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10.1152/jn.2002.88.3.1128
121,739,499
We report here results from 45 primate V4 visual cortical neurons to the preattentive presentations of seven different patterns located in two separate areas of the same receptive field and to combinations of the patterns in the two locations. For many neurons, we could not determine any clear relationship for the resp...
10.1038/nrn1057
An electrophysiological study showing evidence for maximum computation in some neurons in area V4 of monkeys.
10.1126/science.275.5297.213
125,310,102
Activity-driven modifications in synaptic connections between neurons in the neocortex may occur during development and learning. In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found to indu...
10.1038/nrn1057
A study showing that synaptic changes depend on the precise timing of pre- and postsynaptic activity. Spike-time-dependent plasticity is a biologically plausible mechanism for learning temporal order.
10.1111/1467-9280.00245
79,455,251
Humans are very good at perceiving each other's movements. In this article, we investigate the role of time-based information in the recognition of individuals from point light biological motion sequences. We report an experiment in which we used an exaggeration technique that changes temporal properties while keeping ...
10.1038/nrn1057
A psychophysical study showing that, by motion morphing, temporal caricatures of arm movement patterns can be generated that improve the recognition of identity from point-light walkers.
10.1068/p130283
79,444,563
In a film produced by Johansson, a group of moving spots, corresponding to lights attached to the main joints of a walker or a runner, gives instantly a vivid impression of a person walking or running. Even when this film was inverted and run backward, some sort of human movement was still perceived. It was perceived m...
10.1038/nrn1057
A psychophysical experiment showing impaired biological motion recognition for upside-down stimuli.
10.1098/rspb.1978.0020
20,102,735
The human visual process can be studied by examining the computational problems associated with deriving useful information from retinal images. In this paper, we apply this approach to the problem of representing three-dimensional shapes for the purpose of recognition. 1. Three criteria, accessibility, scope and uniqu...
10.1038/nrn1057
A paper on the recognition of articulated figures in terms of structural three-dimensional models.
10.1068/p3072
1,432,709
Johansson's point-light walker figures remain one of the most powerful and convincing examples of the role that motion can play in the perception of form (Johansson, 1973 Perception & Psychophysics14 201–211; 1975 Scientific American232(6) 76–88). In the current work, we use a dual-task paradigm to explore the role...
10.1038/nrn1057
A psychophysical study using a dual-task experiment to show that the tolerance of biological motion recognition against masking depends on attention.
10.1111/j.1467-9280.1990.tb00210.x
102,357,750
Observers viewed pairs of alternating photographs of a human body in different positions. Shortest-path motion solutions were pitted against anatomically possible movements. With short stimulus onset asynchronies (SOAs), observers tended to report the shortest path despite violations of anatomical constraints. However,...
10.1038/nrn1057
A psychophysical investigation of the perceived paths of apparent motion between two photographs of human body configurations. For small ISIs, motion along the shortest paths is perceived, so the percept is dominated by low-level motion perception. For long ISIs, subjects perceive the biologically possible paths, indic...
10.1126/science.aaa7945
38,325,049
Cell type–specific glial networks Glial cells respond to neurotransmitters when nerve cells communicate with each other. Glial cells themselves release gliotransmitters that regulate neural synaptic transmission. Martín et al. studied this reciprocal relationship in a brain region called the dorsal striatum, which has ...
10.1038/nrn.2016.159
This important study investigated how astrocytes modulate synaptic transmission in specific basal ganglia circuits and found that striatal astrocytes differentially regulate neuronal activity in a circuit- and synapse-specific manner.
10.1126/science.1221140
20,697,895
Crucial Cerebellar Glial Cells The role of glial cells and their interaction with neurons in normal behavior is unclear. To address this question, Saab et al. (p. 749 , published online 5 July) studied a special type of glial cell in the cerebellum. Conditional mutant mice were produced in which the two glutamate recep...
10.1038/nrn.2016.159
This work showed that AMPAR signalling in Bergmann glial cells is necessary for Purkinje cell activity and fine motor coordination at the behavioural level.
10.1017/s0033291712000438
102,241,391
Background Suicidal behavior is frequently associated with a history of childhood abuse yet it remains unclear precisely how early life adversity may increase suicide risk later in life. As such, our aim was to examine whether lifetime trajectories of disruptiveness and anxiousness trait dysregulation explain the assoc...
10.1038/nrn3839
Through trajectory analyses, this study gathers longitudinal data to describe the behavioural phenotypes that link ELA to suicide attempts.
10.1126/science.1246632
79,811,550
The distribution of 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid of 68 depressed patients was bimodal. Twenty-nine percent of the patients were in the lower mode, with a concentration of 5-HIAA below 15 nanograms per milliliter. Although there were no differences in overall severity of ...
10.1038/nrn3839
This is the first study to suggest that there is a link between alterations in the serotonergic system and suicidal behaviour.
10.1126/science.277.5332.1659
125,268,017
Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses...
10.1038/nrn3839
This landmark study establishes a link between maternal grooming of pups and regulation of the HPA axis in offspring.
10.1162/089892998563103
106,967,126
This study reports the development of a new, modified delayed matching to sample (DMS) visual recognition memory task that controls the relative novelty of test stimuli and can be used in human and nonhuman primates. We report findings from normal humans and unoperated monkeys, as well as three groups of operated monke...
10.1038/nrn1052
An experiment demonstrating that the processing advantage for contextually novel items, in an otherwise homogeneous list, is dependent on intact perirhinal–frontal interactions.
10.1111/j.1460-9568.1995.tb01108.x
45,383,937
Abstract Activity of single units of the noradrenergic nucleus locus coeruleus was recorded in rats during active exploration of a novel environment. Novelty was controlled by the placement of objects in given holes in a hole board. The basic protocol included a habituation session in which the holes were empty and an ...
