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10.1111/jnc.13266
28,932,717
Abstract Substantial progress has been made in the genetic basis of Parkinson's disease ( PD ). In particular, by identifying genes that segregate with inherited PD or show robust association with sporadic disease, and by showing the same genes are found on both lists, we have generated an outline of the cause of this ...
10.1038/nrn.2016.178
The authors review the proposition that many known PD-related genes can be assigned to pathways that affect autophagy and mitochondrial quality control through mitophagy.
10.1002/mds.26239
60,868,532
Abstract Familial cases of Parkinson's disease (PD) can be associated with overexpression or mutation of α‐synuclein, a synaptic protein reported to be localized mainly in the cytosol and mitochondria. We recently showed that wild‐type α‐synuclein is not present in mitochondria, as previously thought, but rather is loc...
10.1038/nrn.2016.178
This review advances thenovel concept that α-syn affects neuronal function by modulating endoplasmic reticulum–mitochondrial crosstalk.
10.1128/jb.184.4.1140-1154.2002
83,553,832
ABSTRACT Complementary approaches were employed to characterize transitional episodes in Pseudomonas aeruginosa biofilm development using direct observation and whole-cell protein analysis. Microscopy and in situ reporter gene analysis were used to directly observe changes in biofilm physiology and to act as signposts ...
10.1038/nrmicro821
Linked structural development with protein expression in Pseudomonas biofilms thereby demonstrating that biofilms can have regulated 'life-cycles'.
10.1126/science.280.5361.295
104,407,002
Bacteria in nature often exist as sessile communities called biofilms. These communities develop structures that are morphologically and physiologically differentiated from free-living bacteria. A cell-to-cell signal is involved in the development of Pseudomonas aeruginosa biofilms. A specific signaling mutant, a lasI ...
10.1038/nrmicro821
Demonstrated that cell–cell communication molecules, associated with the production of virulence factors, have a role in the structure of Pseudomonas biofilms, opening the concept that biofilm structure was genetically regulated.
10.1146/annurev.micro.57.030502.090720
20,450,833
▪ Abstract The role of biofilms in the pathogenesis of some chronic human infections is now widely accepted. However, the criteria used to determine whether a given infection is caused by biofilms remain unclear. In this chapter we discuss three infections that are caused by biofilms—infectious kidney stones, bacterial...
10.1038/nrmicro821
Discusses biofilm pathogenesis and defines some clinical criteria for classifying infections with a biofilm aetiology.
10.1046/j.1365-2958.2002.02827.x
62,083,978
Summary The genetic and molecular basis of biofilm formation in staphylococci is multifaceted. The ability to form a biofilm affords at least two properties: the adherence of cells to a surface and accumulation to form multilayered cell clusters. A trademark is the production of the slime substance PIA, a polysaccharid...
10.1038/nrmicro821
An excellent review of staphylococcal biofilms and the molecular mechanisms of adhesion and biofilm development in staphylococci.
10.1128/iai.28.2.546-556.1980
41,612,688
Direct electron microscopic examination of postmortem lung material from cystic fibrosis patients infected with Pseudomonas aeruginosa has shown that these bacterial cells form distinct fiber-enclosed microcolonies in the infected alveoli. Similar examination of bronchoscopy material from infected cystic fibrosis patie...
10.1038/nrmicro821
A seminal paper suggesting Pseudomonas pneumonia in cystic fibrosis is a biofilm infection.
10.1128/aem.64.10.4035-4039.1998
18,946,424
ABSTRACT The role of oxygen availability in determining the local physiological activity of Pseudomonas aeruginosa growing in biofilms was investigated. Biofilms grown in an ambient-air environment expressed approximately 1/15th the alkaline phosphatase specific activity of planktonic bacteria subjected to the same pho...
10.1038/nrmicro821
Showed that biofilm cells could exhibit a wide range of physiologies from stationary phase to a highly active phase over very small distances (micrometres), due to the heterogeneity in nutrient distribution (in this case, oxygen) resulting from the mass transfer characteristics and the shape of the biofilm microcolonie...
10.1523/jneurosci.4934-08.2009
17,686,680
In humans, tobacco withdrawal produces symptoms that contribute to the difficulty associated with smoking cessation. Nicotine withdrawal symptoms can also be observed in rodents. A major standing question is which nicotinic receptor subtypes and which areas of the brain are necessary for nicotine withdrawal to occur. U...
10.1038/nrn2849
This study provides evidence for a role of the habenulo–interpeduncular system in nicotine withdrawal.
10.1111/j.1601-183x.2005.00176.x
18,906,300
Patients with schizophrenia exhibit deficits in a range of cognitive functions, particularly working and episodic memory, which are thought to be core features of the disorder. Memory dysfunction in schizophrenia is familial and thus a promising endophenotype for genetic studies. Both human and animal studies suggest a...
10.1038/nrn2849
An elegant demonstration of the contribution of the α7 nAChR subunit to working memory.
10.1523/jneurosci.2950-09.2009
103,216,546
Active response to either natural or pharmacological reward causes synaptic modifications to excitatory synapses on dopamine (DA) neurons of the ventral tegmental area (VTA). Here, we examine these modifications using nicotine, the main addictive component of tobacco, which is a potent regulator of VTA DA neurons. Usin...
10.1038/nrn2849
An in vivo analysis of the top-down regulation of short-term to long-term nicotine consumption in the rat.
10.1523/jneurosci.2402-07.2007
61,483,494
Prenatal exposure to maternal smoking has been linked to cognitive and auditory processing deficits in offspring. Preclinical studies have demonstrated that exposure to nicotine disrupts neurodevelopment during gestation and adolescence, possibly by disrupting the trophic effects of acetylcholine. Given recent clinical...
10.1038/nrn2849
This study demonstrates the long-term consequences of tobacco smoking on white matter organization.
