations when decoding a large population of neurons. As such it is the decoding complement to reference 46. |
10.1002/mds.870100606 | 60,859,198 | Abstract Dyskinesias occur in the majority of patients with Parkinson's disease chronically treated with L ‐DOPA and also occur in several nonhuman primate species after 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and L ‐DOPA treatment. The common marmoset ( Callithrix jacchus ) shows parkinsonian motor deficit... | 10.1038/nrn2471 | This paper provided an example of the MPTP-treated primate model of Parkinson's disease and of the induction of dyskinesia by L-DOPA treatment. |
10.1002/mds.21743 | 40,303,373 | Abstract In a 5‐year, double‐blind study, subjects with Parkinson's disease (PD) who were randomized to initial treatment with ropinirole had a significantly lower incidence of dyskinesia compared with subjects randomized to levodopa, although Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were significa... | 10.1038/nrn2471 | This study investigated the long-term outcome of starting patients with PD on pulsatile L-DOPA therapy versus a longer-acting dopamine agonist. |
10.1046/j.0953-816x.2001.01743.x | 58,526,963 | Abstract Current knowledge of the molecular changes induced by dopamine denervation and subsequent treatment with l ‐DOPA is based on studies performed on relatively acute and young animal models of parkinsonism. It is highly warranted to ask how well these models simulate the state of chronic denervation and sustained... | 10.1038/nrn2471 | This study is an example of the pioneering work with the 6-OHDA-lesioned rat AIMs model of dyskinesia that is being undertaken to understand the gene changes that underlie the expression of involuntary movements. |
10.1111/j.1471-4159.2008.05417.x | 104,048,204 | Abstract Despite recent advances in the treatment of Parkinson disease (PD), levodopa remains the most effective and widely used therapy. A major limitation to the use of levodopa is the development of abnormal involuntary movements, termed levodopa‐induced dyskinesia (LDID), following chronic levodopa treatment. Since... | 10.1038/nrn2471 | This recent paper suggested that the disruption of chromatin structure that is essential for the maintenance of neuronal plasticity might occur in dyskinesia. |
10.1111/j.1471-4159.2008.05835.x | 103,163,499 | Abstract Adolescence is a developmental period which the risk of drug and alcohol abuse increases. Since mesolimbic dopaminergic system undergoes developmental changes during adolescence, and this system is involved in rewarding effects of drugs of abuse, we addressed the hypothesis that ethanol exposure during juvenil... | 10.1038/nrn.2018.10 | This paper reports increases in ethanol intake in adulthood following intermittent exposure to alcohol during adolescence, along with alterations in dopaminergic and glutamatergic neurotransmitter systems and histone acetylation in the mesolimbic system. |
10.1111/adb.12530 | 81,027,534 | Abstract Connectivity of the prefrontal cortex (PFC) matures through adolescence, coinciding with emergence of adult executive function and top‐down inhibitory control over behavior. Alcohol exposure during this critical period of brain maturation may affect development of PFC and frontolimbic connectivity. Adult rats ... | 10.1038/nrn.2018.10 | This seminal study examined resting-state MRI in adult rats and observed decreases in connectivity within the PFC and between the PFC and mesolimbic brain regions following repeated alcohol exposure during adolescence. |
10.1159/000362874 | 107,156,584 | Although adolescence is a common age to initiate alcohol consumption, the long-term consequences of exposure to alcohol at this time of considerable brain maturation are largely unknown. In studies utilizing rodents, behavioral evidence is beginning to emerge suggesting that the hippocampus may be persistently affected... | 10.1038/nrn.2018.10 | This paper presents evidence that repeated exposure to alcohol during adolescence (but not after equivalent exposure in adulthood) exerts long-lasting decreases in neurogenesis that are evident in adulthood well after termination of the chronic exposure. |
10.1523/jneurosci.5587-06.2007 | 20,847,639 | Variations in neural circuitry, inherited or acquired, may underlie important individual differences in thought, feeling, and action patterns. Here, we used task-free connectivity analyses to isolate and characterize two distinct networks typically coactivated during functional MRI tasks. We identified a “salience netw... | 10.1038/nrneurol.2018.23 | This article provides a good overview of the salience network. |
10.1073/pnas.0706625104 | 62,606,619 | The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD... | 10.1038/nrmicro2403 | One of the first large culture-independent studies showing reduced diversity of intestinal microbiota in patients with IBDs. |
10.1002/eji.200939602 | 102,913,114 | Abstract Mouse models of intestinal inflammation resemble aspects of inflammatory bowel disease in humans. These models have provided important insights into mechanisms that control intestinal homeostasis and regulation of intestinal inflammation. This viewpoint discusses themes that have emerged from mouse models of i... | 10.1038/nrmicro2403 | One of the most comprehensive reviews on mouse models of intestinal inflammatory diseases, with a focus on immunological mechanisms. |
