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10.1111/j.1469-8986.2009.00786.x | 107,099,735 | Abstract Past studies indicate that the placebo expectation established by analgesic treatment significantly relieves pain perception, while ataractic treatment significantly alleviates unpleasant arousal evoked by negative picture processing. But it is unclear whether the placebo effect can be transferred from one dom... | 10.1038/nrn3976 | This study, which found that a placebo analgesic also modulated negative affect and EEG responses to unpleasant pictures, represents one of the few studies to formally examine placebo effects across domains. |
10.1126/science.1093065 | 103,828,638 | The experience of pain arises from both physiological and psychological factors, including one's beliefs and expectations. Thus, placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations. However, controversy exists regarding whether placebos alter sensory pain tra... | 10.1038/nrn3976 | This study used a heat pain model to examine the neural basis of placebo analgesia and was the first fMRI study of placebo analgesia. |
10.1126/science.1180142 | 81,580,402 | Functional magnetic resonance imaging of the human spinal cord reveals a mechanism for placebo analgesia. | 10.1038/nrn3976 | This study used fMRI to image the spinal cord and found that spinal responses to noxious stimuli are modulated with placebo, which implicates descending modulation. |
10.1126/science.1067176 | 20,666,574 | It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomogr... | 10.1038/nrn3976 | This PET study was the first to use neuroimaging to investigate mechanisms of the placebo response and found that both placebo analgesia and opioid analgesia induce changes in blood flow in the rostral ACC. |
10.1126/science.1129462 | 62,154,919 | Alpha-synuclein (αSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons αSyn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following αSyn expression in yeast wa... | 10.1038/nrneurol.2017.99 | Study showing that the earliest deficit that results from α-synuclein expression is a block of trafficking from the ER to the Golgi apparatus, explaining the occurrence of ER stress in PD. |
10.1101/gad.1640108 | 107,219,558 | Mutation in Cu/Zn-superoxide dismutase ( SOD1 ) is a cause of familial amyotrophic lateral sclerosis (ALS). Mutant SOD1 protein (SOD1 mut ) induces motor neuron death, although the molecular mechanism of SOD1 mut -induced cell death remains controversial. Here we show that SOD1 mut specifically interacted with Derlin-1... | 10.1038/nrneurol.2017.99 | The first study to show that mutant SOD1 triggers ER stress by interacting with and blocking activity of the ERAD component Derlin-1 in ALS. |
10.1101/gad.1830709 | 83,125,966 | Mutations in superoxide dismutase-1 (SOD1) cause familial amyotrophic lateral sclerosis (fALS). Recent evidence implicates adaptive responses to endoplasmic reticulum (ER) stress in the disease process via a pathway known as the unfolded protein response (UPR). Here, we investigated the contribution to fALS of X-box-bi... | 10.1038/nrneurol.2017.99 | This study showed that inhibition of XBP1 signalling in ALS ameliorates disease pathology through cross-talk with ER stress and autophagy in vivo |
10.1126/science.1245296 | 18,958,028 | From Yeast to Therapeutic? Yeast has shown some promise as a model system to generate lead compounds that could have therapeutic potential for the cellular problems associated with neurodegenerative diseases. Along these lines, Tardiff et al. (p. 979 , published online 24 October) and Chung et al. (p. 983 , published o... | 10.1038/nrneurol.2017.99 | This study showed that cortical neurons derived from iPSCs from patients with Parkinson disease exhibit nitrosative stress and accumulation of ERAD substrates, which trigger ER stress. |
10.1126/science.1201396 | 20,802,201 | Guanabenz, a small-molecule inhibitor, protects cells from lethal accrual of misfolded proteins in the endoplasmic reticulum. | 10.1038/nrneurol.2017.99 | This report identified guanabenz as a potential drug to target the integrated stress response for therapy in protein misfolding disorders. |
10.15252/embj.201592224 | 39,925,864 | Abstract Disturbance of endoplasmic reticulum ( ER ) proteostasis is a common feature of amyotrophic lateral sclerosis ( ALS ). Protein disulfide isomerases ( PDI s) are ER foldases identified as possible ALS biomarkers, as well as neuroprotective factors. However, no functional studies have addressed their impact on t... | 10.1038/nrneurol.2017.99 | The first study to identify mutations in ER chaperones in ALS. |
10.1126/science.144.3618.554 | 15,745,408 | Two determinants of adaptation in a mechanoreceptor (Pacinian corpuscle) are described. Both are filters of non-transients. One, a mechanical filter, prevents static components of the mechanical stimulus from reaching the transducer element (nerve ending). This filter is represented by the laminar capsule of the recept... | 10.1038/nrn2993 | This study was a pioneering work that established the role of the laminar capsule as a mechanical filter in the adaptation properties of the Pacinian corpuscle. |
10.1126/science.287.5461.2229 | 62,058,438 | Mechanosensory transduction underlies a wide range of senses, including proprioception, touch, balance, and hearing. The pivotal element of these senses is a mechanically gated ion channel that transduces sound, pressure, or movement into changes in excitability of specialized sensory cells. Despite the prevalence of m... | 10.1038/nrn2993 | This paper described the identification of the no mechanoreceptor potential C (NOMPC) channel as an essential component of the mechanosensory transduction apparatus in D. melanogaster |
10.1126/science.1193270 | 125,070,423 | Mechanical Responders Identified Although many cells appear to respond to mechanical stimulation through increased conductance of ion channels in the plasma membrane, the actual channels that mediate these effects—which are important in diverse processes from hearing and touch to control of blood pressure—have remained... | 10.1038/nrn2993 | The authors characterized two novel proteins, piezo 1 and piezo 2, as essential components of mechanically activated cation channels. |