10.1038/ismej.2007.2
20,591,009
Abstract Owing to their vast diversity and as-yet uncultivated status, detection, characterization and quantification of microorganisms in natural settings are very challenging, and linking microbial diversity to ecosystem processes and functions is even more difficult. Microarray-based genomic technology for detecting...
10.1038/nrmicro2575
A description of the first comprehensive functional gene array, GeoChip 2.0, and its application for tracking the dynamics of metal-reducing bacteria during in situ bioremediation of a uranium-contaminated site.
10.1073/pnas.0908456107
104,116,915
Mutualistic interactions are taxonomically and functionally diverse. Despite their ubiquity, however, the basic ecological and evolutionary processes underlying their origin and maintenance are poorly understood. A major reason for this is the lack of an experimentally tractable model system. We examine the evolution o...
10.1038/nrmicro2575
The first example of syntrophy evolution observed in real time. This paper is a good example of how research on a Desulfovibrio sp. model system can both affect microbiology and address broad questions in evolutionary biology.
10.1038/ismej.2009.154
82,800,997
Abstract Understanding adaptation of biological communities to environmental change is a central issue in ecology and evolution. Metagenomic analysis of a stressed groundwater microbial community reveals that prolonged exposure to high concentrations of heavy metals, nitric acid and organic solvents (∼50 years) has res...
10.1038/nrmicro2575
The first community-level analysis to document the impact of anthropogenic change on microbial communities and to demonstrate the importance of lateral gene transfer in the adaptation of a microbial community to environmental change.
10.1128/jb.180.11.2975-2982.1998
19,311,436
ABSTRACT Microorganisms that use sulfate as a terminal electron acceptor for anaerobic respiration play a central role in the global sulfur cycle. Here, we report the results of comparative sequence analysis of dissimilatory sulfite reductase (DSR) genes from closely and distantly related sulfate-reducing organisms to ...
10.1038/nrmicro2575
This paper develops the general approach for using the dsrAB genes to characterize the diversity of natural populations of sulphate-reducing microorganisms. Many of the sequences on the GeoChip were derived from these environmental sequences.
10.1038/ismej.2010.46
122,682,597
Abstract A new generation of functional gene arrays (FGAs; GeoChip 3.0) has been developed, with ∼28 000 probes covering approximately 57 000 gene variants from 292 functional gene families involved in carbon, nitrogen, phosphorus and sulfur cycles, energy metabolism, antibiotic resistance, metal resistance and organic...
10.1038/nrmicro2575
This article marks the release of an updated GeoChip 3.0, with details for selected gene families, and describes its use to analyse the effects of plant diversity on the functional diversity and structure of soil microbial communities.
10.1126/science.1195979
20,682,601
Diving into Deep Water The Deepwater Horizon oil spill in the Gulf of Mexico was one of the largest oil spills on record. Its setting at the bottom of the sea floor posed an unanticipated risk as substantial amounts of hydrocarbons leaked into the deepwater column. Three separate cruises identified and sampled deep und...
10.1038/nrmicro2575
This paper details the use of GeoChip 4.0 and other technologies to examine the potential of indigenous microbial communities to degrade contaminants from the oil spill in the Gulf of Mexico.
10.1126/scitranslmed.3007653
41,515,757
The antioxidants acetylcysteine and vitamin E accelerate tumor progression and reduce survival in mouse models of lung cancer by disrupting the ROS-p53 axis.
10.1038/nrneph.2017.59
Discussion of the possibility that antioxidants can worsen cancer; this effect might be related to glutamine reprogramming to the glutathione pathway.
10.1002/ijc.22322
19,926,021
Abstract Recently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable. The efficacy of its antitumor activity largely depends on the level of intracellular ...
10.1038/nrneph.2017.59
The first description of the use of ADI-PEG to target arginine reprogramming in a murine homograft RCC model.
10.1073/pnas.1507228112
124,228,163
The MYC oncogene is frequently mutated and overexpressed in human renal cell carcinoma (RCC). However, there have been no studies on the causative role of MYC or any other oncogene in the initiation or maintenance of kidney tumorigenesis. Here, we show through a conditional transgenic mouse model that the MYC oncogene,...
10.1038/nrneph.2017.59
Discussion of the interaction of c-Myc with glutamine reprogramming in RCC.
10.1093/oso/9780198566960.001.0001
149,038,195
Abstract In the past 15 years parts of the cingulate cortex have been activated in thousands of neuroimaging studies and it has become a primary site of interest in structural and functional analyses of many neurological and psychiatric diseases. There are now more then 20 times the number of annual publications that a...
10.1038/nrn2733
A chapter from a recent book devoted to the entire cingulate cortex, of which the RSC is a component area. This is the first book devoted to the neurobiology of this region since 1993.
10.1002/cne.21346
124,297,919
Abstract We have investigated the cortical efferent projections of the macaque monkey retrosplenial and posterior cingulate cortices by using 3 H‐amino acids as anterograde tracers. All the injections produced extensive local connections to other portions of this region. There were also a number of extrinsic efferent c...
10.1038/nrn2733
The final paper in a series of three that provide the most detailed descriptions to date of the inputs to the RSC in an Old World monkey brain.
10.1111/j.1460-9568.2009.06881.x
19,150,791
Abstract The present study revealed striking task‐dependent differences in immediate‐early gene activity in the two main subregions (granular and dysgranular) of the retrosplenial cortex. In addition, there were activity differences along the rostro‐caudal axis of both subregions. Two groups of rats were trained on a w...
10.1038/nrn2733
Rats were trained on spatial working memory tasks or control tasks, in the radial-arm maze, in either the presence or the absence of visual cues (that is, in the light or in the dark). There was increased immediate-early gene activity in the granular RSC in the working memory group both in the light and in the dark con...
