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10.1111/j.1460-9568.2007.05940.x
82,613,257
Abstract Bone morphogenetic proteins (BMPs) and their endogenous inhibitors, including noggin, chordin and follistatin, have roles in pattern formation and fate specification of neuronal and glial cells during nervous system development. We have examined their influence on glial reactions in the injured central nervous...
10.1038/nrn2495
This article shows that noggin must be blocked before polydendrocytes can be transformed into astrocytes in a neocortical mechanical wound.
10.1083/jcb.200210110
122,570,024
Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan–positive progenitor cells that express the 2′,3′-cyclic nucleotid...
10.1038/nrn2495
This paper, along with subsequently published papers from the same group (see references 95 and 96), demonstrated neuronal differentiation from polydendrocytes.
10.1073/pnas.0709002105
62,582,761
Reactive gliosis is the universal reaction to brain injury, but the precise origin and subsequent fate of the glial cells reacting to injury are unknown. Astrocytes react to injury by hypertrophy and up-regulation of the glial-fibrillary acidic protein (GFAP). Whereas mature astrocytes do not normally divide, a subpopu...
10.1038/nrn2495
This study showed that, in contrast to the neurogenic potential of astrocytes in the mature brain, isolated polydendrocytes did not generate neurospheres.
10.1126/science.1124669
81,407,145
Interactions between neurons and glial cells in the brain may serve important functions in the development, maintenance, and plasticity of neural circuits. Fast neuron-glia synaptic transmission has been found between hippocampal neurons and NG2 cells, a distinct population of macroglia-like cells widely distributed in...
10.1038/nrn2495
This article shows potentiation of EPSCs in hippocampal polydendrocytes following theta-burst stimulation.
10.1073/pnas.1013435107
123,005,677
Molecular oxygen (O 2 ) is the second most abundant gas in the Earth’s atmosphere, but in many natural environments, its concentration is reduced to low or even undetectable levels. Although low-oxygen-adapted organisms define the ecology of low-oxygen environments, their capabilities are not fully known. These capabil...
10.1038/nrmicro2970
This study demonstrates aerobic growth of an E. coli strain at nanomolar concentrations of O 2 — concentrations that are orders of magnitude lower than those previously reported.
10.1073/pnas.1018958108
19,399,810
Aerobic respiration in bacteria, Archaea, and mitochondria is performed by oxygen reductase members of the heme-copper oxidoreductase superfamily. These enzymes are redox-driven proton pumps which conserve part of the free energy released from oxygen reduction to generate a proton motive force. The oxygen reductases ca...
10.1038/nrmicro2970
This report discusses the implications of the adaptation of aerobic respiration to low-O 2 environments.
10.1523/jneurosci.18-18-07426.1998
104,268,651
Although attention is distributed across time as well as space, the temporal allocation of attention has been less well researched than its spatial counterpart. A temporal analog of the covert spatial orientation task [Posner MI, Snyder CRR, Davidson BJ (1980) Attention and the detection of signals. J Exp Psychol Gen 1...
10.1038/nrn.2017.141
This is a landmark brain-imaging study in humans that reveals the brain network involved in temporal orienting of attention and compares and contrasts it with the spatial orienting network.
10.1162/jocn_a_01172
91,826,798
The fundamental role that our long-term memories play in guiding perception is increasingly recognized, but the functional and neural mechanisms are just beginning to be explored. Although experimental approaches are being developed to investigate the influence of long-term memories on perception, these remain mostly s...
10.1038/nrn.2017.141
This recent study in humans demonstrates that long-term memories carry temporal associations that guide perception through temporally selective anticipation of target stimuli.
10.1162/jocn_a_00564
39,143,326
Exposure to rhythmic stimulation results in facilitated responses to events that appear in-phase with the rhythm and modulation of anticipatory and target-evoked brain activity, presumably reflecting “exogenous,” unintentional temporal expectations. However, the extent to which this effect is independent from intention...
10.1038/nrn.2017.141
This is a study in humans that offers a clear demonstration that different types of temporal structures can have dissociable impacts on perception.
10.1111/ejn.13700
124,692,835
Abstract Performance improves when participants respond to events that are structured in repeating sequences, suggesting that learning can lead to proactive anticipatory preparation. Whereas most sequence‐learning studies have emphasised spatial structure, most sequences also contain a prominent temporal structure. We ...
10.1038/nrn.2017.141
This study in humans shows that complex, non-isochronous, temporal sequences are utilized by the brain to align motor preparation to anticipated moments in time.
10.1523/jneurosci.5630-10.2011
81,919,622
Our perception is facilitated if we know where and when a sensory stimulus will occur. This phenomenon is accounted for by spatial and temporal orienting of attention. Whereas spatial orienting of attention has repeatedly been shown to involve spatially specific modulations of ongoing oscillations within sensory cortex...
10.1038/nrn.2017.141
This is a study in humans that shows that modulation of alpha and beta oscillations by spatial attention is dynamically upregulated and downregulated by concurrent temporal expectations.
10.1126/science.1154735
125,207,457
Whereas gamma-band neuronal oscillations clearly appear integral to visual attention, the role of lower-frequency oscillations is still being debated. Mounting evidence indicates that a key functional property of these oscillations is the rhythmic shifting of excitability in local neuronal ensembles. Here, we show that...
10.1038/nrn.2017.141
This is a study in NHPs that introduces phase alignment of low-frequency oscillations with predictable rhythmic stimulation (entrainment) as a putative mechanism for selective temporal attention in the context of rhythmic stimuli.
10.1523/jneurosci.1821-05.2005
82,979,414
We developed a naturalistic behavioral task to investigate the influence of spatial and temporal expectations on attentional orienting to moving targets. In this task, the movement of an object before its disappearance under an occluding barrier generated expectations concerning the location and/or time of its reappear...
10.1038/nrn.2017.141
This is a study in humans that reveals a synergistic interaction between temporal and spatial expectations in enhancing early visual evoked potentials.
