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10.1523/jneurosci.4649-04.2005
20,653,717
When lifting small objects, people apply forces that match the expected weight of the object. This expectation relies in part on information acquired during a previous lift and on associating a certain weight with a particular object. Our study examined the role of the primary motor and dorsal premotor cortices in pred...
10.1038/nrn2621
This paper showed that repetitive TMS applied to the dorsal premotor cortex disrupts associative memory for weight whereas repetitive TMS applied to the primary motor cortex disrupts sensorimotor memory for weight.
10.1126/science.1149639
82,922,465
Natural vision is a highly dynamic process. Frequent body, head, and eye movements constantly bring new images onto the retina for brief periods, challenging our understanding of the neural code for vision. We report that certain retinal ganglion cells encode the spatial structure of a briefly presented image in the re...
10.1038/nrn2621
The authors reported that retinal ganglion cells can encode the spatial structure of a briefly presented image in the relative timing of their first spikes. This mechanism allows the retina to rapidly and reliably transmit new spatial information with the very first spikes emitted by a neural population in a manner tha...
10.1523/jneurosci.2658-05.2005
42,507,148
We investigated how gaze behavior and eye–hand coordination change when subjects learned a challenging visuomotor task that required acquisition of a novel mapping between bimanual actions and their visual sensory consequences. By applying isometric forces and torques to a rigid tool held freely between the two hands, ...
10.1038/nrn2621
This study examined changes in gaze behaviour during a visuomotor task in which subjects gradually learned a novel mapping between their hand actions and the movements of a cursor that they were required to move to targets. During learning, gaze behaviour shifted from a reactive mode, in which the gaze chased the curso...
10.1126/science.1123933
107,237,271
In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression o...
10.1038/nrmicro2745
A study linking vitamin D deficiency to impaired immune defences against tuberculosis in the human population.
10.1002/hbm.22241
26,747,561
Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole‐brain functional c...
10.1038/nrn.2016.111
This study demonstrates functional connectivity abnormalities in depressed individuals with and without histories of maltreatment.
10.1002/cne.10609
107,326,278
Abstract The structure of the human orbital and medial prefrontal cortex (OMPFC) was investigated using five histological and immunohistochemical stains and was correlated with a previous analysis in macaque monkeys [Carmichael and Price ( 1994 ) J. Comp. Neurol. 346:366–402]. A cortical area was recognized if it was d...
10.1038/nrn1343
This paper describes the cytoarchitecture of the medial and orbital PFC. The results are particularly striking because they indicate that BA 10 is larger than all other prefrontal areas in the human brain.
10.1073/pnas.1213653110
16,863,695
Adenoviruses (Ads) have shown promise as vectors for gene delivery in clinical trials. Efficient viral targeting to a tissue of choice requires both ablation of the virus’ original tropism and engineering of an efficient receptor-mediated uptake by a specific cell population. We have developed a series of adapters bind...
10.1038/nrmicro3140
This paper shows the structure-guided design of a clamp-like adaptor that has been engineered on the top of the adenovirus knob domain.
10.1017/s0140525x00041467
123,310,330
Abstract Redundancy of the motor control system is an important feature that gives the central control structures options for solving everyday motor problems. The choice of particular control patterns is based on priorities (coordinative rules) that are presently unknown. Motor patterns observed in unimpaired young adu...
10.1038/nrn939
This paper addresses an important point concerning the self-compensation of a motor deficit and the associated problem of how far it is useful cosmetically to correct secondary changes, such as muscle tone.
10.1073/pnas.81.3.979
122,221,224
The issue of whether brain signals in the absence of peripheral feedback are sufficient to specify accurate movement was evaluated by studying motor performance in patients with loss of somesthetic afferent input as a result of acquired large-fiber sensory neuropathy. With visual guidance, movements and postures were i...
10.1038/nrn939
This paper describes the changes in motor behaviour that are observed in deafferented people (who lack proprioceptive feedback information during movement).
10.1152/jn.2001.86.2.575
125,306,095
To determine whether subjects with somatosensory loss show a compensatory increase in sensitivity to vestibular stimulation, we compared the amplitude of postural lean in response to four different intensities of bipolar galvanic stimulation in subjects with diabetic peripheral neuropathy (PNP) and age-matched control ...
10.1038/nrn939
This study provided evidence of automatic compensation of impaired proprioception by other balance-regulating systems.
10.1152/jn.1997.77.6.3237
59,725,705
Prochazka, Arthur, Deborah Gillard, and David J. Bennett. Implications of positive feedback in the control of movement. J. Neurophysiol. 77: 3237–3251, 1997. In this paper we review some theoretical aspects of positive feedback in the control of movement. The focus is mainly on new theories regarding the reflexive role...
10.1038/nrn939
References 73 and 74 provide convincing evidence for movement control by positive force feedback in the cat.
10.1126/science.2506641
15,743,912
Eye movements exist to improve vision, in part by preventing excessive retinal image slip. A major threat to the stability of the retinal image comes from the observer's own movement, and there are visual and vestibular reflexes that operate to meet this challenge by generating compensatory eye movements. The ocular re...
10.1038/nrn1804
A pioneering study showing for the first time that compensatory eye movements are generated either during translation in darkness (TVOR) or during lamellar optic flow stimulation (OFR).
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/nrn1804
Shows that the population activity of MST neurons might participate in the generation of the short-latency disparity-driven vergence component of the visuomotor responses.
10.1073/pnas.90.5.2092
20,496,110
The cellular mechanism underlying the generation of beta-amyloid in Alzheimer disease and its relationship to the normal metabolism of the amyloid precursor protein are unknown. In this report, we show that 3- and 4-kDa peptides derived from amyloid precursor protein are normally secreted. Epitope mapping and radiolabe...
10.1038/nrn2168
Provides strong evidence that Aβ in neurons is generated by the secretory pathway.
