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10.1126/science.1109090 | 19,647,573 | Accurately predicting noise propagation in gene networks is crucial for understanding signal fidelity in natural networks and designing noise-tolerant gene circuits. To quantify how noise propagates through gene networks, we measured expression correlations between genes in single cells. We found that noise in a gene w... | 10.1038/nrmicro2392 | A classic article about the occurrence of noise in transcriptional circuits. |
10.1073/pnas.0504604102 | 41,564,116 | Gene function is typically evaluated by sampling the continuum of gene expression at only a few discrete points corresponding to gene knockout or overexpression. We argue that this characterization is incomplete and present a library of engineered promoters of varying strengths obtained through mutagenesis of a constit... | 10.1038/nrmicro2392 | A first-class account of the power of directed evolution and the selection of promoter strength. |
10.1073/pnas.061629598 | 101,111,829 | We report here the construction, characterization, and application of a bacterial bioreporter for fructose and sucrose that was designed to monitor the availability of these sugars to microbial colonizers of the phyllosphere. Plasmid pP fruB - gfp [AAV] carries the Escherichia coli fruB promoter upstream from the gfp [... | 10.1038/nrmicro2392 | This article demonstrates the use of bacterial reporters to study sugar availability and heterogeneity on plant leaves. |
10.1146/annurev.pharmtox.40.1.617 | 83,394,702 | The 14-3-3 proteins are a family of conserved regulatory molecules expressed in all eukaryotic cells. A striking feature of the 14-3-3 proteins is their ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. This plethora of interacting prot... | 10.1038/nrn1197 | Together, references 1, 2 and 10 provide excellent reviews discussing structure, function and the roles of 14-3-3 proteins in signal transdcution, cell-cycle control and apoptosis. |
10.1016/0014-5793(95)00598-4 | 81,439,381 | 14‐3‐3 proteins play a role in many cellular functions: they bind to and regulate several proteins which are critical for cell proliferation and differentiation. 14‐3‐3 proteins exist as dimers, and in this study we have shown that diverse 14‐3‐3 proteins can form both homo‐ and heterodimers in vitro (by crosslinking s... | 10.1038/nrn1197 | First evidence that 14-3-3 proteins form homo- and heterodimers with pioneering implications for different modes of action. |
10.1113/jphysiol.2002.027052 | 123,240,052 | The two‐pore‐domain potassium channels TASK‐1, TASK‐3 and TASK‐5 possess a conserved C‐terminal motif of five amino acids. Truncation of the C‐terminus of TASK‐1 strongly reduced the currents measured after heterologous expression in Xenopus oocytes or HEK293 cells and decreased surface membrane expression of GFP‐tagge... | 10.1038/nrn1197 | An excellent study determining a new mode of action of 14-3-3 proteins in mammalian brains in the control of membrane localization and functional expression of ion channels. |
10.1016/0014-5793(87)81194-8 | 122,402,048 | We have found that the 14‐3‐3 protein, an acidic neuronal protein, is substantially identical to the ‘activator’ protein [(1981) J. Biol. Chem. 256, 5404–5409] that activates tryptophan 5‐monooxygenase and tyrosine 3‐monooxygenase in the presence of Ca 2+ ,calmodulin dependent protein kinase II. This finding is based o... | 10.1038/nrn1197 | First study to assign a specific role to 14-3-3 proteins. |
10.1073/pnas.1010005107 | 18,562,951 | Protein synthesis in all living organisms occurs on ribonucleoprotein particles, called ribosomes. Despite the universality of this process, eukaryotic ribosomes are significantly larger in size than their bacterial counterparts due in part to the presence of 80 r proteins rather than 54 in bacteria. Using cryoelectron... | 10.1038/nsmb.2313 | References 15 and 16 describe several principles of evolution of the 80S ribosome, show co-evolution of rRNA and proteins and changes in the functional centers of the ribosome, and describe the behavior of dynamic RNA expansions |