10.1523/jneurosci.0836-15.2016
123,769,320
Predicting not only what will happen, but also when it will happen is extremely helpful for optimizing perception and action. Temporal predictions driven by periodic stimulation increase perceptual sensitivity and reduce response latencies. At the neurophysiological level, a single mechanism has been proposed to mediat...
10.1038/nrn.2017.141
This study in humans suggests distinct mechanisms for behavioural facilitation by different types of predictable temporal structures and demonstrates synergistic interactions between temporal and feature-based expectations.
10.1126/science.1123513
29,129,515
We discovered that when adult rats experience an association between visual stimuli and subsequent rewards, the responses of a substantial fraction of neurons in the primary visual cortex evolve from those that relate solely to the physical attributes of the stimuli to those that accurately predict the timing of reward...
10.1038/nrn.2017.141
This is a study in rodents that demonstrates that neurons in the primary visual cortex are sensitive to temporal expectations about non-visual food rewards.
10.1126/science.1179220
103,069,169
Daily injections into mice of an ammonium sulfate-precipitated immunoglobulin fraction of serum from patients with myasthenia gravis were carried out for up to 14 days. The mice showed reduced amplitudes of miniature endplate potentials and reduced numbers of acetylcholine receptors at the neuromuscular junctions. Some...
10.1038/nrn.2015.27
This study describes the first passive transfer of AChR antibodies from patients with MG to mice.
10.1126/science.180.4088.871
61,177,898
Injection of rabbits with acetylcholine receptor highly purified from the electric organ of Electrophorus electricus emulsified in complete Freund's adjuvant resulted in the production of precipitating antibody to acetylcholine receptor. After the second injection of antigen, the animals developed the flaccid paralysis...
10.1038/nrn.2015.27
This is the first description of an active immunization model of MG in which rabbits injected with AChRs purified from the electric organ of Electrophorus electricus developed AChR antibodies and symptoms similar to those observed in MG.
10.1126/science.182.4109.293
61,276,237
The number of acetylcholine receptors was determined in the neuromuscular junctions of eight patients with typical myasthenia gravis and in five controls, by means of 125 I-labeled α-bungarotoxin binding. The junctional acetylcholine receptors were reduced in the myasthenic muscles as compared with the controls. This r...
10.1038/nrn.2015.27
This study used radioactive bungatoxin labelling in human muscle to identify AChR loss in individuals with MG.
10.1073/pnas.1313944110
42,541,640
Significance MuSK myasthenia gravis (MG) is a debilitating autoimmune disease: one-third of MuSK MG patients experience a life-threatening respiratory crisis, and long-term immunosuppression is the only current treatment option. Here we show that pathogenic human IgG4 MuSK antibodies bind to the first Ig-like domain in...
10.1038/nrn.2015.27
This study showed thatIgG4 autoantibodies from individuals with MuSK antibody-positive MG interfere with LRP4–MuSK signalling, and reduce MuSK phosphorylation.
10.1002/ana.410370513
59,920,839
Abstract In myasthenia gravis, loss of acetylcholine receptors at motor end‐plates is induced by antireceptor autoantibodies. At end‐plates in rats in which myasthenia gravis–like symptoms are induced by chronic treatment with α‐bungarotoxin, acetylcholine release is increased. Within muscles from such rats there is a ...
10.1038/nrn.2015.27
This study showed that AChR autoantibodies, in patients and animal models, produce a compensatory increase in presynaptic quantal release.
10.1002/ana.1097
62,478,113
Abstract Limbic encephalitis (LE) is often associated with lung, thymic, or testicular tumours and antibodies to Hu, CV2, or Ma2 (Ta) antigens. In these cases, it generally has a poor prognosis. Here we describe two patients with symptoms of LE, negative for typical paraneoplastic antibodies, in whom antibodies to volt...
10.1038/nrn.2015.27
This is one of the first reports to show the reversibility of a CNS syndrome associated with autoantibodies by using plasma exchange and corticosteroids.
10.1002/ana.22307
26,987,931
Abstract Objective: To describe a distinctive seizure semiology that closely associates with voltage‐gated potassium channel (VGKC)‐complex/Lgi1 antibodies and commonly precedes the onset of limbic encephalitis (LE). Methods: Twenty‐nine patients were identified by the authors (n = 15) or referring clinicians (n = 14)....
10.1038/nrn.2015.27
This study defined a form of seizure that is strongly associated with the presence of LGI1 autoantibodies.
10.1002/ana.24195
39,054,400
Objective A severe but treatable form of immune‐mediated encephalitis is associated with antibodies in serum and cerebrospinal fluid (CSF) against the GluN1 subunit of the N‐methyl‐D‐aspartate receptor (NMDAR). Prolonged exposure of hippocampal neurons to antibodies from patients with anti‐NMDAR encephalitis caused a r...
10.1038/nrn.2015.27
This detailed study of NMDAR antibodies showed the time course of NMDAR internalization, indicated a degree of homeostatic compensation in cultured neurons and provided important negative results. These results include the findings that the antibodies from patients have no binding preference to inhibitory or excitatory...
10.1152/ajpendo.1980.238.2.e141
113,584,007
5-Thio-D-glucose (5TG) is a novel antimetabolic glucose analogue in which sulfur is substituted for the pyranose ring oxygen. Intracardiac infusion of 5TG caused dose-dependent increases in feeding and blood glucose concentrations. Increased food intake was reliably elicited by molar doses of 5TG that were one-third th...
10.1038/nrn3745
This study provides evidence that the hindbrain is important in responding to neuroglucopenia.
10.1152/ajpregu.00602.2002
20,602,490
The hormones insulin and leptin have been proposed to act in the central nervous system (CNS) as adiposity signals as part of a theoretical negative feedback loop that senses the caloric stores of an animal and orchestrates adjustments in energy balance and food intake. Much research has provided support for both the e...