10.1046/j.1365-2559.2001.01082.x
104,287,378
Aims: Amyloid has recently been shown to accumulate intracellularly in the brains of patients with Alzheimer's disease (AD), yet amyloid plaques are generally thought to arise from gradual extracellular amyloid deposition. We have investigated the possibility of a link between these two apparently conflicting observati...
10.1038/nrn2168
Provides evidence suggesting that in the brains of patients with AD, intracellular Aβ accumulation may lead to neuronal death, and that after being released in the extracellular compartment, it can contribute to the formation of plaques.
10.1073/pnas.1004304107
38,778,092
The cell wall of Staphylococcus aureus is characterized by an extremely high degree of cross-linking within its peptidoglycan (PGN). Penicillin-binding protein 4 (PBP4) is required for the synthesis of this highly cross-linked peptidoglycan. We found that wall teichoic acids, glycopolymers attached to the peptidoglycan...
10.1038/nrmicro3088
This study provides evidence that wall teichoic acids regulate the localization of PBP4, thus controlling the level of peptidoglycan crosslinking in S. aureus
10.1111/j.1365-2958.2004.04420.x
26,839,482
Summary Staphylococcus aureus penicillin‐binding protein PBP2 is an enzyme involved in the last stages of peptidoglycan assembly and is an important player in the mechanism of methicillin resistance of this pathogen. PBP2 localized to the division site but its recruitment to the forming division septum was prevented af...
10.1038/nrmicro3088
This is the first paper to show that a PBP can localize to the division septum by substrate recognition.
10.1111/j.1365-2958.2007.05634.x
82,540,836
Summary Cryo‐electron microscopy of frozen‐hydrated thin sections permits the observation of the real distribution of mass in biological specimens allowing the native structure of bacteria to be seen, including the natural orientation of their surface layers. Here, we use this approach to study the fine ultrastructure ...
10.1038/nrmicro3088
Using cryo-electron microscopy, this work shows the presence of a so-called mid-zone in the complete division septum, which probably represents a highly fragile region required for efficient cell division in S. aureus
10.1046/j.1365-2958.2003.03953.x
102,563,456
Summary Bacterial division requires the co‐ordination of membrane invagination, driven by the constriction of the FtsZ‐ring, and concomitant cell wall synthesis, performed by the high‐molecular‐weight penicillin‐binding proteins (HMW PBPs). Using immunofluorescence techniques, we show in Streptococcus pneumoniae that t...
10.1038/nrmicro3088
Using immunofluorescence, this investigation provides evidence that the localization of certain S. pneumoniae PBPs at mid-cell depends on substrate availability.
10.1073/pnas.1119172109
101,453,838
How the human pathogen Streptococcus pneumoniae coordinates cell-wall synthesis during growth and division to achieve its characteristic oval shape is poorly understood. The conserved eukaryotic-type Ser/Thr kinase of S. pneumoniae , StkP, previously was reported to phosphorylate the cell-division protein DivIVA. Consi...
10.1038/nrmicro3088
The first example of the use of single-cell automated fluorescence microscopy in a coccoid bacterium, showing that StkP coordinates peripheral and septal cell wall synthesis in S. pneumoniae
10.1111/j.1365-2958.2011.07962.x
4,803,332
Summary Eukaryotic‐like serine/threonine‐kinases are involved in the regulation of a variety of physiological processes in bacteria. In Streptococcus pneumoniae , deletion of the single serine/threonine‐kinase gene stkP results in an aberrant cell morphology suggesting that StkP participates in pneumococcus cell divisi...
10.1038/nrmicro3088
Together with reference 50, this work unambiguously shows a role for StkP in controlling pneumococcal growth and cell division.
10.1073/pnas.1108323108
81,357,342
The connection between peptidoglycan remodeling and cell division is poorly understood in ellipsoid-shaped ovococcus bacteria, such as the human respiratory pathogen Streptococcus pneumoniae . In S. pneumoniae , peptidoglycan homeostasis and stress are regulated by the WalRK (VicRK) two-component regulatory system, whi...
10.1038/nrmicro3088
This study provides compelling evidence that the conserved FtsEX complex activates the autolysin PcsB and thereby couples peptidoglycan remodelling to cell division in S. pneumoniae
10.1111/j.1365-2958.2011.07651.x
38,399,120
Summary The Gram‐positive pathogen Staphylococcus aureus divides by synthesizing the septum in three orthogonal planes over three consecutive division cycles. This process has to be tightly coordinated with chromosome segregation to avoid bisection of the nucleoid by the septum. Here we show that deletion of the nucleo...
10.1038/nrmicro3088
This work shows that when Noc is removed from S. aureus , the division sites are frequently misplaced; thus, the authors propose that the axis of chromosome segregation has an important role in division site selection in cocci.
10.1073/pnas.0605305103
104,397,230
Despite recent progress in visualization experiments, the mechanism underlying chromosome segregation in bacteria still remains elusive. Here we address a basic physical issue associated with bacterial chromosome segregation, namely the spatial organization of highly confined, self-avoiding polymers (of nontrivial topo...
10.1038/nrmicro3088
Using computer simulations, this study provides evidence that bacterial chromosomes can segregate spontaneously under certain (topological) conditions by entropy-driven demixing of the DNA–protein polymers.
10.1128/jb.01168-06
122,017,876
ABSTRACT To clarify the function of DivIVA in Streptococcus pneumoniae , we localized this protein in exponentially growing cells by both immunofluorescence microscopy and immunoelectron microscopy and found that S. pneumoniae DivIVA (DivIVA SPN ) had a unique localization profile: it was present simultaneously both as...
10.1038/nrmicro3088
This work shows that DivIVA in S. pneumoniae is involved in the formation and maturation of the future cell poles, and demonstrates an interaction between DivIVA and ParB, hinting at a possible role for DivIVA as a chromosome-tethering factor required for efficient chromosome segregation.
10.1038/ismej.2008.58
103,744,500
Abstract There is considerable interest in understanding the biological mechanisms that regulate carbon exchanges between the land and atmosphere, and how these exchanges respond to climate change. An understanding of soil microbial ecology is central to our ability to assess terrestrial carbon cycle–climate feedbacks,...
