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10.1111/j.1365-2958.2012.08081.x | 26,837,893 | Summary Quantitative spatial distributions of ribosomes (S2‐YFP) and RNA polymerase (RNAP; β′‐yGFP) in live Escherichia coli are measured by superresolution fluorescence microscopy. In moderate growth conditions, nucleoid–ribosome segregation is strong, and RNAP localizes to the nucleoid lobes. The mean copy numbers pe... | 10.1038/nrmicro2930 | The findings of this study prompted a major rethink about how mRNAs enter a decay pathway. |
10.1126/science.1077349 | 103,154,774 | Uncertainty is critical in the measure of information and in assessing the accuracy of predictions. It is determined by probability P , being maximal at P = 0.5 and decreasing at higher and lower probabilities. Using distinct stimuli to indicate the probability of reward, we found that the phasic activation of dopamine... | 10.1038/nrn1764 | Shows that in tasks that involve uncertainty, dopaminergic neurons burst at trial onset and at the expected time of reward, and show sustained activation throughout the trial. |
10.1126/science.1091573 | 83,502,531 | Attention modulates our subjective perception of time. The less we attend to an event's duration, the shorter it seems to last. Attention to time or color stimulus attributes was modulated parametrically in an event-related functional magnetic resonance imaging study. Linear increases in task performance were accompani... | 10.1038/nrn1764 | A state-of-the-art neuroimaging study using a dynamic control task and parametric variation of the interval-timing procedure. |
10.1126/science.6166046 | 123,160,207 | Peroxidase-containing cell bodies were found in the ipsilateral trigeminal ganglia after horseradish peroxidase was applied to the proximal segment of the middle cerebral artery in seven cats. Cell bodies containing the enzyme marker were located among clusters of cells that project via the first division. The existenc... | 10.1038/nrneurol.2017.137 | This important contribution draws up the neuroanatomical background for the trigeminovascular system. |
10.1002/ana.410200409 | 104,149,297 | Abstract Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), and calcitonin gene–related peptide (CGRP) were seen in the adventitia or at the adventitia–media border of the human temporal artery. Pharmacological experiments on isolated temporal artery segments reveal... | 10.1038/nrneurol.2017.137 | The first detailed description of neuropeptides in the human cerebral arteries. |
10.1046/j.1468-2982.2002.00310.x | 38,212,552 | Calcitonin gene-related peptide (CGRP) has been detected in increased amounts in external jugular venous blood during migraine attacks. However, it is unknown whether this is secondary to migraine or whether CGRP may cause headache. In a double-blind crossover study, the effect of human αCGRP (2 μg/min) or placebo infu... | 10.1038/nrneurol.2017.137 | The first human experimental evidence that CGRP can trigger migraine. |
10.1177/0333102412451360 | 83,290,000 | Background: Prostaglandin E 2 (PGE 2 ) has been suggested to play an important role in the pathogenesis of migraine. In the present experiment we investigated if an intravenous infusion of PGE 2 would induce migraine-like attacks in patients with migraine. Methods: Twelve patients with migraine without aura were random... | 10.1038/nrneurol.2017.137 | Demonstration that PGE2 causes migraine-like attacks immediately after administration, whereas most other triggering substances cause a delayed migraine-like response. |
10.1002/art.39239 | 59,113,291 | Objective Patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) have a high frequency of venous thromboembolic events and a hypercoagulable state. As C5a‐primed neutrophils play an important role in the development of AAV, we investigated whether C5a‐induced neutrophil tissue factor (TF)–express... | 10.1038/nrneph.2017.37 | This paper found that C5a links the inflammation and coagulation process in AAV. |
10.1073/pnas.1008688107 | 102,879,126 | DNA methylation of the cytosine in the CpG dinucleotide is typically associated with gene silencing. Genomic analyses have identified low CpG promoters that are both methylated and transcriptionally active, but the mechanism underlying the activation of these methylated promoters remains unclear. Here we show that CpG ... | 10.1038/nsmb.2910 | This paper shows that the transcription factor C/EBPα binds to a methylated CRE sequence to activate transcription during differentiation |
10.1101/gr.114843.110 | 81,894,024 | DNA methylation is a tightly regulated epigenetic mark associated with transcriptional repression. Next-generation sequencing of purified methylated DNA obtained from early Xenopus tropicalis embryos demonstrates that this genome is heavily methylated during blastula and gastrula stages. Although DNA methylation is lar... | 10.1038/nsmb.2910 | This paper reveals a temporal uncoupling between CpG-island methylation and repression of transcription during early Xenopus laevis development |
10.1162/0898929042947829 | 61,459,365 | Understanding one's own and other individual's emotional states is essential for maintaining emotional equilibrium and strong social bonds. Although the neural substrates supporting reflection upon one's own feelings have been investigated, no studies have directly examined attributions about the internal emotional sta... | 10.1038/nrn1884 | An important demonstration of the role of the MFC in emotion attributions, and a detailed review of MFC activation associated with inferring emotional responses of the self and others. |
10.1126/science.1093535 | 83,453,750 | Our ability to have an experience of another's pain is characteristic of empathy. Using functional imaging, we assessed brain activity while volunteers experienced a painful stimulus and compared it to that elicited when they observed a signal indicating that their loved one—present in the same room—was receiving a sim... | 10.1038/nrn1884 | Reveals functional segregation of the anterior cingulate in relation to sensory and affective properties of pain. |
10.1073/pnas.071043098 | 62,588,051 | Medial prefrontal cortex (MPFC) is among those brain regions having the highest baseline metabolic activity at rest and one that exhibits decreases from this baseline across a wide variety of goal-directed behaviors in functional imaging studies. This high metabolic rate and this behavior suggest the existence of an or... | 10.1038/nrn1884 | A classic paper examining the functional significance of 'resting activity' in fMRI studies. The authors suggest that self-referential processes correspond to the default mode of function in the MFC. |