10.1111/1467-9450.00233
60,970,070
The clinical and neuroimaging literatures are surveyed in order to collate for the first time the available data on retrosplenial involvement in human navigation. Several notable features emerge from consideration of the case reports of relatively pure topographical disorientation in the presence of a retrosplenial les...
10.1038/nrn2733
A range of single case reports of patients with RSC damage are reviewed. The effect on the patients' spatial navigation is considered in conjunction with functional neuroimaging studies of navigation that results in RSC activation.
10.1098/rstb.2001.0948
17,592,499
The computational role of the hippocampus in memory has been characterized as: (i) an index to disparate neocortical storage sites; (ii) a time–limited store supporting neocortical long–term memory; and (iii) a content–addressable associative memory. These ideas are reviewed and related to several general aspects of ep...
10.1038/nrn2733
Presents a neural-level model of the medial temporal and parietal roles in retrieval of the spatial context of an event. The central tenet is that medial temporal allocentric representations are used in long-term storage, whereas parietal egocentric representations are used to imagine, manipulate and re-experience the ...
10.1073/pnas.0710279105
82,812,418
The fresh water discharged by large rivers such as the Amazon is transported hundreds to thousands of kilometers away from the coast by surface plumes. The nutrients delivered by these river plumes contribute to enhanced primary production in the ocean, and the sinking flux of this new production results in carbon sequ...
10.1038/nrmicro2594
A paper detailing how the Amazon River enhances N 2 fixation and how the different diazotrophs present affect carbon sequestration in the area.
10.1111/j.1758-2229.2009.00016.x
124,945,729
Summary Approximately 50% of the global natural fixation of nitrogen occurs in the oceans supporting a considerable part of the new primary production. Virtually all nitrogen fixation in the ocean occurs in the tropics and subtropics where the surface water temperature is 25°C or higher. It is attributed almost exclusi...
10.1038/nrmicro2594
An intriguing paper presenting a hypothesis to explain why free-living heterocystous cyanobacteria are found in cold waters and non-heterocystous filamentous cyanobacteria are found in warm waters.
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/nrn2698
The first identification of the canonical stripe antigen zebrin II. The zones and stripes revealed by the zebrin II expression map are widely used as a reference frame to correlate maps derived from different experimental techniques.
10.1002/cne.901740304
82,958,845
Abstract After lesions of inferior olive, survival times of 5 to 12 days and Nauta staining, degeneration is present in white matter and central cerebellar nuclei and Deiters' nucleus. Shorter survival times from 40 to 60 hours and Fink‐Heimer impregnation reveal degenerating climbing fiber terminals in the molecular l...
10.1038/nrn2698
One of the earlier anatomical studies by Voogd's group that provides important evidence to support the concept of longitudinal zones. The topography of olivocerebellar projections was systematically mapped in cats using degeneration and tritiated leucine methods. Small parts of the inferior olive were found to provide ...
10.1113/jphysiol.1994.sp020126
4,617,588
The purpose of the present work was to identify sites in the cerebellar cortex which are likely to control eyeblink. This work was motivated by findings suggesting that the cerebellum is involved in the learning and/or performance of the classically conditioned eyeblink response. The identification was based on climbin...
10.1038/nrn2698
An electrophysiological mapping study in decerebrate cats that demonstrates the existence of four spatially separate 'eyeblink' microzones on each side of the cerebellar cortex. It shows a close topographical correspondence between climbing fibre input from the ipsilateral periorbital area and motor output to control m...
10.1523/jneurosci.23-11-04645.2003
80,291,985
Individual cerebellar cortical zones defined by the somatotopy of climbing fiber responses and by their olivo-cortico-nuclear connections located in the paramedian lobule and the copula pyramidis of the rat cerebellum were microinjected with cholera toxin B subunit. Collateral branches of climbing and mossy fibers were...
10.1038/nrn2698
A combined electrophysiological and neuroanatomical tract tracing study in rats, presenting evidence that collateral branches of climbing fibres and mossy fibres associated with a particular longitudinal zone have a congruent spatial organization within the cerebellar cortex that relates to zebrin II stripes, suggestin...
10.1126/science.1114383
20,820,469
Organisms in fluctuating environments must constantly adapt their behavior to survive. In clonal populations, this may be achieved through sensing followed by response or through the generation of diversity by stochastic phenotype switching. Here we show that stochastic switching can be favored over sensing when the en...
10.1038/nrmicro2504
A theoretical analysis of the conditions that select for responsive versus spontaneous initiation of dormancy.
10.1073/pnas.0706787104
101,658,255
Recent claims of cultivable ancient bacteria within sealed environments highlight our limited understanding of the mechanisms behind long-term cell survival. It remains unclear how dormancy, a favored explanation for extended cellular persistence, can cope with spontaneous genomic decay over geological timescales. Ther...
10.1038/nrmicro2504
Strong empirical evidence for ancient ( ∼ 0.5 million years old) and viable bacteria in permafrost samples.
10.1073/pnas.95.15.8916
103,959,280
Viable cells of Micrococcus luteus secrete a factor, which promotes the resuscitation and growth of dormant, nongrowing cells of the same organism. The resuscitation-promoting factor (Rpf) is a protein, which has been purified to homogeneity. In picomolar concentrations, it increases the viable cell count of dormant M....
10.1038/nrmicro2504
This article describes the isolation of a quorum sensing protein that is responsible for resuscitating dormant bacteria.
10.1126/science.1195227
20,662,519
α-Synuclein and Aging Transgenic α-synuclein can reverse the otherwise lethal neurodegeneration of cysteine string protein-α knockout mice via changes in SNARE proteins, which mediate synaptic vesicle release. Using experiments with purified recombinant proteins, triple αβγ-synuclein knockout mice, and studies of mouse...
10.1038/nrn3406
This paper identifies α-synuclein as a non-classical chaperone that binds and promotes SNARE-complex assembly.