10.1126/science.1172890 | 83,064,722 | Mysterious Merkel cells Anatomists have known about the existence of Merkel cells in our skin for over a century. However, the function of these cells has been unclear and controversial. To solve this mystery, Maricich et al. (p. 1580 ) created a genetic deletion of Merkel cells. When Atoh1, a transcription factor expr... | 10.1038/nrn2993 | The authors showed loss of type I slowly adapting (SAI) responses normally mediated by Merkel cell–neurite complexes in Atoh1CKO animals, suggesting that Merkel cells are indispensable for the normal neurophysiological SAI response. |
10.1073/pnas.0504321102 | 20,826,314 | Many crucial biological processes operate with surprisingly small numbers of molecules, and there is renewed interest in analyzing the impact of noise associated with these small numbers. Twenty-five years ago, Berg and Purcell showed that bacterial chemotaxis, where a single-celled organism must respond to small chang... | 10.1038/nrn2258 | This paper uses a first-principle approach to show that there are noise limits to biochemical signalling. These noise limits are of importance in olfaction, intracellular and synaptical signalling. |
10.1162/089976698300017089 | 42,570,948 | The firing reliability and precision of an isopotential membrane patch consisting of a realistically large number of ion channels is investigated using a stochastic Hodgkin-Huxley (HH) model. In sharp contrast to the deterministic HH model, the biophysically inspired stochastic model reproduces qualitatively the differ... | 10.1038/nrn2258 | This paper shows that even when large numbers of stochastic ion channels are present in a neuron, fluctuations can become critical near the AP threshold. |
10.1152/jn.2002.88.3.1533 | 62,652,216 | It has been proposed that the invariant kinematics observed during goal-directed movements result from reducing the consequences of signal-dependent noise (SDN) on motor output. The purpose of this study was to investigate the presence of SDN during isometric force production and determine how central and peripheral co... | 10.1038/nrn2258 | This paper provides experimental and theoretical evidence that the linear scaling of force variability (signal-dependent noise) is a natural by-product of the organization of motor neurons and muscle fibres (the size principle). |
10.1152/jn.1999.81.3.1355 | 19,189,292 | Integration of proprioceptive and visual position-information: an experimentally supported model. To localize one’s hand, i.e., to find out its position with respect to the body, humans may use proprioceptive information or visual information or both. It is still not known how the CNS combines simultaneous propriocepti... | 10.1038/nrn2258 | This paper provided the first evidence of a strategy for the optimal integration of multi-dimensional cues. When integrating proprioception and visual information in the plane (two-dimensional cues), subjects use knowledge of direction-dependent variability to generate an optimal estimate. |
10.1073/pnas.0506806103 | 123,188,827 | We pursue the hypothesis that neuronal placement in animals minimizes wiring costs for given functional constraints, as specified by synaptic connectivity. Using a newly compiled version of the Caenorhabditis elegans wiring diagram, we solve for the optimal layout of 279 nonpharyngeal neurons. In the optimal layout, mo... | 10.1038/nrn.2016.182 | This study demonstrates that wiring minimization principles can be used to predict the placement of many neurons in the C. elegans connectome. |
10.1073/pnas.1200430109 | 7,249,886 | The wide diversity of dendritic trees is one of the most striking features of neural circuits. Here we develop a general quantitative theory relating the total length of dendritic wiring to the number of branch points and synapses. We show that optimal wiring predicts a 2/3 power law between these measures. We demonstr... | 10.1038/nrn.2016.182 | This study found that key aspects in the branching structure of dendrites follow scaling laws, which can be predicted by a simple model of wiring cost minimization. |
10.1113/jphysiol.2004.063388 | 62,607,912 | Indigenous microbiota have several beneficial effects on host physiological functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiological system response. To test the idea that such microbes may affect the developm... | 10.1038/nrn3346 | A landmark study showing that germ-free mice have altered HPA axis function, which can be reversed by colonization with specific bacterial strains early in life. |
10.1073/pnas.1102999108 | 62,590,448 | There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. G... | 10.1038/nrn3346 | An important study demonstrating the ability of a potential probiotic to modify the stress response, behaviours relevant to anxiety, depression and cognition and alter central levels of GABA receptors. Moreover, it demonstrates that these effects are dependent on the vagus nerve. |
10.1128/jb.188.5.1775-1785.2006 | 80,296,070 | ABSTRACT The Bordetella master virulence regulatory system, BvgAS, controls a spectrum of gene expression states, including the virulent Bvg + phase, the avirulent Bvg − phase, and at least one Bvg-intermediate (Bvg i ) phase. We set out to define the species- and strain-specific features of this regulon based on globa... | 10.1038/nrmicro3235 | This study identifies the breadth of regulatory activity controlled by the BvgAS system and demonstrates the complexity of its regulon. |
10.1128/iai.00110-13 | 27,909,884 | ABSTRACT Whooping cough results from infection of the respiratory tract with Bordetella pertussis , and the secreted adenylate cyclase toxin (ACT) is essential for the bacterium to establish infection. Despite extensive study of the mechanism of ACT cytotoxicity and its effects over a range of concentrations in vitro ,... | 10.1038/nrmicro3235 | This study quantifies the amount of adenylate cyclase toxin (ACT) in nasopharyngeal washes of infants and baboons infected with B. pertussis and suggests that physiologically relevant concentrations of ACT are much lower than the concentrations that are used in many in vitro experiments. |
10.1128/iai.00136-11 | 101,126,811 | ABSTRACT Although Bordetella pertussis contains and transcribes loci encoding type III secretion system (TTSS) homologues, expression of TTSS-associated proteins has been reported only for non-laboratory-adapted Irish clinical isolates. Here we confirm such a result for clinical isolates obtained from patients treated ... | 10.1038/nrmicro3235 | This study confirms T3SS activity in clinical isolates of B. pertussis , which suggests that laboratory adaptation might lead to loss of T3SS protein expression and, contradictory to previous understanding, that T3SS is probably important for B. pertussis virulence. |
