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10.1073/pnas.0704008104 | 60,362,289 | Terminase enzyme complexes, which facilitate ATP-driven DNA packaging in phages and in many eukaryotic viruses, constitute a wide and potentially diverse family of molecular motors about which little dynamic or mechanistic information is available. Here we report optical tweezers measurements of single DNA molecule pac... | 10.1038/nrmicro2632 | This investigation defines the basic rate and force parameters of the phage T4 packaging motor. |
10.1073/pnas.0701323104 | 59,464,957 | In many viruses, DNA is confined at such high density that its bending rigidity and electrostatic self-repulsion present a strong energy barrier in viral assembly. Therefore, a powerful molecular motor is needed to package the DNA into the viral capsid. Here, we investigate the role of electrostatic repulsion on single... | 10.1038/nrmicro2632 | This paper describes the X-ray structure of phage T4 TerL, the ATPase that powers DNA packaging. |
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/nrn.2016.167 | This paper highlights the impact of common 'questionable research practices' on study outcomes and proposes a set of guidelines to prevent false-positive findings. |
10.1073/pnas.1602413113 | 41,630,985 | The most widely used task functional magnetic resonance imaging (fMRI) analyses use parametric statistical methods that depend on a variety of assumptions. In this work, we use real resting-state data and a total of 3 million random task group analyses to compute empirical familywise error rates for the fMRI software p... | 10.1038/nrn.2016.167 | This paper shows that some commonly used methods for cluster-based multiple-comparison correction can exhibit inflated false-positive rates. |
10.1126/science.aac4716 | 20,808,720 | Empirically analyzing empirical evidence One of the central goals in any scientific endeavor is to understand causality. Experiments that seek to demonstrate a cause/effect relation most often manipulate the postulated causal factor. Aarts et al. describe the replication of 100 experiments reported in papers published ... | 10.1038/nrn.2016.167 | This paper reports a large-scale collaboration that quantified the replicability of research in psychology, showing that less than half of the published findings were replicable. |
10.1152/jn.1996.76.3.2071 | 59,333,043 | 1. The lateral intraparietal area (LIP) of the posterior parietal cortex lies within the dorsal cortical stream for spatial vision and processes visual information to plan saccadic eye movements. We investigated how LIP neurons respond when a monkey makes saccades to the remembered location of sound sources in the abse... | 10.1038/nrn873 | References 7–9 established for the first time the existence of eye-centred response fields for visually guided reaching in PRR, and eye-centred and intermediate response fields for auditory targets in LIP and PRR. |
10.1152/jn.2000.83.5.2580 | 125,068,078 | In this study, we mainly investigated the visual selectivity of hand-manipulation-related neurons in the anterior intraparietal area (area AIP) while the animal was grasping or fixating on three-dimensional (3D) objects of different geometric shapes, sizes, and orientations. We studied the activity of 132 task-related ... | 10.1038/nrn873 | References 18–21 described for the first time a role of area AIP in the sensorimotor processing for grasping movements. |
10.1159/000013783 | 81,564,411 | In a series of experiments on New World and Old World monkeys, architectonic features of auditory cortex were related to tone frequency maps and patterns of connections to generate and evaluate theories of cortical organization. The results suggest that cortical processing of auditory information involves a number of f... | 10.1038/nrn873 | This paper highlights a new organizational scheme for the auditory cortex in non-human primates. |
10.1523/jneurosci.18-04-01583.1998 | 81,799,440 | Establishing a coherent internal reference frame for visuospatial representation and maintaining the integrity of this frame during eye movements are thought to be crucial for both perception and motor control. A stable headcentric representation could be constructed by internally comparing retinal signals with eye pos... | 10.1038/nrn873 | This human psychophysical study provides evidence that the remembered locations of visual targets for reaching are stored in an eye-coordinate representation, and that this representation compensates for intervening saccades. |
10.1073/pnas.0508640103 | 102,421,288 | Calcium signaling pathways control a variety of cellular events such as gene transcription, protein phosphorylation, nucleotide metabolism, and ion transport. These pathways often involve a large number of calcium-binding proteins collectively known as the calmodulin or EF-hand protein superfamily. Many EF-hand protein... | 10.1038/nrn2093 | An overview of the diversity of EF-hand-containing Ca 2+ -binding proteins. |
10.1083/jcb.200306042 | 101,121,551 | Hippocalcin is a neuronal calcium sensor protein that possesses a Ca2+/myristoyl switch allowing it to translocate to membranes. Translocation of hippocalcin in response to increased cytosolic [Ca2+] was examined in HeLa cells expressing hippocalcin–enhanced yellow fluorescent protein (EYFP) to determine the dynamics a... | 10.1038/nrn2093 | Analysis of the Ca 2+ /myristoyl switch of hippocalcin in living cells, through the use of confocal imaging and elevation of intracellular Ca 2+ by photolysis of caged calcium. |
10.1002/pmic.200500489 | 80,899,106 | Abstract Intracellular Ca 2+ signals are transduced by the binding of Ca 2+ to sensor proteins, which subsequently modify the activity of their target proteins. Identification of these target proteins is, therefore, important for an understanding of cellular signalling processes. We have investigated the binding partne... | 10.1038/nrn2093 | A demonstration of the range, diversity and specificity of interacting proteins for members of the NCS and Ca 2+ -binding protein families. |
10.1177/108705470200500302 | 20,349,766 | The present study examined gender differences in ADHD through a meta-analysis. Effect size estimates for the primary symptoms and correlates of ADHD were calculated in an attempt to replicate and extend a previous meta-analysis on gender differences in the disorder. Relatively lenient inclusion criteria were used in or... | 10.1038/s41386-018-0137-2 | An important meta-analysis of gender differences in the presentation of attention deficit hyperactivity disorder symptoms |