10.1073/pnas.90.23.11282
20,541,939
A neuropathological hallmark of Alzheimer disease (AD) is a widespread amyloid deposition. We analyzed the entire amino acid sequences in an amyloid preparation and found, in addition to the major beta/A4-protein (A beta) fragment, two unknown peptides. We raised antibodies against synthetic peptides using subsequences...
10.1038/nrn3406
This is the first report of the NAC being a 140-amino-acid protein.
10.1073/pnas.0908005106
41,620,662
Cytoplasmic inclusions containing α-synuclein (α-Syn) fibrils, referred to as Lewy bodies (LBs), are the signature neuropathological hallmarks of Parkinson's disease (PD). Although α-Syn fibrils can be generated from recombinant α-Syn protein in vitro, the production of fibrillar α-Syn inclusions similar to authentic L...
10.1038/nrn3406
These authors showed that α-syn seeds can recruit endogenous soluble α-syn protein to form pathological species.
10.1126/science.1101738
82,980,469
Aberrant α-synuclein degradation is implicated in Parkinson's disease pathogenesis because the protein accumulates in the Lewy inclusion bodies associated with the disease. Little is known, however, about the pathways by which wild-type α-synuclein is normally degraded. We found that wild-type α-synuclein was selective...
10.1038/nrn3406
This paper identified lysosomes for degradation of wild-type α-syn by the chaperone-mediated autophagy pathway.
10.1111/j.1742-4658.2012.08489.x
41,579,012
Parkinson’s disease (PD) and dementia with Lewy bodies are common disorders of the aging population and characterized by the progressive accumulation of α‐synuclein (α‐syn) in the central nervous system. Aggregation of α‐syn into oligomers with a ring‐like appearance has been proposed to play a role in toxicity. Howeve...
10.1038/nrn3406
Computational modelling shows that α-synuclein can form ring-like structures that penetrate the membrane.
10.1523/jneurosci.16-03-01173.1996
18,183,421
Both the dorsomedial hypothalamic nucleus (DMH) and the paraventricular hypothalamic nucleus (PVN) have been implicated in the neural control of the cardiovascular response to stress. We used the GABAA agonist muscimol to inhibit neuronal activation and attempted to identify hypothalamic nuclei required for the cardiov...
10.1038/nrn2647
One of several excellent papers from the DiMicco laboratory demonstrating the importance of the DMH in stress regulation. This study used a microinjection strategy to prove the primacy of the DMH in regulating cardiovascular stress responses. See other papers from this group for more information.
10.1046/j.0953-816x.2001.01733.x
100,394,744
Abstract It has been hypothesized that the brain categorizes stressors and utilizes neural response pathways that vary in accordance with the assigned category. If this is true, stressors should elicit patterns of neuronal activation within the brain that are category‐specific. Data from previous immediate–early gene e...
10.1038/nrn2647
A key paper from the Day laboratory, demonstrating that lesions of the MeA but not the CeA block ACTH responses and PVN activation by psychogenic stress.
10.1523/jneurosci.4297-06.2006
29,281,964
The medial prefrontal cortex (mPFC) is an important neural substrate for integrating cognitive-affective information and regulating the hypothalamo–pituitary–adrenal (HPA) axis response to emotional stress. mPFC modulation of stress responses is effected in part via the paraventricular hypothalamic nucleus (PVH), which...
10.1038/nrn2647
The most recent paper on the role of the medial prefrontal cortex in stress regulation, showing differential actions of the dorsal and the ventromedial prefrontal cortex in HPA axis inhibition and activation of PVN preautonomic neurons, respectively.
10.1073/pnas.0406458102
39,741,664
Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is a hallmark of major depressive disorder. A number of studies have shown that this dysregulation is correlated with impaired forebrain glucocorticoid receptor (GR) function. To determine whether a primary, acquired deficit in forebrain GR signaling is an ...
10.1038/nrn2647
Used a region-specific knockout mouse to indicate the requirement of the hippocampal and cortical GR in normal stress termination and glucocorticoid negative feedback.
10.1523/jneurosci.4301-06.2007
102,947,352
Limbic and cortical neurocircuits profoundly influence hypothalamic–pituitary–adrenal (HPA) axis responses to stress yet have little or no direct projections to the hypothalamic paraventricular nucleus (PVN). Numerous lines of evidence suggest that the bed nucleus of the stria terminalis (BST) is well positioned to rel...
10.1038/nrn2647
A paper from our group demonstrating selective involvement of distinct BST cell populations in activation and inhibition of HPA axis stress responses.
10.1002/cne.903320102
20,556,771
Abstract The axonal projections of the ventral subiculum to the bed nucleus of the stria terminalis (BST) were examined in the rat with the anterograde neuronal tracer Phaseolus vulgaris ‐ leucoagglutinin (PHA‐L). Axons originating in the ventral subiculum coursed to the BST through either the fimbria‐fornix, or a path...
10.1038/nrn2647
This study used dual tracing methods to demonstrate innervation of PVN-projecting neurons by ventral subiculum (that is, hippocampal) efferents. It also documented the predominantly GABAergic phenotype of most PVN-projecting regions in the BST.
10.1152/ajpregu.00614.2001
44,370,318
Depressed patients with and without a history of cardiovascular pathology display signs, such as elevated heart rate, decreased heart rate variability, and increased physiological reactivity to environmental stressors, which may indicate a predisposition to cardiovascular disease. The specific physiological mechanisms ...
10.1038/nrn2647
A demonstration of the influence of chronic stress on autonomic function in the rat.
10.1101/gad.1709408
38,735,037
Previous studies of synaptonemal complex assembly in budding yeast have suggested that chromosome synapsis initiates at the sites of crossing over. The data presented here, however, indicate that centromeric regions are preferred sites for synapsis initiation. At early times during meiosis in wild type, the Zip1 protei...