10.1038/nrmicro2439
This paper highlights the central role of soil microorganisms in land–atmosphere carbon exchange and its consequences for climate change.
10.2136/sssaj2004.0347
20,431,807
This paper reviews the current knowledge of microbial processes affecting C sequestration in agroecosystems. The microbial contribution to soil C storage is directly related to microbial community dynamics and the balance between formation and degradation of microbial byproducts. Soil microbes also indirectly influence...
10.1038/nrmicro2439
This paper provides an in-depth discussion on the contribution of soil microorganisms to carbon sequestration and suggests mechanisms by which carbon sequestration could be better managed.
10.1073/pnas.0903507106
40,132,589
Many marine bacteria have evolved to grow optimally at either high (copiotrophic) or low (oligotrophic) nutrient concentrations, enabling different species to colonize distinct trophic habitats in the oceans. Here, we compare the genome sequences of two bacteria, Photobacterium angustum S14 and Sphingopyxis alaskensis ...
10.1038/nrmicro2439
This investigation provides evidence that ecological and trophic classification of uncultivable bacteria can be obtained from their genomic data without a need to culture them.
10.1073/pnas.201243998
100,701,387
Neurodevelopmental models for the pathology of schizophrenia propose both polygenetic and environmental risks, as well as early (pre/perinatal) and late (usually adolescent) developmental brain abnormalities. With the use of brain mapping algorithms, we detected striking anatomical profiles of accelerated gray matter l...
10.1038/nrn782
This paper describes a four-dimensional approach that is sensitive to dynamic events in a changing brain. Changes over time present a unique challenge to databases, but one that is crucial to understanding developing, degenerating or otherwise changing brain structure or function.
10.1126/science.280.5360.69
83,368,665
The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K + channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the ...
10.1038/nrn727
This article reports the first crystal structure of an ion-selective filter, using the bacterial K + channel KcsA as a model system. This study laid the foundation for understanding mechanisms of ion selection and permeation.
10.1126/science.285.5424.73
58,564,361
The intramembrane molecular events underlying activation gating in the Streptomyces K + channel were investigated by site-directed spin-labeling methods and electron paramagnetic resonance spectroscopy. A comparison of the closed and open conformations of the channel revealed periodic changes in spin-label mobility and...
10.1038/nrn727
This article reports the structural framework for the dynamics of channel activation, using KcsA as a model system.
10.1152/jn.01100.2002
56,454,034
A fundamental question in vertebrate locomotion is whether distinct spinal networks exist that are capable of generating rhythmic output for each group of muscle synergists. In many vertebrates including the lamprey, it has been claimed that burst activity depends on reciprocal inhibition between antagonists. This ques...
10.1038/nrn1137
A demonstration of locomotor burst generation in hemisegments, and without inhibition.
10.1152/jn.1994.72.4.1852
74,075,839
1. The possible involvement of calcium-dependent potassium channels (KCa) in the termination of locomotor bursts was investigated by administration of a specific blocker, apamin, in the lamprey spinal cord in vitro. The effects were examined by recording the efferent activity in ventral roots and by intracellular recor...
10.1038/nrn1137
A description of the role of calcium-dependent potassium channels in the locomotor network.
10.1111/j.1469-7793.2001.0023b.x
108,839,514
The intrinsic function of the spinal network that generates locomotion can be studied in the isolated brainstem‐spinal cord of the lamprey, a lower vertebrate. The motor pattern underlying locomotion can be elicited in the isolated spinal cord. The network consists of excitatory glutamatergic and inhibitory glycinergic...
10.1038/nrn1137
A review of ion channels that are important for pattern generation in the lamprey.
10.1073/pnas.091096198
58,555,097
Transient A-type K + channels ( I A ) in neurons have been implicated in the delay of the spike onset and the decrease in the firing frequency. Here we have characterized biophysically and pharmacologically an I A current in lamprey locomotor network neurons that is activated by suprathreshold depolarization and is spe...
10.1038/nrn1137
A study on the role of Kv3.4-like channels in locomotor pattern generation.
10.1152/jn.2002.87.6.2676
32,840,929
Spinal neurons undergo large cyclic membrane potential oscillations during fictive locomotion in lamprey. It was investigated whether these oscillations were due only to synaptically driven excitatory and inhibitory potentials or if voltage-dependent inward conductances also contribute to the depolarizing phase by usin...
10.1038/nrn1137
A demonstration of the potentiation of locomotor drive synaptic potentials by soma-dendritic Na + channels.
10.1098/rstb.1999.0441
17,583,541
The neuronal generation of vertebrate locomotion has been extensively studied in the lamprey. Models at different levels of abstraction are being used to describe this system, from abstract nonlinear oscillators to interconnected model neurons comprising multiple compartments and a Hodgkin–Huxley representation of the ...
10.1038/nrn1137
A simulation of lamprey locomotor movements based on a biologically realistic network.
10.1111/j.1748-1716.1980.tb06533.x
4,592,529
Kittens were subjected to a complete transection of the spinal cord (Th 10–12) 1–2 weeks after birth. A few days after the operation they could perform alternating limb movements and somewhat later walking movements with their hindlimbs on a treadmill. The stepcycle of the hindlimbs could be divided into a flexion phas...
10.1038/nrn1137
The first description of well coordinated locomotor movements and EMG pattern in a spinal animal.
10.1111/j.1469-7793.2001.0015b.x
60,702,778
The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intr...
10.1038/nrn1137
An elegant study that reveals the plasticity of the postural and locomotor systems in spinal animals.
10.1177/107385840100700514
42,524,407
Recovery of locomotion has been considered unattainable following a clinically complete or severe incomplete spinal cord injury even after conventional therapy. However, the locomotion of spinal animals can be improved by training that provides complex temporal patterns of sensory information related to stepping that i...