10.1111/j.1365-2958.2006.05392.x | 124,783,896 | Summary Two‐partner secretion (TPS) is the most widely distributed secretion pathway known. These systems export large exoproteins through highly conserved channel‐forming β‐barrel proteins. Filamentous haemagglutinin (FHA), expressed by Bordetella species, is the prototypical TPS family member. Here we show that the C... | 10.1038/nrmicro3235 | This study identifies the C terminus of mature filamentous haemagglutinin (FHA) as the distal domain that is responsible for adherence to respiratory epithelium. |
10.1111/j.1365-2958.2009.06623.x | 45,322,955 | Summary Bacteria of the Bordetella genus cause respiratory tract infections. Both broad host range (e.g. Bordetella bronchiseptica ) and human‐adapted (e.g. Bordetella pertussis ) strains produce a surface‐exposed and secreted protein called filamentous haemagglutinin (FHA) that functions in adherence and immunomodulat... | 10.1038/nrmicro3235 | This study describes the interchangeability of the genes that encode filamentous haemagglutinin (FHA) between B. pertussis and B. bronchiseptica |
10.1128/cvi.00717-13 | 19,921,254 | ABSTRACT Pertussis has shown a striking resurgence in the United States, with a return to record numbers of reported cases as last observed in the 1950s. Bordetella pertussis isolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting that B. pertussis is losin... | 10.1038/nrmicro3235 | This study describes the increased prevalence of pertactin-deficient B. pertussis strains in the United States within the past 4 years. |
10.1128/iai.01346-09 | 38,842,577 | ABSTRACT Bordetella pertussis endotoxin is a key modulator of the host immune response, mainly due to the role of its lipid A moiety in Toll-like receptor 4 (TLR4)-mediated signaling. We have previously demonstrated that the lipid A phosphate groups of B. pertussis BP338 can be substituted with glucosamine in a BvgAS-r... | 10.1038/nrmicro3235 | This study shows that glucosamine modification of lipid A is required for B. pertussis endotoxin to induce pro-inflammatory cytokine production in human, but not mouse, macrophages, which highlights the importance of being cautious when extrapolating results from studies using B. pertussis in mouse models to human infe... |
10.1073/pnas.1314688110 | 123,907,634 | Significance Pertussis has reemerged as an important public health concern since current acellular pertussis vaccines (aP) replaced older whole-cell vaccines (wP). In this study, we show nonhuman primates vaccinated with aP were protected from severe symptoms but not infection and readily transmitted Bordetella pertuss... | 10.1038/nrmicro3235 | Using the baboon model of pertussis, this study describes a major shortcoming of the aP vaccines; vaccinated baboons can become infected with B. pertussis and, although protected from developing disease symptoms, they are capable of transmitting B. pertussis |
10.1542/peds.2009-2860 | 122,019,030 | OBJECTIVES: Bordetella pertussis is a common, underrecognized, and vaccine-preventable cause of critical illness with a high mortality in infants worldwide. Patients with severe cases present with extreme leukocytosis and develop refractory hypoxemia and pulmonary hypertension that is unresponsive to maximal intensive ... | 10.1038/nrmicro3235 | This study describes the potential efficacy of leukodepletion as a treatment for infants with severe pertussis. |
10.1542/peds.2012-3144 | 38,811,335 | BACKGROUND: Infants <2 months of age are at highest risk of pertussis morbidity and mortality. Until recently, the US Advisory Committee on Immunization Practices (ACIP) recommended protecting young infants by “cocooning” or vaccination of postpartum mothers and other close contacts with tetanus toxoid, reduced ... | 10.1038/nrmicro3235 | This study suggests that maternal vaccination with aP vaccines during pregnancy as well as cocooning postpartum may reduce the risk of infant pertussis. |
10.1128/iai.06310-11 | 122,571,365 | ABSTRACT Pertussis is a highly contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis . Despite nearly universal vaccine coverage, pertussis rates in the United States have been rising steadily over the last 20 years. Our failure to comprehend and counteract this important public he... | 10.1038/nrmicro3235 | This study describes the baboon model as a suitable model for B. pertussis infection. |
10.1002/hbm.10093 | 20,429,493 | Abstract The KE family is a large three‐generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel‐based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [ 2002 ... | 10.1038/nrn1605 | The most recent voxel-based morphometric analysis of MRI datasets using a conjunction analysis that compares grey matter densities bilaterally in affected members with those in unaffected members and matched controls. Results showed that the affected members have bilateral reductions of grey matter in a number of regio... |
10.1126/science.1135801 | 125,070,437 | Theoretical models have long pointed to the dentate gyrus as a possible source of neuronal pattern separation. In agreement with predictions from these models, we show that minimal changes in the shape of the environment in which rats are exploring can substantially alter correlated activity patterns among place-modula... | 10.1038/nrn.2017.45 | This was the first in vivo electrophysiology study to show that signals from the entorhinal cortex can be decorrelated both by the dentate gyrus and by the recruitment of nonoverlapping cell assemblies in CA3. |
10.1126/science.1173215 | 29,293,637 | Neurogenesis and Spatial Memory The dentate gyrus of the hippocampus is one of two sites in the brain where new neurons are produced throughout life. Adult-born neurons integrate into the dentate gyrus circuitry and are thought to play a role in learning and memory. However, their contribution to hippocampal function r... | 10.1038/nrn.2017.45 | This was the first study to show that neurogenesis is necessary for behavioural pattern separation. |
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/nrn.2017.45 | This study generated an artificial fear memory and was able to induce fearful behaviour by activating this memory. |