10.1038/nrn1052
A direct demonstration of novelty-related responses in single neurons of the locus coeruleus of freely behaving rats.
10.4319/lo.1998.43.1.0129
29,348,304
The physiological processes of natural phytoplankton mortality due to environmental stress (vs. that caused by sedimentation and predation) are poorly understood. Cell survival was examined in batch cultures of the diatom Thalassiosira weissflogii and the chlorophyte Dunaliella tertiolecta during deprivation of fixed n...
10.1038/nrmicro956
The first demonstration of altered proteolytic profiles in marine phytoplankton during environmental stress, indicating the activation of cryptic proteases.
10.1104/pp.102.017129
122,542,041
Abstract Apoptosis is essential for normal growth and development of multicellular organisms, including metazoans and higher plants. Although cell death processes have been reported in unicellular organisms, key elements of apoptotic pathways have not been identified. Here, we show that when placed in darkness, the uni...
10.1038/nrmicro956
The first study to hint at the presence of caspase-like proteases in a unicellular phytoplankton and their role in autocatalytic cell death
10.4319/lo.2004.49.4.0997
103,167,738
We present experimental laboratory evidence and field observations of an autocatalyzed, programmed cell death (PCD) pathway in the nitrogen‐fixing cyanobacterium Trichodesmium spp., which forms massive blooms in the subtropical and tropical oceans. The PCD pathway was induced in response to phosphorus and iron starvati...
10.1038/nrmicro956
Demonstrates a role for caspase-like proteases in an evolutionary ancient bacterial representative of phytoplankton, indicating early evolution of these proteases.
10.1073/pnas.95.6.2891
81,369,397
Phage exclusion is a form of programmed cell death in prokaryotes in which death is triggered by infection with phage, a seemingly altruistic response that limits multiplication of the phage and its spread through the population. One of the best-characterized examples of phage exclusion is the exclusion of T-even phage...
10.1038/nrmicro956
Demonstration of a viral-exclusion strategy in a bacterium on sensing infection
10.1126/science.291.5507.1279
61,363,849
A comparison of the proteins encoded in the recently (nearly) completed human genome to those from the fly and nematode genomes reveals a major increase in the complexity of the apoptotic molecular machinery in vertebrates, in terms of both the number of proteins involved and their domain architecture. Several componen...
10.1038/nrmicro956
A demonstration of the increased specialization of the cell-death machinery in animals, especially in its regulation.
10.1126/science.281.5381.1312
104,248,926
REVIEW Apoptosis, an evolutionarily conserved form of cell suicide, requires specialized machinery. The central component of this machinery is a proteolytic system involving a family of proteases called caspases. These enzymes participate in a cascade that is triggered in response to proapoptotic signals and culminates...
10.1038/nrmicro956
A clear and concise presentation of caspases: regulation, activity, targets and effects.
10.1111/j.1550-7408.2005.05202003_1_64.x
26,941,222
The genome size of marine phytoplankton is in the order of 106–1011 base pairs. Within the phytoplankton it has often been assumed that dinoflagellates have extraordinarily large genomes that significantly contribute to their nutrient requirements. We test this hypothesis by compiling cell size and genome size data fro...
10.1038/nrmicro956
A comprehensive article that details the evolution of phytoplankton through geologic time scales and explores why the oceans are dominated by representatives of the red phytoplankton lineage.
10.1128/jvi.37.1.411-419.1981
101,116,385
The secondary structural features in the 70S RNAs of the Prague strain of avian Rous sarcoma virus, subgroup A (PR-RSV-A), and Moloney murine leukemia virus (M-MuLV) were compared by electron microscopy. The PR-RSV-A genome contained two subunits joined by a linkage structure as in the genomes of M-MuLV and other mamma...
10.1038/nrmicro903
References 1–4 provided definitive proof that retroviral RNA is dimeric in virions.
10.1128/jvi.70.12.8348-8354.1996
18,801,026
In retroviruses, the genomic RNA is in the form of a 60S-70S complex composed of two identical genome-length RNA molecules tightly associated through numerous interactions. A major interaction, called the dimer linkage structure, has been found near the RNA 5' end and is probably involved in the control of translation,...
10.1038/nrmicro903
References 79–82 and 85 were among the first to show the role of RNA dimerization in retroviral replication, RNA packaging and reverse transciption.
10.1128/jvi.71.4.3250-3254.1997
80,660,693
To characterize the cis-acting determinants that function in RNA dimer formation and maintenance, we examined the stability of RNA dimers isolated from virus particles containing mutations in the encapsidation region of human immunodeficiency virus type 1 (HIV-1). The genomic RNAs of all mutants containing lesions in e...
10.1038/nrmicro903
References 87 and 88 show that the dimer linkage structure is not the only region for dimeric RNA interaction.
10.1073/pnas.062652199
60,378,559
The retroviral Gag polyprotein directs budding from the plasma membrane of infected cells. Until now, it was believed that Gag proteins of type C retroviruses, including the prototypic oncoretrovirus Rous sarcoma virus, were synthesized on cytosolic ribosomes and targeted directly to the plasma membrane. Here we reveal...
10.1038/nrmicro903
References 108–109, 113 and 114 present a strong correlation that the trafficking of retroviral Gag might influence the dimerization of viral RNA genomes.
10.1128/jvi.16.5.1161-1170.1975
101,194,145
Extracellular maturation of Bratislava 77(B77) sarcoma virus RNA involves a stabilization of linkage between 35S subunits since the Tm of 60 to 70S RNA in the presence of 0.5 M NaCl increases from 56 to 67.5 C as the age of the virus increases. This stabilization process is strongly temperature dependent; the rate at 4...