10.1073/pnas.211415698 | 41,729,308 | Cooperation between individuals requires the ability to infer each other's mental states to form shared expectations over mutual gains and make cooperative choices that realize these gains. From evidence that the ability for mental state attribution involves the use of prefrontal cortex, we hypothesize that this area i... | 10.1038/nrn1884 | The first demonstration of a role for the MFC in trust and reciprocity games. |
10.1126/science.1188462 | 29,223,835 | Initiator for Coated Pit Assembly During clathrin-mediated endocytosis, it has been thought that the sensing and binding of the clathrin adaptor protein AP2 to cargo and lipids leads to the recruitment of clathrin, nucleating the formation of a clathrin-coated pit. Henne et al. (p. 1281 , published online 6 May) have n... | 10.1038/nrmicro3072 | A demonstration of the importance of rim complex proteins in the formation of clathrin-coated vesicles. |
10.1083/jcb.201105152 | 85,528,694 | Bacterial pathogens recruit clathrin upon interaction with host surface receptors during infection. Here, using three different infection models, we observed that host–pathogen interactions induce tyrosine phosphorylation of clathrin heavy chain. This modification was critical for recruitment of actin at bacteria–host ... | 10.1038/nrmicro3072 | Work highlighting the importance of clathrin heavy chain phosphorylation in stabilizing the clathrin coat and creating a platform for actin assembly. |
10.1068/p160761 | 109,167,656 | A case of ‘chromatic–lexical’ (colour–word) synaesthesia is described, and its genuineness confirmed using the criterion of stable cross-modality imagery across time. The synaesthesia could not be accounted for by a memory hypothesis, nor was it associated with any psychiatric condition. Further analysis did not identi... | 10.1038/nrn702 | Many papers have documented the consistency of synaesthetic experiences over time. This paper was the first to provide comparative data from a non-synaesthetic control on a 'test of consistency', which has become something of a gold standard in the field. The study also examined the effect of orthography and phonology ... |
10.1002/0470018860.s00295 | 39,362,576 | Abstract Synaesthesia is experienced when stimulation of one sensory modality gives rise to a perception in a second modality, without that second modality having received any direct stimulation. | 10.1038/nrn702 | This edited volume contains several historical and contemporary papers on synaesthesia. It covers numerous topics, including genetic and developmental aspects, brain imaging, cognition, consciousness and theories of synaesthesia. |
10.1068/p251073 | 98,033,641 | Synaesthesia is a condition in which a mixing of the senses occurs; for example, sounds trigger the experience of colour. Previous reports suggest this may be familial, but no systematic studies exist. In addition, there are no reliable prevalence or sex-ratio figures for the condition, which is essential for establish... | 10.1038/nrn702 | The only published study to provide a reliable estimate of the prevalence of synaesthesia in the adult population (1 in 2,000), and the first to report details of possible patterns of inheritance. |
10.1126/science.1237905 | 38,310,167 | DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome rec... | 10.1038/nrn.2016.41 | This was the first whole-genome bisulfite sequencingexamination of DNA methylation dynamics in brain development in humans and mice. |
10.1101/gr.119131.110 | 20,533,458 | DNA methylation is essential for embryonic and neuronal differentiation, but the function of most genomic DNA methylation marks is poorly understood. Generally the human genome is highly methylated (>70%) except for CpG islands and gene promoters. However, it was recently shown that the IMR90 human fetal lung fibrob... | 10.1038/nrn.2016.41 | PMDs mark distinct subsets of developmentally important genes in the neuronal cell line SH-SY5Y. These findings suggest that PMDs may be regions of DNA methylation that are relevant to the epigenetic regulation of ASD candidate genes acting at synapses. |
10.1073/pnas.0406458102 | 39,741,664 | Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis is a hallmark of major depressive disorder. A number of studies have shown that this dysregulation is correlated with impaired forebrain glucocorticoid receptor (GR) function. To determine whether a primary, acquired deficit in forebrain GR signaling is an ... | 10.1038/nrn1846 | The authors used transgenic mice, in which Cre recombinase is expressed under the control of the calcium/calmodulin-dependent protein kinase II promoter, to generate a forebrain-specific knockdown of the glucocorticoid receptor and show the resulting behavioural and neuroendocrine phenotype. |
10.1073/pnas.0402208101 | 85,547,334 | The molecular mechanisms that control the range and stability of emotions are unknown, yet this knowledge is critical for understanding mood disorders, especially bipolar illness. Here, we show that the glucocorticoid receptor (GR) modulates these features of emotional responsiveness. We generated transgenic mice overe... | 10.1038/nrn1846 | Mice with targeted overexpression of glucocorticoid receptors in the forebrain show enhanced negative affective responses in new or stressful situations and increased responsiveness to monoamine-based antidepressants. |
10.1073/pnas.0402141101 | 39,291,060 | Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice imp... | 10.1038/nrn1846 | Used an inducible, cell-targeted knockout system to obtain one of the best demonstrations so far that forebrain BDNF is necessary for antidepressant efficacy in the forced swim test. |
10.1073/pnas.0503584102 | 103,701,436 | Although there are clear interactions between circadian rhythms and drug addiction, mechanisms for such interactions remain unknown. Here we establish a role for the Clock gene in regulating the brain's reward circuit. Mice lacking a functional Clock gene display an increase in cocaine reward and in the excitability of... | 10.1038/nrn1846 | Demonstrates that mice lacking functional clock protein show enhanced behavioural responses to cocaine and enhanced firing of ventral tegmental area dopamine neurons. This is one of an increasing number of reports that circadian genes act outside the SCN to regulate complex behaviour. |