10.1101/gad.1616208 | 123,112,819 | Neural stem cells (NSCs) yield both neuronal and glial progeny, but their differentiation potential toward multiple region-specific neuron types remains remarkably poor. In contrast, embryonic stem cell (ESC) progeny readily yield region-specific neuronal fates in response to appropriate developmental signals. Here we ... | 10.1038/nrn.2016.46 | This was the first highly sophisticated study to classify the different types of NPCs that can be derived from hPSCs and demonstrate that in vitro neural differentiation follows the rules of in vivo development. |
10.1101/gad.251694.114 | 123,039,641 | Although important for gene regulation, most studies of genome organization use either fluorescence in situ hybridization (FISH) or chromosome conformation capture (3C) methods. FISH directly visualizes the spatial relationship of sequences but is usually applied to a few loci at a time. The frequency at which sequence... | 10.1038/nrn.2016.124 | This paper provides a scholarly and competent discussion on the advantages and limitations of commonly used techniques to map chromosomal contacts. |
10.1083/jcb.141.7.1589 | 19,822,578 | Merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene, is a member of the protein 4.1 superfamily that is most closely related to ezrin, radixin, and moesin (ERM). NF2 is a dominantly inherited disease characterized by the formation of bilateral acoustic schwannomas and other benign tumors ass... | 10.1038/nrn1407 | This study provides evidence that merlin regulates cell proliferation in D. melanogaster , and that the FERM domain can provide all the necessary functions of D. melanogaster merlin. |
10.1073/pnas.98.3.1235 | 58,555,110 | In the adult peripheral nerve, microvillous processes of myelinating Schwann cells project to the nodes of Ranvier; their composition and physiologic function have not been established. As the ezrin-radixin-moesin (ERM) proteins are expressed in the microvilli of many epithelial cells, we have examined the expression a... | 10.1038/nrn1407 | This study demonstrates that nodes of Ranvier form in contact with the myelinating Schwann cells that are highly enriched in ERM proteins. |
10.1083/jcb.200303039 | 104,269,797 | Nodes of Ranvier are specialized, highly polarized axonal domains crucial to the propagation of saltatory action potentials. In the peripheral nervous system, axo–glial cell contacts have been implicated in Schwann cell (SC) differentiation and formation of the nodes of Ranvier. SC microvilli establish axonal contact a... | 10.1038/nrn1407 | Employing a myelinating explant culture system, this study provides evidence for the localized Rho-mediated activation of ERM proteins at the Schwann cell cap, and its influence on the efficiency of node formation. |
10.1101/gad.14.13.1617 | 133,917,764 | Hemizygosity for the NF2 gene in humans causes a syndromic susceptibility to schwannoma development. However, Nf2 hemizygous mice do not develop schwannomas but mainly osteosarcomas. In the tumors of both species, the second Nf2 allele is inactivated. We report that conditional homozygous Nf2 knockout mice with Cre-med... | 10.1038/nrn1407 | This study shows that conditional inactivation of merlin in Schwann cells can result in Schwann cell hyperplasia and schwannomas. |
10.1101/gad.189601 | 102,877,526 | The neurofibromatosis-2 ( NF2 ) gene encodes merlin, an ezrin-radixin-moesin-(ERM)-related protein that functions as a tumor suppressor. We found that merlin mediates contact inhibition of growth through signals from the extracellular matrix. At high cell density, merlin becomes hypo-phosphorylated and inhibits cell gr... | 10.1038/nrn1407 | This study suggests that merlin might confer its tumour suppressor function through its interaction with the cytoplasmic tail of CD44 in response to elevated levels of hyaluronate, the ligand for CD44. |
10.1083/jcb.143.2.443 | 79,456,015 | In this study we have examined the cellular functions of ERM proteins in developing neurons. The results obtained indicate that there is a high degree of spatial and temporal correlation between the expression and subcellular localization of radixin and moesin with the morphological development of neuritic growth cones... | 10.1038/nrn1407 | Employing antisense mediated suppression, this study shows that radixin and moesin have a key role in generating and maintaining the normal structure of growth cones in rat hippocampal neurons. |
10.1083/jcb.200111076 | 125,319,298 | Ayeast two-hybrid library was screened using the cytoplasmic domain of the axonal cell adhesion molecule L1 to identify binding partners that may be involved in the regulation of L1 function. The intracellular domain of L1 bound to ezrin, a member of the ezrin, radixin, and moesin (ERM) family of membrane–cytoskeleton ... | 10.1038/nrn1407 | This study shows that cell adhesion molecule L1 binds directly to ERM proteins and suggests that this association might coordinate aspects of axonal morphogenesis. |
10.1073/pnas.0431098100 | 122,799,678 | Bacillus anthracis secretes two bipartite toxins thought to be involved in anthrax pathogenesis and resulting death of the host. The current model for intoxication is that protective antigen (PA) toxin subunits bind a single group of cell-surface anthrax toxin receptors (ATRs), encoded by the tumor endothelial marker 8... | 10.1038/nrmicro977 | Identified CMG2 as an anthrax toxin receptor and demonstrated the ability of a soluble form of this receptor to effectively neutralize PA at a 3:1 molar ratio. |
10.1083/jcb.200305098 | 20,362,045 | Botulinum neurotoxins (BoNTs) cause botulism by entering neurons and cleaving proteins that mediate neurotransmitter release; disruption of exocytosis results in paralysis and death. The receptors for BoNTs are thought to be composed of both proteins and gangliosides; however, protein components that mediate toxin entr... | 10.1038/nrmicro977 | Synaptotagmins I and II are identified as receptors for BoNT and soluble forms of these receptors are able to block intoxication in vivo |
10.1073/pnas.172229899 | 60,319,921 | The botulinum neurotoxins (BoNTs) cause the paralytic human disease botulism and are one of the highest-risk threat agents for bioterrorism. To generate a pharmaceutical to prevent or treat botulism, monoclonal antibodies (mAbs) were generated by phage display and evaluated for neutralization of BoNT serotype A (BoNT/A... | 10.1038/nrmicro977 | Demonstrated that, although single monoclonal antibodies do not exhibit strong toxin neutralizing activity, a cocktail of three antibodies to non-overlapping epitopes is an effective antitoxin in vivo |