10.1038/ncomms10838 | 84,486,450 | Abstract Established memories may interfere with the encoding of new memories, particularly when existing and new memories overlap in content. By manipulating levels of hippocampal neurogenesis, here we show that neurogenesis regulates this form of proactive interference. Increasing hippocampal neurogenesis weakens exi... | 10.1038/nrn.2017.45 | This study showed that neurogenesis minimizes proactive memory interference, which could be important for cognitive flexibility. |
10.1126/science.1083328 | 83,449,212 | Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A rece... | 10.1038/nrn.2017.45 | This was the first study to show that neurogenesis is necessary for some of the behavioural effects of antidepressants. |
10.1523/jneurosci.20-24-09104.2000 | 20,673,162 | Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for... | 10.1038/nrn.2017.45 | This was the first study to show that different antidepressant treatments increase adult hippocampal neurogenesis. |
10.1126/science.1152882 | 62,576,662 | Pattern separation, the process of transforming similar representations or memories into highly dissimilar, nonoverlapping representations, is a key component of many functions ascribed to the hippocampus. Computational models have stressed the role of the hippocampus and, in particular, the dentate gyrus and its proje... | 10.1038/nrn.2017.45 | This fMRI study provided the first evidence for a role of the dentate gyrus–CA3 in pattern separation in humans. |
10.1126/science.1234733 | 41,649,946 | Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)–ventromedial striatum (VMS... | 10.1038/nrn.2015.8 | An important study that demonstrated that chronic optogenetic stimulation of the cortico-striatal pathway induces repetitive OCD-like grooming behaviour in mice. |
10.1126/science.1232380 | 62,628,713 | Dysfunctions in frontostriatal brain circuits have been implicated in neuropsychiatric disorders, including those characterized by the presence of repetitive behaviors. We developed an optogenetic approach to block repetitive, compulsive behavior in a mouse model in which deletion of the synaptic scaffolding gene, Sapa... | 10.1038/nrn.2015.8 | An important study showing that pathological OCD-like grooming in Sapap3 -mutant mice can be corrected by optogenetic stimulation of orbitostriatal pathways, including the lateral orbitofrontal cortex and its terminals in the striatum. |
10.1139/y04-061 | 83,198,756 | Natural rodent grooming and other instinctive behavior serves as a natural model of complex movement sequences. Rodent grooming has syntactic (rule-driven) sequences and more random movement patterns. Both incorporate the same movements—only the serial structure differs. Recordings of neural activity in the dorsolatera... | 10.1038/nrn.2015.8 | A detailed summary of the role of the basal ganglia in the sequencing of complex behaviours such as self-grooming. |
10.1146/annurev.neuro.29.051605.112851 | 123,143,844 | Scientists in many different fields have been attracted to the study of habits because of the power habits have over behavior and because they invoke a dichotomy between the conscious, voluntary control over behavior, considered the essence of higher-order deliberative behavioral control, and lower-order behavioral con... | 10.1038/nrn.2015.8 | This article discusses an important conceptual argument linking habits and rituals to normal and pathological behaviours, with a useful expert discussion of their respective underlying circuits. |
10.1002/dneu.22128 | 123,053,685 | ABSTRACT The genetic heterogeneity of neuropsychiatric disorders is high, but some pathways emerged, notably synaptic functioning. A large number of mutations have been described in genes such as neuroligins, neurexins, and SHANK that play a role in the formation and the maintenance of synapses. This review focuses on ... | 10.1038/nrn.2015.8 | A rigorous analysis of the association between mutations in SHANK genes and brain disorders with a particular focus on the genetics of repetitive behaviours. |
10.1126/science.290.5492.739 | 62,260,712 | Communication between neurons in the brain occurs primarily through synapses made onto elaborate treelike structures called dendrites. New electrical and optical recording techniques have led to tremendous advances in our understanding of how dendrites contribute to neuronal computation in the mammalian brain. The vari... | 10.1038/nrn810 | A comprehensive review of the experimental evidence for the ways in which signal processing can be carried out in dendrites. |
10.1126/science.290.5492.744 | 40,404,266 | Our understanding of the function of dendrites has been greatly enriched by an inspiring dialogue between theory and experiments. Rather than functionally ignoring dendrites, representing neurons as single summing points, we have realized that dendrites are electrically and chemically distributed nonlinear units and th... | 10.1038/nrn810 | A clear, state-of-the-art account, largely from a modelling point of view, of how dendrites are fundamental in neuronal information processing. |
10.1113/jphysiol.1995.sp020862 | 62,260,488 | 1. We have used dendrite‐attached patch‐clamp techniques to record single Na+ and Ca2+ channel activity from the apical dendrites (up to 350 microns away from soma) of CA1 pyramidal neurons in rat hippocampal slices (ages: 2‐8 weeks). 2. Na+ channels were found in every patch examined (range: 2 to > 20 channels per ... | 10.1038/nrn810 | A pioneering, accurate characterization of properties and distributions of dendritic Na + and Ca 2+ channels in hippocampal pyramidal neurons. |
10.1152/jn.2001.85.2.855 | 61,170,911 | Despite the wealth of recent research on active signal propagation along the dendrites of layer V neocortical pyramidal neurons, there is still little known regarding the traffic of subthreshold synaptic signals. We present a study using three simultaneous whole cell recordings on the apical dendrites of these cells in... | 10.1038/nrn810 | One of few studies on the properties and distribution of a dendritic channel up to 800 μm from the soma in a neocortical neuron. |
10.1097/00004647-200110000-00001 | 125,150,076 | Anatomic and physiologic data are used to analyze the energy expenditure on different components of excitatory signaling in the grey matter of rodent brain. Action potentials and postsynaptic effects of glutamate are predicted to consume much of the energy (47% and 34%, respectively), with the resting potential consumi... | 10.1038/nrn810 | A lucid account of how neuronal encoding might be constrained by energetic requirements, with particular reference to synaptic activity in cortical dendrites. |