10.1126/science.1082795 | 4,250,625 | Animal behavior is synchronized to the 24-hour light:dark (LD) cycle by regulatory programs that produce circadian fluctuations in gene expression throughout the body. In mammals, the transcription factor CLOCK controls circadian oscillation in the suprachiasmatic nucleus of the brain; its paralog, neuronal PAS domain ... | 10.1038/nrn1846 | This and related studies by the same authors document a role for NPAS2, a clock-like transcription factor, in circadian variations in feeding, sleeping and other complex behaviours.These effects of NPAS2 are independent of the SCN and apparently mediated via forebrain regions. |
10.1083/jcb.200306033 | 62,283,326 | Here, using a genetic approach, we dissect the roles of EphB receptor tyrosine kinases in dendritic spine development. Analysis of EphB1, EphB2, and EphB3 double and triple mutant mice lacking these receptors in different combinations indicates that all three, although to varying degrees, are involved in dendritic spin... | 10.1038/nrn2075 | Shows that neurons from mice lacking EphB1–3 have a near total absence of excitatory synapses and spines in vitro , and reduced spine density and size in vivo |
10.1073/pnas.0807041106 | 125,317,145 | Relatively little is known about the long-term neurobiological sequelae of chronic stress, which predisposes susceptible patients to neuropsychiatric conditions affecting the prefrontal cortex (PFC). Animal models and human neuroimaging experiments provide complementary insights, yet efforts to integrate the two are of... | 10.1038/nrn2648 | This paper includes data on how chronic stress weakens prefrontal connectivity in both human subjects and rats exposed to chronic stress. |
10.1523/jneurosci.3630-06.2006 | 19,248,778 | Previous experience with stressors over which the subject has behavioral control blocks the typical behavioral consequences of subsequent exposure to stressors over which the organism has no behavioral control. The present experiments explored the involvement of the ventral medial prefrontal cortex (mPFCv) in mediating... | 10.1038/nrn2648 | This study showed that it is the PFC that ascertains (rightly or wrongly) whether we are in control over a stressor. The PFC suppresses the brainstem stress response even when the perceived control is only an illusion. |
10.1101/lm.92405 | 27,645,744 | The prefrontal cortex (PFC) is known to actively hold information “online” for a period of seconds in working memory for guiding goal-directed behavior. It has been proposed that relevant information is stored in other brain regions, which is retrieved and held in working memory for subsequent assimilation by the PFC i... | 10.1038/nrn2648 | This important study demonstrated that distinct memory processes can be modulated in very different ways, even in the same brain region. |
10.1126/science.112679 | 125,318,814 | Depletion of dopamine in a circumscribed area of association cortex in rhesus monkeys produces an impairment in spatial delayed alternation performance nearly as severe as that caused by surgical ablation of the same area. This behavioral deficit can be pharmacologically reversed with dopamine agonists such as L-dopa a... | 10.1038/nrn2648 | This is the landmark paper that first showed that catecholamines are essential to dorsolateral prefrontal working memory abilities. Although the paper focused on dopamine, it is now known that noradrenaline also has an essential role. |
10.1002/dneu.20361 | 125,063,445 | Abstract Extracellular matrix molecules—including chondroitin sulfate proteoglycans, hyaluronan, and tenascin‐R—are enriched in perineuronal nets (PNs) associated with subsets of neurons in the brain and spinal cord. In the present study, we show that similar cell type‐dependent extracellular matrix aggregates are form... | 10.1038/nrn2898 | This is the first demonstration that removal of the chondroitin sulphate-rich ECM modulates firing of perisomatic interneurons. |
10.1126/science.1072699 | 62,247,072 | In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of t... | 10.1038/nrn2898 | This study proposed that the chondroitin sulphate-rich ECM in the visual cortex serves as an inhibitory 'barrier' that restrains ocular dominance plasticity. |
10.1126/science.1174146 | 83,065,530 | Adult Fears Why are fear memories almost impossible to get rid of—even with extensive extinction training? Animal studies have shown that the efficacy of extinction learning depends on age. Fear memories in young animals can be permanently erased, but in adults they can be easily recovered after extinction training. Pe... | 10.1038/nrn2898 | Using ChABC injections in the amygdala, the authors revealed the role of the chondroitin sulphate-rich ECM in the formation of erasure-resistant emotional memories. |
10.1111/j.1471-4159.2005.03565.x | 103,165,907 | Abstract Rats learning the Morris water maze exhibit hippocampal changes in synaptic morphology and physiology that manifest as altered synaptic efficacy. Learning requires structural changes in the synapse, and multiple cell adhesion molecules appear to participate. The activity of these cell adhesion molecules is, in... | 10.1038/nrn2898 | This article characterizes MMP9 as an essential player in hippocampal learning-related behaviour. |
10.1073/pnas.0904024106 | 18,938,207 | Rotaviruses, major causes of childhood gastroenteritis, are nonenveloped, icosahedral particles with double-strand RNA genomes. By the use of electron cryomicroscopy and single-particle reconstruction, we have visualized a rotavirus particle comprising the inner capsid coated with the trimeric outer-layer protein, VP7,... | 10.1038/nrmicro2673 | This report describes the unusual 'grip arm' mode of VP7 assembly onto the rotavirus subviral particle. |
10.1128/jvi.02360-10 | 122,978,034 | ABSTRACT The innermost VP2 core shell of the triple-layered, icosahedral rotavirus particle surrounds the viral genome and RNA processing enzymes, including the RNA-dependent RNA polymerase (VP1). In addition to anchoring VP1 within the core, VP2 is also an essential cofactor that triggers the polymerase to initiate do... | 10.1038/nrmicro2673 | This investigation identifies the sites of interaction between the viral RNA polymerase and the VP2 decamer that are necessary for triggering RNA synthesis. |