10.1126/science.109563 | 1,778,296 | The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and bl... | 10.1038/nrmicro977 | Identified a dominant-negative mutant of anthrax toxin PA that allows formation of toxin complexes, but blocks pore formation and toxin translocation. |
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/nrn3837 | References 49 and 50 used anterograde and retrograde tracers to reveal neurons that send projections to orexin neurons. These studies showed that inputs from the limbic system are likely to have an important role in activating orexin neurons in response to cues that predict fear or reward. |
10.1523/jneurosci.1130-13.2013 | 38,881,307 | The noradrenergic (NA) projections arising from the locus ceruleus (LC) to the amygdala and bed nucleus of the stria terminalis have been implicated in the formation of emotional memory. Since NA neurons in the LC (LC-NA neurons) abundantly express orexin receptor-1 (OX1R) and receive prominent innervation by orexin-pr... | 10.1038/nrn3837 | This work showed that the orexin system modulates the formation and expression of fear memory via OX1R in multiple pathways. In particular, OX1R in LC NA neurons plays an important part in cue-dependent fear-memory formation and/or retrieval. |
10.1073/pnas.0507480102 | 41,291,587 | Hypocretin-1 and -2 (Hcrt-1 and Hcrt-2), also referred to as orexin-A and -B, are neuropeptides synthesized by a few thousand neurons in the lateral hypothalamus. Hypocretin-containing neurons project throughout the brain, with a prominent input to basal forebrain structures involved in motivation, reward, and stress. ... | 10.1038/nrn3837 | This study suggested a previously unidentified role for orexins in driving drug seeking through the activation of stress pathways in the brain. |
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/nrn3837 | This paper relates the independent discovery of the transcript that encodes hypocretins (orexins), the prediction of two peptides encoded by the transcript and the detection of the peptides in dense-core vesicles at synapses. |
10.1094/phyto.2004.94.2.147 | 41,165,125 | Seed treatment with Trichoderma harzianum strain T22, which results in colonization of plant roots but little or no colonization of shoots or leaves, had substantial effects on growth of and disease expression in maize inbred line Mo17. Shoots and roots of 10-day-old seedlings grown in a sandy loam field soil were larg... | 10.1038/nrmicro797 | References 43, 51, 63, 64, 66 and 72 provide the primary basis of this article and provide the data upon which many of our new concepts are based. |
10.1073/pnas.0511311103 | 39,747,216 | Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A ( MAOA ) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functio... | 10.1038/nrn3042 | This study investigated the effect of the MAOA genetic polymorphism on brain structure and functions, and found differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression. |
10.1126/science.1072290 | 26,771,260 | We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A ( MAOA ) was found to moderate t... | 10.1038/nrn3042 | A landmark study providing evidence for a gene–environment interaction in humans that is linked to violence in the MAOA VNTR genetic polymorphism. |
10.1126/science.1248955 | 82,952,426 | Taking Flight Anyone who has tried to swat a fly knows that their powers of avoidance are impressive. Executing such rapid avoidance requires that the sensory recognition of an approaching threat be translated into evasive movement almost instantaneously. Muijres et al. (p. 172 ) used high-speed videos and winged robot... | 10.1038/nrn3799 | This study demonstrates the incredible manoeuvrability of D. melanogaster , as revealed by high-speed video and sophisticated online visual stimulation in free flight. |
10.1038/ncomms11552 | 81,522,320 | Abstract CA3–CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at... | 10.1038/nrn.2017.10 | This study demonstrates that STDPat CA3–CA3 synapses occurs independently of temporal order and proposes that the symmetric STDP rule enables reliable storage of information in the autoassociative network. |
10.1113/jp270372 | 83,230,880 | Key points We investigated the cellular mechanisms underlying mossy fibre‐induced heterosynaptic long‐term potentiation of perforant path (PP) inputs to CA3 pyramidal cells. Here we show that this heterosynaptic potentiation is mediated by downregulation of Kv1.2 channels. The downregulation of Kv1.2 preferentially enh... | 10.1038/nrn.2017.10 | This study shows that activity-dependent downregulation of Kv1.2 in distal dendrites of CA3 PCs mediates heterosynaptic plasticity at PP synapses induced by mossy fibres. |
10.1126/science.aaf1836 | 104,277,972 | The hippocampal CA3 region plays a key role in learning and memory. Recurrent CA3–CA3 synapses are thought to be the subcellular substrate of pattern completion. However, the synaptic mechanisms of this network computation remain enigmatic. To investigate these mechanisms, we combined functional connectivity analysis w... | 10.1038/nrn.2017.10 | Combining functional connectivity analysis and modelling, this study shows a high enrichment in specific unitary connection motifs between CA3 neurons, which is proposed to serve as efficient memory storage. |
10.1126/science.287.5451.273 | 18,031,296 | A puzzling feature of the neocortex is the rich array of inhibitory interneurons. Multiple neuron recordings revealed numerous electrophysiological-anatomical subclasses of neocortical γ-aminobutyric acid–ergic (GABAergic) interneurons and three types of GABAergic synapses. The type of synapse used by each interneuron ... | 10.1038/nrn1519 | The first study to report three distinct types of GABA synapse and several principles that determine which type of synapse is deployed by different anatomical and electrophysiological types of interneuron when inhibitory connections are formed. |