10.1038/nrmicro903
Collectively, references 36–38, 102, 103 and 129 show that a virion RNA genome undergoes conformational changes during virion maturation.
10.1128/jvi.71.8.5723-5732.1997
80,663,353
During human immunodeficiency virus type 1 (HIV-1) virion assembly, cleavage of the Gag precursor by the viral protease results in the transient appearance of a nucleocapsid-p1-p6 intermediate product designated p15NC. Utilizing the p15NC precursor protein produced with an in vitro transcription-translation system or p...
10.1038/nrmicro903
Together, references 83–84, 95 and 133 show that the RNA sequence itself might have an important role in virion protein processing.
10.1073/pnas.0306764101
20,420,740
Genetic recombination is believed to assist HIV-1 diversification and escape from host immunity and antiviral therapies, yet this process remains largely unexamined within the natural target-cell populations. We developed a method for measuring HIV-1 recombination directly that employs reporter viruses bearing function...
10.1038/nrmicro903
References 151–153 demonstrate that double infection of HIV-1 and recombinations are likely to occur frequently in vivo
10.1002/cne.20859
125,003,643
Abstract Emotions, stress, hunger, and circadian rhythms all promote wakefulness and behavioral arousal. Little is known about the pathways mediating these influences, but the orexin‐producing neurons of the hypothalamus may play an essential role. These cells heavily innervate many wake‐promoting brain regions, and mi...
10.1038/nrn2092
References 14 – 15 map the neuronal input to orexin neurons.
10.1002/cne.1190
83,036,661
Abstract Orexins (hypocretins) are neuropeptides synthesized in the central nervous system exclusively by neurons of the lateral hypothalamus. Orexin‐containing neurons have widespread projections and have been implicated in complex physiological functions including feeding behavior, sleep states, neuroendocrine functi...
10.1038/nrn2092
Comprehensive report on the distribution of orexin receptor mRNAs in the rat brain.
10.1073/pnas.0400590101
108,955,376
Narcolepsy-cataplexy is a neurological disorder associated with the inability to maintain wakefulness and abnormal intrusions of rapid eye movement sleep-related phenomena into wakefulness such as cataplexy. The vast majority of narcoleptic-cataplectic individuals have low or undetectable levels of orexin (hypocretin) ...
10.1038/nrn2092
Demonstrates rescue of the narcolepsy–cataplexy phenotype of orexin neuron-ablated mice by genetic and pharmacological means, providing evidence that receptor agonists might be of potential value for treating human narcolepsy.
10.1073/pnas.95.1.322
20,687,273
We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The...
10.1038/nrn2092
Describes the independent discovery of the transcript that encodes orexins, the prediction that two peptides are encoded by the transcript, and the detection of the peptides in dense-core vesicles at synapses.
10.1126/science.1118370
103,714,907
Hsp90 is a molecular chaperone for many signal transducers and may influence evolution by releasing previously silent genetic variation in response to environmental change. In fungi separated by ∼800 million years of evolution, Hsp90 potentiated the evolution of drug resistance in a different way, by enabling new mutat...
10.1038/nrmicro2875
A summary of the role of Hsp90 in the evolution of antifungal drug resistance.
10.1126/science.aaf2693
41,531,100
A dietary supplement protects aging muscle The oxidized form of cellular nicotinamide adenine dinucleotide (NAD + ) is critical for mitochondrial function, and its supplementation can lead to increased longevity. Zhang et al. found that feeding the NAD + precursor nicotinamide riboside (NR) to aging mice protected them...
10.1038/nrn.2017.42
This study demonstrates that nicotinamide riboside treatment improves muscle stem cell function in aged mice and extends lifespan when the treatment starts at 2 years of age.
10.1126/science.275.5306.1593
41,713,287
The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work h...
10.1038/nrn2119
Comprehensively describes the theoretical basis of reinforcement learning models of dopamine in monkeys.
10.1146/annurev.neuro.25.112701.142754
83,244,313
▪ Abstract A combination of genetic susceptibility and environmental perturbations appear to be necessary for the expression of schizophrenia. In addition, the pathogenesis of the disease is hypothesized to be neurodevelopmental in nature based on reports of an excess of adverse events during the pre- and perinatal per...
10.1038/nrn3155
A general overview of the evidence that supports the idea that schizophrenia is a consequence of abnormal brain development.
10.1073/pnas.0910302107
83,189,966
Neuregulin 1 (NRG1) is a trophic factor thought to play a role in neural development. Recent studies suggest that it may regulate neurotransmission, mechanisms of which remain elusive. Here we show that NRG1, via stimulating GABA release from interneurons, inhibits pyramidal neurons in the prefrontal cortex (PFC). Abla...
10.1038/nrn3155
In this study, the authors show that deletion of Erbb4 from PV + neurons in mice leads to increased activity of pyramidal cells and behavioural abnormalities.
10.1073/pnas.0704774104
61,823,343
Here, we report generation and characterization of Disrupted-In-Schizophrenia-1 (DISC1) genetically engineered mice as a potential model for major mental illnesses, such as schizophrenia. DISC1 is a promising genetic risk factor for major mental illnesses. In this transgenic model, a dominant-negative form of DISC1 (DN...
10.1038/nrn3155
This article reports on several phenotypes caused by the expression of a disease-associated form of DISC1 . These phenotypes include cortical interneuron abnormalities.
10.1073/pnas.0904289106
39,155,015
Dysbindin has been implicated in the pathogenesis of schizophrenia, but little is known about how dysbindin affects neuronal function in the circuitry underlying psychosis and related behaviors. Using a dysbindin knockout line (dys −/− ) derived from the natural dysbindin mutant Sandy mice, we have explored the role of...