10.1126/science.1211204 | 122,270,322 | The 3.5 angstrom–resolution structure provides insights into the architecture of the eukaryotic ribosome and its regulation. | 10.1038/nsmb.2313 | The X-ray structure of the large ribosomal subunit from T. thermophila reports the location and architecture of eukaryote-specific proteins and rRNA expansions |
10.1126/science.1212642 | 19,683,684 | A close-up view of the ribosome’s 79 proteins and 5500 RNA nucleotides. | 10.1038/nsmb.2313 | X-ray structure of the complete 80S ribosome from S. cerevisiae reports the precise location, architecture and registry of all eukaryote-specific proteins and almost all eukaryote-specific rRNA moieties, and describes interactions between ribosomal subunits |
10.1126/science.1194294 | 38,763,134 | Crystal structures of prokaryotic ribosomes have described in detail the universally conserved core of the translation mechanism. However, many facets of the translation process in eukaryotes are not shared with prokaryotes. The crystal structure of the yeast 80 S ribosome determined at 4.15 angstrom resolution reveals... | 10.1038/nsmb.2313 | The first X-ray structure of a eukaryotic ( S. cerevisiae ) ribosome |
10.1017/s0140525x99002034 | 20,624,528 | By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of ante... | 10.1038/nrn1178 | An important paper providing evidence that different anatomical circuits, including the hippocampus and perirhinal cortex, are involved in recollection and familiarity, respectively. |
10.1162/089892903322370744 | 101,385,202 | Several decades of research into the function of the frontal lobes in brain-damaged patients, and more recently in intact individuals using function brain imaging, has delineated the complex executive functions of the frontal cortex. And yet, the mechanisms by which the brain achieves these functions remain poorly unde... | 10.1038/nrn1178 | A computational model of the interaction between the prefrontal and medial temporal regions in long-term memory. |
10.1126/science.290.5494.1170 | 62,458,506 | The hippocampal CA1 region is crucial for converting new memories into long-term memories, a process believed to continue for week(s) after initial learning. By developing an inducible, reversible, and CA1-specific knockout technique, we could switch N -methyl- d -aspartate (NMDA) receptor function off or on in CA1 dur... | 10.1038/nrn1607 | Genetic disruption of NMDAR function in the CA1 region of the hippocampus immediately following training blocks memory consolidation. This study is consistent with the idea that hippocampal replay drives memory consolidation, and shows that NMDAR-mediated mechanisms have a central role. |
10.1126/science.2218534 | 103,286,210 | Clinical and experimental studies have shown that the hippocampal formation and related structures in the medial temporal lobe are important for learning and memory. Retrograde amnesia was studied prospectively in monkeys to understand the contribution of the hippocampal formation to memory function. Monkeys learned to... | 10.1038/nrn1607 | Using circumscribed lesions of the hippocampal formation, this is the first study to provide evidence for graded retrograde amnesia in non-human primates. |
10.1126/science.1073538 | 1,329,596 | Conversion of new memories into a lasting form may involve the gradual refinement and linking together of neural representations stored widely throughout neocortex. This consolidation process may require coordinated reactivation of distributed components of memory traces while the cortex is “offline,” i.e., not engaged... | 10.1038/nrn1607 | This study provides the first evidence that coordinated replay occurs in multiple cortical regions and supports the idea that offline reactivation of distributed cortical traces is crucial for cortical consolidation. |
10.1126/science.1094804 | 83,027,763 | Although the molecular, cellular, and systems mechanisms required for initial memory processing have been intensively investigated, those underlying permanent memory storage remain elusive. We present neuroanatomical, pharmacological, and genetic results demonstrating that the anterior cingulate cortex plays a critical... | 10.1038/nrn1607 | This paper combines cellular imaging, mouse genetic and pharmacological inactivation approaches to establish a crucial role for the anterior cingulate cortex in processing remote contextual fear memories. |