10.1038/nrn3745
This is one of the first reviews to describe the role of the adiposity hormones in the regulation of the reward system.
10.1111/j.1365-2958.2006.05522.x
104,165,966
Summary Conditions that impair protein folding in the Gram‐negative bacterial envelope cause stress. The destabilizing effects of stress in this compartment are recognized and countered by a number of signal transduction mechanisms. Data presented here reveal another facet of the complex bacterial stress response, rele...
10.1038/nrmicro3525
This report presents genetic and biochemical evidence to support a model whereby OMV release can rid the envelope of misfolded proteins and affect antibiotic resistance.
10.1100/2012/402919
19,659,390
Bacterial infections can be aggravated by antibiotic treatment that induces SOS response and vesiculation. This leads to a hypothesis concerning association of SOS with vesiculation. To test it, we conducted multiple analyses of outer membrane vesicles (OMVs) produced from the Pseudomonas aeruginosa wild type in which ...
10.1038/nrmicro3525
This work shows the long-range effect of vesiculation and the importance of OMVs in bacterial physiology.
10.1073/pnas.1410551111
62,196,855
Significance Bacterial nanowires from Shewanella oneidensis MR-1 were previously shown to be conductive under nonphysiological conditions. Intense debate still surrounds the molecular makeup, identity of the charge carriers, and cellular respiratory impact of bacterial nanowires. In this work, using in vivo fluorescenc...
10.1038/nrmicro3525
This study develops a new aspect of OMV physiology: how OMVs attached to bacteria can play a part in energy acquisition.
10.1126/science.1177486
83,540,122
Growing on You The human gut and skin harbor diverse microbial communities that are known to vary strikingly among individuals. Here, Costello et al. (p. 1694 , published online 5 November) analyzed microbial diversity among several distinct body habitats (including the gut, mouth, inside the ears and nose, and skin) o...
10.1038/nrmicro2473
A comprehensive analysis of the human microbiota and documentation of its variability across sites and between individuals.
10.1073/pnas.1004204107
19,000,081
Diabetics frequently suffer from chronic, nonhealing wounds. Although bacterial colonization and/or infection are generally acknowledged to negatively impact wound healing, the precise relationship between the microbial community and impaired wound healing remains unclear. Because the host cutaneous defense response is...
10.1038/nrmicro2473
An important study showing a selective shift in the microbiota of the skin in association with immune responses to wounds.
10.1073/pnas.0700440104
62,561,641
The mechanisms by which probiotic strains enhance the health of the host remain largely uncharacterized. Here we demonstrate that Lactobacillus salivarius UCC118, a recently sequenced and genetically tractable probiotic strain of human origin, produces a bacteriocin in vivo that can significantly protect mice against i...
10.1038/nrmicro2473
An elegant illustration of bacteriocin helping an organism to protect the gut from infection.
10.1073/pnas.0709266105
58,412,641
Microbes occupy countless ecological niches in nature. Sometimes these environments may be on or within another organism, as is the case in both microbial infections and symbiosis of mammals. Unlike pathogens that establish opportunistic infections, hundreds of human commensal bacterial species establish a lifelong coh...
10.1038/nrmicro2473
This study shows the crucial role of capsular polysaccharides in host–symbiont mutualism.
10.1073/pnas.0136863100
123,558,418
The lung is the primary target of infection with Mycobacterium tuberculosis . It is well established that, in mouse lung, expression of adaptive, Th1-mediated host immunity inhibits further multiplication of M. tuberculosis . Here, real-time RT-PCR was used to define the pattern of expression against time of lung infec...
10.1038/nrmicro749
Defines the transcription signature of M. tuberculosis as it transitions from growth to persistence in the mouse lung. The bacterial transcription changes measured are likely to be induced by nitric oxide generated by infected macrophages.
10.1084/jem.20030205
19,062,906
An estimated two billion persons are latently infected with Mycobacterium tuberculosis. The host factors that initiate and maintain this latent state and the mechanisms by which M. tuberculosis survives within latent lesions are compelling but unanswered questions. One such host factor may be nitric oxide (NO), a produ...
10.1038/nrmicro749
A model postulating that, in granulomas, inhibition of respiration by nitric oxide production and oxygen limitation constrains mycobacterial replication rates in people with latent TB.
10.1126/science.291.5508.1544
107,363,195
The mammalian innate immune system retains from Drosophila a family of homologous Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we show that TLR2 activation leads to killing of intracellular Mycobacterium tuberculosis in both mouse and human macrophages, through distinct mechanisms. In m...
10.1038/nrmicro749
First paper to show that mammalian TLRs respond to microbial ligands and can activate antimicrobial effector pathways at the site of infection.
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/nrmicro749
References 81 and 82 show that DC-SIGN mediates the entry of M. tuberculosis into dendritic cells in vivo and is likely to influence bacterial persistence and host immunity.
10.1002/bies.10045
82,006,108
Abstract The radial symmetric cnidarians are regarded as being close to the common metazoan ancestor before bilaterality evolved. It is proposed that a large fraction of the body of this gastrula‐like organism gave rise to the head of more evolved organisms. The trunk was added later in evolution from an unfolding of a...
10.1038/nrn1175
This paper departs radically from traditional thinking about cnidarian nervous systems by equating the entire epidermal nerve net to the CNS.
10.1073/pnas.112021499
29,128,270
As the closest outgroup to the Bilateria, the Phylum Cnidaria is likely to be critical to understanding the origins and evolution of body axes. Proteins of the decapentaplegic (DPP)/bone morphogenetic protein (BMP) 2/4 subfamily are central to the specification of the dorsoventral (D/V) axis in bilateral animals, albei...
10.1038/nrn1175
In situ hybridization of histologically difficult material indicates that cnidarians might have a second (presumably dorsoventral) axis in addition to their oral/aboral axis.
10.1242/dev.129.13.3021
104,339,611
Many regulatory genes appear to be utilized in at least superficially similar ways in the development of particular body parts in Drosophila and in chordates. These similarities have been widely interpreted as functional homologies, producing the conventional view of the last common protostome-deuterostome ancestor (PD...