10.1038/nrn1137
An evaluation of treadmill training for paralysed patients with spinal cord injury.
10.1111/j.1460-9568.1995.tb00686.x
45,383,574
Abstract Rehabilitation of locomotion in spinal cord (s.c.) injured patients is unsatisfactory. Here we report the effects of a novel ‘Laufband (LB; treadmill) therapy’ based on ‘rules of spinal locomotion’ derived from lower vertebrates. Eighty‐nine incompletely paralysed (44 chronic and 45 acute) para‐ and tetraplegi...
10.1038/nrn1137
An initial report of the beneficial effect of treadmill training on patients with spinal cord injury.
10.1083/jcb.200309132
124,606,765
Misfolded proteins retained in the endoplasmic reticulum (ER) are degraded by the ER-associated degradation pathway. The mechanisms used to sort them from correctly folded proteins remain unclear. Analysis of substrates with defined folded and misfolded domains has revealed a system of sequential checkpoints that recog...
10.1038/nsmb.2793
Refs. 26 and 27 elucidated different routes by which distinct classes of misfolded ER proteins are retrotranslocated for degradation
10.1073/pnas.0607651104
20,433,687
Biofilms, in which cells attach to surfaces and secrete slime (polymeric substances), are central to microbial life. Biofilms are often thought to require high levels of cooperation because extracellular polymeric substances are a shared resource produced by one cell that can be used by others. Here we examine this hyp...
10.1038/nrmicro2415
An important and inspiring discussion on microbial interactions, including the role of the matrix.
10.1146/annurev-marine-010816-060656
102,073,864
Quorum sensing (QS) is a form of chemical communication used by certain bacteria that regulates a wide range of biogeochemically important bacterial behaviors. Although QS was first observed in a marine bacterium nearly four decades ago, only in the past decade has there been a rise in interest in the role that QS play...
10.1038/nrmicro2415
A classic review of microbial interactions, including the role of EPS.
10.1177/0956797611417632
125,227,296
In this article, we accomplish two things. First, we show that despite empirical psychologists’ nominal endorsement of a low rate of false-positive findings (≤ .05), flexibility in data collection, analysis, and reporting dramatically increases actual false-positive rates. In many cases, a researcher is more likely to ...
10.1038/nrn3475
This article empirically illustrates that flexible study designs and data analysis dramatically increase the possibility of obtaining a nominally significant result. However, conclusions drawn from these results are almost certainly false.
10.1177/1740774507079441
125,126,666
Background The published clinical research literature may be distorted by the pursuit of statistically significant results. Purpose We aimed to develop a test to explore biases stemming from the pursuit of nominal statistical significance. Methods The exploratory test evaluates whether there is a relative excess of for...
10.1038/nrn3475
This study describes a test that evaluates whether there is an excess of significant findings in the published literature. The number of expected studies with statistically significant results is estimated and compared against the number of observed significant studies.
10.1177/1745691612462588
29,223,285
Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replication is rarely practiced or published. The Reproducibility Project is an open, large-scale, collaborative effort to systematically examine the rate and predictors of...
10.1038/nrn3475
This article describes the Reproducibility Project — an open, large-scale, collaborative effort to systematically examine the rate and predictors of reproducibility in psychological science. This will allow the empirical rate of replication to be estimated.
10.1046/j.1471-4159.1999.0732415.x
80,472,967
Abstract : Long‐term facilitation (LTF) of the sensory‐to‐motor synapses that mediate defensive reflexes in Aplysia requires induction of the transcription factor Aplysia CCAAT/enhancer binding protein (ApC/EBP) as an early response gene. We examined the time course of ApC/EBP DNA binding during the induction of LTF : ...
10.1038/nrn961
This paper shows that a transcription factor required for the induction of long-term synaptic plasticity (Ap-C/EBP) is degraded by the ubiquitin–proteasome pathway, and that phosphorylation by MAP kinase makes the transcription factor resistant to ubiquitin-mediated degradation.
10.1073/pnas.90.16.7436
19,681,211
In Aplysia, behavioral sensitization of defensive reflexes and the underlying presynaptic facilitation of sensory-to-motor neuron synapses lasts for several minutes (short term) or days to weeks (long term). Short-term sensitization has been explained by modulation of ion-channel function through cAMP-dependent protein...
10.1038/nrn961
The first demonstration that a subunit of a protein kinase (PKA) that is crucial for synaptic plasticity is a substrate of the ubiquitin–proteasome pathway.
10.1073/pnas.1500374112
20,660,721
Urinary tract infections (UTIs) are among the most common bacterial infections, causing considerable morbidity in females. Infection is highly recurrent despite appropriate antibiotic treatment. Uropathogenic Escherichia coli (UPEC), the most common causative agent of UTIs, invades bladder epithelial cells (BECs) and d...
10.1038/nrurol.2017.25
This paper highlights the activation of caspase-1-dependent pyroptosis by UPEC virulence factor, α-haemolysin. Additionally, it demonstrates increased urothelium exfoliation and reduced murine bladder infection upon α-haemolysin overexpression.
10.4049/jimmunol.1102543
20,405,638
Abstract Group B Streptococcus (GBS) is a frequent agent of life-threatening sepsis and meningitis in neonates and adults with predisposing conditions. We tested the hypothesis that activation of the inflammasome, an inflammatory signaling complex, is involved in host defenses against this pathogen. We show in this stu...
10.1038/nrurol.2017.25
This paper investigates the activation of the NLRP3 inflammasome by Group B Streptroccocus via its virulence factor β-haemolysin.
10.1155/2009/810791
44,229,429
Urinary tract infections may induce severe inflammation, transient impairment in renal function and scar formation, ranging in severity from acute symptomatic pyelonephritis to chronic pyelonephritis, and have the potential to lead to renal failure and death. In the present study, the relationship between production of...
10.1038/nrurol.2017.25
This paper suggests a role for neutrophils in P. aeruginosa -induced pyelonephritis.