10.1128/jvi.02082-10 | 109,041,870 | ABSTRACT Rotavirus (RV) cell entry is an incompletely understood process, involving VP4 and VP7, the viral proteins composing the outermost layer of the nonenveloped RV triple-layered icosahedral particle (TLP), encasing VP6. VP4 can exist in three conformational states: soluble, cleaved spike, and folded back. In orde... | 10.1038/nrmicro2673 | This evaluation of the rotavirus entry process identifies several cellular requirements and provides support for predicted conformational changes in the virion. |
10.1126/science.aab2276 | 104,213,495 | The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform “identification of direct RNA interacting proteins” (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors—including c... | 10.1038/nsmb.3370 | In this study, the authors used iDRiP to identify multiple Xist interactors, including architectural proteins. The paper describes a role for Xist in Xi-specific cohesin reorganization and chromosome conformation. |
10.1073/pnas.1609643113 | 39,250,680 | During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the “Barr body.” Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three struc... | 10.1038/nsmb.3370 | In this study, the authors dissected the role of the DXZ4 boundary element in maintaining the megadomain structure of the human Xi. Deletion of DXZ4 revealed the importance of the element for the 3D Xi conformation, but not for Xi silencing. |
10.1126/science.3291116 | 62,638,399 | How the immense population of neurons that constitute the human cerebral neocortex is generated from progenitors lining the cerebral ventricle and then distributed to appropriate layers of distinctive cytoarchitectonic areas can be explained by the radial unit hypothesis. According to this hypothesis, the ependymal lay... | 10.1038/nrn2719 | A review of the initial evidence that phenotype, and laminar and areal position of cortical neurons are specified at the proliferative zones and are only later influenced by the incoming axonal input (protomap hypothesis). The article also proposes the radial unit hypothesis of cortical development and evolution that h... |
10.1002/cne.901450105 | 62,189,460 | Abstract Golgi and electronmicroscopic methods were used to define the shapes and intercellular relationships of cells migrating from their sites of origin near the ventricular surface across the intermediate zone to the superficial neocortical layers of the parietooccipital region in the brains of 75‐ to 97‐day monkey... | 10.1038/nrn2719 | This paper presents evidence from a combination of the Golgi method and serial electron microscopy that postmitotic neurons in the large and convoluted primate cerebrum follow the increasingly elongated and curvilinear shafts of the radial glial cells, some of which do not divide while serving transiently as migratory ... |
10.1523/jneurosci.01-01-00027.1981 | 67,436,494 | The cytological composition of the proliferative zones in the fetal monkey occipital lobe was examined at the light and electron microscopic levels by immunoperoxidase localization of glial fibrillary acid protein (GFA), a protein that is present in astrocytes and radial glial cells but not neurons. During the peak of ... | 10.1038/nrn2719 | The first evidence that neuronal and glial cell lines can be distinguished at the initial stages of corticoneurogenesis in primates, the finding that has been confirmed in human post-mortem material (see references 54 and 55). |
10.1126/science.1064252 | 4,579,897 | A classic model proposes that the mammalian neocortex is divided into areas early in neurogenesis, but the molecular mechanisms that generate the area map have been elusive. Here we provide evidence that FGF8 regulates development of the map from a source in the anterior telencephalon. Using electroporation-mediated ge... | 10.1038/nrn2719 | The authors use in utero microelectroporation-mediated gene transfer to introduce an extra source of FGF8 into the occipital pole which results in an extra somato-sensory (barrel) cytoarchitectonic field with a nearly perfect duplication of the topographic map. |
10.1073/pnas.0702225104 | 38,496,628 | The frontal cortex (FC) is the seat of higher cognition. The genetic mechanisms that control formation of the functionally distinct subdivisions of the FC are unknown. Using a set of gene expression markers that distinguish subdivisions of the newborn mouse FC, we show that loss of Fgf17 selectively reduces the size of... | 10.1038/nrn2719 | The experimental evidence that prospective cytoarchitectonic areas are specified in the proliferative zones, as predicted by the protomap hypothesis (see reference 12). The authors also show that the manipulation of cell proliferation rate in the ventricular zone can independently change the size of a selected cortical... |
10.1002/cne.903240108 | 59,797,278 | Abstract The cytological features, origin, migration, and fate of the subpial granular layer cells of the human embryonic cerebral cortex are studied with light and electron microscopy, Golgi impregnations, and immunocytochemical staining with the microtubule associated protein 2 and glial fibrillary acidic protein ant... | 10.1038/nrn2719 | The detailed study of the subpial granular layers in the developing human cerebral cortex that, in spite of its large size in human (see reference 87) is neglected in the literature because of its absence in rodents. |
10.1002/cne.902970309 | 20,392,496 | Abstract The cytological organization and the timetable of emergence and dissolution of the transient subplate zone subjacent to the developing visual and somatosensory cortex were studied in a series of human and monkey fetal brains. Cerebral walls processed with Nissl, Golgi, electron‐microscopic, and histochemical m... | 10.1038/nrn2719 | The detailed temporal and regional description of the subplate zone in developing human and non-human primate cerebrum which shows its enlargements subjacent to the prospective association areas (see reference 117). |
10.1126/science.1126308 | 123,125,284 | The molecular organization of presynaptic active zones during calcium influx–triggered neurotransmitter release is the focus of intense investigation. The Drosophila coiled-coil domain protein Bruchpilot (BRP) was observed in donut-shaped structures centered at active zones of neuromuscular synapses by using subdiffrac... | 10.1038/nrn2948 | Loss of function of the active zone protein BRP in Drosophila melanogaster is shown to disrupt active zone assembly and cause defects in calcium channel clustering and presynaptic release. |