10.1038/nrn1175
This up-to-date review orchestrates findings from such disjunct fields as developmental genetics and Precambrian palaeontology to shed light on the evolutionary origin of the last common ancestor of the protostomes and deuterostomes.
10.1002/cne.901390405
18,127,833
Abstract Histological techniques have been used to study the layer of Purkinje cells in the cerebellum of the albino rat. A method has been devised for “unfolding” the layer into two dimensions. The shape after unfolding strikingly resembled the shape of the unfolded human cerebellar cortex. The total area of the Purki...
10.1038/nrn3886
Histological study showing that there is considerable local variation in Purkinje cell packing density.
10.1523/jneurosci.18-10-03606.1998
123,915,489
Antibodies to an excitatory amino acid transporter (EAAT4) label a glycoprotein of ∼65 kDa strongly in the cerebellum and weakly in the forebrain. Cross-linking of cerebellar proteins with bis(sulfosuccinimidyl) suberate before solubilization causes dimer bands of EAAT4 and both dimer and trimer bands of the other glut...
10.1038/nrn3886
First demonstration that the Purkinje cell-specific glutamate transporter EAAT4 is expressed in a zebrin II band pattern.
10.1002/cne.20912
80,774,837
Abstract Transverse boundaries divide the cerebellar cortex into four transverse zones, and within each zone the cortex is further subdivided into a symmetrical array of parasagittal stripes. Several molecules believed to mediate long‐term depression at the parallel fiber–Purkinje cell synapse are known to be expressed...
10.1038/nrn3886
First demonstration that two key components involved in the transduction of GluR1-mediated responses, PLCβ3 and PLCβ4, are confined to zebrin II + and zebrin II − Purkinje cells, respectively.
10.1002/cne.902910405
59,798,295
Abstract Monoclonal antibody mab‐zebrin II was generated against a crude homogenate of cerebellum and electrosensory lateral line lobe from the weakly electric fish Apteronotus leptorhynchus . On Western blots of fish cerebellar proteins, mab‐zebrin II recognizes a single polypeptide antigen of apparent molecular weigh...
10.1038/nrn3886
The first identification of the canonical stripe antigen zebrin II.
10.1113/jphysiol.2011.221846
103,623,948
Non‐technical summary Cerebellar vermis consists of 10 lobules, and each lobule receives different sensory information. Afferent inputs are integrated in cerebellar Purkinje cells (PCs) which are the sole output of the cerebellar cortex. We show that intrinsic membrane properties are widely different between PCs in the...
10.1038/nrn3886
An in vitro electrophysiological study showing that Purkinje cells can display four distinct firing patterns, and that the differences in electrophysiological firing patterns are lobule-specific.
10.1152/jn.00717.2010
80,962,712
The parallel fibers (PFs) in the cerebellar cortex extend several millimeters along a folium in the mediolateral direction. The PFs are orthogonal to and cross several parasagittal zones defined by the olivocerebellar and corticonuclear pathways and the expression of molecular markers on Purkinje cells (PCs). The funct...
10.1038/nrn3886
Combined electrophysiological and fluorescent imaging study showing that zebrin II + and zebrin II − bands differ markedly in their responses to parallel fibre stimulation.
10.1002/cne.10522
18,413,256
Abstract Niemann Pick disease type C1 (NPC1) is an inherited, autosomal recessive, lipid‐storage disorder with major neurological involvement. Purkinje cell death is a prominent feature of the neuropathology of NPC. We have investigated Purkinje cell death in two murine models of NPC1, BALB/c npc nih and C57BLKS/J spm ...
10.1038/nrn3886
An example of an inherited, autosomal recessive lipid-storage disorder in which Purkinje cell death is a prominent feature of the neuropathology. The progressive pattern of Purkinje cell death is complex but reflects the fundamental compartmentalization of the cerebellum.
10.1128/jvi.02245-06
40,562,762
ABSTRACT Infection of newborn Lewis rats with Borna disease virus (neonatal Borna disease [NBD]) results in cerebellar damage without the cellular inflammation associated with infections in later life. Purkinje cell (PC) damage has been reported for several models of early-life viral infection, including NBD; however, ...
10.1038/nrn3886
This study examined Purkinje cell death in a model of neonatal viral infection and found a link between cell death and with the expression ofzebrin II and EAAT4.
10.55782/ane-2009-1736
148,185,287
Tottering mouse is an ataxic mutant that carries a mutation in a gene encoding for the ?1A subunit of P/Q-type Ca2+ channel (Cav2.1). This study revisited to examine whether a Purkinje cell loss occurred in the cerebellum of tottering mice. In tottering mice, Calbindin D-28k negative gaps were apparent in the vermis bu...
10.1038/nrn3886
The first anatomical study showing that in the ataxic tottering mouse, the pattern of Purkinje cell loss is characterized by a selective loss of Purkinje cells in zebrin II − bands in the anterior vermis and in zebrin II + bands in the posterior vermis.
10.1523/jneurosci.0197-12.2012
38,876,704
The cerebellum is a site of complex sensorimotor integration and contains up to 80% of the neurons in the brain, yet comparatively little is known about the organization of sensorimotor systems within the cerebellum. It is known that afferent projections and Purkinje cell (PC) response properties are organized into sag...
10.1038/nrn3886
An electrophysiological study showing that Purkinje cell complex spike activity of a given zebrin II stripe pair in the uvula of the pigeon responds to particular patterns of optic flow.
10.1126/science.279.5352.873
62,403,667
Legionella pneumophila , the causative agent of Legionnaires' pneumonia, replicates within alveolar macrophages by preventing phagosome-lysosome fusion. Here, a large number of mutants called dot (defective for organelle trafficking) that were unable to replicate intracellularly because of an inability of the bacteria ...