10.1073/pnas.2534546100 | 61,315,137 | It is now well established that the intestinal flora plays an important role in the pathogenesis of inflammatory bowel disease (IBD). However, whether bacteria serve as the sole target of the immune response in this process or whether they act indirectly by triggering an anti-self response is still unclear. We have pre... | 10.1038/nrmicro2403 | Study showing that a T cell clone recognizing a single bacterial epitope of a chronic intestinal pathogen can elicit colitis in H. hepaticus -infected mice. |
10.1111/j.1365-2958.2005.05020.x | 125,167,537 | Summary Microbes construct structurally complex multicellular communities (biofilms) through production of an extracellular matrix. Here we present evidence from scanning electron microscopy showing that a wild strain of the Gram positive bacterium Bacillus subtilis builds such a matrix. Genetic, biochemical and cytolo... | 10.1038/nrmicro2960 | A study showing that TasA and EPS are components of the extracellular matrix and essential for biofilm formation. |
10.1073/pnas.191384198 | 125,166,784 | Spore formation by the bacterium Bacillus subtilis has long been studied as a model for cellular differentiation, but predominantly as a single cell. When analyzed within the context of highly structured, surface-associated communities (biofilms), spore formation was discovered to have heretofore unsuspected spatial or... | 10.1038/nrmicro2960 | The first paper describing B. subtilis colony and pellicle biofilms. |
10.1101/gad.1645008 | 83,409,209 | Bacteria form architecturally complex communities known as biofilms in which cells are held together by an extracellular matrix. Biofilms harbor multiple cell types, and it has been proposed that within biofilms individual cells follow different developmental pathways, resulting in heterogeneous populations. Here we de... | 10.1038/nrmicro2960 | This work describes the spatiotemporal regulation of gene expression within biofilms. |
10.1146/annurev.micro.62.081307.163002 | 41,687,637 | Clonal populations of microbial cells often show a high degree of phenotypic variability under homogeneous conditions. Stochastic fluctuations in the cellular components that determine cellular states can cause two distinct subpopulations, a property called bistability. Phenotypic heterogeneity can be readily obtained ... | 10.1038/nrmicro2960 | An excellent review discussing phenotypic variability in clonal bacterial populations. |
10.1126/science.1188628 | 41,534,301 | Biofilm Today, Gone Tomorrow Most bacteria can form complex, matrix-containing multicellular communities known as biofilms, which protect residents from environmental stresses such as antibiotic exposure. However, as biofilms age, nutrients become limiting and waste products accumulate, and biofim disassembly is trigge... | 10.1038/nrmicro2960 | This work determined that d -amino acids, which are secreted late in biofilm formation, inhibit B. subtilis biofilms, as well as those of other species. |
10.1126/science.1157877 | 104,291,765 | Biofilms are multicellular aggregates of sessile bacteria encased by an extracellular matrix and are important medically as a source of drug-resistant microbes. In Bacillus subtilis , we found that an operon required for biofilm matrix biosynthesis also encoded an inhibitor of motility, EpsE. EpsE arrested flagellar ro... | 10.1038/nrmicro2960 | A beautiful example of the multiple levels of regulation which ensure that matrix-producing cells are non-motile. |
10.1073/pnas.0910560107 | 83,397,540 | Bacillus subtilis forms biofilms whose constituent cells are held together by an extracellular matrix. Previous studies have shown that the protein TasA and an exopolysaccharide are the main components of the matrix. Given the importance of TasA in biofilm formation, we characterized the physicochemical properties of t... | 10.1038/nrmicro2960 | In this work, TasA is shown to form amyloid-like fibres in the extracellular matrix. |
10.1111/j.1365-2958.2012.08094.x | 100,337,597 | Summary Biofilms are surface‐associated bacterial aggregates, in which bacteria are enveloped by polymeric substances known as the biofilm matrix. Bacillus subtilis biofilms display persistent resistance to liquid wetting and gas penetration, which probably explains the broad‐spectrum resistance of the bacteria in thes... | 10.1038/nrmicro2960 | A recent study showing that BslA has a role in conferring hydrophobicity to B. subtilis biofilms. |
10.1101/gad.1915010 | 104,112,498 | Growing cells of Bacillus subtilis are a bistable mixture of individual motile cells in which genes for daughter cell separation and motility are ON, and chains of sessile cells in which these genes are OFF. How this ON/OFF switch is controlled has been mysterious. Here we report that a complex of the SinR and SlrR pro... | 10.1038/nrmicro2960 | This study shows that SlrR binds to and re-purposes the repressor SinR to regulate a different set of genes. |