10.1083/jcb.200908082 | 125,101,507 | The presynaptic terminal contains a complex network of filaments whose precise organization and functions are not yet understood. The cryoelectron tomography experiments reported in this study indicate that these structures play a prominent role in synaptic vesicle release. Docked synaptic vesicles did not make membran... | 10.1038/nrn2948 | References 105 and 106 provide ultrastructural evidence for the existence of tethers connecting synaptic vesicles to the active zone. |
10.1073/pnas.0905181106 | 20,414,576 | Chemoreceptors are key components of the high-performance signal transduction system that controls bacterial chemotaxis. Chemoreceptors are typically localized in a cluster at the cell pole, where interactions among the receptors in the cluster are thought to contribute to the high sensitivity, wide dynamic range, and ... | 10.1038/nrmicro2505 | A detailed cryotomography study showing that bacterial chemoreceptor arrays have a conserved structure in a diverse range of species. |
10.1126/scisignal.2000724 | 20,754,784 | The bacterial chemotaxis system evolved from simpler regulatory proteins that primarily control transcription. | 10.1038/nrmicro2505 | A detailed genomics survey of the chemotaxis pathways of sequenced bacterial species. |
10.1046/j.1365-2958.2003.03716.x | 81,250,395 | Summary Components of bacterial chemosensory pathways which sense via transmembrane receptors have been shown to localize to the cell poles. Many species, however, have operons encoding multiple putative chemosensory pathways, some including putative cytoplasmic receptors. In‐genome fusions to single or multiple genes ... | 10.1038/nrmicro2505 | The demonstration that there are two separate chemotaxis clusters in R. sphaeroides |
10.1073/pnas.0808010105 | 77,661,459 | Phosphorylation-based signaling pathways employ dephosphorylation mechanisms for signal termination. Histidine to aspartate phosphosignaling in the two-component system that controls bacterial chemotaxis has been studied extensively. Rhodobacter sphaeroides has a complex chemosensory pathway with multiple homologues of... | 10.1038/nrmicro2505 | The identification of a CheA protein with in-built phosphatase activity in R. sphaeroides |
10.1146/annurev.micro.091208.073221 | 103,424,608 | Bacteria sense the chemical world using a variety of mechanisms that include the frequently described two-component system (TCS), which comprises a sensor kinase and response regulator, to regulate gene expression in response to environmental cues. One of the best and most widely studied versions of the TCS is the syst... | 10.1038/nrmicro2505 | A survey of the chemosensory pathways that regulate processes other than chemotaxis. |
10.1099/00221287-143-9-2945 | 98,341,903 | Summary: Past experiments have shown that CheA and CheY are required to generate smooth swimming signals in Bacillus subtilis chemotaxis. This study, as anticipated from in vivo experiments, demonstrates in vitro that an attractant-bound chemoreceptor leads to an increase in CheA activity, which in turn leads to an inc... | 10.1038/nrmicro2505 | The demonstration that chemotactic signalling in B. subtilis is reversed with respect to E. coli , with increases in attractant concentration activating CheA autophosphorylation. |
10.1152/jn.1986.56.4.1196 | 45,497,282 | The sensory contribution of the cortex containing the cortical barrel of the C1 vibrissa was studied in rats using the ablation-behavior method. Three independent experiments were performed, each requiring stimulus transduction by the C1 vibrissa but varying in their perceptual demands. The first required detection of ... | 10.1038/nrn2411 | This classic paper presents a spatial task that can be performed without visual input and proves that rats require an intact pathway from one whisker to one cortical barrel in order to perform the task. |
10.1159/000121327 | 61,322,695 | Polychlorinated dibenzo-<i>p</i>-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), commonly known as dioxins (PCDD/Fs), are toxic environmental pollutants formed from various sources. Elimination of these pollutants from the environment is a difficult task due to their persistent and ubiquitous nat... | 10.1038/nrmicro2519 | A comprehensive survey summarizing the most recent advances in the degradation and biotransformation of dioxins by bacteria and fungi. |
10.1021/bp00033a001 | 82,976,442 | Abstract Only within the past decade has the potential of metal biosorption by biomass materials been well established. For economic reasons, of particular interest are abundant biomass types generated as a waste byproduct of large‐scale industrial fermentations or certain metal‐binding algae found in large quantities ... | 10.1038/nrmicro2519 | This excellent review gives deep insights into the mechanism and efficiencies of heavy-metal sorption to biomass. |
10.1126/science.274.5294.1926 | 125,289,760 | Learners rely on a combination of experience-independent and experience-dependent mechanisms to extract information from the environment. Language acquisition involves both types of mechanisms, but most theorists emphasize the relative importance of experience-independent mechanisms. The present study shows that a fund... | 10.1038/nrn3838 | This study shows that young infants can quickly segment words from speech by picking up on the statistical regularities in the speech sound. |
10.1073/pnas.1112895108 | 124,170,766 | One of the most fundamental functions of the brain is to predict upcoming events on the basis of the recent past. A closely related function is to signal when a prediction has been violated. The identity of the brain regions that mediate these functions is not known. We set out to determine whether they are implemented... | 10.1038/nrn3838 | This single-unit recording study provides evidence for the notion that neurons in the visual system make experience-based predictions and respond more strongly when these predictions are violated. |
10.1073/pnas.1000233107 | 20,375,854 | Even within the early sensory areas, the majority of the input to any given cortical neuron comes from other cortical neurons. To extend our knowledge of the contextual information that is transmitted by such lateral and feedback connections, we investigated how visually nonstimulated regions in primary visual cortex (... | 10.1038/nrn3838 | This study shows that even in the absence of any bottom-up input, V1 contains information about the global scene, suggesting that the surrounding context may bias activity patterns in V1 to reflect expected input. |