10.1038/nrmicro753
Reports the discovery of a type IV secretion system that is evolutionarily related to the IncI plasmids and functions dually in conjugative transfer and effector translocation.
10.1046/j.1365-2958.2001.02520.x
60,271,416
Neisseria gonorrhoeae (the gonococcus) is the causative agent of the sexually transmitted disease gonorrhoea. Most gonococcal infections remain localized to the genital tract but, in a small proportion of untreated cases, the bacterium becomes systemic to produce the serious complication of disseminated gonococcal infe...
10.1038/nrmicro753
References 6–8 report the discoveries of new type IV translocation systems, herein termed the 'DNA uptake and release' subfamily.
10.1046/j.1365-2958.2003.03669.x
61,770,655
Summary Agrobacterium tumefaciens transfers oncogenic DNA and effector proteins to plant cells during the course of infection. Substrate translocation across the bacterial cell envelope is mediated by a type IV secretion (TFS) system composed of the VirB proteins, as well as VirD4, a member of a large family of inner m...
10.1038/nrmicro753
Reports the first direct evidence for recruitment of a protein effector to a coupling protein, supporting a proposal that the coupling proteins function as general recruitment factors for type IV secretion substrates.
10.1126/science.290.5493.979
83,032,123
The Agrobacterium VirB/D4 transport system mediates the transfer of a nucleoprotein T complex into plant cells, leading to crown gall disease. In addition, several Virulence proteins must somehow be transported to fulfill a function in planta. Here, we used fusions between Cre recombinase and VirE2 or VirF to directly ...
10.1038/nrmicro753
This elegant study supplied the first incontrovertible evidence for protein trafficking by the A. tumefaciens VirB/D4 type IV secretion system.
10.1046/j.1365-2958.2003.03400.x
28,225,846
Summary Legionella pneumophila establishes a replication vacuole within phagocytes that requires the bacterial Dot/Icm apparatus for its formation. This apparatus is predicted to translocate effectors into host cells. We hypothesized that some translocated proteins also function to maintain the integrity of the Dot/Icm...
10.1038/nrmicro753
Describes the discovery of a novel effector, LidA, that is required for elaboration of the L. pneumophila Dot/Icm complex in the bacterium and, on translocation, functions in vesicle recruitment during biogenesis of the replication vacuole.
10.1073/pnas.172390299
102,691,767
Numerous bacterial pathogens use type IV secretion systems (T4SS) to deliver virulence factors directly to the cytoplasm of plant, animal, and human host cells. Here, evidence for interactions among components of the Agrobacterium tumefaciens vir -encoded T4SS is presented. The results derive from a high-resolution yea...
10.1038/nrmicro753
Reports a comprehensive linkage map of the VirB proteins by yeast dihybrid screens.
10.1126/science.1081919
17,559,733
Helicobacter pylori translocates the protein CagA into gastric epithelial cells and has been linked to peptic ulcer disease and gastric carcinoma. We show that injected CagA associates with the epithelial tight-junction scaffolding protein ZO-1 and the transmembrane protein junctional adhesion molecule, causing an ecto...
10.1038/nrmicro753
Shows that non-phosphorylated CagA induces formation of an aberrant apical-junction protein complex, resulting in loss of cell polarity, proliferation and differentiation.
10.1126/science.1179850
41,545,070
Columns, Connections, and Correlations What is the nature of interactions between neurons in neural circuits? The prevalent hypothesis suggests that dense local connectivity causes nearby cortical neurons to receive substantial amounts of common input, which in turn leads to strong correlations between them. Now two st...
10.1038/nrn3084
Using a combination of theoretical modelling and population recording from rodent cortex, this paper shows how cortical networks can maintain a desynchronized state despite strong and dense recurrent connectivity.
10.1126/science.1171402
82,969,531
Attention and Synchrony Neural activity in the visual cortex becomes synchronized with attention and other behavioral states. However, the source of this synchrony is still unknown. Gregoriou et al. (p. 1207 ) tested the hypothesis that synchronized activity from the frontal eye field is one of the causes of the synchr...
10.1038/nrn3084
Recording simultaneously in area V4 and the FEF, the authors show that attention enhances neuronal synchronization in the gamma frequency range between these areas.
10.1242/dev.128.24.5201
41,758,865
The mechanisms that regulate the growth of the brain remain unclear. We show that Sonic hedgehog (Shh) is expressed in a layer-specific manner in the perinatal mouse neocortex and tectum, whereas the Gli genes, which are targets and mediators of SHH signaling, are expressed in proliferative zones. In vitro and in vivo ...
10.1038/nrn704
Provides evidence for a role of SHH signalling in controlling the growth of the dorsal brain, and the initiation and possible maintenance of brain tumorigenesis, including gliomagenesis.
10.1242/dev.125.12.2203
20,673,406
Within the developing vertebrate nervous system, it is not known how progenitor cells interpret the positional information provided by inducing signals or how the domains in which distinct groups of neural cells differentiate are defined. Gli proteins may be involved in these processes. In the frog neural plate, we hav...
10.1038/nrn704
Elaborates on the regulation of Gli transcription by SHH signalling, showing an antagonism between SHH/Gli1 and Gli3, as well as providing evidence for the combinatorial and context-dependent action of the Gli proteins.
10.1242/dev.124.1.113
20,839,848
The correct patterning of vertebrate skeletal elements is controlled by inductive interactions. Two vertebrate hedgehog proteins, Sonic hedgehog and Indian hedgehog, have been implicated in skeletal development. During somite differentiation and limb development, Sonic hedgehog functions as an inductive signal from the...
10.1038/nrn704
Genetic evidence that Gli2 and Gli3 have partially overlapping functions in mice.
10.1242/dev.127.19.4293
41,630,277
The Cubitus interruptus (Ci) and Gli proteins are transcription factors that mediate responses to Hedgehog proteins (Hh) in flies and vertebrates, respectively. During development of the Drosophila wing, Ci transduces the Hh signal and regulates transcription of different target genes at different locations. In vertebr...