10.1038/nsmb.3208
This paper shows that the SC is initially assembled at centromeres through a recombination-independent mechanism, thus suggesting that there are two classes of SC assembly in yeast
10.1083/jcb.201506103
81,993,429
During meiotic prophase I, proteinaceous structures called synaptonemal complexes (SCs) connect homologous chromosomes along their lengths via polymeric arrays of transverse filaments (TFs). Thus, control of TF polymerization is central to SC formation. Using budding yeast, we show that efficiency of TF polymerization ...
10.1038/nsmb.3208
This paper provides evidence that a positive feedback mechanism may drive SC extension, results supporting the well-known self-assembly properties of the SC
10.1083/jcb.200410144
41,477,805
Homologous chromosome pairs (bivalents) undergo restructuring during meiotic prophase to convert a configuration that promotes crossover recombination into one that promotes bipolar spindle attachment and localized cohesion loss. We have imaged remodeling of meiotic chromosome structures after pachytene exit in Caenorh...
10.1038/nsmb.3208
This paper determines that the crossover is the symmetry-breaking event triggering the asymmetric disassembly of the SC
10.1126/science.1120847
80,403,066
How do animals discriminate self-generated from external stimuli during behavior and prevent desensitization of their sensory pathways? A fundamental concept in neuroscience states that neural signals, termed corollary discharges or efference copies, are forwarded from motor to sensory areas. Neurons mediating these si...
10.1038/nrn2457
This report is one of a series of elegant studies carried out by the authors in which they homed in on, and both anatomically and physiologically identified, a CDI in the cricket auditory system.
10.1126/science.7291985
109,170,776
In electric fish of the mormyrid family, an efference copy is present in the brain region that receives afferent input from ampullary electroreceptors. The efference copy is elicited by the motor command to fire the electric organ. Its effect is always opposite that of ampullary afferents responding to the electric org...
10.1038/nrn2457
This was a pioneering study that unveiled a plastic CD in the mormyrid that was modifiable by recent sensory experience.
10.1126/science.1069590
62,067,169
It is essential to keep track of the movements we make, and one way to do that is to monitor correlates, or corollary discharges, of neuronal movement commands. We hypothesized that a previously identified pathway from brainstem to frontal cortex might carry corollary discharge signals. We found that neuronal activity ...
10.1038/nrn2457
This was the first study to identify a CD pathway in the primate brain.
10.1073/pnas.90.24.11688
16,765,125
Glutamate mediates fast synaptic transmission at the majority of excitatory synapses throughout the central nervous system by interacting with different types of receptor channels. Cloning of glutamate receptors has provided evidence for the existence of several structurally related subunit families, each composed of s...
10.1038/nrn3335
These authors, for the first time, recorded pharmacologically isolated kainate receptor-mediated currents from neurons derived from the CNS using a newly developed non-competitive AMPA receptor antagonist, thereby setting the stage for subsequent detection of postsynaptic kainate receptors.
10.1146/annurev.neuro.24.1.203
20,784,016
▪ Abstract Binocular disparity provides the visual system with information concerning the three-dimensional layout of the environment. Recent physiological studies in the primary visual cortex provide a successful account of the mechanisms by which single neurons are able to signal disparity. This work also reveals tha...
10.1038/nrn2131
A core review article that comprehensively and critically summarises the field.
10.1152/jn.01042.2003
19,704,133
Stereoscopic vision relies mainly on relative depth differences between objects rather than on their absolute distance in depth from where the eyes fixate. However, relative disparities are computed from absolute disparities, and it is not known where these two stages are represented in the human brain. Using functiona...
10.1038/nrn2131
This ingenious paper made a clear quantitative justification for a division of stereoscopic depth functions between the dorsal and ventral streams on the basis of human fMRI results.
10.1152/jn.2001.85.5.2245
95,547,677
Single-unit discharges were recorded in the medial superior temporal area (MST) of five behaving monkeys. Brief (230-ms) horizontal disparity steps were applied to large correlated or anticorrelated random-dot patterns (in which the dots had the same or opposite contrast, respectively, at the two eyes), eliciting verge...
10.1038/nrn2131
An elegant analysis that demonstrates that the firing within the neuronal population of MST is sufficient to account for the vergence eye movement responses to binocularly correlated and anticorrelated visual patterns.
10.1126/science.2396096
2,602,952
The possibility has been explored that a subset of physiologically identifiable cells in the visual cortex is especially suited for the processing of stereoscopic depth information. First, characteristics of a disparity detector that would be useful for such processing were outlined. Then, a method was devised by which...
10.1038/nrn2131
A highly influential and successful model of the responses of disparity-selective neurons in the primary visual cortex.
10.1038/jcbfm.2009.240
18,685,617
Chemokines and their receptors have crucial roles in the trafficking of leukocytes, and are of particular interest in the context of the unique immune responses elicited in the central nervous system (CNS). The chemokine system CC ligand 2 (CCL2) with its receptor CC receptor 2 (CCR2), as well as the receptor CXCR2 and...
10.1038/nrneurol.2017.13
Excellent review on the several crucial roles of chemokines and their receptors in response to traumatic brain injury, with a focus on two of the best-studied chemokines, CCL2 and CXCL8.
10.1186/1742-2094-9-137
101,458,360
Abstract The complement system, a major component of the innate immune system, is becoming increasingly recognised as a key participant in physiology and disease. The awareness that immunological mediators support various aspects of both normal central nervous system (CNS) function and pathology has led to a renaissanc...
10.1038/nrneurol.2017.13
Review of complement activation and dysregulation after brain and spinal cord injury, including several complement-targeted therapeutics.
10.1158/1078-0432.ccr-13-2308
99,861,648
Abstract Purpose: To investigate the impact of prostate cancer cell surface glycosylation as part of the tumor cell–endothelial cell interaction in prostate cancer metastasis. Experimental Design: Glycosyltransferase expression was profiled in metastasis-derived prostate cancer cell lines and compared with primary epit...