10.1126/science.279.5352.870 | 103,695,198 | The calcium-calmodulin–dependent kinase II (CaMKII) is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)–dependent activity, CaMKII can undergo autophosphorylation, resulting in CaM-independent activity. A point mutation was introduced into the αCaMK... | 10.1038/nrn3192 | This paper demonstrates that mutation of a single amino acid, T286, onCaMKIIα prevents LTP induction and has profound effects on memory. |
10.1126/science.280.5371.1940 | 60,522,194 | Long-term potentiation (LTP) at the Schaffer collateral–CA1 synapse involves interacting signaling components, including calcium (Ca 2+ )/calmodulin–dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) pathways. Postsynaptic injection of thiophosphorylated inhibitor-1 protein, a specific inhib... | 10.1038/nrn3192 | Paper discussing the control of CaMKII activation by phosphatase and the role of cAMP in the control of phosphatase. |
10.1126/science.284.5411.162 | 103,695,199 | Calcium-calmodulin–dependent protein kinase II (CaMKII) is thought to increase synaptic strength by phosphorylating postsynaptic density (PSD) ion channels and signaling proteins. It is shown that N -methyl- D -aspartate (NMDA) receptor stimulation reversibly translocates green fluorescent protein–tagged CaMKII from an... | 10.1038/nrn3192 | A classic study that demonstrates that CaMKII translocates towards the synapse after activation. |
10.1126/science.272.5262.716 | 20,620,897 | Characterization of the diffusional and electrotonic coupling of spines to the dendritic shaft is crucial to understanding neuronal integration and synaptic plasticity. Two-photon photobleaching and photorelease of fluorescein dextran were used to generate concentration gradients between spines and shafts in rat CA1 py... | 10.1038/nrn3192 | The localization of the biochemistry of LTP to the activated spine is strongly dependent on diffusion restriction that is a consequence of the narrow spine neck. This paper provides quantification of that restriction. |
10.1523/jneurosci.3114-05.2005 | 82,012,269 | In the adult hippocampus and olfactory bulb, neural progenitor cells generate neurons that functionally integrate into the existing circuits. To understand how neuronal differentiation occurs in the adult hippocampus, we labeled dividing progenitor cells with a retrovirus expressing green fluorescent protein and studie... | 10.1038/nrn2822 | The first systematic characterization of the process of adult hippocampal neurogenesis regarding the morphological and physiological maturation of adult-born DGCs. |
10.1523/jneurosci.4941-06.2007 | 82,475,653 | Neural circuits in the dentate gyrus are continuously modified by adult neurogenesis, whose level is affected by the animal's experience. However, it is not known whether this experience-dependent anatomical modification alters the functional properties of the dentate gyrus. Here, using the expression of immediate earl... | 10.1038/nrn2822 | The authors showed that the experiences of mice when the adult-born DGCs are in a hyper-excitable stage affect the subsequent responsiveness of these DGCs to various inputs. |
10.1126/science.1173215 | 29,293,637 | Neurogenesis and Spatial Memory The dentate gyrus of the hippocampus is one of two sites in the brain where new neurons are produced throughout life. Adult-born neurons integrate into the dentate gyrus circuitry and are thought to play a role in learning and memory. However, their contribution to hippocampal function r... | 10.1038/nrn2822 | The first study to suggest an involvement of adult hippocampal neurogenesis in pattern separation, a proposed function for the dentate gyrus. |
10.1523/jneurosci.3362-09.2009 | 123,071,750 | Adult-born dentate granule cells (DGCs) contribute to learning and memory, yet it remains unknown when adult-born DGCs become involved in the cognitive processes. During neurogenesis, immature DGCs display distinctive physiological characteristics while undergoing morphological maturation before final integration into ... | 10.1038/nrn2822 | This study showed that adult-born DGCs contribute to learning and memory before their full maturation, at a stage when they have enhanced excitability. |