10.1038/nrn3155
This study demonstrates a link between dysbindin and the normal functioning of cortical PV + interneurons.
10.1073/pnas.081620098
83,117,723
Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins. Moreover, elevated Aβ42 levels and the ɛ4 allele of the lipid-carrier apolipoprotein E are regarded as risk factors for sporadic and familial Alzheimer's disease. Here we...
10.1038/nrn1728
The cholesterol-lowering statins simvastatin and lovastatin reduce intra- and extracellular levels of amyloid-β (Aβ) proteins, which are involved in the pathogenesis of Alzheimer's disease, so opening up novel avenues for therapeutic intervention. As the Aβ efflux from brain cells is thought to be mediated by Pgp, the ...
10.1002/ana.20369
83,506,605
Abstract Parkinson's disease (PD) is associated with a loss of neurons from the midbrain. The cause of PD is unknown, but it is established that certain neurotoxins can cause similar syndromes. The brain is normally protected from these noxious blood‐borne chemicals by the blood–brain barrier which includes specialized...
10.1038/nrn1728
The first demonstration that [ 11 C]-verapamil can be used as a PET probe for in vivo Pgp function in the BBB in patients, supporting the idea that a dysfunctional BBB is a causative mechanism in Parkinson's disease.
10.1177/37.2.2463300
57,481,658
Using peroxidase immunohistochemistry, we examined the distribution of P170, a multidrug transport protein, in normal tissues by use of two different monoclonal antibodies (MAb). MAb MRK16 is a MAb that has been shown to react with an epitope in P170 located on the external face of the plasma membrane of multidrug-resi...
10.1038/nrn1728
The first demonstration that Pgp is localized in blood capillaries in the brain, but not capillaries in most other tissues, which indicates that Pgp in the BBB might limit the entry of potentially toxic compounds in blood to the brain by actively pumping them back into the blood.
10.1073/pnas.94.8.4028
80,117,774
The mdr1-type P-glycoproteins (P-gps) confer multidrug resistance to cancer cells by active extrusion of a wide range of drugs from the cell. To study their physiological roles, we have generated mice genetically deficient in the mdr1b gene [ mdr1b (−/−) mice] and in both the mdr1a and mdr1b genes [ mdr1a/1b (−/−) mice...
10.1038/nrn1728
Mice that are genetically deficient in both the Mdr1a and Mdr1b genes, which together seem to fulfill the same functions as the single human MDR1 gene, show similar increases in brain penetration of drugs to mice that are deficient in Mdr1a alone, which indicates that Pgp in the BBB is predominantly encoded by Mdr1a in...
10.1111/j.1528-1157.1995.tb01657.x
62,333,331
Summary: Why some patients with seizures are successfully treated with antiepileptic drugs (AEDs) and others prove medically intractable is not known. Inadequate intraparenchymal drug concentration is a possible mechanism of resistance to AEDs. The multiple drug resistance gene (MDRI) encodes P‐glycoprotein, an energy‐...
10.1038/nrn1728
The first study to show that MDR1 and Pgp are overexpressed in the brain capillary endothelium and astrocytes of patients with drug-resistant epilepsy.
10.1523/jneurosci.22-14-05833.2002
19,247,746
The causes and mechanisms underlying multidrug resistance (MDR) in epilepsy are still elusive and may depend on inadequate drug concentration in crucial brain areas. We studied whether limbic seizures or anticonvulsant drug treatments in rodents enhance the brain expression of the MDR gene ( mdr ) encoding a permeabili...
10.1038/nrn1728
An elegant study showing that seizure-induced overexpression of Pgp in the hippocampus of mice is associated with a significant decrease in the brain/plasma ratio of the AED phenytoin.
10.1177/153537020523000206
11,260,373
The central nervous system (CNS) effects of many therapeutic drugs are blunted because of restricted entry into the brain. The basis for this poor permeability is the brain capillary endothelium, which comprises the blood-brain barrier. This tissue exhibits very low paracellular (tight-junctional) permeability and expr...
10.1038/nrn1728
An excellent review on the current understanding of the various mechanisms by which Pgp in the BBB is modulated, which might provide strategies for selectively manipulating BBB permeability for a large number of drugs.
10.1073/pnas.93.24.14164
38,332,895
Immunoliposomes (antibody-directed liposomes) were used in the present study for delivery of the antineoplastic agent daunomycin to the rat brain. A coupling procedure was introduced, which allows conjugation of a thiolated antibody to maleimide-grafted 85-nm liposomes sterically stabilized with PEG. Antibody was there...
10.1038/nrn1728
Antibody-directed liposomes were used to deliver the anti-cancer drug daunomycin to the rat brain by coupling of liposomes to the OX26 monoclonal antibody against the rat transferrin receptor, which is selectively enriched at the brain microvascular endothelium that comprises the BBB.
10.1111/1467-9280.00090
122,424,072
Although the influence of emotional arousal on declarative memory has been documented behaviorally, the mechanisms underlying arousal-memory interactions and their representation in the human brain remain uncertain. One route through which arousal achieves its effects on memory performance is by regulating consolidatio...
10.1038/nrn1825
One of the only experiments to test emotional recall in patients with amygdala lesions over multiple retention intervals to specify deficits in the consolidation phase of declarative memory.
10.1073/pnas.162356599
103,474,026
Psychological studies have found better memory in women than men for emotional events, but the neural basis for this difference is unknown. We used event-related functional MRI to assess whether sex differences in memory for emotional stimuli is associated with activation of different neural systems in men and women. B...
10.1038/nrn1825
A functional neuroimaging view of how emotional memory processing differs in male and female brains.