10.1038/nrurol.2016.65
Positive binding of the Helix pomatia (HPA) lectin is associated with disease progression and metastasis in a range of cancer types; however, in prostate cancer, binding of HPA is reduced in metastatic disease and patients with HPA-negative tumours have worse overall survival and faster progression.
10.1073/pnas.95.20.11981
81,163,844
Aquaporin (AQP) water channels are abundant in the brain and spinal cord, where AQP1 and AQP4 are believed to play major roles in water metabolism and osmoregulation. Immunocytochemical analysis of the brain recently revealed that AQP4 has a highly polarized distribution, with marked expression in astrocyte end-feet th...
10.1038/nrn3468
This paper provides one of the earliest descriptions of AQP4 expression in the brain.
10.1084/jem.20050304
104,305,751
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serv...
10.1038/nrn3468
This study identifies AQP4 as the target of NMO autoantibodies.
10.1046/j.1600-0854.2003.00156.x
41,728,945
The uroepithelium lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, where it forms a tight barrier that allows for retention of urine, while preventing the unregulated movement of ions, solutes, and toxic metabolites across the epithelial barrier. In the case of the bladder, the permeab...
10.1038/nrn2401
This is an excellent review of the properties of the urothelium.
10.1111/j.1469-7793.1997.503bb.x
87,060,699
The responses of rabbit urinary bladder to hydrostatic pressure changes and to electrical stimulation have been investigated using both the Ussing chamber and a superfusion apparatus. These experiments enabled us to monitor changes in both ionic transport across the tissue and cellular ATP release from it. The urinary ...
10.1038/nrn2401
This was the first study to show the release of ATP from the urothelium.
10.1046/j.1464-410x.2003.03802.x
79,727,799
OBJECTIVES To describe the ultrastructure and relationship to nerves of the myofibroblast in the human bladder lamina propria, and discuss its possible role in bladder function, including sensing stretch, as the response of the bladder to stretch has been thoroughly investigated by afferent nerve recordings, but specia...
10.1038/nrn2401
In this paper, meticulous ultrastructural studies that identified myofibroblasts in the human bladder led to the hypothesis that these myofibroblasts form a structure that has the necessary characteristics to constitute the stretch receptor that signals bladder distension.
10.1002/cne.20753
124,074,372
Abstract The central control of the bladder is a complex, multilevel process. Recent advances in functional brain imaging have allowed research into this control in humans. This article reviews the functional imaging studies published to date and discusses the regions of the brain that have been implicated in the centr...
10.1038/nrn2401
This is a comprehensive review of brain-imaging studies related to the CNS control of micturition.
10.1146/annurev.pharmtox.41.1.691
81,496,539
The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the urinary bladder, urethra, and external urethral sphincter. This activity is in turn controlled by neural circuits in the brain, spinal cord, and peripheral ganglia. Vari...
10.1038/nrn2401
This is a comprehensive review of the pharmacology of the lower urinary tract.
10.1126/science.170679
109,447,717
Bacteria with motility directed by the local geomagnetic field have been observed in marine sediments. These magnetotactic microorganisms possess flagella and contain novel structured particles, rich in iron, within intracytoplasmic membrane vesicles. Conceivably these particles impart to cells a magnetic moment. This ...
10.1038/nrmicro842
The first report to describe the phenomenon of magnetotaxis in bacteria.
10.1128/jb.141.3.1399-1408.1980
122,399,399
The ultrastructure of a magnetotactic bacterium (strain MS-1) was examined by transmission, scanning, and scanning-transmission electron microscopy. The organism resembled other spirilla in general cell morphology, although some differences were detected at the ultrastructural level. Electron-dense particles within mag...
10.1038/nrmicro842
The first to describe the ultrastructural details of the magnetosome.
10.1126/science.203.4387.1355
82,930,558
A previously undescribed magnetotactic spirillum isolated from a freshwater swamp was mass cultured in the magnetic as well as the nonmagnetic state in chemically defined culture media. Results of Mössbauer spectroscopic analysis applied to whole cells identifies magnetite as a constituent of these magnetic bacteria.
10.1038/nrmicro842
This pioneering paper not only describes the discovery of magnetite in bacteria but also represents the first report of metal crystals in bacteria.
10.1126/science.259.5096.803
102,452,031
Magnetosomes are intracellular, iron-rich, membrane-enclosed magnetic particles that allow magnetotactic bacteria to orient in the earth's geomagnetic field as they swim. The magnetosomes of most magnetotactic bacteria contain iron oxide particles, but some magnetotactic species contain iron sulfide particles instead. ...
10.1038/nrmicro842
The first and only paper so far to report the phylogenetic analysis of a greigite-producing magnetotactic bacterium.
10.1126/science.285.5435.1892
17,603,052
A series of carefully controlled laboratory studies was carried out to investigate oxygen and iron isotope fractionation during the intracellular production of magnetite (Fe 3 O 4 ) by two different species of magnetotactic bacteria at temperatures between 4° and 35°C under microaerobic and anaerobic conditions. No det...
10.1038/nrmicro842
This study shows that magnetotactic bacteria do not fractionate iron in magnetite magnetosomes.
10.1128/jb.170.2.834-841.1988
122,399,364
Intact magnetosomes of Aquaspirillum magnetotacticum were purified from broken cells by a magnetic separation technique. Electron microscopic and chemical analyses revealed the magnetite to be enclosed by a lipid bilayer admixed with proteins. Lipids were recovered in fractions expected to contain (i) neutral lipids an...
10.1038/nrmicro842
The first report of the presence of unique proteins in the magnetosome membrane and the first description of the magnetosome membrane as a lipid bilayer.