10.1113/jphysiol.2001.012959 | 123,923,030 | Whole‐cell voltage recordings were obtained from 64 synaptically coupled excitatory layer 4 (L4) spiny neurones and L2/3 pyramidal cells in acute slices of the somatosensory cortex (‘barrel’ cortex) of 17‐ to 23‐days‐old rats. Single action potentials (APs) in the L4 spiny neurone evoked single unitary EPSPs in the L2/... | 10.1038/nrn1519 | The first study to reveal a unidirectional pathway from spiny stellate cells in layer IV to layer II/III pyramidal neurons. |
10.1152/jn.1985.54.4.782 | 104,316,561 | Slices of sensorimotor and anterior cingulate cortex from guinea pigs were maintained in vitro and bathed in a normal physiological medium. Electrophysiological properties of neurons were assessed with intracellular recording techniques. Some neurons were identified morphologically by intracellular injection of the flu... | 10.1038/nrn1519 | The pioneering study that revealed basic differences in discharge between pyramidal neurons and interneurons. |
10.1073/pnas.81.20.6526 | 56,566,218 | Neurons in the cat and monkey cerebral cortex were stained immunocytochemically for glutamic acid decarboxylase (GluDCase; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), somatostatin (SRIF), neuropeptide Y (NPY), and cholecystokinin octapeptide (CCK). In all areas of cortex examined (somatic sensory, motor, parietal and vi... | 10.1038/nrn1519 | References 98 and 99 reported the differential expression of intestinal peptides in GABA neurons. |
10.1152/jn.1988.60.6.1896 | 59,002,901 | 1. Using isolated slices of rat cingulate and sensorimotor cortex, intracellular recordings were obtained from pyramidal neurons in layer III. Simultaneous extracellular recordings were obtained from neurons in ventral layer III and layer IV. Spike-triggered averaging was employed to investigate synaptic connections fr... | 10.1038/nrn1519 | This paper reported the first dual recordings of synaptically connected neurons in the neocortex. |
10.1073/pnas.95.9.5323 | 124,388,090 | The nature of information stemming from a single neuron and conveyed simultaneously to several hundred target neurons is not known. Triple and quadruple neuron recordings revealed that each synaptic connection established by neocortical pyramidal neurons is potentially unique. Specifically, synaptic connections onto th... | 10.1038/nrn1519 | The first direct demonstration that the same axon from a neocortical neuron can form both depressing and facilitating synapses. |
10.1113/jphysiol.2004.060962 | 100,349,916 | It is well established that sensory stimulation results in the activity of multiple functional columns in the neocortex. The manner in which neurones within each column are active in relation to each other is, however, not known. Multiple whole‐cell recordings in activated neocortical slices from rat revealed diverse c... | 10.1038/nrn1519 | The first study to show that subthreshold voltage cross-correlations correspond to the form of synaptic dynamics. |
10.1523/jneurosci.3467-06.2006 | 104,189,993 | General anesthetics, including etomidate, act by binding to and enhancing the function of GABA type A receptors (GABA A Rs), which mediate inhibitory neurotransmission in the brain. Here, we used a radiolabeled, photoreactive etomidate analog ([ 3 H]azietomidate), which retains anesthetic potency in vivo and enhances G... | 10.1038/nrn2372 | This impressive piece of work identified a binding site for etomidate on the GABA A receptor using photoaffinity labelling. |
10.1073/pnas.0604304103 | 123,276,467 | The neurotransmitter GABA mediates the majority of rapid inhibition in the CNS. Inhibition can occur via the conventional mechanism, the transient activation of subsynaptic GABA A receptors (GABA A -Rs), or via continuous activation of high-affinity receptors by low concentrations of ambient GABA, leading to “tonic” in... | 10.1038/nrn2372 | This paper provided a definitive demonstration that the key pharmacological effects of the sedative agent gaboxadol are mediated by α4-subunit-containing GABA A receptors, which are thought to be predominantly expressed extrajunctionally. |
10.1152/jn.1999.81.4.1795 | 20,831,253 | Mechanism of anesthesia revealed by shunting actions of isoflurane on thalamocortical neurons. By using thalamic brain slices from juvenile rats and the whole cell recording technique, we determined the effects of aqueous applications of the anesthetic isoflurane (IFL) on tonic and burst firing activities of ventrobasa... | 10.1038/nrn2372 | This study showed that isoflurane could affect the firing properties of thalamocortical neurons by enhancing their baseline K + conductance. |
10.1523/jneurosci.19-13-05506.1999 | 20,641,961 | In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofo... | 10.1038/nrn2372 | This paper, together with reference 95, highlights the relatively selective deactivation of the thalamus and other specific brain regions that occurs at, or during, anaesthetic-induced loss of consciousness. |
10.1097/00000542-200309000-00015 | 39,741,862 | Background Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to perturb cerebral homeostasis and vascular reactivity. The authors quantified the effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow (rCBF), metabolic r... | 10.1038/nrn2372 | This was a comprehensive study into the effects of anaesthetics on regional cerebral blood flow in humans. |
10.1126/science.8235588 | 62,410,905 | Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis ... | 10.1038/nrn2372 | This paper provided a beautifully clear description of how thalamocortical oscillations are generated during the initiation and maintenance of sleep. |
10.1113/expphysiol.1991.sp003471 | 83,491,548 | The results presented in this lecture show that anaesthetic agents impede the transfer of information from the periphery to the cerebral cortex. This is shown both as a reduction in the amplitudes of the initial positive and negative waves of the cerebral cortical response evoked by simulation of the periphery and as a... | 10.1038/nrn2372 | This paper reviewed a series of comprehensive studies designed to investigate at the anatomical level how anaesthetics affect the transmission of sensory information from the periphery to the cortex. Although it did not address anaesthetic-induced LOC, the article drew particular attention to the role of the thalamus a... |
10.1097/00000542-199604000-00023 | 23,728,698 | Background Halothane anesthesia causes spindles in the electroencephalogram (EEG), but the cellular and molecular mechanisms generating these spindles remain incompletely understood. The current study tested the hypothesis that halothane-induced EEG spindles are regulated, in part, by pontine cholinergic mechanisms. Me... | 10.1038/nrn2372 | This paper provided evidence that the spindles in the EEG that are generated by halothane might be regulated by pontine cholinergic mechanisms. |