10.1101/gad.1813709 | 18,842,442 | Cellular differentiation is triggered by extracellular signals that cause target cells to adopt a particular fate. Differentiation in bacteria typically involves autocrine signaling in which all cells in the population produce and respond to the same signal. Here we present evidence for paracrine signaling in bacterial... | 10.1038/nrmicro2960 | This work finds that not all of the genes in a clonal population produce quorum sensing signals and that the cells which produce the signal are not the cells that respond to it. |
10.1126/scisignal.2000350 | 80,029,497 | Analysis of multiple “omic” data sets with a prize-collecting Steiner tree algorithm reveals components of signaling networks that are not obvious by analyzing the data individually. | 10.1038/nrmicro3036 | The description of a computational method (based on the Steiner tree problem) that provides a general framework for building models of regulatory networks from high-throughput data sets. |
10.1126/science.1093712 | 19,681,245 | The anaphase-promoting complex (APC) is highly expressed in postmitotic neurons, but its function in the nervous system was previously unknown. We report that the inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth. Cdh1 knockdown in cerebellar slice overlay assays and in the developing rat ce... | 10.1038/nrn3009 | This is the first paper to demonstrate a key function of APC in postmitotic neurons. |
10.1126/science.1145727 | 58,358,968 | Stereotyped synaptic connectivity can arise both by precise recognition between appropriate partners during synaptogenesis and by selective synapse elimination. The molecular mechanisms that underlie selective synapse removal are largely unknown. We found that stereotyped developmental elimination of synapses in the Ca... | 10.1038/nrn3009 | This study describes the mechanism by which the regulation of a specific SCF complex controls synapse elimination. |
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/nrn3380 | This study analyses the consequences of kinesin disruption in mice and provides evidence for a role of kinesin in neurofilament transport. |
10.1126/science.1152993 | 83,441,153 | Dynein and kinesin motor proteins transport cellular cargoes toward opposite ends of microtubule tracks. In neurons, microtubules are abundantly decorated with microtubule-associated proteins (MAPs) such as tau. Motor proteins thus encounter MAPs frequently along their path. To determine the effects of tau on dynein an... | 10.1038/nrn3380 | This report demonstrates that tau detaches kinesin from microtubules and reverses the direction of dynein transport. |
10.1083/jcb.150.1.165 | 123,865,172 | Neurofilaments are transported through axons by slow axonal transport. Abnormal accumulations of neurofilaments are seen in several neurodegenerative diseases, and this suggests that neurofilament transport is defective. Excitotoxic mechanisms involving glutamate are believed to be part of the pathogenic process in som... | 10.1038/nrn3380 | This study shows that excitotoxic insults can cause axonal transport defects that are responsible for neurofilament accumulation in neurodegenerative disease. |
10.1111/j.1471-4159.2006.03932.x | 62,183,990 | Abstract Peripherin is a type III neuronal intermediate filament detected in motor neuron inclusions of amyotrophic lateral sclerosis (ALS) patients. We previously reported that overexpression of peripherin provokes late‐onset motor neuron dysfunction in transgenic mice. Here, we show that peripherin overexpression slo... | 10.1038/nrn3380 | This paper shows that peripherin overexpression can cause axonal protein aggregates, defective axonal transport and motor neuron death during ageing. |
10.1073/pnas.1200658109 | 78,382,822 | Axonal transport deficits have been reported in many neurodegenerative conditions and are widely assumed to be an immediate causative step of axon and synapse loss. By imaging changes in axonal morphology and organelle transport over time in several animal models of amyotrophic lateral sclerosis (ALS), we now find that... | 10.1038/nrn3380 | This study demonstrates that transport deficits do not necessarily cause axon degeneration in a mouse model of ALS and that disturbances of organelle transport are not a necessary step in the emergence of motor neuron degeneration. |
10.1084/jem.20111313 | 82,223,870 | TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic lateral sclerosis (ALS). In this study, we report that TDP-43 and nuclear factor κB (NF-κB) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with... | 10.1038/nrn3380 | This paper proposes a new pathogenic pathway in ALS based on hyperactivation of NF-κB. |
10.1111/j.1464-5491.2012.03698.x | 104,095,122 | Diabet. Med. 29, 855–862 (2012) Abstract Aims To estimate the current and future economic burdens of Type 1 and Type 2 diabetes in the UK. Methods A top‐down approach was used to estimate costs for 2010/2011 from aggregated data sets and literature. Prevalence and population data were used to project costs for 2035/203... | 10.1038/nrneph.2018.9 | This article highlights the morbidity, mortality and economic costs of DKD. |
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