10.1111/j.1440-1797.2007.00819.x
26,804,453
SUMMARY: Aim: Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin (IL)‐1β is an important inflammatory mediator that appears early during bacterial infection. This prospective study examined urine IL‐1β levels in children with acute pyelonephritis docume...
10.1038/nrurol.2017.25
This paper examines the correlation between IL-1β levels in the urine and acute polynephritis.
10.1083/jcb.87.1.264
101,041,559
When BHK-21 cells with Semliki Forest virus (SFV) bound at the plasma membrane are briefly treated with low pH medium (pH 5-6), fusion between the viral membrane and the plasma membrane occurs, releasing the viral nucleocapsid into the cytoplasm. The fusion reaction resembles that described previously for Sendai virus ...
10.1038/nrmicro817
Shows that a low pH can trigger rapid and efficient fusion of SFV with plasma membranes, which leads to delivery of the viral genome in a form that is suitable for replication.
10.1073/pnas.94.26.14306
19,500,090
Enveloped viruses enter cells by protein-mediated membrane fusion. For influenza virus, membrane fusion is regulated by the conformational state of the hemagglutinin (HA) protein, which switches from a native (nonfusogenic) structure to a fusion-active (fusogenic) conformation when exposed to the acidic environment of ...
10.1038/nrmicro817
Proposes that the native structure of HA is trapped in a metastable state and that the fusogenic conformation is released by destabilization of the native structure.
10.1126/science.2994218
19,614,217
The three-dimensional structure of poliovirus has been determined at 2.9 Å resolution by x-ray crystallographic methods. Each of the three major capsid proteins (VP1, VP2, and VP3) contains a "core" consisting of an eight-stranded antiparallel beta barrel with two flanking helices. The arrangement of beta strands and h...
10.1038/nrmicro817
References 21 and 22 describe the first crystal structures of human viruses with important implications for understanding their mechanisms of entry and design of inhibitors.
10.1126/science.272.5263.872
62,430,334
A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy. This protein, designated “fusin,” is a putative G protein-coupled receptor with seven transmembrane segments. Recombinant fusin enabled CD4-expressing ...
10.1038/nrmicro817
Identification of the first HIV-1 co-receptor that opened a new field with important implications for understanding entry mechanisms, and for the development of inhibitors and vaccines.
10.1083/jcb.136.1.81
109,246,783
While the specificity and timing of membrane fusion in diverse physiological reactions, including virus–cell fusion, is determined by proteins, fusion always involves the merger of membrane lipid bilayers. We have isolated a lipid-dependent stage of cell–cell fusion mediated by influenza hemagglutinin and triggered by ...
10.1038/nrmicro817
Finds that HA-mediated membrane fusion is consistent with the stalk hypothesis of fusion, indicating that fusion proteins begin membrane fusion by promoting the formation of a bent, lipid-containing, stalk intermediate.
10.1111/j.0021-8782.2004.00343.x
80,789,408
Abstract The remarkable resilience of cognitive functions to focal brain damage suggests that multiple degenerate neuronal systems can sustain the same function either via similar mechanisms or by implementing different cognitive strategies. In degenerate functional neuroanatomy, multiple degenerate neuronal systems mi...
10.1038/nrn3901
This paper reviews different forms of neural degeneracy and how they support cognition following brain lesions.
10.1073/pnas.1322173111
83,209,436
Significance Thought depends on the brain, and cognitive neuroscience has shown that different sets of brain regions (systems) support different cognitive abilities. We hypothesized that complex cognition might be especially supported by hub brain locations that participate in many such systems. We studied neurological...
10.1038/nrn3901
This was the first demonstration in human patients that damage to putative bridge hubs of the brain results in widespread neuropsychological impairment.
10.1139/b09-032
45,420,056
Limitations in the supply of the antimalarial compound artemisinin from Artemisia annua L. have led to an interest in understanding its biosynthesis and enhancing its production. Recent biochemical and molecular genetic data have implicated dihydroartemisinic aldehyde as a precursor to the corresponding acid, which is ...
10.1038/nrmicro3240
This study reports the identification of the A. annua aldehyde dehydrogenase, which is required for high-level production of artemisinic acid in S. cerevisiae
10.1126/science.2047876
45,477,394
Application of recombinant DNA methods to restructure metabolic networks can improve production of metabolite and protein products by altering pathway distributions and rates. Recruitment of heterologous proteins enables extension of existing pathways to obtain new chemical products, alter posttranslational protein pro...
10.1038/nrmicro3240
This paper provides an early description and vision of metabolic engineering.
10.1101/gad.8.17.2008
81,222,396
To assess the functions of the retinoblastoma protein (RB) during normal development, we have analyzed mouse embryos that lack a functional copy of the retinoblastoma gene (genotype: Rb-1 delta 20/Rb-1 delta 20). Our findings demonstrate that RB plays an important role in the regulation of the neuronal cell cycle. In m...
10.1038/nrn2124
A detailed description of how a cell cycle protein can also be a potent pro-differentiation agent.
10.1242/dev.121.8.2385
62,606,534
Unexpected nerve cell death has been reported in several experimental situations where neurons have been forced to re-enter the cell cycle after leaving the ventricular zone and entering the G0, non-mitotic stage. To determine whether an association between cell death and unscheduled cell cycling might be found in conj...
10.1038/nrn2124
The first demonstration that natural examples of developmental cell death are preceded by cell cycle activation.
10.1083/jcb.200505075
38,599,864
The origin recognition complex (ORC) ensures exactly one round of genome replication per cell cycle through acting as a molecular switch that precisely controls the assembly, firing, and inactivation of the replication initiation machinery. Recent data indicate that it may also coordinate the processes of mitosis and c...
10.1038/nrn2124
Analysis of the unexplained presence of proteins normally associated with DNA replication biochemistry in the mature neuronal synapse.
10.1242/dev.01432
83,272,867
Programmed cell death or apoptosis plays an important role in the development of multicellular organisms and can also be induced by various stress events. In the Drosophila wing imaginal disc there is little apoptosis in normal development but X-rays can induce high apoptotic levels,which eliminate a large fraction of ...