10.1073/pnas.0409848102
38,334,656
The memory-enhancing effect of emotion can be powerful and long-lasting. Most studies investigating the neural bases of this phenomenon have focused on encoding and early consolidation processes, and hence little is known regarding the contribution of retrieval processes, particularly after lengthy retention intervals....
10.1038/nrn1825
Shows that functional interactions between the amygdala and MTL memory regions extend beyond encoding and consolidation to promote recollection-based successful retrieval of 1-year-old emotional memories.
10.1126/science.7652558
19,270,654
A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the ...
10.1038/nrn1825
An excellent example of the value of neuropsychological approaches showing how patients with selective lesions to adjacent MTL structures perform differently on declarative and non-declarative aspects of the same emotional learning task.
10.1073/pnas.79.21.6712
81,419,043
The capacitance of the surface membrane of small adrenal chromaffin cells was measured with patch-clamp pipettes. Continuous and discrete changes of capacitance were observed. They were interpreted as changes of surface area connected to exocytotic or endocytotic processes. Most of the measurements were performed in th...
10.1038/nsmb.1449
Besides opening up the study of exocytosis to electrical measurements, this paper was the first report of capacitance flickers, one of the hallmarks of kiss-and-run.
10.1126/science.1095801
41,732,391
The fusion pore of regulated exocytosis is a channel that connects and spans the vesicle and plasma membranes. The molecular composition of this important intermediate structure of exocytosis is unknown. Here, we found that mutations of some residues within the transmembrane segment of syntaxin (Syx), a plasma membrane...
10.1038/nsmb.1449
The first study to locate a molecule, syntaxin, as a structural component of a fusion pore in Ca 2+ -triggered exocytosis.
10.1101/gr.1330003
4,495,401
The availability of genome-scale gene expression data sets has initiated the development of methods that use this data to infer transcriptional regulatory networks. Alternatively, such regulatory network structures can be reconstructed based on annotated genome information, well-curated databases, and primary research ...
10.1038/nrmicro2419
An informative study illustrating the limitations of expression-based network inference for E. coli and S. cerevisiae
10.1073/pnas.0913357107
41,078,930
Numerous methods have been developed for inferring gene regulatory networks from expression data, however, both their absolute and comparative performance remain poorly understood. In this paper, we introduce a framework for critical performance assessment of methods for gene network inference. We present an in silico ...
10.1038/nrmicro2419
A discussion about the current limitations of network inference methods based on submissions to the DREAM3 in silico challenge.
10.1073/pnas.0902925106
102,958,659
In most mammalian species, a key process of placenta development is the fusion of trophoblast cells into a highly specialized, multinucleated syncytiotrophoblast layer, through which most of the maternofetal exchanges take place. Little is known about this process, despite the recent identification of 2 pairs of envelo...
10.1038/nrmicro2783
The first unequivocal evidence that a protein encoded by an ERV has a key role in vertebrate development.
10.1242/dev.091066
80,135,089
At the protochordate-vertebrate transition, a new predatory lifestyle and increased body size coincided with the appearance of a true head. Characteristic innovations of this head are a skull protecting and accommodating a centralized nervous system, a jaw for prey capture and gills as respiratory organs. The neural cr...
10.1038/nature14436
This paper identifies gill pillar cells, which are crucial for gill structure throughout vertebrates, as neural crest derivatives.
10.1101/gr.076208.108
123,955,988
The emergence of the neural crest has been proposed to play a key role in early vertebrate evolution by remodeling the chordate head into a “new head” that enabled early vertebrates to shift from filter feeding to active predation. Here we show that the genome of the basal chordate, amphioxus, contains homologs of most...
10.1038/nature14436
This paper showed that an AmphiFoxD regulatory element was capable of driving expression in chicken somites, but not in neural crest, suggesting that novel regulatory elements were required for AmphiFoxD incorporation into the neural crest GRN.
10.1242/dev.093534
39,117,309
The neural crest is a multipotent stem cell population that arises from the dorsal aspect of the neural tube and generates both non-ectomesenchymal (melanocytes, peripheral neurons and glia) and ectomesenchymal (skeletogenic, odontogenic, cartilaginous and connective tissue) derivatives. In amniotes, only cranial neura...
10.1038/nature14436
This recent paper finds that neural crest cells at trunk levels do not contribute to fin mesenchyme, in contrast to earlier claims.
10.1126/science.1253281
20,761,752
The peripheral autonomic nervous system reaches far throughout the body and includes neurons of diverse functions, such as sympathetic and parasympathetic. We show that the parasympathetic system in mice—including trunk ganglia and the cranial ciliary, pterygopalatine, lingual, submandibular, and otic ganglia—arise fro...
10.1038/nature14436
One of two papers demonstrating that Schwann-cell precursors also give rise to parasympathetic neurons.
10.1126/science.1253286
62,277,108
Neural crest cells migrate extensively and give rise to most of the peripheral nervous system, including sympathetic, parasympathetic, enteric, and dorsal root ganglia. We studied how parasympathetic ganglia form close to visceral organs and what their precursors are. We find that many cranial nerve-associated crest ce...
10.1038/nature14436
The second of two papers demonstrating that Schwann-cell precursors are a source of parasympathetic neurons.
10.1126/science.1157535
38,441,260
The multiprotein mTORC1 protein kinase complex is the central component of a pathway that promotes growth in response to insulin, energy levels, and amino acids and is deregulated in common cancers. We find that the Rag proteins—a family of four related small guanosine triphosphatases (GTPases)—interact with mTORC1 in ...
10.1038/nature14190
References 54 and 55 report the identification of the Rag GTPases as the direct link between amino-acids levels and mTORC1, regulating mTORC1's subcellular localization.