10.1073/pnas.0701757104 | 101,165,837 | Although the nuclear envelope is a dynamic structure that disassembles and reforms during mitosis, the formation of membranous vesicles derived from the nuclear envelope has not yet been described in noninfected cells. However, during herpesvirus maturation, intranuclear capsids initiate transit to the cytosol for fina... | 10.1038/nrmicro2559 | This paper provides evidence that pUL31 and pUL34 are sufficient for budding at the INM. |
10.1126/science.1071506 | 103,364,168 | The passage of large-sized herpesviral capsids through the nuclear lamina and the inner nuclear membrane to leave the nucleus requires a dissolution of the nuclear lamina. Here, we report on the functions of M50/p35, a β-herpesviral protein of murine cytomegalovirus. M50/p35 inserts into the inner nuclear membrane and ... | 10.1038/nrmicro2559 | This paper provides evidence that host cell protein kinases are recruited to the nuclear membrane to depolymerize the lamina and promote virus egress. |
10.1073/pnas.0703790104 | 101,166,499 | Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (NM). To reach the cytoplasm these enveloped particles must fuse with the outer NM and ... | 10.1038/nrmicro2559 | This study provides evidence that herpesirus fusion glycoproteins can promote de-envelopment. |
10.1073/pnas.91.14.6529 | 27,977,748 | To examine the transmission of herpes simplex virus (HSV) from axon to epidermal cell, an in vitro model was constructed consisting of human fetal dorsal root ganglia cultured in the central chamber of a dual-chamber tissue culture system separated from autologous skin explants in an exterior chamber by concentric stee... | 10.1038/nrmicro2559 | This paper describes the first evidence for Separate transport of HSV capsids and glycoproteins in the anterograde direction in neuronal axons. |
10.1242/dev.01915 | 38,287,463 | Choroid plexus (CP) produces the cerebrospinal fluid (CSF) of the central nervous system (CNS), but little is known about the mechanisms underlying development of this important tissue. CP forms in the hindbrain (4th ventricle), diencephalon (3rd ventricle) and dorsomedial telencephalon bilaterally (lateral ventricles)... | 10.1038/nrn3921 | This study reveals that most epithelial cells of the ChP differentiate from GDF7-expressing roof plate cells, with the exception of the posterior domains of the telencephalic ChP, which are induced by the roof plate in a non-cell-autonomous manner. |
10.1242/dev.003095 | 121,823,119 | Both hindbrain roof plate epithelium (hRPe) and hindbrain choroid plexus epithelium (hCPe) produce morphogens and growth factors essential for proper hindbrain development. Despite their importance, little is known about how these essential structures develop. Recent genetic fate maps indicate that hRPe and hCPe descen... | 10.1038/nrn3921 | This study reveals that the rhombic lip as well as distinct spatiotemporal fields of the hindbrain roof plate differentially contribute to hindbrain ChP development. |
10.1242/dev.033795 | 16,840,859 | Choroid plexuses (ChPs) are vascularized secretory organs involved in the regulation of brain homeostasis, and function as the blood-cerebrospinal fluid(CSF) barrier. Despite their crucial roles, there is limited understanding of the regulatory mechanism driving ChP development. Sonic hedgehog (Shh), a secreted signal ... | 10.1038/nrn3921 | This study identifies a SHH-responsive progenitor domain adjacent to the lower rhombic lip that regulates progenitor proliferation and hindbrain ChP development. |
10.1073/pnas.0910786107 | 109,045,949 | The cerebellar rhombic lip and telencephalic cortical hem are dorsally located germinal zones which contribute substantially to neuronal diversity in the CNS, but the mechanisms that drive neurogenesis within these zones are ill defined. Using genetic fate mapping in wild-type and Lmx1a −/− mice, we demonstrate that Lm... | 10.1038/nrn3921 | This study identifies LMX1A as critical for the development of the roof plate and subsequent specification of dorsal cell fates in the developing CNS. |
10.1523/jneurosci.3227-12.2012 | 17,639,077 | Choroid plexus epithelial cells (CPECs) have essential developmental and homeostatic roles related to the CSF and blood–CSF barrier they produce. Accordingly, CPEC dysfunction has been implicated in many neurological disorders, such as Alzheimer's disease, and transplant studies have provided proof-of-concept for CPEC-... | 10.1038/nrn3921 | This study found that BMP4 is sufficient to induce ChP epithelial cells from embryonic stem cell-derived neuroepithelial cells, which hold tremendous promise for the treatment of neurological diseases. |
10.1126/science.1119133 | 26,994,136 | In the adult brain, neuroblasts born in the subventricular zone migrate from the walls of the lateral ventricles to the olfactory bulb. How do these cells orient over such a long distance and through complex territories? Here we show that neuroblast migration parallels cerebrospinal fluid (CSF) flow. Beating of ependym... | 10.1038/nrn3921 | This study identified gradients of CSF proteins — in particular, SLIT — that influence the migration of newly born adult neurons. |
10.1126/science.1252945 | 83,342,959 | Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)–dependent gene expression profile that was also ... | 10.1038/nrn3921 | This study identified an ageing-induced IFN response in the ChP and that the modulation of this response can influence cognitive function. |
10.1126/science.8303277 | 83,045,050 | The success of Mycobacterium species as pathogens depends on their ability to maintain an infection inside the phagocytic vacuole of the macrophage. Although the bacteria are reported to modulate maturation of their intracellular vacuoles, the nature of such modifications is unknown. In this study, vacuoles formed arou... | 10.1038/nrmicro840 | This paper showed for the first time that mycobacterial phagosomes do not recruit the ATP-dependent H + pumps that bring about acidification to their membranes. |
10.1084/jem.142.1.1 | 20,043,358 | Tubercle bacilli of the pathogenic human strain H37Rv had previously been shown to multiply, after ingestion by cultured mouse peritoneal macrophages, within phagosomes that tended to remain unfused with secondary lysosomes. Means were sought therefore for promoting experimentally a modification of the host response so... | 10.1038/nrmicro840 | This is the first report of the failure of phagosomes in cells infected with pathogenic mycobacteria to fuse with lysosomes. |