10.1073/pnas.1019295108 | 59,410,069 | An approach based on mosquitoes carrying a conditional dominant lethal gene (release of insects carrying a dominant lethal, RIDL) is being developed to control the transmission of dengue viruses by vector population suppression. A transgenic strain, designated OX3604C, of the major dengue vector, Aedes aegypti , was en... | 10.1038/nrmicro2968 | A description of the RIDL technology and the efficacy of this technology in caged mosquito populations. |
10.1073/pnas.0600479103 | 20,520,495 | Mosquitoes ( Aedes aegypti ) were genetically modified to exhibit impaired vector competence for dengue type 2 viruses (DENV-2). We exploited the natural antiviral RNA interference (RNAi) pathway in the mosquito midgut by constructing an effector gene that expresses an inverted-repeat (IR) RNA derived from the premembr... | 10.1038/nrmicro2968 | A discussion about RNAi constructs that reduce the ability of mosquitoes to become infected with dengue. |
10.1126/science.1165326 | 62,584,477 | Most pathogens require a relatively long period of development in their mosquito vector before they can be transmitted to a new human host; hence, only older insects are of epidemiological importance. The successful transfer of a life-shortening strain of the inherited bacterial symbiont, Wolbachia , into the major mos... | 10.1038/nrmicro2968 | A report showing the lifespan reduction of the dengue vector following transinfection with Wolbachia |
10.1073/pnas.94.26.14924 | 83,293,731 | Glucocorticoid hormones, acting via nuclear receptors, regulate many metabolic processes, including hepatic gluconeogenesis. It recently has been recognized that intracellular glucocorticoid concentrations are determined not only by plasma hormone levels, but also by intracellular 11β-hydroxysteroid dehydrogenases (11β... | 10.1038/nrneph.2017.30 | This key review describes the impact of oxidative stress in CKD. |
10.1162/089976698300017052 | 104,005,088 | We review the pros and cons of analog and digital computation. We propose that computation that is most efficient in its use of resources is neither analog computation nor digital computation but, rather, a mixture of the two forms. For maximum efficiency, the information and information-processing resources of the hyb... | 10.1038/nrn1784 | Suggests that the division of neural processing into 'analogue' (dendrites) and 'digital' (axons) modes reflects evolution's minimization of brain energy use. |
10.1126/science.1089662 | 83,375,608 | Brains perform with remarkable efficiency, are capable of prodigious computation, and are marvels of communication. We are beginning to understand some of the geometric, biophysical, and energy constraints that have governed the evolution of cortical networks. To operate efficiently within these constraints, nature has... | 10.1038/nrn1784 | A review that explains a wide range of CNS design features. |
10.1073/pnas.1306428110 | 8,072,058 | Neural representations of a moving object’s distance and approach speed are essential for determining appropriate orienting responses, such as those observed in the localization behaviors of the weakly electric fish, Apteronotus leptorhynchus . We demonstrate that a power law form of spike rate adaptation transforms an... | 10.1038/nrn4037 | This paper describes the role of power law adaptation in generating a timescale-free code for looming motion, providing a velocity-independent estimate of looming object distance. This form of adaptation is one of two important types in primary EAs. |
10.1073/pnas.1418224112 | 118,346,583 | Understanding how the brain processes sensory information is often complicated by the fact that neurons exhibit trial-to-trial variability in their responses to stimuli. Indeed, the role of variability in sensory coding is still highly debated. Here, we examined how variability influences neural responses to naturalist... | 10.1038/nrn4037 | This work describes a correlation coding mechanism for populations of neurons, demonstrating its involvement in processing envelopes in the electrosense and mammalian vestibular system. |