10.1038/nrn704
Shows that vertebrate Gli proteins have specific functions in vivo ; also shows the differential regulation of repressor and activator functions by HH signalling in flies.
10.1126/science.1058624
28,143,141
Little is known about how patterns of cell types are organized to form brain structures of appropriate size and shape. To study this process, we employed in vivo electroporation during midbrain development to create ectopic sources of Sonic Hedgehog, a signaling molecule previously shown to specify different neuronal c...
10.1038/nrn704
Shows that early ectopic SHH can ventralize and repattern the dorsal midbrain.
10.1242/dev.126.14.3089
83,395,781
The molecular bases of brain development and CNS malignancies remain poorly understood. Here we show that Sonic hedgehog (Shh) signaling controls the development of the cerebellum at multiple levels. SHH is produced by Purkinje neurons, it is required for the proliferation of granule neuron precursors and it induces th...
10.1038/nrn704
Shows the requirement of SHH signalling in the development and growth of the cerebellum, providing the basis for a model of morphological plasticity of this structure. Also provides a rational cellular context for the development of medulloblastomas (see also references 40 and 41
10.1046/j.1471-4159.1998.70031327.x
102,437,341
Abstract: In vertebrates, Sonic Hedgehog (Shh), Desert Hedgehog (Dhh), and Indian Hedgehog (Ihh) genes encode a family of morphogen proteins that are implicated in a wide range of signaling activities, particularly during embryonic development. These secreted proteins are proposed to mediate their effects on target cel...
10.1038/nrn704
This work indicates the presence of SHH signalling in the mature brain.
10.1242/dev.126.17.3915
83,436,391
Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling in vertebrates. The question remains unanswered, however, as to how these Gli proteins participate in the Shh signaling pathway. In this study, regulatory activities associated with the Gli2 protein were investigated in relation to the Shh ...
10.1038/nrn704
Evidence that the early mediation of SHH signals involves Gli2 function.
10.1242/dev.124.6.1227
104,252,496
In the Drosophila wing imaginal disc, the Hedgehog (Hh) signal molecule induces the expression of decapentaplegic (dpp) in a band of cells abutting the anteroposterior (A/P) compartment border. It has been proposed that Dpp organizes the patterning of the entire wing disc. We have tested this proposal by studying the r...
10.1038/nrn704
This work, together with references 97 and 98 , provides evidence that HH acts as a morphogen.
10.1242/dev.127.2.333
20,326,048
Patterning of the vertebrate neural tube depends on intercellular signals emanating from sources such as the notochord and the floor plate. The secreted protein Sonic hedgehog and the extracellular matrix protein Vitronectin are both expressed in these signalling centres and have both been implicated in the generation ...
10.1038/nrn704
Highlights the importance of the extracellular matrix in the control of SHH signalling.
10.1126/science.280.5363.602
125,043,684
The type III secretion system of Salmonella typhimurium directs the translocation of proteins into host cells. Evolutionarily related to the flagellar assembly machinery, this system is also present in other pathogenic bacteria, but its organization is unknown. Electron microscopy revealed supramolecular structures spa...
10.1038/nrmicro3456
This study reveals and characterizes the first T3SS isolated from S . Typhimurium by EM.
10.1126/science.1102610
81,129,912
Type III secretion systems (TTSSs) mediate translocation of virulence factors into host cells. We report the 17-angstrom resolution structures of a central component of Salmonella typhimurium TTSS, the needle complex, and its assembly precursor, the bacterial envelope–anchored base. Both the base and the fully assemble...
10.1038/nrmicro3456
This paper provides the first structural insights into a T3SS needle complex.
10.1126/science.1166101
18,466,125
Type IV secretion systems (T4SSs) are important virulence factors used by Gram-negative bacterial pathogens to inject effectors into host cells or to spread plasmids harboring antibiotic resistance genes. We report the 15 angstrom resolution cryo–electron microscopy structure of the core complex of a T4SS. The core com...
10.1038/nrmicro3456
This paper describes the assembly, purification and EM structure of the core–OM complex of a T4SS.
10.1126/science.1095211
60,571,541
Bacteria use conjugation systems, a subfamily of the type IV secretion systems, to transfer DNA to recipient cells. Despite 50 years of research, the architecture and mechanism of action of the channel mediating DNA transfer across the bacterial cell envelope remains obscure. By use of a sensitive, quantifiable assay t...
10.1038/nrmicro3456
This study defines the translocation pathway for a DNA substrate through the bacterial T4SS.
10.1073/pnas.93.15.8001
60,379,897
It has been known for more than 40 years that images fade from perception when they are kept at the same position on the retina by abrogating eye movements. Although aspects of this phenomenon were described earlier, the use of close-fitting contact lenses in the 1950s made possible a series of detailed observations on...
10.1038/nrn1348
This study showed that visual fading due to retinal stabilization can happen extremely quickly, in less than 80 ms. This fast fading of retinal images in the absence of eye movements has made the field reconsider the dynamics of neural adaptation during normal vision.
10.1073/pnas.212500599
109,136,906
When images are stabilized on the retina, visual perception fades. During voluntary visual fixation, however, constantly occurring small eye movements, including microsaccades, prevent this fading. We previously showed that microsaccades generated bursty firing in the primary visual cortex (area V-1) in the presence of...
10.1038/nrn1348
The parameters of bursts of spikes following microsaccades in the lateral geniculate nucleus and in area V1 depend on whether the visual stimuli presented are optimal or non-optimal for each of these areas.
10.1126/science.150.3702.1459
107,175,642
The maximum velocities of microsaccades (flicks) are an increasing function of amplitude of movement. Measured velocities fall on the extrapolation of the curve of maximum velocity versus amplitude for voluntary saccades and involuntary corrective saccades. Hence all these movements are produced by a common physiologic...