10.1038/nrn2124
'Undead' cells signal with mitogens to neighbouring cells; the authors take a first pass at identifying the signalling molecules involved.
10.1126/science.273.5277.956
41,133,944
Cardiac Na + ,Ca 2+ exchange is activated by a mechanism that requires hydrolysis of adenosine triphosphate (ATP) but is not mediated by protein kinases. In giant cardiac membrane patches, ATP acted to generate phosphatidylinositol-4,5-bisphosphate (PIP 2 ) from phosphatidylinositol (PI). The action of ATP was abolishe...
10.1038/nrn2257
This study provided the first electrophysiological demonstration of the sensitivity of membrane transport proteins to membrane phosphoinositides.
10.1085/jgp.116.5.599
84,335,541
Phosphatidylinositol 4,5-bisphosphate (PIP2) activates KATP and other inward rectifier (Kir) channels. To determine residues important for PIP2 regulation, we have systematically mutated each positive charge in the COOH terminus of Kir6.2 to alanine. The effects of these mutations on channel function were examined usin...
10.1038/nrn2257
This study carried out a systematic determination of the critical sites on the C termini of K ATP channels that mediate PIP 2 sensitivity.
10.1073/pnas.96.26.15292
38,655,990
In the COS7 cells transfected with cDNAs of the Kir6.2, SUR2A, and M 1 muscarinic receptors, we activated the ATP-sensitive potassium (K ATP ) channel with a K + channel opener and recorded the whole-cell K ATP current. The K ATP current was reversibly inhibited by the stimulation of the M 1 receptor, which is linked t...
10.1038/nrn2257
This paper provided the first published evidence that the muscarinic-receptor-mediated suppression of K + channel currents is due to depletion of PIP 2 . Pharmacological blockade of PLC activity, and of phosphoinositide kinases, is used in mammalian cells to prevent current suppression or its recovery after receptor st...
10.1523/jneurosci.2597-05.2005
104,041,301
Voltage-gated Kv7 (KCNQ) channels underlie important K + currents, including the neuronal M current, and are thought to be sensitive to membrane phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and PIP 2 depletion to underlie muscarinic receptor inhibition. We studied regulation of Kv7.2-7.4 channels by PIP 2 in Chinese ...
10.1038/nrn2257
This study demonstrated, using single-channel recordings, that the divergent open probabilities among KCNQ channels are due to their differential apparent affinity for PIP 2 . It also used HPLC analysis to show that muscarinic stimulation can deplete PIP 2 in mammalian cells.
10.1523/jneurosci.3231-04.2005
103,216,874
The relationship between receptor-induced membrane phosphatidylinositol-4′5′-bisphosphate (PIP 2 ) hydrolysis and M-current inhibition was assessed in single-dissociated rat sympathetic neurons by simultaneous or parallel recording of membrane current and membrane-to-cytosol translocation of the fluorescent PIP 2 /inos...
10.1038/nrn2257
This study provided quantitative calculations of changes in PIP 2 abundance in sympathetic neurons upon receptor stimulation or phosphoinositide kinase overexpression and correlated those changes with M-current suppression. Its findings suggested that some receptors in neurons can stimulate PIP 2 synthesis.
10.1083/jcb.200301070
59,332,755
We studied the bradykinin-induced changes in phosphoinositide composition of N1E-115 neuroblastoma cells using a combination of biochemistry, microscope imaging, and mathematical modeling. Phosphatidylinositol-4,5-bisphosphate (PIP2) decreased over the first 30 s, and then recovered over the following 2–3 min. However,...
10.1038/nrn2257
This study used the Virtual Cell computer model of phosphoinositide metabolism, and PIP 2 hydrolysis probes in individual cells, to predict changes in PIP 2 and IP 3 levels upon receptor stimulation.
10.1523/jneurosci.3869-04.2004
19,249,082
Modulation of voltage-gated Ca 2+ channels via G-protein-coupled receptors is a prime mechanism regulating neurotransmitter release and synaptic plasticity. Despite extensive studies, the molecular mechanism underlying G q/11 -mediated modulation remains unclear. We found cloned and native N-type Ca 2+ channels to be r...
10.1038/nrn2257
This paper provided the first demonstration that neuronal N-type Ca 2+ channels in sympathetic neurons are sensitive to receptor-mediated PIP 2 depletion. The authors also suggest a hypothesis for receptor-specific PIP 2 signalling.
10.1113/jphysiol.2004.081935
100,346,709
Two‐pore (2‐P) domain potassium channels are implicated in the control of the resting membrane potential, hormonal secretion, and the amplitude, frequency and duration of the action potential. These channels are strongly regulated by hormones and neurotransmitters. Little is known, however, about the mechanism underlyi...
10.1038/nrn2257
This paper suggested that TASK, TREK and TRAAK two-pore channels are sensitive to PIP 2 abundance and that PIP 2 depletion underlies current suppression by receptor stimulation.
10.1073/pnas.0507710103
17,238,150
Two-pore-domain K + channels provide neuronal background currents that establish resting membrane potential and input resistance; their modulation provides a prevalent mechanism for regulating cellular excitability. The so-called TASK channel subunits (TASK-1 and TASK-3) are widely expressed, and they are robustly inhi...
10.1038/nrn2257
This study suggested that the suppression of TASK two-pore channel currents by receptor stimulation is due to the direct interaction of the channels with G αq , rather than a result of PIP 2 depletion.
10.1152/jn.01139.2002
123,156,503
Vasoneuroactive substances were applied through intradermal microdialysis membranes and characterized as itch- or pain-inducing in psychophysical experiments. Histamine always provoked itching and rarely pain, capsaicin always pain but never itching. Prostaglandin E 2 (PGE 2 ) led preferentially to moderate itching. Se...