10.1126/science.154.3753.1189
107,159,541
A crystalline germination stimulant (trivial name strigol) for the root parasite, witchweed ( Striga lutea Lour.), has been isolated from cotton root exudates and characterized as a C 19 H 22 O 6 compound. Although apparently different from known plant hormones, the stimulant is active at hormonal levels, causing germi...
10.1038/nchembio.2340
The first report of the identification of strigolactones in vascular plants
10.1126/science.1218094
82,890,715
Making Carlactone Germination of parasitic witchweeds depends on strigolactones, which also regulate plant branching and signal in the context of mycorrhizal symbioses. The biosynthetic pathways that lead to strigolactones are founded in carotenoid biosynthesis, but further steps have been obscure. Alder et al. (p. 134...
10.1038/nchembio.2340
This report and ref. 23 were key to understanding how SLs are synthesized from carotenoids through carlactone
10.1242/dev.129.5.1131
104,442,284
Plant shoots elaborate their adult form by selective control over the growth of both their primary shoot apical meristem and their axillary shoot meristems. We describe recessive mutations at two loci in Arabidopsis, MAX1 and MAX2, that affect the selective repression of axillary shoots. All the first order (but not hi...
10.1038/nchembio.2340
The first report suggesting a role for F-box-mediated proteolysis in strigolactones signaling
10.1242/dev.074567
125,171,509
Karrikins are butenolides derived from burnt vegetation that stimulate seed germination and enhance seedling responses to light. Strigolactones are endogenous butenolide hormones that regulate shoot and root architecture, and stimulate the branching of arbuscular mycorrhizal fungi. Thus, karrikins and strigolactones ar...
10.1038/nchembio.2340
A report suggesting that D14-type and HTL/KAI2-type α/β hydrolase receptors differentiate between related butenolide compounds and regulate different plant processes
10.1126/science.aab1140
60,711,450
How plant parasites evolved to find hosts The seeds of parasitic plants need to be able to sense their host's presence to germinate at the correct time and in the correct place. This is done through the detection of plant hormones, strigolactones. However, the origin of this sensory system is unknown. Conn et al. inves...
10.1038/nchembio.2340
This report, along with refs. 77 and 78 , suggests that HTL/KAI2-type α/β hydrolases are strigolactone receptors in Striga hermonthica
10.1038/ncomms4012
38,301,075
Abstract Advancing the debate on quantum effects in light-initiated reactions in biology requires clear identification of non-classical features that these processes can exhibit and utilize. Here we show that in prototype dimers present in a variety of photosynthetic antennae, efficient vibration-assisted energy transf...
10.1038/nature21425
Theoretical analysis suggests that vibronic coherence can be rigorously quantum mechanical
10.1126/science.1150609
125,149,782
The β 2 -adrenergic receptor (β 2 AR) is a well-studied prototype for heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) that respond to diffusible hormones and neurotransmitters. To overcome the structural flexibility of the β 2 AR and to facilitate its crystallization, we engineer...
10.1038/nature11896
Description of the T4 lysozyme fusion strategy that led to the first high-resolution β 2 -AR structure using the lipidic cubic phase crystallization technique 3 , which has been subsequently used to facilitate the crystallization of many other GPCRs.
10.1126/science.1202793
83,281,719
Changes associated with conformationally selective agonist binding shed light on G protein–coupled receptor activation.
10.1038/nature11896
Along with ref. 11, this paper describes the structure of A 2A R in an agonist-bound active-like state that shows common features of activation compared to β 2 -AR.
10.1073/pnas.1104614108
26,961,934
How drugs bind to their receptors—from initial association, through drug entry into the binding pocket, to adoption of the final bound conformation, or “pose”—has remained unknown, even for G-protein-coupled receptor modulators, which constitute one-third of all marketed drugs. We captured this pharmaceutically critica...
10.1038/nature11896
Long timescale molecular dynamics simulations are used to define a potential intermediate in the GPCR conformational change from the active to inactive state, and shows the potential for studying the activation mechanism of GPCR through molecular simulations.
10.1002/adfm.201302631
62,245,071
As one important component of sulfur cathodes, the carbon host plays a key role in the electrochemical performance of lithium‐sulfur (Li‐S) batteries. In this paper, a mesoporous nitrogen‐doped carbon (MPNC)‐sulfur nanocomposite is reported as a novel cathode for advanced Li‐S batteries. The nitrogen doping in the MPNC...
10.1038/nenergy.2016.132
One of the first papers to demonstrate the excellent properties of nitrogen-doped carbons as Li–S cathode hosts using both experiment and theory.
10.1039/c5ee02367j
89,129,926
The anatomy of a truffle inspired sulfur particle for a battery cathode.
10.1038/nenergy.2016.132
A multilayer approach to creating polyelectrolyte coatings on sulfur particles was described, leading to very stable cycling behaviour.
10.1002/anie.201410174
62,651,049
Abstract Lithium–sulfur batteries are amongst the most promising candidates to satisfy emerging energy‐storage demands. Suppression of the polysulfide shuttle while maintaining high sulfur content is the main challenge that faces their practical development. Here, we report that 2D early‐transition‐metal carbide conduc...
10.1038/nenergy.2016.132
This paper reported that the exfoliated MXene family of 2D materials chemically bind polysulfides via Lewis acid–base metal–sulfur bonding.
10.1063/1.2841917
47,034,215
We present investigations on the resistive switching effect in SrRuO3∕PbZr0.2Ti0.8O3∕Pt ferroelectric capacitors. Using a conductive atomic force microscope, the out-of-plane piezoelectric response and the capacitive and resistive current were simultaneously measured as a function of applied bias voltage. We observed t...