10.1073/pnas.90.15.7265 | 122,837,437 | The Campylobacter fetus surface-layer (S-layer) proteins mediate both complement resistance and antigenic variation in mammalian hosts. Wild-type strain 23D possesses the sapA gene, which encodes a 97-kDa S-layer protein, and several sapA homologs are present in both wild-type and mutant strains. Here we report that a ... | 10.1038/nrmicro3213 | This paper provides the first description of site-specific recombination between SLP genes as a mechanism for antigenic variation. |
10.1155/2011/127870 | 64,406,777 | The amazing repertoire of glycoconjugates present on bacterial cell surfaces includes lipopolysaccharides, capsular polysaccharides, lipooligosaccharides, exopolysaccharides, and glycoproteins. While the former are constituents of Gram-negative cells, we review here the cell surface S-layer glycoproteins of Gram-positi... | 10.1038/nrmicro3213 | This study provides the first complete description of a pathway for glycosylation of an S-layer protein. |
10.1523/jneurosci.5041-06.2007 | 59,267,834 | GABA, the main inhibitory neurotransmitter in the adult nervous system, evokes depolarizing membrane responses in immature neurons, which are crucial for the generation of early network activity. Although it is well accepted that depolarizing GABA actions are caused by an elevated intracellular Cl − concentration ([Cl ... | 10.1038/nrn3819 | The authors show how to rigorously quantify NKCC1-mediated Cl − uptake using an electrophysiological approach. |
10.1152/jn.00728.2004 | 60,903,726 | In the mature brain, the K + /Cl − cotransporter KCC2 is important in maintaining low [Cl − ] i , resulting in hyperpolarizing GABA responses. Decreases in KCC2 after neuronal injuries result in increases in [Cl − ] i and enhanced neuronal excitability due to depolarizing GABA responses. We used the gramicidin perforat... | 10.1038/nrn3819 | This study demonstrates that measurements of E GABA obtained in the absence of experimental Cl − loading are not necessarily sufficient to prove compromised Cl − extrusion following neuronal damage. |
10.1523/jneurosci.4390-07.2007 | 83,000,555 | GABA A receptor-mediated inhibition depends on the maintenance of intracellular Cl − concentration ([Cl − ] in ) at low levels. In neurons in the developing CNS, [Cl − ] in is elevated, E GABA is depolarizing, and GABA consequently is excitatory. Depolarizing GABAergic synaptic responses may be recapitulated in various... | 10.1038/nrn3819 | A seminal study on the erosion of inhibition and loss of the dentate 'seizure barrier' following seizure-induced downregulation of KCC2. |
10.1126/science.1214592 | 104,237,504 | Long-term loss of fearful memories can be achieved through a combination of antidepressant drugs and exposure therapy. | 10.1038/nrn3819 | This study opens up a novel field of research for studies on CCC functions in so-called induced plasticity brought about by antidepressant drugs. |
10.1073/pnas.1107893108 | 102,533,178 | The K-Cl cotransporter KCC2 plays an essential role in neuronal chloride homeostasis, and thereby influences the efficacy and polarity of GABA signaling. Although KCC2 is expressed throughout the somatodendritic membrane, it is remarkably enriched in dendritic spines, which host most glutamatergic synapses in cortical ... | 10.1038/nrn3819 | This study demonstrated that KCC2 regulates the efficacy of glutamatergic synapses by constraining AMPA receptors in spines. |
10.1161/circresaha.113.301814 | 59,936,466 | Rationale: Increased arginine-vasopressin (AVP) secretion is a key physiological response to hyperosmotic stress and may be part of the mechanism by which high-salt diets induce or exacerbate hypertension. Objective: Using deoxycorticosterone acetate-salt hypertension model rats, we sought to test the hypothesis that c... | 10.1038/nrn3819 | This pioneering work shows that GABAergic inhibition is converted into NKCC1-dependent excitation of vasopressin-releasing hypothalamic neurons in a rat model of hypertension. This also implies that CCCs are promising drug targets for the treatment of hypertension. |
10.1113/jphysiol.2009.181826 | 107,134,354 | GABAergic excitatory [K + ] o transients can be readily evoked in the mature rat hippocampus by intense activation of GABA A receptors (GABA A Rs). Here we show that these [K + ] o responses induced by high‐frequency stimulation or GABA A agonist application are generated by the neuronal K + –Cl − cotransporter KCC2 an... | 10.1038/nrn3819 | This study showed that, paradoxically, KCC2 can promote seizures by contributing to pro-ictal extracellular K + transients. |