10.1038/nrn3641
Using microneurography to record neuronal activity from unmeylinated C-fibres in human, this paper showed that some mechano-insensitive C-fibres are pruriceptive and respond to histamine, although they also respond to a wide range of chemicals including algogens. Others are non-pruriceptive and respond to algogens but ...
10.1152/jn.90482.2008
124,105,810
Recent findings suggest that itch produced by intradermal insertion of cowhage spicules in human is histamine independent. Neuronal mechanisms underlying nonhistaminergic itch are poorly understood. To investigate which nerve fibers mediate cowhage induced itch in man, action potentials were recorded from cutaneous C-f...
10.1038/nrn3641
Using microneurography in humans, this study found that histamine and cowhage active two separate, non-overlapping populations of unmyelinated C-fibres: that is, mechano-insensitive C-fibres and mechano-sensitive C-fibres. These findings suggest that histaminergic and non-histaminergic itch are mediated through separat...
10.1152/jn.00206.2012
83,215,236
Itch of peripheral origin requires information transfer from the spinal cord to the brain for perception. Here, primate spinothalamic tract (STT) neurons from lumbar spinal cord were functionally characterized by in vivo electrophysiology to determine the role of these cells in the transmission of pruriceptive informat...
10.1038/nrn3641
With the use of antidromic stimulation at the thalamus to identify spinothalamic dorsal horn neurons in monkeys, this study, together with reference 52, found that separate populations of nociceptive dorsal horn neurons in primate are activated by histamine and cowhage spicules.
10.1126/science.1174868
19,243,166
A Separate System for Itch Processing It has been a long-standing question if itch is a subquality of pain involving the same neuronal elements or if distinct, so-called labeled lines exist in the nervous system for both sensations. To address this question directly, Sun et al. (p. 1531 , published online 6 August) des...
10.1038/nrn3641
These findings, along with those of reference 58, support the conclusion that neurons in the dorsal horn that express the receptor for GRP are necessary for itch-like behaviour in the mouse.
10.1111/sms.12333
124,785,338
Tendon injury is thought to involve both damage accumulation within the matrix and an accompanying cell response. While several studies have characterized cell and matrix response in chronically injured tendons, few have assessed the initial response of tendon to overload‐induced damage. In this study, we assessed cell...
10.1038/nrrheum.2016.213
Important study that highlights the link between mechanical tendon overload and inflammatory mechanisms in tendon disease.
10.1038/ncomms7774
83,461,272
Abstract MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing the common human condition tendinopathy as a model system to explore the cross-regulation of immediate inflammation and matrix synthesis by miRNA we...
10.1038/nrrheum.2016.213
This article describes cytokine and extracellular matrix (ECM) crosstalk and provides a mechanistic dissection of changes in collagen in the ECM in tendon disease.
10.1126/scitranslmed.aac4269
122,985,216
Resolution of inflammatory pathway gene expression signatures in diseased tendons correlates with reduced tendon pain.
10.1038/nrrheum.2016.213
Study showing inflammatory signatures defining resolution of symptoms in supraspinatus tendons from patients experiencing pain before and after surgical treatment.
10.1073/pnas.0710618105
41,045,272
Root endosymbioses vitally contribute to plant nutrition and fitness worldwide. Nitrogen-fixing root nodulation, confined to four plant orders, encompasses two distinct types of associations, the interaction of legumes (Fabales) with rhizobia bacteria and actinorhizal symbioses, where the bacterial symbionts are actino...
10.1038/nrmicro2990
This work shows that the pathway for the recognition of Frankia spp. shares genetic components with the pathway for the recognition of rhizobia in legumes.
10.1105/tpc.108.063255
40,861,455
Abstract The mechanism underlying perinuclear calcium spiking induced during legume root endosymbioses is largely unknown. Lotus japonicus symbiosis-defective castor and pollux mutants are impaired in perinuclear calcium spiking. Homology modeling suggested that the related proteins CASTOR and POLLUX might be ion chann...
10.1038/nrmicro2990
A study defining the role of the cation channels in symbiotic signalling.
10.1105/tpc.108.064501
38,271,671
Abstract The symbiotic association of legumes with rhizobia involves bacterially derived Nod factor, which is sufficient to activate the formation of nodules on the roots of the host plant. Perception of Nod factor by root hair cells induces calcium oscillations that are a component of the Nod factor signal transductio...
10.1038/nrmicro2990
A study that uncovers the role of the symbiotic transcription factors.
10.1105/tpc.108.062414
102,377,285
Abstract Knowledge about signaling in arbuscular mycorrhizal (AM) symbioses is currently restricted to the common symbiosis (SYM) signaling pathway discovered in legumes. This pathway includes calcium as a second messenger and regulates both AM and rhizobial symbioses. Both monocotyledons and dicotyledons form symbioti...
10.1038/nrmicro2990
This paper reports the most complete characterization of the common symbiosis signalling pathway in cereals and its role in the association with AMF.
10.1073/pnas.95.11.6419
61,959,741
Fourteen different genes included in a DNA fragment of 18 kb are involved in the aerobic degradation of phenylacetic acid by Pseudomonas putida U. This catabolic pathway appears to be organized in three contiguous operons that contain the following functional units: ( i ) a transport system, ( ii ) a phenylacetic acid ...
10.1038/nrmicro2652
A summary of the early information on the phenylacetyl-CoA oxidation pathway, mainly based on genetic evidence.
10.1073/pnas.1005399107
107,206,911
Aromatic compounds constitute the second most abundant class of organic substrates and environmental pollutants, a substantial part of which (e.g., phenylalanine or styrene) is metabolized by bacteria via phenylacetate. Surprisingly, the bacterial catabolism of phenylalanine and phenylacetate remained an unsolved probl...
10.1038/nrmicro2652
A study that identifies the individual intermediates and enzyme steps of phenylacetyl-CoA oxidation.
10.1073/pnas.94.12.6484
125,099,333
A reductive benzoate pathway is the central conduit for the anaerobic biodegradation of aromatic pollutants and lignin monomers. Benzene ring reduction requires a large input of energy and this metabolic capability has, so far, been reported only in bacteria. To determine the molecular basis for this environmentally im...