10.1126/science.271.5246.216 | 123,170,299 | The rostral hypothalamus and adjacent basal forebrain participate in the generation of sleep, but the neuronal circuitry involved in this process remains poorly characterized. Immunocytochemistry was used to identify the FOS protein, an immediate-early gene product, in a group of ventrolateral preoptic neurons that is ... | 10.1038/nrn2372 | This paper, together with reference 126, showed the importance of the activation of VLPO neurons during sleep. |
10.1073/pnas.1208160109 | 45,530,374 | The Antarctic and Arctic regions offer a unique opportunity to test factors shaping biogeography of marine microbial communities because these regions are geographically far apart, yet share similar selection pressures. Here, we report a comprehensive comparison of bacterioplankton diversity between polar oceans, using... | 10.1038/nrmicro3549 | Insightful study teasing apart the roles of isolation and ocean connectivity in influencing the distribution of microbial communities in polar ocean waters. |
10.1038/ismej.2009.113 | 104,347,784 | Abstract Perennially cold habitats are diminishing as a result of climate change; however, little is known of the diversity or biogeography of microbes that thrive in such environments. Here we use targeted 16S rRNA gene surveys to evaluate the global affinities of cold-dwelling cyanobacteria from lake, stream and ice ... | 10.1038/nrmicro3549 | Interesting study rationalizing the dispersal and selection of polar-distributed cyanobacteria, which formed the foundation for subsequent metagenomic studies. |
10.1038/ismej.2010.28 | 16,882,707 | Abstract Green sulfur bacteria (GSB) (Chlorobiaceae) are primary producers that are important in global carbon and sulfur cycling in natural environments. An almost complete genome sequence for a single, dominant GSB species (‘C-Ace’) was assembled from shotgun sequence data of an environmental sample taken from the O2... | 10.1038/nrmicro3549 | First Antarctic metaproteomics study describing an almost complete metagenome-derived genome sequence and high metaproteome coverage of an ecologically important lake microorganism. |
10.1038/ismej.2010.185 | 58,643,184 | Abstract In nature, the complexity and structure of microbial communities varies widely, ranging from a few species to thousands of species, and from highly structured to highly unstructured communities. Here, we describe the identity and functional capacity of microbial populations within distinct layers of a pristine... | 10.1038/nrmicro3549 | First shotgun metagenomics and metaproteomics study describing the identity and functional capacity of microbial populations throughout an entire lake, including a mathematical model describing the effects of environmental parameters on key populations. |
10.1073/pnas.1307090110 | 18,731,979 | Significance Horizontal gene exchange across species boundaries is considered infrequent relative to vertical inheritance that maintains species coherence. However, haloarchaea living in hypersaline environments take a more relaxed approach to gene exchange. Here we demonstrate that in Deep Lake, Antarctica, haloarchae... | 10.1038/nrmicro3549 | Study demonstrating the interplay between promiscuous gene exchange and niche adaptation in shaping Antarctic microbial communities and generating a low-complexity, hierarchically structured ecosystem. |
10.1073/pnas.1208607109 | 104,255,012 | The permanent ice cover of Lake Vida (Antarctica) encapsulates an extreme cryogenic brine ecosystem (−13 °C; salinity, 200). This aphotic ecosystem is anoxic and consists of a slightly acidic (pH 6.2) sodium chloride-dominated brine. Expeditions in 2005 and 2010 were conducted to investigate the biogeochemistry of Lake... | 10.1038/nrmicro3549 | Careful consideration of the role of geochemical and biological processes occurring in an unusual ice-covered lake. |
10.1073/pnas.1018221108 | 80,319,289 | Viruses are abundant ubiquitous members of microbial communities and in the marine environment affect population structure and nutrient cycling by infecting and lysing primary producers. Antarctic lakes are microbially dominated ecosystems supporting truncated food webs in which viruses exert a major influence on the m... | 10.1038/nrmicro3549 | First paper to describe an ecological role for virophages, indicating that virophages regulate host–virus interactions, influence overall carbon flux and have previously unrecognized roles in diverse aquatic ecosystems. |
10.1126/science.1167350 | 20,681,929 | An active microbial assemblage cycles sulfur in a sulfate-rich, ancient marine brine beneath Taylor Glacier, an outlet glacier of the East Antarctic Ice Sheet, with Fe(III) serving as the terminal electron acceptor. Isotopic measurements of sulfate, water, carbonate, and ferrous iron and functional gene analyses of ade... | 10.1038/nrmicro3549 | Colourful description of a fascinating subglacial system gleaned from the analysis of a spectacular glacier outflow. |
10.1038/ismej.2012.31 | 28,238,583 | Abstract Antarctic surface oceans are well-studied during summer when irradiance levels are high, sea ice is melting and primary productivity is at a maximum. Coincident with this timing, the bacterioplankton respond with significant increases in secondary productivity. Little is known about bacterioplankton in winter ... | 10.1038/nrmicro3549 | First study using metagenomics to identify seasonal shifts in Southern Ocean communities, highlighting the role of chemolithoautotrophic microorganisms in fixing CO 2 in winter. |
10.1038/ismej.2013.190 | 62,432,297 | Abstract High-latitude environments, such as the Antarctic McMurdo Dry Valley lakes, are subject to seasonally segregated light–dark cycles, which have important consequences for microbial diversity and function on an annual basis. Owing largely to the logistical difficulties of sampling polar environments during the d... | 10.1038/nrmicro3549 | First pyrosequencing study to identify shifts in lake communities during the transition to polar darkness and identifying the potentially important role of chemolithoautotrophic carbon fixation. |