10.1038/nrn1348
This classic study showed a linear relationship between microsaccade amplitudes and velocities. This followed the extrapolation of the same relationship for large saccades, and indicated that both large saccades and microsaccades might be generated by the same neural mechanisms.
10.1162/089976601300014529
101,594,033
Using evolutionary simulations, we develop autonomous agents controlled by artificial neural networks (ANNs). In simple lifelike tasks of foraging and navigation, high performance levels are attained by agents equipped with fully recurrent ANN controllers. In a set of experiments sharing the same behavioral task but di...
10.1038/nrn729
This study was one of the first to evolve general, recurrent controlling networks, manifesting the spontaneous emergence of biological-like command neurons that switch between distinct behavioural modes.
10.1177/105971239900700202
100,808,123
This paper presents how neural swimming controllers for a simulated lamprey can be developed using evolutionary algorithms. A genetic algorithm is used for evolving the architecture of a connectionist model which determines the muscular activity of a simulated body in interaction with water. This work is inspired by th...
10.1038/nrn729
This paper describes an elaborate study that evolved swimming controllers, showing the power of EAAs in generating biologically relevant network models that outperform existing handcrafted ones.
10.1098/rstb.1997.0100
86,105,779
The vast majority of work in machine vision emphasizes the representation of perceived objects and events: it is these internal representations that incorporate the ‘knowledge’ in knowledge–based vision or form the ‘modelsrsquo; in model–based vision. In this paper, we discuss simple machine vision systems developed by...
10.1038/nrn729
This paper reviews a series of EAA studies of visual processing to conclude that this task is performed in a distributed, complex manner that is fundamentally different from the top–down, hierarchical processing used in classical computational/engineering approaches.
10.1177/105971239400300202
101,824,426
This article illustrates an artificial developmental system that is a computationally efficient technique for the automatic generation of complex artificial neural networks (ANNs). The artificial developmental system can develop a graph grammar into a modular ANN made of a combination of simpler subnetworks. A genetic ...
10.1038/nrn729
This paper presents graph grammar phenotype-to-genotype encodings that achieve highly compact encodings, leading to modular network architectures.
10.1177/1545968315583720
83,222,498
Background. Motor capability is commonly assessed inside the clinic, but motor performance in real-world settings (ie, outside of the clinic) is seldom assessed because measurement tools are lacking. Objective. To quantify real-world bilateral upper-limb (UL) activity in nondisabled adults and adults with stroke using ...
10.1038/nrn.2017.26
This study provides a clear demonstration, based on data from accelerometers worn on the wrists, of how dramatically stroke alters the use of the paretic and non-paretic hands.
10.1177/1545968312452631
42,619,343
Background. Constraint-induced movement therapy (CIMT) has proven effective in increasing functional use of the affected arm in patients with chronic stroke. The mechanism of CIMT is not well understood. Objective. To demonstrate, in a proof-of-concept study, the feasibility of using kinematic measures in conjunction w...
10.1038/nrn.2017.26
Findings from this study indicate that compensation underlies the improvements in paretic upper-limb function that result from CIMT.
10.1073/pnas.1514682113
17,295,046
We determined whether rehabilitation after cortical injury also drives dynamic dendritic and spine changes in functionally distinct subsets of neurons, resulting in functional recovery. Moreover, given known requirements for cholinergic systems in mediating complex forms of cortical plasticity, including skilled motor ...
10.1038/nrn.2017.26
This article provides an excellent example of the major neuronal structural changes in ipsilesional cortex that can result from motor skill training focused on the paretic forelimb, as examined in rats.
10.1177/1545968315624783
59,048,399
Background and objective. Prior studies have suggested that after stroke there is a time-limited period of increased responsiveness to training as a result of heightened plasticity—a sensitive period thought to be induced by ischemia itself. Using a mouse model, we have previously shown that most training-associated re...
10.1038/nrn.2017.26
This study in a mouse model provides particularly compelling support for the idea that there is a period after stroke during which there is increased sensitivity to the effects of rehabilitative training on paretic forelimb performance.
10.1126/science.1070502
60,045,943
In the insect olfactory system, oscillatory synchronization is functionally relevant and reflects the coherent activation of dynamic neural assemblies. We examined the role of such oscillatory synchronization in information transfer between networks in this system. The antennal lobe is the obligatory relay for olfactor...
10.1038/nrn1650
Direct experimental evidence for the functional significance of oscillatory synchronization.
10.1073/pnas.0407858101
4,417,771
Odor recognition encompasses both clustering and fine discrimination. Clustering joins together sets of odors, and fine discrimination distinguishes between odors belonging to the same cluster. We hypothesize that these two aspects of odor recognition are encoded in parallel by two brain areas of the insect olfactory s...
10.1038/nrn1650
A modelling study complementing the work on synchronization in the insect olfactory system and providing important information on the functional consequences of oscillatory synchronization.
10.1523/jneurosci.3907-04.2004
103,216,820
Inferior olivary (IO) neurons display spontaneous oscillatory activity, yet the importance of these oscillations for shaping the responses of this system to its afferents is uncertain. We used multiple electrode recording of crus 2a Purkinje cell complex spikes (CSs) in ketamine-xylazine-anesthetized rats to investigat...
10.1038/nrn1650
The authors studied the resonance properties of rat inferior olives to afferents from the motor cortex at varying frequencies and observed nonlinear effects.
10.1073/pnas.97.4.1867
38,270,566
Experimental and modeling efforts suggest that rhythms in the CA1 region of the hippocampus that are in the beta range (12–29 Hz) have a different dynamical structure than that of gamma (30–70 Hz). We use a simplified model to show that the different rhythms employ different dynamical mechanisms to synchronize, based o...
10.1038/nrn1650
Based on computational models, the authors describe properties of different frequencies of neuronal oscillations and the consequences for synchronization.
10.1523/jneurosci.3524-04.2004
82,952,957
The wake-sleep cycle, a spontaneous succession of global brain states that correspond to major overt behaviors, occurs in all higher vertebrates. The transitions between these states, at once rapid and drastic, remain poorly understood. Here, intracranial local field potentials (LFPs) recorded in the cortex, hippocampu...