10.4049/jimmunol.166.5.3392 | 82,803,755 | Abstract Mycobacterium tuberculosis successfully parasitizes macrophages by disrupting the maturation of its phagosome, creating an intracellular compartment with endosomal rather than lysosomal characteristics. We have recently demonstrated that live M. tuberculosis infect human macrophages in the absence of an increa... | 10.1038/nrmicro840 | This paper gives a clear demonstration of the role of Ca 2+ - and calmodulin-mediated signalling pathways in blocking the maturation of phagosomes bearing pathogenic mycobacteria. |
10.1073/pnas.0737613100 | 20,702,461 | The tubercle bacillus parasitizes macrophages by inhibiting phagosome maturation into the phagolysosome. This phenomenon underlies the tuberculosis pandemic involving 2 billion people. We report here how Mycobacterium tuberculosis causes phagosome maturation arrest. A glycosylated M. tuberculosis phosphatidylinositol [... | 10.1038/nrmicro840 | References 32 and 33 describe the host cell signalling molecules that are involved in mycobacterial phagosome maturation and also define mycobacterial glycolipids, such as Man-LAM, as critical mycobacterial virulence factors that block phagolysosomal trafficking. |
10.1084/jem.20021468 | 101,619,401 | Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least ... | 10.1038/nrmicro840 | Together with reference 73, these authors describe how mycobacteria enter dendritic cells and that certain receptor pathways allow the pathogens to escape bactericidal killing by modulating TLR signalling pathways. |
10.1046/j.1365-2958.2003.03425.x | 20,778,364 | Summary Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we de... | 10.1038/nrmicro840 | These authors characterized the genes essential for mycobacterial growth using a technique involving random mutagenesis of the mycobacterial genome with transposons. They identified several STPKs as essential for mycobacterial growth in vitro |
10.1046/j.1365-2958.2003.03712.x | 81,241,396 | Summary Protein tyrosine kinases and tyrosine phosphatases from several bacterial pathogens have been shown to act as virulence factors by modulating the phosphorylation and dephosphorylation of host proteins. The identification and characterization of two tyrosine phosphatases namely MptpA and MptpB from Mycobacterium... | 10.1038/nrmicro840 | This paper describes, for the first time, the role of protein tyrosine phosphatases in the pathogenesis of M. tuberculosis and possible implications for interaction with IFN-γ signalling pathways in host cells. |
10.1152/ajpregu.00428.2014 | 79,969,961 | The development of the kidney arterioles is poorly understood. Mature arterioles contain several functionally and morphologically distinct cell types, including smooth muscle, endothelial, and juxtaglomerular cells, and they are surrounded by interconnected pericytes, fibroblasts, and other interstitial cells. We have ... | 10.1038/nrneph.2017.186 | This study shows that the FOXD1 + stromal cell is a progenitor for renin-expressing cells in the kidney. |
10.1152/ajprenal.00247.2015 | 102,106,995 | Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but are highly restricted, specialized endocrine cells in adults. With a functi... | 10.1038/nrneph.2017.186 | This study demonstrates conservation of the roles of renin-expressing cells in mammals and fish. |
10.1152/ajprenal.90448.2008 | 77,625,174 | During metanephric kidney development, renin expression in the renal vasculature begins in larger vessels, shifting to smaller vessels and finally remaining restricted to the terminal portions of afferent arterioles at the entrance into the glomerular capillary network. The mechanisms determining the successive express... | 10.1038/nrneph.2017.186 | This study shows that the cAMP pathway is crucial for the development of the renin-expressing cell. |
10.1152/ajpheart.01152.2007 | 58,415,564 | The renin-angiotensin system (RAS) regulates blood pressure and fluid-electrolyte homeostasis. A key step in the RAS cascade is the regulation of renin synthesis and release by the kidney. We and others have shown that a major mechanism to control renin availability is the regulation of the number of cells capable of m... | 10.1038/nrneph.2017.186 | This study shows that the identity of the renin phenotype is mediated by cAMP and epigenetic changes. |
10.1182/blood-2016-11-752006 | 81,697,113 | Key Points ACE plays an important physiological role in neutrophil antibacterial activity. ACE upregulation in mice neutrophils strongly enhances bactericidal activity via increased reduced NAD phosphate oxidase production of ROS. | 10.1038/nrneph.2017.186 | This study demonstrates that ACE in neutrophils confers enhanced resistance to infection independently of angiotensin generation. |
10.1073/pnas.1218510110 | 107,189,234 | The subplate zone is a highly dynamic transient sector of the developing cerebral cortex that contains some of the earliest generated neurons and the first functional synapses of the cerebral cortex. Subplate cells have important functions in early establishment and maturation of thalamocortical connections, as well as... | 10.1038/nrn3915 | The first transcriptomic evidence for subplate involvement in neurodevelopmental diseases. |
10.1073/pnas.1323816111 | 102,094,660 | Significance Early-generated subplate cells play important roles in development of the cerebral cortex. Although it has been assumed that most subplate cells are generated in the cortical germinative zone, here we describe an alternative site of neurogenesis, the rostromedial telencephalic wall. The rostromedial telenc... | 10.1038/nrn3915 | Evidence for a novel, extracortical site of subplate neurogenesis, and the first evidence for co-generation of GABAergic and excitatory neurons in the same neuroepithelial compartment. |
10.1146/annurev-neuro-060909-153244 | 83,458,376 | The developing mammalian cerebral cortex contains a distinct class of cells, subplate neurons (SPns), that play an important role during early development. SPns are the first neurons to be generated in the cerebral cortex, they reside in the cortical white matter, and they are the first to mature physiologically. SPns ... | 10.1038/nrn3915 | A comprehensive review of the circuit function and electrophysiological properties of the subplate and its constituent neurons. |