10.1126/science.1179287 | 123,260,059 | Shivering Viromes Despite its icy reputation, freshwater ponds and lakes do occur in Antarctica, and open freshwater can be found for a few brief weeks during the austral summer. The ecology of these lakes is, as expected, rather specialized to cope with the extreme seasonal conditions. In a metagenomic study, López-Bu... | 10.1038/nrmicro3549 | First metagenome study of an Antarctic environment, identifying a high level of new unique viruses and illustrating virus dynamics associated with physical changes occurring in the lake. |
10.1111/mec.13321 | 100,308,589 | Abstract RNA viruses exist as complex mixtures of genotypes, known as quasispecies, where the evolution potential resides in the whole community of related genotypes. Quasispecies structure and dynamics have been studied in detail for virus infecting animals and plants but remain unexplored for those infecting micro‐or... | 10.1038/nrmicro3549 | First study describing RNA viruses in an Antarctic lake, identifying the important but uncharacterized roles that RNA viruses have in Antarctic aquatic systems. |
10.1073/pnas.2235619100 | 123,562,771 | All animals detect osmotic and mechanical stimuli, but the molecular basis for these responses is incompletely understood. The vertebrate transient receptor potential channel vanilloid subfamily 4 (TRPV4) (VR-OAC) cation channel has been suggested to be an osmo/mechanosensory channel. To assess its function in vivo , w... | 10.1038/nrn2149 | TRPV4 rescues worms carrying mutated OSM-9 showing that OSM-9 is a key part of the conduction pathway for nose touch and osmosensation in C. elegans . TRPV4's pore alone rescues the mutant worms, suggesting that OSM-9 is not necessary for the gating of the channel mediating this sensation. |
10.1126/science.287.5461.2229 | 62,058,438 | Mechanosensory transduction underlies a wide range of senses, including proprioception, touch, balance, and hearing. The pivotal element of these senses is a mechanically gated ion channel that transduces sound, pressure, or movement into changes in excitability of specialized sensory cells. Despite the prevalence of m... | 10.1038/nrn2149 | The transduction channel for bristle deflection in Drosophila is fast enough to be directly gated. Mutations in TRPN1 abolish the receptor current, implicating for the first time a TRP channel in mechanosensation. |
10.1126/science.1084370 | 62,058,253 | The senses of hearing and balance in vertebrates rely on the sensory hair cells (HCs) of the inner ear. The central element of the HC's transduction apparatus is a mechanically gated ion channel of unknown identity. Here we report that the zebrafish ortholog of Drosophila no mechanoreceptor potential C ( nompC ), which... | 10.1038/nrn2149 | Presents the first experimental evidence that a TRP channel is the hair-cell transduction channel. Later studies, such as reference 84, lessen the strength of this evidence. |
10.1126/science.1129663 | 107,311,422 | A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF M... | 10.1038/nrn2649 | The authors generated mice that duplicate the Val66Met polymorphism in the BDNF gene seen in humans, and demonstrate differences in emotional behaviour and other behavioural domains. |
10.31887/dcns.2005.7.2/mmeaney | 20,522,388 | Early experience permanently alters behavior and physiology. These effects are, in part, mediated by sustained alterations in gene expression in selected brain regions. The critical question concerns the mechanism of these environmental "programming" effects. We examine this issue with an animal model that studies the ... | 10.1038/nrn2649 | This review summarizes the authors' elegant work in rats, which has demonstrated a role for methylation of the GR gene in the hippocampus in mediating life-long effects of maternal care on an individual's behaviour. |
10.1523/jneurosci.2063-07.2007 | 62,279,959 | Although depressed mood is a normal occurrence in response to adversity in all individuals, what distinguishes those who are vulnerable to major depressive disorder (MDD) is their inability to effectively regulate negative mood when it arises. Investigating the neural underpinnings of adaptive emotion regulation and th... | 10.1038/nrn2649 | In this fMRI study, the authors demonstrate abnormalities in top-down regulation of the amygdala by the PFC in depressed individuals. |
10.31887/dcns.2006.8.4/smaier | 60,692,821 | The degree of control that an organism has over a stressor potently modulates the impact of the stressor, with uncontrollable stressors producing a constellation of outcomes that do not occur if the stressor is behaviorally controllable. It has generally been assumed that this occurs because uncontrollability actively ... | 10.1038/nrn2649 | In this article the authors review their findings that demonstrate, in animals, that control over stressful events limits the deleterious consequences on the individual. |
10.1146/annurev.immunol.19.1.65 | 41,269,089 | This review describes the contribution of noncytolytic mechanisms to the control of viral infections with a particular emphasis on the role of cytokines in these processes. It has long been known that most cell types in the body respond to an incoming viral infection by rapidly secreting antiviral cytokines such as int... | 10.1038/nrmicro878 | Excellent review of the role of soluble virus suppressor factors in HBV and other viral infections. |
10.1126/science.2431484 | 61,173,626 | Lymphocytes bearing the CD8 marker were shown to suppress replication of human immunodeficiency virus (HIV) in peripheral blood mononuclear cells. The effect was dose-dependent and most apparent with autologous lymphocytes; it did not appear to be mediated by a cytotoxic response. This suppression of HIV replication co... | 10.1038/nrmicro878 | Provides the first description of soluble HIV suppressor activity released by CD8 + T cells. This activity was later called CAF. |
10.1126/science.270.5243.1811 | 19,870,409 | Evidence suggests that CD8 + T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1α, and MIP-1β were identified as the major HIV-SF produced by CD8 + T cells. T... | 10.1038/nrmicro878 | The first report to identify a new HIV suppressor factor and reveal that certain chemokines are components of CAF. The paper also showed that soluble suppressor activities are composed of multiple components. |
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/nrmicro878 | This seminal paper demonstrates that certain chemokine receptors act as entry co-receptors for HIV-1. |