10.1126/science.1195870 | 41,580,065 | Internal models of the environment optimize as the brain develops. | 10.1038/nrn3838 | By sampling spontaneous neural activity in the visual cortex of awake ferrets during different stages of development, the authors observed increasing similarity between spontaneous activity and activity evoked by natural images with increasing age. They suggest that spontaneous activity might reflect a prior world mode... |
10.1152/physrev.00017.2004 | 38,263,097 | At specific stages of development, nerve and muscle cells generate spontaneous electrical activity that is required for normal maturation of intrinsic excitability and synaptic connectivity. The patterns of this spontaneous activity are not simply immature versions of the mature activity, but rather are highly speciali... | 10.1038/nrn2759 | This comprehensive review includes detailed descriptions of the physiological changes underlying spontaneous activity in developing circuits. |
10.1152/physrev.00017.2006 | 62,282,771 | Developing networks follow common rules to shift from silent cells to coactive networks that operate via thousands of synapses. This review deals with some of these rules and in particular those concerning the crucial role of the neurotransmitter γ-aminobuytric acid (GABA), which operates primarily via chloride-permeab... | 10.1038/nrn2759 | This review describes the many functions of depolarizing GABA throughout the development of the nervious system, including the generation of giant depolarizing potentials. |
10.1002/cne.901800310 | 124,244,207 | Abstract In this study the location of dopamine (DA) neuron perikarya in the rostral mesencephalon of the rat was determined using the glyoxylic acid fluorescence histochemical technique. Subsequently the topography of the projection of these mesencephalic neurons on the basal forebrain and striatum was analyzed using ... | 10.1038/nrn1406 | This classic paper first characterized the midbrain dopamine system as a single system with topologically graded projections rather than a set of independent, non-overlapping systems. This anatomical perspective is fundamental to the suggestion that dopamine plays similar parts in various of its projection fields. |
10.1073/pnas.74.10.4537 | 41,615,243 | The 16S ribosomal RNAs from 10 species of methanogenic bacteria have been characterized in terms of the oligonucleotides produced by T 1 RNase digestion. Comparative analysis of these data reveals the methanogens to constitute a distinct phylogenetic group containing two major divisions. These organisms appear to be on... | 10.1038/nrmicro2482 | A cornerstone of the discovery of the third domain: the first SSU rRNA sequences of methanogens. |
10.1073/pnas.74.11.5088 | 83,525,241 | A phylogenetic analysis based upon ribosomal RNA sequence characterization reveals that living systems represent one of three aboriginal lines of descent: ( i ) the eubacteria, comprising all typical bacteria; ( ii ) the archaebacteria, containing methanogenic bacteria; and ( iii ) the urkaryotes, now represented in th... | 10.1038/nrmicro2482 | The quintessential description of the third domain that started it all. |
10.1073/pnas.87.12.4576 | 20,811,577 | Molecular structures and sequences are generally more revealing of evolutionary relationships than are classical phenotypes (particularly so among microorganisms). Consequently, the basis for the definition of taxa has progressively shifted from the organismal to the cellular to the molecular level. Molecular compariso... | 10.1038/nrmicro2482 | The proposal for the formal description of the three domains — a must-read for all educational purposes. |
10.1128/mmbr.61.4.456-502.1997 | 28,215,255 | Since the late 1970s, determining the phylogenetic relationships among the contemporary domains of life, the Archaea (archaebacteria), Bacteria (eubacteria), and Eucarya (eukaryotes), has been central to the study of early cellular evolution. The two salient issues surrounding the universal tree of life are whether all... | 10.1038/nrmicro2482 | An extensive review of the evolution of the universal tree of life, with particular emphasis on protein phylogeny. |
10.1073/pnas.0603780103 | 17,582,498 | A dynamical theory for the evolution of the genetic code is presented, which accounts for its universality and optimality. The central concept is that a variety of collective, but non-Darwinian, mechanisms likely to be present in early communal life generically lead to refinement and selection of innovation-sharing pro... | 10.1038/nrmicro2482 | A major advance in considering the role of Darwinian versus Lamarckian influences on the evolution of the genetic code, the translation process and cellular organization. |
10.1098/rstb.2009.0033 | 16,840,843 | Horizontal gene transfer (HGT) is often considered to be a source of error in phylogenetic reconstruction, causing individual gene trees within an organismal lineage to be incongruent, obfuscating the ‘true’ evolutionary history. However, when identified as such, HGTs between divergent organismal lineages are useful, p... | 10.1038/nrmicro2482 | A provocative view of the evolution of life (in particular, concerning what might be inferred about extinct lineages). |
10.1126/science.276.5313.734 | 62,606,536 | Over three decades of molecular-phylogenetic studies, researchers have compiled an increasingly robust map of evolutionary diversification showing that the main diversity of life is microbial, distributed among three primary relatedness groups or domains: Archaea, Bacteria, and Eucarya. The general properties of repres... | 10.1038/nrmicro2482 | An insightful review capturing the excitement emerging from the use of DNA sequence data to reveal the extent of the previously unknown phylogenetic and functional diversity in the microbial world. |
10.1126/science.273.5278.1058 | 81,568,347 | The complete 1.66-megabase pair genome sequence of an autotrophic archaeon, Methanococcus jannaschii , and its 58- and 16-kilobase pair extrachromosomal elements have been determined by whole-genome random sequencing. A total of 1738 predicted protein-coding genes were identified; however, only a minority of these (38 ... | 10.1038/nrmicro2482 | A historical, eye-opening article documenting the first genome sequence of an archaeon, and the third complete genome sequence of an organism. |
10.1126/science.1100025 | 103,821,049 | Microbial methane consumption in anoxic sediments significantly impacts the global environment by reducing the flux of greenhouse gases from ocean to atmosphere. Despite its significance, the biological mechanisms controlling anaerobic methane oxidation are not well characterized. One current model suggests that relati... | 10.1038/nrmicro2482 | An illustration of how metagenomics can be used to tease out a previously unknown pathway when there is evidence that the process (in this case, anaerobic oxidation of methane) occurs. |