10.1038/ncomms5289
Key article emphasizing the need to independently probe ferroelectric switching and resistive switching in ferroelectric tunnel junctions in order to distinguish tunnel electroresistance from defects-related resistive switching
10.1126/science.1171200
61,855,461
Ferroelectric Patterning with High Fields Ferroelectric oxides have a net polarization that can switch direction upon application of a sufficiently high electric field. In principle, a ferroelectric thin film should be able to act as a polar switch—tunneling an electron through the film would effectively switch on or o...
10.1038/ncomms5289
First demonstration of simultaneous ferroelectric and resistive switching in Fowler-Nordheim tunnelling across a ferroelectric combining local probes
10.1126/science.1184028
41,506,469
Spin into Control Spintronics—the use of the spin direction of subatomic particles to control on and off states, instead of electric charge—has the potential to create low-power electronics, because less energy is needed to flip spin states than to flip switches to create voltage barriers. Theoretical work hints that s...
10.1038/ncomms5289
First indirect evidence of interfacial magnetoelectric coupling probed by tunnel magnetoresistance in artificial multiferroic tunnel junctions
10.1890/120144
20,804,864
Despite growing interest and investment in ecosystem services across global science and policy arenas, it remains unclear how ecosystem services – and particularly changes in those services – should be measured. The social and ecological factors, and their interactions, that create and alter ecosystem services are inhe...
10.1038/nature13945
This paper reports that policy-related indicators for development goals have focused almost entirely on ecosystems, without effective monitoring of the socioeconomic systems that often drive ecosystem change.
10.1177/0951692803015003002
123,883,666
The study of collective action has matured dramatically since Mancur Olson challenged scholars by positing a general theory in his pathbreaking book on The Logic of Collective Action (1965). Olson's theoretical predictions related to the incapacity of individuals, except under limited conditions, to solve on their own ...
10.1038/nature13945
This paper lays out a set of premises that explain the conditions that determine the effectiveness of institutions in common property systems.
10.2307/2269582
58,458,199
We examine the relationship between socioeconomic equity in opportunity and sustainability, as reflected in patterns of food production and fertility. Our analysis spans various levels of social organization, from within the household (gender‐ and age‐related equity) to relations among households (of different material...
10.1038/nature13945
This paper reports that increasing equity can help to increase food production and reduce fertility rates, but runaway consumption must be curbed for sustainability.
10.1046/j.1523-1739.1996.10020328.x
62,171,597
As the human population grows and natural resources decline, there is pressure to apply increasing levels of top‐down, command‐and‐control management to natural resources. This is manifested in attempts to control ecosystems and in socioeconomic institutions that respond to erratic or surprising ecosystem behavior with...
10.1038/nature13945
This paper states that attempts to maximize offtake from production systems often create vulnerabilities in those systems, leading to collapse.
10.1002/asl.289
61,542,774
Abstract The atmospheric composition of West Africa reflects the interaction of various dynamical and chemical systems (i.e. biogenic, urban, convective and long‐range transport) with signatures from local to continental scales. Recent measurements performed during the African Monsoon Multidisciplinary Analyses (AMMA) ...
10.1038/nclimate2727
This paper provides a broad overview of knowledge of the regional atmospheric composition over West Africa.
10.1126/science.1198469
83,477,215
Bacteria of the genus Clostridium promote the induction of suppressor T cells in the colons of mice.
10.1038/nchembio.741
This study reports that Clostridium species induce regulatory T cells and maintain immunological homeostasis via stimulating matrix metalloprotease-TGF-β signaling.
10.1126/science.1166382
84,387,472
The Vibrio parahaemolyticus type III effector VopS is implicated in cell rounding and the collapse of the actin cytoskeleton by inhibiting Rho guanosine triphosphatases (GTPases). We found that VopS could act to covalently modify a conserved threonine residue on Rho, Rac, and Cdc42 with adenosine 5′-monophosphate (AMP)...
10.1038/nchembio.741
This study shows that VopS has AMPylation activity and modifies conserved threonine residues in Rho GTPase, thereby disrupting Rho GTPase signaling and regulating actin cytoskeleton remodeling.
10.1126/science.1193844
80,269,876
Gee-Up, NEDD8 Diverse bacterial pathogens, such as Burkholderia pseudomallei and enteropathogenic Escherichia coli (EPEC), inject effector proteins into eukaryotic host cells to subvert host cell biology. Cui et al. (p. 1215 ; published online 5 August) show that certain bacterial effector proteins promoted the glutami...
10.1038/nchembio.741
This study reveals that Cif deaminates NEDD8 and interferes with its function, resulting in cell cycle arrest.
10.1073/pnas.69.11.3199
20,505,186
When species diversity S on an island is displaced from the equilibrium value by injection or removal of species, S relaxes to equilibrium by an imbalance between immigration and extinction rates. Estimates of exponential relaxation times, t r , for avifaunas of New Guinea satellite islands are calculated from analysis...
10.1038/ncomms9862
This paper established the phenomenon of delayed extinctions (later known as extinction debt) by noticing that all large islands isolated at end of Pleistocene lay above the SAR
10.1126/science.1083182
29,286,054
Human antibody 2G12 neutralizes a broad range of human immunodeficiency virus type 1 (HIV-1) isolates by binding an unusually dense cluster of carbohydrate moieties on the “silent” face of the gp120 envelope glycoprotein. Crystal structures of Fab 2G12 and its complexes with the disaccharide Manα1-2Man and with th...
10.1038/nchembio.1685
This paper discloses the crystal structure of bnAb 2G12 (Fab) 2 bound to Man 9 GlcNAc 2 , revealing the unique domain-exchanged structure of this antibody, and proposes a model of the gp120-2G12 interaction.