10.1111/j.1432-1033.1995.665_2.x
124,912,364
Cytochrome cd 1 , nitrite reductase was isolated from magnetite‐containing cells of the magnetotactic bacterium Magnetospirillum (formerly Aquaspirillum ) magnetotacticum , which was microaerobically cultivated under denitrifying conditions. The enzyme showed absorption maxima at 643 nm and 409 nm in the oxidized form,...
10.1038/nrmicro842
First evidence for a role of an enzyme involved in nitrogen oxide reduction in magnetite synthesis in a magnetotactic bacterium.
10.1126/science.273.5277.924
38,208,264
Fresh fracture surfaces of the martian meteorite ALH84001 contain abundant polycyclic aromatic hydrocarbons (PAHs). These fresh fracture surfaces also display carbonate globules. Contamination studies suggest that the PAHs are indigenous to the meteorite. High-resolution scanning and transmission electron microscopy st...
10.1038/nrmicro842
This paper provides several lines of evidence based on geological and chemical aspects of Martian meteorite ALH84001 that indicate that life existed on ancient Mars.
10.1530/jme-13-0064
82,122,762
Astrocytes exert a wide variety of functions with paramount importance in brain physiology. After injury or infection, astrocytes become reactive and they respond by producing a variety of inflammatory mediators that help maintain brain homeostasis. Loss of astrocyte functions as well as their excessive activation can ...
10.1038/nrn3657
This is a comprehensive review focusing on the anti-inflammatory and neuroprotective role of melanocortins in the CNS.
10.1111/gbb.12057
103,037,112
While it is known that mice lacking melanocortin 4 receptor ( MC4R ) expression develop hyperphagia resulting in early‐onset obesity, the specific neural circuits that mediate this process remain unclear. Here, we report that selective restoration of MC4R expression within dopamine‐1 receptor‐expressing neurons [ MC4R ...
10.1038/nrn3657
This study elucidates the physiological role of MC4R-mediated signalling within D1R-expressing neurons and the behavioural response to cocaine.
10.1073/pnas.1308195110
16,920,394
Compulsive behavior is a debilitating clinical feature of many forms of neuropsychiatric disease, including Tourette syndrome, obsessive-compulsive spectrum disorders, eating disorders, and autism. Although several studies link striatal dysfunction to compulsivity, the pathophysiology remains poorly understood. Here, w...
10.1038/nrn3657
This is the first study to show that constitutive and induced genetic deletion of MC4R normalizes compulsive grooming in SAPAP3-null mice, offering insights into the treatment of compulsive behavioural and eating disorders.
10.2337/db12-0598
103,016,822
The melanocortin-4 receptor (MC4R) is well recognized as an important mediator of body weight homeostasis. Activation of MC4R causes dramatic weight loss in rodent models, and mutations in human are associated with obesity. This makes MC4R a logical target for pharmacological therapy for the treatment of obesity. Howev...
10.1038/nrn3657
This study demonstrates, for the first time, that highly selective melanocortin peptide drugs can be used for the treatment of weight loss.
10.1073/pnas.89.21.10499
103,259,777
Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca(2+)-impermeable, Ca(2+)-permeable kainate...
10.1038/nrn1106
One of the earliest demonstrations that post-ischaemic modifications in neurotransmitter receptor structure influence excitotoxic neuronal death.
10.1073/pnas.88.24.11158
80,565,452
Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cere...
10.1038/nrn1106
The first study that used transgenic mice to demonstrate the importance of oxidative stress in ischaemic brain injury.
10.1126/science.7522345
102,952,492
The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased...
10.1038/nrn1106
The first study using knockout mouse technology to show that the neuronal isoform of nitric oxide synthase has a detrimental role in focal stroke.
10.1126/science.1072221
20,855,366
Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. PARP-1 is also a mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. We show that PARP-1 activation is required for translocation of apopt...
10.1038/nrn1106
This study shows important organelle cross-talk linking mitochondrial dysfunction, energy deficits related to PARP activation and caspase-independent cell death mediated by AIF.
10.1073/pnas.94.5.2007
18,016,649
The interleukin 1β converting enzyme (ICE) family plays a pivotal role in programmed cell death and has been implicated in stroke and neurodegenerative diseases. During reperfusion after filamentous middle cerebral artery occlusion, ICE-like cleavage products and tissue immunoreactive interleukin 1β (IL-1β) levels incr...
10.1038/nrn1106
The first study demonstrating proof-of-concept that pharmacological inhibition of caspases protects brain in experimental stroke models.
10.1097/00004647-200102000-00001
103,404,055
Programmed cell death (PCD) is an ordered and tightly controlled set of changes in gene expression and protein activity that results in neuronal cell death during brain development. This article reviews the molecular pathways by which PCD is executed in mammalian cells and the potential relation of these pathways to pa...
10.1038/nrn1106
A comprehensive review surveying the evidence for multiple pathways of apoptotic-like cell death in stroke.
10.1126/science.1073634
20,507,665
Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of neurodegenerative diseases and stroke. However, the mechanism of MMP activation remains unclear. We report that MMP activation involves S-nitrosylation. During cerebral ischemia in vivo, MMP-9 colocalized with neuronal nitric oxide synthase. S-Nitro...
10.1038/nrn1106
Provides evidence that NOS nitrosylates MMPs and mediates anoikis-like cell death in neurons, thereby providing a link between nitrosative stress and extracellular proteolysis.
10.1097/00004647-200107000-00009
60,562,646
The integrity of cerebral microvessels requires the close apposition of the endothelium to the astrocyte endfeet. Integrins α 1 β 1 and α 6 β 4 are cellular matrix receptors that may contribute to cerebral microvascular integrity. It has been hypothesized that focal ischemia alters integrin expression in a characterist...
10.1038/nrn1106
This study showed that microvascular injury was related to neuronal cell death and therefore linked the response of these two cell components of the neurovascular unit.