10.1038/nrn1650
Intracranial LFP measurements in rats revealed specific spectral trajectories that are associated with specific brain states and their transitions.
10.1002/cne.902290106
60,166,998
Abstract The time course and specificity of the changes in dendritic morphology following deafferentation were examined in nucleus laminaris of young chickens. The dendrites of nucleus laminaris neurons are segregated into dorsal and ventral domains, which are innervated separately from the ipsilateral and contralatera...
10.1038/nrn941
This study clearly shows that afferent activity maintains dendritic structure in a highly localized manner in an in vivo system.
10.1152/jn.00501.2001
79,897,013
Saccades are typically separated by inter-saccadic fixation intervals (ISFIs) of ≥125 ms. During this time, the saccadic system selects a goal and completes the preparatory processes required prior to executing the subsequent movement. However, in tasks in which competing stimuli are presented, two sequentially execute...
10.1038/nrn1114
This paper shows that evidence of concurrent motor programming in behaviour is associated with competing motor plans in the activity of superior colliculus neurons.
10.1146/annurev.neuro.22.1.241
79,458,086
▪ Abstract We review neural correlates of perceptual and motor decisions, examining whether the time they occupy explains the duration and variability of behavioral reaction times. The location of a salient target is identified through a spatiotemporal evolution of visually evoked activation throughout the visual syste...
10.1038/nrn1114
An excellent review article describing target selection and visual masking.
10.1152/jn.00657.2002
17,671,534
When saccadic eye movements are made in a search task that requires selecting a target from distractors, the movements show greater curvature in their trajectories than similar saccades made to single stimuli. To test the hypothesis that this increase in curvature arises from competitive interactions between saccade go...
10.1038/nrn1114
This paper shows that competing motor plans in the superior colliculus are associated with saccadic curvature in spontaneous behaviour and demonstrates that artificially providing a competing motor plan also produces curvature.
10.1162/089892902760807249
86,382,341
The phenomenon of inhibition of return (IOR) has generated considerable interest in cognitive neuroscience because of its putative functional role in visual search, that of placing inhibitory tags on objects that have been recently inspected so as to direct further search to novel items. Many behavioral parameters of t...
10.1038/nrn1114
This paper was the first to show that inhibition of return results from reduced target-related activity in the superior colliculus.
10.1126/science.1962197
18,541,165
Inferior temporal (IT) cortex is critical for visual memory, but it is not known how IT neurons retain memories while new information is streaming into the visual system. Single neurons were therefore recorded from IT cortex of two rhesus monkeys performing tasks that required them to hold items in memory while concurr...
10.1038/nrn1114
This was the first study to consider that attenuated object-related processing in visual areas was linked to repetition priming.
10.1126/science.274.5286.427
38,402,700
When humans respond to sensory stimulation, their reaction times tend to be long and variable relative to neural transduction and transmission times. The neural processes responsible for the duration and variability of reaction times are not understood. Single-cell recordings in a motor area of the cerebral cortex in b...
10.1038/nrn1114
This study tests different models of reaction time and shows that the variable rise-to-threshold model best fits the neurophysiological data.
10.1152/jn.00258.2001
80,713,828
Synaptic transmission in the neocortex is dynamic, such that the magnitude of the postsynaptic response changes with the history of the presynaptic activity. Therefore each response carries information about the temporal structure of the preceding presynaptic input spike train. We quantitatively analyze the information...
10.1038/nrn1475
This modelling study used experimentally determined parameters of depressing and facilitating cortical synapses to examine the dependence of postsynaptic firing on the history of presynaptic firing. Depressing and facilitating synapses produce maximum information in their postsynaptic responses at different presynaptic...
10.1152/jn.00562.2003
79,424,985
Retinal ganglion cells (RGC) transmit visual signals to thalamocortical relay neurons in the lateral geniculate nucleus via retinogeniculate synapses. Relay neuron spike patterns do not simply reflect those of RGCs, but the mechanisms controlling this transformation are not well understood. We therefore examined synapt...
10.1038/nrn1475
This follow up to reference 9 used current- and dynamic-clamp recordings to study the effects of single RGC inputs on the firing of thalamocortical neurons in brain slice. The AMPA component of the EPSC elicited precisely timed spikes whereas the NMDA component allowed a single presynaptic spike to evoke brief bursts o...
10.1073/pnas.89.24.12180
20,807,371
Infection by certain human papillomavirus types is regarded as the major risk factor in the development of cervical cancer, one of the most common cancers of women worldwide. Analysis of the immunogenic and structural features of papillomavirus virions has been hampered by the inability to efficiently propagate the vir...
10.1038/nrmicro2872
The initial report of self-assembly of L1 VLPs and their induction of high-titre neutralizing antibodies.
10.1073/pnas.0908502106
101,054,588
Using a murine challenge model, we previously determined that human papillomavirus (HPV) pseudovirions initially bind preferentially to the cervicovaginal basement membrane (BM) at sites of trauma. We now report that the capsids undergo a conformational change while bound to the BM that results in L2 cleavage by a prop...
10.1038/nrmicro2872
This article describes the unique mechanism of HPV infection of cervicovaginal tissue in vivo
10.1152/ajpregu.1980.238.5.r333
61,266,782
The effects of intravenous infusion of hypertonic NaCl, sucrose, glucose, urea, or isotonic NaCl solution on thirst and plasma arginine vasopressin concentration (AVP) were studied in five conscious dogs. The changes in osmolality and sodium concentration of plasma and cerebrospinal fluid (CSF) were measured at the thr...
10.1038/nrn2400
This study examined the effects of intravenous infusions of various solutions on changes in thirst and VP release, together with changes in the composition of the cerebrospinal fluid. The data indicated that cerebral osmoreceptors that mediate thirst and VP release are located on the blood side of the blood–brain barri...