10.1126/science.1069556 | 20,855,411 | Genes encoding methanogenic methylamine methyltransferases all contain an in-frame amber (UAG) codon that is read through during translation. We have identified the UAG-encoded residue in a 1.55 angstrom resolution structure of the Methanosarcina barkeri monomethylamine methyltransferase (MtmB). This structure reveals ... | 10.1038/nrmicro2482 | An important description of pyrrolysine and the mechanism of its incorporation into proteins. |
10.1073/pnas.0912072106 | 80,099,912 | tRNA His guanylyltransferase (Thg1) post-transcriptionally adds a G (position −1) to the 5′-terminus of tRNA His . The Methanosarcina acetivorans Thg1 (MaThg1) gene contains an in-frame TAG (amber) codon. Although a UAG codon typically directs translation termination, its presence in Methanosarcina mRNA may lead to pyr... | 10.1038/nrmicro2482 | An interesting description of what a novel amino acid and its cognate aaRSs can explain about evolution. |
10.1126/science.289.5486.1902 | 41,744,670 | Extremely halophilic archaea contain retinal-binding integral membrane proteins called bacteriorhodopsins that function as light-driven proton pumps. So far, bacteriorhodopsins capable of generating a chemiosmotic membrane potential in response to light have been demonstrated only in halophilic archaea. We describe her... | 10.1038/nrmicro2482 | An important study describing a previously unknown phototrophic system for marine heterotrophs. |
10.1073/pnas.94.6.2626 | 19,499,668 | New methods that allow, for the first time, genetic analysis in Archaea of the genus Methanosarcina are presented. First, several autonomously replicating plasmid shuttle vectors have been constructed based on the naturally occurring plasmid pC2A from Methanosarcina acetivorans . These vectors replicate in 9 of 11 Meth... | 10.1038/nrmicro2482 | A striking example of the development of a novel, high-efficiency gene transfer system. |
10.1126/science.170.3965.1416 | 61,153,766 | A thermophilic, acidophilic procaryote lacking a cell wall has been isolated from a coal refuse pile which had undergone self-heating. Electron micrographs, chemical assays for hexosamine, and the inability of vancomycin to inhibit growth confirm the lack of a cell wall. The apparent ability of the organism to reproduc... | 10.1038/nrmicro2482 | The discovery of an unusual archaeon before the knowledge that a third domain existed. |
10.1073/pnas.0911711107 | 103,651,348 | ATP synthase catalyzes ATP synthesis at the expense of an electrochemical ion gradient across a membrane that can be generated by different exergonic reactions. Sulfur reduction is the main energy-yielding reaction in the hyperthermophilic strictly anaerobic Crenarchaeon Ignicoccus hospitalis. This organism is unusual ... | 10.1038/nrmicro2482 | Insight into the unusual relationship between an archaeal host and archaeal symbiont or parasite, with possible implications for the evolution of a eukaryote-like cell type. |
10.1073/pnas.89.12.5685 | 107,137,895 | Archaea (archaebacteria) are a phenotypically diverse group of microorganisms that share a common evolutionary history. There are four general phenotypic groups of archaea: the methanogens, the extreme halophiles, the sulfate-reducing archaea, and the extreme thermophiles. In the marine environment, archaeal habitats a... | 10.1038/nrmicro2482 | Along with reference 132, this paper describes the new insight that archaea are important members of marine environments. |
10.1073/pnas.0704662104 | 81,124,813 | We have developed a microfluidic device that allows the isolation and genome amplification of individual microbial cells, thereby enabling organism-level genomic analysis of complex microbial ecosystems without the need for culture. This device was used to perform a directed survey of the human subgingival crevice and ... | 10.1038/nrmicro2857 | Reference 44 and 45 both sequenced TM7, a phylum lacking any sequenced members. |
10.1073/pnas.94.20.10931 | 125,309,046 | Increasing resistance of Plasmodium falciparum malaria parasites to chloroquine and the dihydrofolate reductase (DHFR) inhibitors pyrimethamine and cycloguanil have sparked renewed interest in the antimalarial drugs WR99210 and proguanil, the cycloguanil precursor. To investigate suggestions that WR99210 and proguanil ... | 10.1038/nrmicro3450 | This crucial study provided the P. falciparum research field with its most powerful selectable marker approach. |
10.1126/science.7761856 | 107,994,617 | Genetic manipulation of malaria parasites would revolutionize the study of this group of pathogens and have implications for vaccine and drug development. This report describes the stable, drug-selectable genetic transformation of the clinically relevant intracellular blood stages of a malaria parasite. A plasmid trans... | 10.1038/nrmicro3450 | This seminal paper was the first to describe transfection in rodent malaria. |
10.1073/pnas.92.4.973 | 41,411,454 | Plasmodium falciparum malaria parasites within human red blood cells (RBCs) have been successfully transfected to produce chloramphenicol acetyltransferase (CAT). Electroporation of parasitized RBCs was used to introduce plasmids that have CAT-encoding DNA flanked by 5' and 3' untranslated sequences of the P. falciparu... | 10.1038/nrmicro3450 | This seminal paper was the first to describe stable transfection of P. falciparum |
10.1073/pnas.0500112102 | 101,580,870 | Genetic manipulation has revolutionized research in the Apicomplexan parasite Plasmodium falciparum , the most important causative agent of malaria. However, to date no techniques have been established that allow modifications that are deleterious to blood-stage growth, such as the disruption of essential genes or the ... | 10.1038/nrmicro3450 | This was the first paper to show regulatable gene expression in P. falciparum |
10.1126/science.1188191 | 83,427,491 | It's a Knockout The malaria parasite is one of the most important pathogens of humans. Increasing drug-resistance is an imminent public health disaster, and we urgently need to find new drugs. The recently acquired malarial genomes provide a plethora of targets. However, due to the genetic intractability of the parasit... | 10.1038/nrmicro3450 | This is one of the best demonstrations of conditional mutagenesis in Plasmodium spp., highlighting the power of the FKBP approach. |