10.1128/jvi.74.10.4505-4511.2000 | 101,115,625 | ABSTRACT It is now recognized that, in addition to drug-mediated therapies against human immunodeficiency virus type 1 (HIV-1), the immune system can exert antiviral effects via CD8 + T-cell-generated anti-HIV factors. This study demonstrates that (i) supernatants from peripheral blood mononuclear cells (PBMC) stimulat... | 10.1038/nrmicro878 | Identifies IFN as an important component of the soluble HIV-1 suppressor factor that is released following influenza virus stimulation. |
10.1128/jvi.74.10.4456-4464.2000 | 81,269,232 | ABSTRACT CD8 + lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4 + T cells by a noncytolytic mechanism involving secreted CD8 + -cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4 + T cells infec... | 10.1038/nrmicro878 | Demonstrates that CTLs against non-HIV antigens also release active concentrations of non-cytolytic HIV-1 suppressor factors. |
10.1073/pnas.240469997 | 122,765,586 | To test the hypothesis that β-chemokine levels may be relevant to the control of HIV in vivo , we compared RANTES, MIP-1α, and MIP-1β production from purified CD8 + T cells from 81 HIV-infected subjects and from 28 uninfected donors. Asymptomatic HIV + subjects produced significantly higher levels of MIP-1α and MIP-1β,... | 10.1038/nrmicro878 | This cross-sectional study shows that a natural capacity to release increased concentrations of CCR5 ligands on stimulation correlates with better clinical status in HIV-1 infection. |
10.1046/j.1365-2567.2000.00993.x | 56,957,905 | Summary A non‐cognate mechanism of protection against human immunodeficiency virus‐1 (HIV‐1) infection involves up‐regulation of β‐chemokines, which bind and may down‐modulate the CCR5 co‐receptors, thereby preventing transmission of M‐tropic HIV‐1. The objective of this investigation was to evaluate this mechanism in ... | 10.1038/nrmicro878 | Evidence from a primate infection model which indicates that vaccines might afford protection from HIV-1 infection by modulating the capacity of the immune system to release soluble suppressor factors. |
10.1126/science.1215691 | 104,104,020 | Translation Block MicroRNAs (miRNAs) are small, noncoding RNA genes that are found in the genomes of most eukaryotes, where they play an important role in the regulation of gene expression. Although whether gene activity is repressed by blocking translation of messenger RNA (mRNA) targets, or by promoting their deadeny... | 10.1038/nsmb.2311 | References 44 and 45 show for the first time how a miRNA affects ribosome occupancy prior to deadenylation |
10.1523/jneurosci.5289-06.2007 | 62,079,455 | Recognition memory requires judgments of the previous occurrence of stimuli made on the basis of the relative familiarity of individual objects, or by integrating information concerning objects and location, or by using recency information. The present study examined the role of the medial prefrontal cortex (mPFC) and ... | 10.1038/nrn.2017.74 | This study provides compelling evidence that ipsilateral pathways between the PFC and the hippocampus are essential for memory. |
10.1126/science.1229534 | 20,832,715 | The Thalamus in Fear and Memory The medial prefrontal cortex (mPFC) mediates the cognitive control of many high-level brain functions. However, it is unclear which synaptic projections from the mPFC to subcortical regions are critical for maintaining the proper balance between retention and generalization of fear memor... | 10.1038/nrn.2017.74 | This study provided the first evidence of a key role for the Re in prefrontal–hippocampal interactions that support memory. |
10.1523/jneurosci.3891-12.2013 | 80,723,474 | Hippocampal neurons encode events within the context in which they occurred, a fundamental feature of episodic memory. Here we explored the sources of event and context information represented by hippocampal neurons during the retrieval of object associations in rats. Temporary inactivation of the medial prefrontal cor... | 10.1038/nrn.2017.74 | This study shows that top-down control of memory by the PFC involves suppression of inappropriate memories in the hippocampus. |
10.1111/ene.12022 | 104,086,218 | Background A Task Force was convened by the EFNS / MDS ‐ ES Scientist Panel on P arkinson's disease ( PD ) and other movement disorders to systemically review relevant publications on the diagnosis of PD . Methods Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation l... | 10.1038/nrn.2017.62 | This is a definitive and practical recommendation for the diagnostic process in PD. |
10.1002/ana.20160 | 82,933,640 | Abstract Olfactory dysfunction is an early and common symptom in Parkinson's disease (PD). In an effort to determine whether otherwise unexplained (idiopathic) olfactory dysfunction is associated with an increased risk of developing PD, we designed a prospective study in a cohort of 361 asymptomatic relatives (parents,... | 10.1038/nrn.2017.62 | This study highlights the importance of hyposmia as an often missed non-motor symptom in what we now know as prodromal PD. |
10.1002/mds.22142 | 40,212,667 | Abstract Pain is a frequent, but poorly studied symptom of Parkinson's disease (PD). DoPaMiP survey aimed to assess the prevalence of chronic pain in PD, to describe PD patients with chronic pain, and to record analgesic consumption. About 450 parkinsonian patients underwent structured standardized clinical examination... | 10.1038/nrn.2017.62 | This is a controlled comprehensive study addressing the prevalence of various types of pain in PD. |
10.1002/mds.22868 | 100,587,743 | Abstract The nonmotor symptoms (NMS) of Parkinson's disease (PD) are less well recognised and can be more troublesome to patients and carers than classical motor features. NMS are frequently missed during routine consultations and such under‐recognition may have implications on quality of care given that many NMS are t... | 10.1038/nrn.2017.62 | This is the first international prospective study to reveal the under-reporting of 30 common non-motor symptoms of PD. |
10.1002/mds.25020 | 60,868,685 | Abstract Background: Despite clinicopathological evidence that Parkinson's disease (PD) may begin in peripheral tissues, identification of premotor Parkinson's disease is not yet possible. Alpha‐synuclein aggregation underlies Parkinson's disease pathology, and its presence in peripheral tissues may be a reliable disea... | 10.1038/nrn.2017.62 | This is an interesting study proposing that α -synuclein pathology appears in the colon years before the diagnosis of PD. |