10.1038/nrmicro2652
A report on the genes involved in anaerobic benzoate metabolism.
10.1111/j.1432-1033.1996.0661w.x
100,345,577
Toluene is degraded anoxically to CO 2 by the denitrifying bacterium Thauera aromatica. Toluene first becomes oxidized to benzoyl‐CoA by O 2 ‐independent reactions. Benzoyl‐CoA is then reduced to non‐aromatic products by benzoyl‐CoA reductase. We set out to study the reactions employed for the initial activation of tol...
10.1038/nrmicro2652
A classic paper demonstrating that the addition of fumarate to a hydrocarbon constitutes the initial attack not only on toluene, but also on various other hydrocarbon compounds.
10.1002/ajmg.a.20496
61,455,950
Abstract Most individuals with Williams syndrome (WS) have a 1.6 Mb deletion in chromosome 7q11.23 that encompasses the elastin ( ELN ) gene, while most families with autosomal dominant supravalvar aortic stenosis (SVAS) have point mutations in ELN . The overlap of the clinical phenotypes of the two conditions (cardiov...
10.1038/nrn1906
123A Provides evidence that GTF2I is important for normal intellectual ability.
10.1162/0898929042304741
20,511,362
We examined the role of the amygdala in the development of nonhuman primate social behavior. Twenty-four rhesus monkeys received bilateral ibotenic acid lesions of either the amygdala or the hippocampus or received a sham surgical procedure at 2 weeks of age. Subjects were reared with their mothers and were provided da...
10.1038/nrn1906
Dissociation of social/non-social fears in the primate after neonatal lesions.
10.1101/gad.1025702
103,906,061
The hedgehog signaling pathway organizes the developing ventral neural tube by establishing distinct neural progenitor fates along the dorsoventral axis. Smoothened ( Smo ) is essential for all Hedgehog (Hh) signaling, and genetic inactivation of Smo cells autonomously blocks the ability of cells to transduce the Hh si...
10.1038/nrn1843
Demonstrates that HH signalling is required directly in ventral cells for the specification of all ventral spinal cord fates, with the possible exception of some V0 cells. Along with references 34 and 36, this provides conclusive evidence that SHH acts as a morphogen in the ventral spinal cord.
10.1242/dev.129.21.4963
20,673,490
Considerable data suggest that sonic hedgehog (Shh) is both necessary and sufficient for the specification of ventral pattern throughout the nervous system, including the telencephalon. We show that the regional markers induced by Shh in the E9.0 telencephalon are dependent on the dorsoventral and anteroposterior posit...
10.1038/nrn1843
References 21 and 22 show that ventral telencephalic patterning requires HH signalling, but appears normal when GLI3 is also knocked out.
10.1242/dev.01726
109,130,157
In the developing spinal cord and telencephalon, ventral patterning involves the interplay of Hedgehog (Hh), Retinoic Acid (RA) and Fibroblast Growth Factor (FGF) signaling. In the eye, ventral specification involves Hh signaling, but the roles of RA and FGF signaling are less clear. By overexpression assays in Xenopus...
10.1038/nrn1843
Results suggest that the ventral regionalization of the eye is specified by interactions among HH, RA and FGF.
10.1101/gad.325905
41,366,556
During development, many signaling factors behave as morphogens, long-range signals eliciting different cellular responses according to their concentration. In ventral regions of the spinal cord, Sonic Hedgehog (Shh) is such a signal and controls the emergence, in precise spatial order, of distinct neuronal subtypes. T...
10.1038/nrn1843
Shows that different levels of GLI transcription factor activity are sufficient to cell-autonomously induce all of the different ventral fates in the spinal cord.
10.1242/dev.01379
41,739,963
During spinal cord development, distinct classes of interneurons arise at stereotypical locations along the dorsoventral axis. In this paper, we demonstrate that signaling through bone morphogenetic protein (BMP) type 1 receptors is required for the formation of two populations of commissural neurons, DI1 and DI2, that...
10.1038/nrn1843
These authors used a combination of a mouse knockout of BMP receptor BMPR1B and a conditional knockout that only eliminates BMP receptor BMPR1A in the neural tube to show that BMP signalling is directly required for the specification of D1 and D2 dorsal interneuron fates. However, more ventral fates are not affected in...
10.1242/dev.01308
59,335,546
The organisation of the telencephalon into its major structures depends on its early regionalisation along the dorsoventral axis. Previous studies have provided evidence that sonic hedgehog (SHH) is required for the generation of telencephalic cells of ventral character, and that sequential WNT and fibroblast growth fa...
10.1038/nrn1843
Provides evidence for a role of RA in LGE specification and FGF in MGE specification.
10.1073/pnas.91.12.5607
80,624,577
We have isolated a brain-specific cDNA that encodes a Na(+)-dependent inorganic phosphate (Pi) cotransporter (BNPI). The nucleotide sequence of BNPI predicts a protein of 560 amino acids with 6-8 putative transmembrane-spanning segments that is approximately 32% identical to the rabbit kidney Na(+)-dependent Pi cotrans...
10.1038/nrn2969
This is the seminal paper describing the molecular cloning of the first vesicular glutamate transporter. Subsequently renamed VGLUT1, this protein was initially characterized as a brain-specific plasma membrane sodium-dependent inorganic phosphate transporter.
10.1046/j.1471-4159.2003.02277.x
102,574,797
Abstract Dopamine neurons have been suggested to use glutamate as a cotransmitter. To identify the basis of such a phenotype, we have examined the expression of the three recently identified vesicular glutamate transporters (VGLUT1‐3) in postnatal rat dopamine neurons in culture. We found that the majority of isolated ...
10.1038/nrn2969
This was the first report demonstrating the presence of a vesicular glutamate transporter in dopamine neurons, thus providing a molecular explanation for their ability to release glutamate — at least in vitro