10.1073/pnas.0504679102 | 20,787,499 | Functional analysis of the Plasmodium falciparum genome is restricted because of the limited ability to genetically manipulate this important human pathogen. We have developed an efficient transposon-mediated insertional mutagenesis method much needed for high-throughput functional genomics of malaria parasites. A drug... | 10.1038/nrmicro3450 | This article describes a key first step toward saturation mutagenesis, and hence non-chemical forward genetics, in Plasmodium spp.. |
10.1101/gr.3455305 | 38,513,676 | Recently, we mapped the sites of transcription across ∼30% of the human genome and elucidated the structures of several hundred novel transcripts. In this report, we describe a novel combination of techniques including the rapid amplification of cDNA ends (RACE) and tiling array technologies that was used to further ch... | 10.1038/nsmb.2480 | This systematic study reveals the complex organization of gene loci that is a common feature within the genome's modular architecture |
10.1126/science.1084274 | 4,914,002 | The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27),... | 10.1038/nsmb.2480 | This work shows the recruitment of the Eed–Ezh2 complex to mediate H3K27 methylation at the inactive X chromosome by Xist |
10.1126/science.1117705 | 79,411,567 | Homeotic genes contain cis-regulatory trithorax response elements (TREs) that are targeted by epigenetic activators and transcribed in a tissue-specific manner. We show that the transcripts of three TREs located in the Drosophila homeotic gene Ultrabithorax ( Ubx ) mediate transcription activation by recruiting the epi... | 10.1038/nsmb.2480 | A model for the local recruitment of the epigenetic regulator Ash1 by lncRNAs is proposed |
10.1128/jb.129.3.1266-1271.1977 | 38,844,066 | Formation of the lateral flagella (L-flagella) of Vibrio parahaemolyticus was studied immunologically, using specific antiserum against L-flagella. On solid medium, L-flagella were formed at both high (37 degrees C) and low (25 degrees C) temperatures, although at high temperatures they became dissociated from the cell... | 10.1038/nrmicro2405 | The first observation that synthesis of lateral flagella is induced in V. parahaemolyticus by contact with a surface. |
10.1073/pnas.0912804107 | 41,385,146 | When grown in a rich medium on agar, many bacteria elongate, produce more flagella, and swim in a thin film of fluid over the agar surface in swirling packs. Cells that spread in this way are said to swarm. The agar is a solid gel, with pores smaller than the bacteria, so the swarm/agar interface is fixed. Here we show... | 10.1038/nrmicro2405 | A simple and fascinating approach to measuring the thickness of the fluid surrounding a swarm, including the unexpected finding that the top surface of the swarm fluid is relatively static. |
10.1128/jb.180.23.6384-6388.1998 | 61,199,481 | ABSTRACT A nonswarming Serratia liquefaciens mutant deficient in serrawettin W2 production was constructed by transposon mutagenesis. Sequence homology indicated that insertion had occurred in gene swrA , which encodes a putative peptide synthetase. Expression of swrA is controlled by quorum sensing. | 10.1038/nrmicro2405 | A superb analysis of the genetics, regulation and physiology of surfactants and swarming motility. |
10.1128/jb.167.1.210-218.1986 | 103,505,154 | Two distinctly different organelles of locomotion are produced by Vibrio parahaemolyticus. The polar flagellum is responsible for motility in a liquid environment (swimming), and the lateral flagella enable the bacteria to move over surfaces (swarming). Synthesis of lateral flagella occurs when V. parahaemolyticus is g... | 10.1038/nrmicro2405 | The authors couple luciferase expression to expression of a lateral flagellar gene and determine that viscosity is an inducer of the swarming state. |
10.1128/jb.178.22.6525-6538.1996 | 84,465,545 | Proteus mirabilis colonies exhibit striking geometric regularity. Basic microbiological methods and imaging techniques were used to measure periodic macroscopic events in swarm colony morphogenesis. We distinguished three initial phases (lag phase, first swarming phase, and first consolidation phase) followed by repeat... | 10.1038/nrmicro2405 | A detailed analysis of the macroscopic bull's eye pattern formation during swarming motility in P. mirabilis |
10.1139/m66-017 | 61,282,530 | This paper describes the changes in nuclear complement, cytoplasm, and cell wall which take place when short rods of Proteus mirabilis differentiate into long swarmers. In the swarmers themselves, definite cellular units are mapped out at intervals of 1.2 to 1.8 μ. These units consist of a nucleus (or paired nuclei) an... | 10.1038/nrmicro2405 | This paper documents the filamentous, aseptate, multinucleoid cell type that is associated with P. mirabilis swarming. |
10.1073/pnas.95.5.2568 | 38,417,341 | The chemotaxis system plays an essential role in swarm cell differentiation and motility. We show in this study that two (Tsr and Tar) of the four chemoreceptors in Escherichia coli can support swarming individually, but sensing their most powerful chemoattractants is not necessary. Conditions that abolish chemotaxis t... | 10.1038/nrmicro2405 | This important work provides genetic and physiological data that separate chemotaxis from swarming motility. |
10.1073/pnas.0910934107 | 83,412,272 | Swarming bacteria move in multicellular groups and exhibit adaptive resistance to multiple antibiotics. Analysis of this phenomenon has revealed the protective power of high cell densities to withstand exposure to otherwise lethal antibiotic concentrations. We find that high densities promote bacterial survival, even i... | 10.1038/nrmicro2405 | This study shows that the apparent enhanced antibiotic resistance that is enjoyed by swarming cells is due to their inherent high cell density and rapid movement. |
10.1146/annurev.neuro.27.070203.144216 | 83,395,704 | Plasticity is an intrinsic property of the human brain and represents evolution's invention to enable the nervous system to escape the restrictions of its own genome and thus adapt to environmental pressures, physiologic changes, and experiences. Dynamic shifts in the strength of preexisting connections across distribu... | 10.1038/nrn2758 | Review comparing neuroplasticity in both sensory and motor systems, including a discussion of possible underlying neurophysiological mechanisms. |
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