10.1002/cne.902970309 | 20,392,496 | Abstract The cytological organization and the timetable of emergence and dissolution of the transient subplate zone subjacent to the developing visual and somatosensory cortex were studied in a series of human and monkey fetal brains. Cerebral walls processed with Nissl, Golgi, electron‐microscopic, and histochemical m... | 10.1038/nrn3915 | A highly detailed description of the different stages of subplate formation in the human cerebral cortex. |
10.1152/jn.1991.66.6.2059 | 95,476,899 | 1. The development of excitatory activation in the visual cortex was studied in fetal and neonatal cats. During fetal and neonatal life, the immature cerebral cortex (the cortical plate) is sandwiched between two synaptic zones: the marginal zone above, and an area just below the cortical plate, the subplate. The subpl... | 10.1038/nrn3915 | The first circuit-level analysis of subplate function, which highlights the transient and dynamic nature of subplate integration into the developing thalamocortical connectivity. |
10.1126/science.1084152 | 83,007,732 | The subplate forms a transient circuit required for development of connections between the thalamus and the cerebral cortex. When subplate neurons are ablated, ocular dominance columns do not form in the visual cortex despite the robust presence of thalamic axons in layer 4. We show that subplate ablation also prevents... | 10.1038/nrn3915 | The first evidence for subplate involvement in circuit maturation beyond direct effects on thalamocortical afferents. |
10.1111/j.1469-7580.2010.01283.x | 16,395,974 | Abstract In this historical review, we trace the early history of research on the fetal subplate zone, subplate neurons and interstitial neurons in the white matter of the adult nervous system. We arrive at several general conclusions. First, a century of research clearly testifies that interstitial neurons, subplate n... | 10.1038/nrn3915 | An interesting historical review of early studies on cortical development that identifies much of the terminology previously used to refer to the subplate compartment. |
10.1152/jn.01145.2004 | 100,785,496 | We studied the subcellular correlates of spreading depression (SD) in the CA1 rat hippocampus by combining intrasomatic and intradendritic recordings of pyramidal cells with extracellular DC and evoked field and unitary activity. The results demonstrate that during SD only specific parts of the dendritic membranes are ... | 10.1038/nrn3770 | In this study, simultaneous intracellular recordings from somata and dendrites in hippocampal pyramidal cells (combined with extracellular recordings from the same regions) revealed longitudinal gradients of depolarization within individual neurons during some phases of CSD. The results support the initiation of CSD in... |
10.1523/jneurosci.0721-07.2007 | 38,881,899 | Spreading depression (SD) is a propagating wave of neuronal depolarization and ionic shifts, seen in stroke and migraine. In vitro , SD is associated with astrocytic [Ca 2+ ] waves, but it is unclear what role they play and whether they influence cerebral blood flow, which is altered in SD. Here we show that SD in vivo... | 10.1038/nrn3770 | This study provides in vivo evidence that the CSD-associated neuronal Ca 2+ wave precedes the astrocytic Ca 2+ wave and is unaffected by suppression of the intracellular Ca 2+ concentration increase in astrocytes, indicating that neurons lead the CSD propagation (see reference 15 for previous similar evidence in vitro |
10.1038/jcbfm.2009.73 | 60,135,324 | Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is the mechanism of migraine, and involved in progressive neuronal injury in stroke and head trauma. Here we tested t... | 10.1038/nrn3770 | Polygraph recordings from the rodent cortex showing the consequences of CSD on sustained increases in oxygen utilization and uncoupling of the neurovascular response. |
10.1152/jn.00237.2002 | 20,651,691 | In spite of five decades of study, the biophysics of spreading depression (SD) is incompletely understood. Earlier we have modeled seizures and SD, and we have shown that currents through ion channels normally present in neuron membranes can generate SD-like depolarization. In the present study, we define the condition... | 10.1038/nrn3770 | A computational model defining the minimal biophysical machinery capable of generating CSD and spreading depolarizations and supporting the idea that a regenerative increase in [K + e is an essential component of the positive-feedback cycle that ignites CSD (see reference 31 for the original proposal for the key role o... |
10.1523/jneurosci.0765-08.2008 | 42,507,773 | Spreading depression (SD) is wave of profound depolarization that propagates throughout brain tissue and can contribute to the spread of injury after stroke or traumatic insults. The contribution of Ca 2+ influx to SD differs depending on the stimulus, and we show here that Zn 2+ can play a critical complementary role ... | 10.1038/nrn3770 | This is the first study to show that Zn 2+ influx and associated mitochondrial depolarization can play a crucial part in the generation of spreading depolarizations but are not involved in the initiation of CSD. |
10.1038/jcbfm.2013.113 | 100,945,794 | Spreading depression (SD) is a slowly propagating neuronal depolarization that underlies certain neurologic conditions. The wave-like pattern of its propagation suggests that SD arises from an unusual form of neuronal communication. We used enzyme-based glutamate electrodes to show that during SD induced by transiently... | 10.1038/nrn3770 | Pharmacological evidence that [Ca 2+ e -independent mechanisms of glutamate release (involving presynaptic NMDARs and Ca 2+ efflux from mitochondria) contribute to the initiation and propagation of CSD induced by diffuse and relatively prolonged high [K + ] applications. |
10.1126/science.1231897 | 41,088,440 | How Migraine Develops Migraine is a common medical disorder. Unfortunately, how and why migraine headache is initiated is unclear. Karatas et al. (p. 1092 ) now describe a signaling pathway between stressed neurons and meningeal trigeminal afferents, which may explain how migraine headaches can be generated. | 10.1038/nrn3770 | A study detailing a novel mechanism that links CSD and an intracortical signaling mechanism that involves PANX1 channel to release of pro-inflammatory substances that may activate the meningeal trigeminovascular system to cause pain. |