10.1097/00004647-199908000-00001
122,435,920
Contrary to previous dogmas, it is now well established that brain cells can produce cytokines and chemokines, and can express adhesion molecules that enable an in situ inflammatory reaction. The accumulation of neutrophils early after brain injury is believed to contribute to the degree of brain tissue loss. Support f...
10.1038/nrn1106
A comprehensive review of the multifaceted aspects of inflammation in cerebral ischaemia.
10.1038/sj.bjp.0701871
108,776,261
Excitotoxic and apoptotic mechanisms have been implicated in the pathophysiology of cerebral ischaemia. Both MK‐801, an NMDA receptor antagonist, or peptide inhibitors of the caspase family (z‐VAD.FMK and z‐DEVD.FMK), protect mouse brain from ischaemic cell damage. In this study, we examined whether these drugs which a...
10.1038/nrn1106
The first demonstration that anti-apoptosis agents can be combined with anti-excitotoxic therapies enhance benefit in experimental stroke.
10.1038/jcbfm.1987.127
18,801,886
We have tested whether small intraischemic variations in brain temperature influence the outcome of transient ischemia. To measure brain temperature, a thermocouple probe was placed stereotaxically into the left dorsolateral striatum of rats prior to 20 min of four-vessel occlusion. Rectal temperature was maintained at...
10.1038/nrn1106
The first demonstration that very small reductions in brain temperature profoundly protect against ischaemic injury, indicating that tissue survival was independent of lowered metabolic rate.
10.1073/pnas.95.15.8880
38,211,028
The treatment of ischemic strokes is limited to prophylactic agents that block the coagulation cascade. Here, we show that cholesterol-lowering agents, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, protect against cerebral injury by a previously unidentified mechanism involving the selective up-regulation ...
10.1038/nrn1106
This study showed that statins protect brain from ischaemic injury by directly upregulating endogenous eNOS levels and improving blood flow.
10.1126/science.1126548
103,697,799
Glycoprotein B (gB) is the most conserved component of the complex cell-entry machinery of herpes viruses. A crystal structure of the gB ectodomain from herpes simplex virus type 1 reveals a multidomain trimer with unexpected homology to glycoprotein G from vesicular stomatitis virus (VSV G). An α-helical coiled-coil c...
10.1038/nrmicro2548
Determines the structure of HSV-1 gB, providing the first direct evidence that herpesvirus gB is a viral fusion protein.
10.1073/pnas.0810530106
79,699,430
Epstein–Barr virus (EBV) is a herpesvirus that is associated with development of malignancies of lymphoid tissue. EBV infections are life-long and occur in >90% of the population. Herpesviruses enter host cells in a process that involves fusion of viral and cellular membranes. The fusion apparatus is comprised of en...
10.1038/nrmicro2548
Reports the crystal structure of the EBV gB ectodomain, revealing differences in domain orientation, surface charges and structural details between EBV gB and HSV-1 gB.
10.1002/bip.10273
40,875,265
Abstract Spontaneous cortical activity of single neurons is often either dismissed as noise, or is regarded as carrying no functional significance and hence is ignored. Our findings suggest that such concepts should be revised. We explored the coherent population activity of neuronal assemblies in primary sensory area ...
10.1038/nrn3293
This summarizes a lecture given by A. Grinvald entitled Seeing the Brain in Action . It describes how voltage-imaging data at the population level reflect single-cell activity, and the similarities between internal circuit dynamics and evoked responses.
10.1126/science.1093173
123,109,792
How can neural activity propagate through cortical networks built with weak, stochastic synapses? We find precise repetitions of spontaneous patterns of synaptic inputs in neocortical neurons in vivo and in vitro. These patterns repeat after minutes, maintaining millisecond accuracy. Calcium imaging of slices reveals r...
10.1038/nrn3293
A classic paper providing experimental evidence for precise repetitions of activity patterns in neocortical neurons, suggesting a modular temporal circuit dynamics.
10.1126/science.271.5257.1870
101,987,942
The correlated activity of rat hippocampal pyramidal cells during sleep reflects the activity of those cells during earlier spatial exploration. Now the patterns of activity during sleep have also been found to reflect the order in which the cells fired during spatial exploration. This relation was reliably stronger fo...
10.1038/nrn3293
A classic paper describing sequential patterns of hippocampal activity during sleep that reflect the order in which the cells fired during previous spatial exploration, thereby implying reactivation of perceptional experience in memory consolidation.
10.1146/annurev-neuro-061010-113817
41,538,035
Genetically encoded, single-component optogenetic tools have made a significant impact on neuroscience, enabling specific modulation of selected cells within complex neural tissues. As the optogenetic toolbox contents grow and diversify, the opportunities for neuroscience continue to grow. In this review, we outline th...
10.1038/nrn3293
A comprehensive introduction to the field of optogenetic actuators based on microbial opsins.
10.1073/pnas.1221113110
80,140,726
Significance Our ability to manipulate objects relies fundamentally on sensory signals originating from the hand. To restore motor function with upper-limb neuroprostheses requires that somatosensory feedback be provided to the tetraplegic patient or amputee. Accordingly, we have developed approaches to convey sensory ...
10.1038/nrn3724
This study describes approaches to convey information about contact location, force and timing through a biomimetic strategy of ICMS applied to the somatosensory cortex.
10.1073/pnas.0808113105
16,774,264
Efforts to study the neural correlates of learning are hampered by the size of the network in which learning occurs. To understand the importance of learning-related changes in a network of neurons, it is necessary to understand how the network acts as a whole to generate behavior. Here we introduce a paradigm in which...
10.1038/nrn3724
This study emulates the classic 'visual rotation' studies by systematically (rather than randomly) remapping the decoder output. It reveals a combination of global and local adaptive changes in neural tuning.