10.1126/science.1245625
83,549,503
Knowing the Enemy Infection of host cells by HIV-1 is mediated by an envelope glycoprotein (Env) trimeric spike on the surface of the virus. Proteins comprising the Env trimer must be cleaved for infectivity, and thus viral fusion involves three Env conformations. The flexibility of the Env trimer has made it a challen...
10.1038/nchembio.1685
This paper reports the first crystal structure of a gp120-related construct in trimeric form. This structure also includes bound PGT122 Fab, showing for the first time the interaction of a glycan-binding bnAb with a more or less complete gp120 construct, at this resolution.
10.1073/pnas.1317855110
27,967,873
Significance A current key goal of HIV-1 vaccine development is to learn how to induce antibodies that will neutralize many diverse HIV-1 strains. Current HIV-1 vaccines elicit strain-specific neutralizing antibodies, whereas broadly neutralizing antibodies (BnAbs) are not induced and only arise in select HIV-1 chronic...
10.1038/nchembio.1685
This paper reports the most antigenic PG9 epitope mimic glycopeptide synthesized to date and shows that it is also recognized well by germline PG9.
10.1073/pnas.1217537110
20,397,292
PG9 is the founder member of an expanding family of glycan-dependent human antibodies that preferentially bind the HIV (HIV-1) envelope (Env) glycoprotein (gp) trimer and broadly neutralize the virus. Here, we show that a soluble SOSIP.664 gp140 trimer constructed from the Clade A BG505 sequence binds PG9 with high aff...
10.1038/nchembio.1685
This paper reports cryo-EM data showing that PG9 binds the apex of the gp120 trimer at the interface of two gp120 protomers.
10.1126/science.1104819
104,264,564
Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. The widely held view is that these antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Here, I review emerging evidence supporting an a...
10.1038/nature10144
This review presents evidence for vascular abnormalities in tumours, and the therapeutic potential to normalize these vessels for treatment of cancer and other diseases characterized by abnormal vessels.
10.1093/oso/9780198515708.001.0001
148,989,907
Abstract The relationship between biodiversity and ecosystem functioning has emerged as one of the most exciting and dynamic areas in contemporary ecology. Increasing domination of ecosystems by humans is steadily transforming them into depauperate systems. How will this loss of biodiversity affect the functioning and ...
10.1038/nature11148
This book, which followed a 2000 conference in Paris, summarized the first decade of BEF research.
10.1111/j.1466-8238.2010.00592.x
29,326,467
ABSTRACT Aim An important issue regarding biodiversity concerns its influence on ecosystem functioning. Experimental work has led to the proposal of mechanisms such as niche complementarity. However, few attempts have been made to confirm these in natural systems, especially in forests. Furthermore, one of the most int...
10.1038/nature11148
This paper, along with ref. 21, exemplifies how to quantify biodiversity effects on ecosystem functions at large scales in real ecosystems.
10.1111/j.1461-0248.2006.00963.x
103,841,939
Abstract Concern is growing about the consequences of biodiversity loss for ecosystem functioning, for the provision of ecosystem services, and for human well being. Experimental evidence for a relationship between biodiversity and ecosystem process rates is compelling, but the issue remains contentious. Here, we prese...
10.1038/nature11148
This paper, along with ref. 25, was the first to synthesize BEF research via statistical meta-analyses.
10.1126/science.1060391
125,128,812
Plant diversity and niche complementarity had progressively stronger effects on ecosystem functioning during a 7-year experiment, with 16-species plots attaining 2.7 times greater biomass than monocultures. Diversity effects were neither transients nor explained solely by a few productive or unviable species. Rather, m...
10.1038/nature11148
This experiment continues to be one of the largest and longest running biodiversity studies ever conducted.
10.1126/science.1205106
41,673,304
Until recently, large apex consumers were ubiquitous across the globe and had been for millions of years. The loss of these animals may be humankind’s most pervasive influence on nature. Although such losses are widely viewed as an ethical and aesthetic problem, recent research reveals extensive cascading effects of th...
10.1038/nature11148
This paper summarizes how the extinction of large carnivores has an impact on ecosystem processes, emphasizing the urgent need to integrate trophic interactions into BEF and BES research.
10.1073/pnas.0704716104
62,618,295
Global environmental change affects the sustained provision of a wide set of ecosystem services. Although the delivery of ecosystem services is strongly affected by abiotic drivers and direct land use effects, it is also modulated by the functional diversity of biological communities (the value, range, and relative abu...
10.1038/nature11148
This paper outlined a framework for linking species functional traits to ecosystem services, which moves the field of BES research towards more predictive models.
10.1073/pnas.0711697105
104,041,813
The persistence of Mycobacterium tuberculosis despite prolonged chemotherapy represents a major obstacle for the control of tuberculosis. The mechanisms used by Mtb to persist in a quiescent state are largely unknown. Chemical genetic and genetic approaches were used here to study the physiology of hypoxic nonreplicati...
10.1038/nature09657
Important research demonstrating the effect of inhibition of the respiratory chain for killing dormant TB bacilli.
10.1126/science.1167498
45,518,045
β-lactam antibiotics are ineffective against Mycobacterium tuberculosis , being rapidly hydrolyzed by the chromosomally encoded blaC gene product. The carbapenem class of β-lactams are very poor substrates for BlaC, allowing us to determine the three-dimensional structure of the covalent BlaC-meropenem covalent complex...
10.1038/nature09657
Renewed interest in β-lactams and their combination with broad-spectrum lactamase inhibitors for TB treatment.
10.1073/pnas.0500469102
124,069,047
Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. Analysis of the Mtb genome predicts the existence of a branched aerobic respiratory chain terminating in a cytochrome bd system and a cytochrome aa 3 system. Both chains can be initiat...
10.1038/nature09657
An interesting demonstration of targeting NADH dehydrogenase for identifying new TB drugs or re-purposing old drug classes.