10.1073/pnas.071582498 | 62,367,389 | Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (... | 10.1038/nrn3770 | A functional MRI study in a patient showing perturbations in the occipital cortex during visual aura that are consistent with features of CSD in the rodent cortex. |
10.1002/ana.20778 | 20,620,755 | Abstract Objective Topiramate, valproate, propranolol, amitriptyline, and methysergide have been widely prescribed for migraine prophylaxis, but their mechanism or site of action is uncertain. Cortical spreading depression (CSD) has been implicated in migraine and as a headache trigger and can be evoked in experimental... | 10.1038/nrn3770 | In vivo pharmacological rodent study showing that five preventative drugs for migraine raise the CSD threshold in the cortex, suggesting a common action for these agents. |
10.1002/ana.21390 | 101,805,592 | Abstract Objective Cortical spreading depression (CSD) and periinfarct depolarization (PID) have been shown in various experimental models of stroke to cause secondary neuronal damage and infarct expansion. For decades it has been questioned whether CSD or PID occur in human ischemic stroke. Here, we describe CSD and P... | 10.1038/nrn3770 | A study showing that following middle cerebral artery occlusion, individuals with acute stroke exhibit recurrent spreading depolarizations, which can be detected by recordings from the exposed cortex. |
10.1128/jb.179.21.6609-6617.1997 | 61,126,247 | A total of 188 Bordetella strains were characterized by the electrophoretic mobilities of 15 metabolic enzymes and the distribution and variation in positions and copy numbers of three insertion sequences (IS). The presence or absence of IS elements within certain lineages was congruent with estimates of overall geneti... | 10.1038/nrmicro886 | Highlights the use of MLEE in defining relationships between different bacterial strains or species. These studies were pivotal for formulating current hypotheses explaining the evolution of the bordetellae. |
10.1128/jb.186.5.1484-1492.2004 | 61,822,608 | ABSTRACT Pathogens of the bacterial genus Bordetella cause respiratory disease in humans and animals. Although virulence and host specificity vary across the genus, the genetic determinants of this diversity remain unidentified. To identify genes that may underlie key phenotypic differences between these species and cl... | 10.1038/nrmicro886 | Highlights the use of post-genomic technologies for defining relationships between bacterial strains or species. This genome-wide analysis generated large amounts of data regarding the nature of differences between different bacteria but indicates that older methodologies, such as MLEE, are accurate predictors of evolu... |
10.1128/iai.66.10.4640-4650.1998 | 101,106,175 | ABSTRACT Random minitransposon mutagenesis was used to identify genes involved in the survival of Bordetella bronchiseptica within eukaryotic cells. One of the mutants which exhibited a reduced ability to survive intracellularly harbored a minitransposon insertion in a locus ( ris ) which displays a high degree of homo... | 10.1038/nrmicro886 | Highlights the fact that regulatory systems other than the BvgAS system operate in the Bordetella . It is likely that the genome sequence data will identify further regulatory circuits in these bacteria. |
10.1084/jem.20021153 | 61,604,263 | Pathogen attachment is a crucial early step in mucosal infections. This step is mediated by important virulence factors called adhesins. To exert these functions, adhesins are typically surface-exposed, although, surprisingly, some are also released into the extracellular milieu, the relevance of which has previously n... | 10.1038/nrmicro886 | Reveals new information about how FHA might mediate adherence and proposes that secreted forms of FHA could be important in this process. |
10.1002/mds.25844 | 20,679,181 | ABSTRACT With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson's disease (PD), the International Parkinson and Movement Disorders Society (MDS)... | 10.1038/nrn.2016.178 | This article reviews clinical and biological knowledge on PD showing that LP is not essential for cPD and occurs in a large proportion of patients who may not have cPD. |
10.1002/mds.25952 | 28,046,983 | Abstract To gain a better understanding of the significance of α‐synuclein pathological conditions during disease progression in Parkinson's disease, we investigated whether 1) nigral neuronal loss in incidental Lewy body disease and Parkinson's disease donors is associated with the local burden α‐synuclein pathologica... | 10.1038/nrn.2016.178 | This paper describes a negative correlation between neuronal density and local α-syn burden in the SN of patients with PD and shows that the severity of neurodegeneration and local burden of α-syn pathological conditions are closely coupled during disease progression. |
10.1126/science.1227157 | 20,881,057 | Synthetic Parkinson's Parkinson's disease (PD) and related α-synucleinopathies are defined by the accumulation of α-synuclein (α-Syn)–containing intraneuronal inclusions—Lewy bodies (LBs) and Lewy neurites (LNs)—in association with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and other ... | 10.1038/nrn.2016.178 | This was the first demonstration that pre-formed α-syn fibrils can propagate from one neuron to another and induce cell death in vivo when inoculated into the brain of mice. |
10.1084/jem.20160368 | 83,272,435 | Parkinson’s disease (PD) is characterized by the progressive appearance of intraneuronal Lewy aggregates, which are primarily composed of misfolded α-synuclein (α-syn). The aggregates are believed to propagate via neural pathways following a stereotypical pattern, starting in the olfactory bulb (OB) and gut. We hypothe... | 10.1038/nrn.2016.178 | This paper provides the first clear evidence of transneuronal propagation of pre-formed α-syn fibril-induced pathology from the olfactory bulb in mice. |
10.1002/ana.24066 | 41,756,557 | Objective Mounting evidence suggests that α‐synuclein, a major protein component of Lewy bodies (LB), may be responsible for initiating and spreading the pathological process in Parkinson disease (PD). Supporting this concept, intracerebral inoculation of synthetic recombinant α‐synuclein fibrils can trigger α‐synuclei... | 10.1038/nrn.2016.178 | This paper used purified pathological α-syn from the SN of patients with PD to show the intracellular and presynaptic accumulation of endogenous α-syn and the progressive axon-initiated neurodegeneration. |
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