10.1002/mds.22596 | 4,838,035 | Abstract Switching from oral medications to continuous infusion of levodopa/carbidopa gel reduces motor complications in advanced Parkinson's disease (PD), but effects on nonmotor symptoms (NMSs) are unknown. In this prospective open‐label observational study, we report the effects of intrajejunal levodopa/carbidopa ge... | 10.1038/nrn.2017.62 | This is one of the first studies to address the effect of continuous drug delivery of intrajejunal levodopa and its effect on non-motor symptoms as a whole. |
10.1111/j.1462-2920.2007.01397.x | 4,578,201 | Summary Phosphonates are organophosphorus molecules that contain the highly stable C–P bond, rather than the more common, and more labile, C–O–P phosphate ester bond. They have ancient origins but their biosynthesis is widespread among more primitive organisms and their importance in the contemporary biosphere is incre... | 10.1038/nrmicro3011 | This review describes phosphonate turnover in the marine environment and provides a bioinformatic analysis of the distribution of both C–P lyase and C–P hydrolases. |
10.1073/pnas.1104922108 | 62,435,783 | Organophosphonate utilization by Escherichia coli requires the 14 cistrons of the phnCDEFGHIJKLMNOP operon, of which the carbon-phosphorus lyase has been postulated to consist of the seven polypeptides specified by phnG to phnM . A 5,660-bp DNA fragment encompassing phnGHIJKLM is cloned, followed by expression in E. co... | 10.1038/nrmicro3011 | This article is the first to report the purification of a soluble complex of the five proteins central to the reaction catalysed by bacterial C–P lyase. |
10.1126/science.1219875 | 20,477,504 | Ocean Methane Is methylphosphonate a natural product? If it is, then its catabolism by microrganisms seeking phosphorus might explain the ubiquity of methane in the oceans. Anaerobic Archaea, so far, are the only significant source of methane known. Thus, Metcalf et al. (p. 1104 ) looked for evidence of methylphosphona... | 10.1038/nrmicro3011 | This paper provides evidence for the production of methylphosphonate by the marine archaeon N. maritimus , a finding that might help to further resolve the oceanic methane paradox. |
10.1126/science.1194637 | 20,828,539 | Primitive Origins for Microglia Microglia are the resident macrophages of the central nervous system and are associated with neurodegeneration and brain inflammatory diseases. Although the developmental origins of other tissue macrophage populations are well established, the origins of microglia remain controversial. G... | 10.1038/nrn3053 | This study provides evidence that microglia in the adult brain are derived from primitive myeloid progenitors in the yolk sac very early in embryonic development |
10.1126/science.1142883 | 38,373,632 | The cellular immune response to tissue damage and infection requires the recruitment of blood leukocytes. This process is mediated through a classical multistep mechanism, which involves transient rolling on the endothelium and recognition of inflammation followed by extravasation. We have shown, by direct examination ... | 10.1038/nrn3053 | Intravital confocal microscopy imaging study showing that 'resident' monocytes crawl along the resting endothelial cells. This patrolling behaviour is dependent on the integrin LFA1 and CX3CR1. |
10.1002/cne.21149 | 29,116,157 | Abstract We have studied the spatial and temporal distribution of six proinflammatory cytokines and identified their cellular source in a clinically relevant model of spinal cord injury (SCI). Our findings show that interleukin‐1β (IL‐1β) and tumor necrosis factor (TNF) are rapidly (<5 and 15 minutes, respectively) ... | 10.1038/nrn3053 | A study that used in situ hybridization combined with immunofluorescence to identify the cell types that express various pro-inflammatory cytokines in the injured spinal cord after contusion injury. |
10.1146/annurev-physiol-021909-135919 | 125,319,153 | The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals. Individual SCN neurons in dispersed culture can generate independent circadian oscillations of clock gene expression and neuronal firing. However, SCN rhythmicity depends on sufficient membrane depolarization and levels of intracellular ca... | 10.1038/nrn3086 | This review focuses on what is known about how cell-autonomous oscillators are coupled within the SCN circuit. |
10.1126/science.1089287 | 103,663,958 | Individual cellular clocks in the suprachiasmatic nucleus (SCN), the circadian center, are integrated into a stable and robust pacemaker with a period length of about 24 hours. We used real-time analysis of gene expression to show synchronized rhythms of clock gene transcription across hundreds of neurons within the ma... | 10.1038/nrn3086 | An important study that used real-time analysis of gene expression to show synchronized, topographically patterned rhythms of clock gene transcription across hundreds of individual neurons within the SCN in organotypic slice culture. Application of TTX reduced the amplitude of single cell oscillations in SCN neurons. |
10.1073/pnas.0902768106 | 123,458,597 | Circadian rhythms are modeled as reliable and self-sustained oscillations generated by single cells. The mammalian suprachiasmatic nucleus (SCN) keeps near 24-h time in vivo and in vitro, but the identity of the individual cellular pacemakers is unknown. We tested the hypothesis that circadian cycling is intrinsic to a... | 10.1038/nrn3086 | A very sophisticated combination of experimental and modelling work to explore the network properties of the SCN circuit. The firing rate and Per2 gene expression were measured in isolated and interconnected SCN neurons. The analysis suggests that individual SCN neurons can generate circadian oscillations but that netw... |
10.1126/science.1169657 | 19,252,168 | Quiet Clock Many physiological processes have circadian rhythms driven by a biological clock in the suprachiasmatic nuclei (SCN) of the brain. Within the SCN, some neurons express the molecular components of the clock and others do not. Exactly how the clock mechanism is coupled to neuronal activity is not precisely un... | 10.1038/nrn3086 | During the day, SCN neurons are under strong depolarizing drive, which enables them to generate spontaneous action potentials. This intriguing study suggests that some SCN neurons are so depolarized that they cannot generate action potentials and are functionally silenced. |
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