10.1126/scisignal.2005050 | 104,407,084 | Structural analysis reveals how chloride inhibits the activation of a kinase implicated in hypertension. | 10.1038/nrn3819 | This work suggests that WNK1 acts as a sensor of the intracellular Cl − level through direct binding of a Cl − ion to its active site, inhibiting autophosphorylation. |
10.1046/j.0953-816x.2001.01600.x | 38,548,714 | Abstract Immunocytochemical visualization of the neuron‐specific K + /Cl – cotransporter, KCC2, at the cellular and subcellular level revealed an area‐ and layer‐specific diffuse labelling, and a discrete staining outlining the somata and dendrites of some interneurons in all areas of the rat hippocampus. KCC2 was high... | 10.1038/nrn3819 | This the first study to report the surprising finding that KCC2 levels are particularly high in and around spines. This boosted subsequent work on a possible structural role for KCC2 in spine formation. |
10.1126/science.1121325 | 62,596,762 | Axons in the cerebral cortex receive synaptic input at the axon initial segment almost exclusively from γ-aminobutyric acid–releasing (GABAergic) axo-axonic cells (AACs). The axon has the lowest threshold for action potential generation in neurons; thus, AACs are considered to be strategically placed inhibitory neurons... | 10.1038/nrn3819 | The authors show that E GABA is spatially non-uniform in cortical pyramidal neurons. Whether the depolarizing GABAergic input at the AIS is functionally excitatory is being debated. |
10.1523/jneurosci.2761-07.2007 | 104,102,528 | Changes in chloride (Cl − ) homeostasis may be involved in the generation of some epileptic activities. In this study, we asked whether Cl − homeostasis, and thus GABAergic signaling, is altered in tissue from patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis. Slices prepared from this h... | 10.1038/nrn3819 | This work showed that a depolarized E GABA and consequent interictal activity in subicular tissue from patients with temporal lobe epilepsy are based on a loss of KCC2 in a subpopulation of principal neurons. |
10.1126/science.1112070 | 83,441,269 | The cerebral cortex of the human brain is a sheet of about 10 billion neurons divided into discrete subdivisions or areas that process particular aspects of sensation, movement, and cognition. Recent evidence has begun to transform our understanding of how cortical areas form, make specific connections with other brain... | 10.1038/nrn2097 | A powerful synthesis of how intrinsic and extrinsic mechanisms determine arealization in the cerebral cortex. |
10.1523/jneurosci.17-20-07763.1997 | 81,799,332 | Cortical neurons are generated in the germinal zones lining the ventricles before migrating predominantly radially. To investigate regional differences in the cell-cycle kinetics of neuroblasts, pulse [ 3 H]-thymidine injections were made throughout corticogenesis, and labeled neuron counts were compared in areas 3, 6,... | 10.1038/nrn2097 | Provides evidence for area-specific regulation of cell-cycle kinetics in the germinal zones of the rodent cortex. |
10.1242/jcs.00825 | 103,444,722 | The G1 phase of the cell cycle of neuroepithelial cells, the progenitors of all neurons of the mammalian central nervous system, has been known to lengthen concomitantly with the onset and progression of neurogenesis. We have investigated whether lengthening of the G1 phase of the neuroepithelial cell cycle is a cause,... | 10.1038/nrn2097 | Demonstrates that cell-cycle duration of cortical precursors is heterogeneous and provides in vivo evidence for differentiative divisions having longer cell-cycle duration than proliferative divisions. |
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/nrn2097 | An influential review, which needs to be read in detail, lays the foundation of the protomap hypothesis. |
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/nrn2097 | A breakthrough study showing that FGF signalling affects both the relative dimensions and identity of cortical regions. |
10.1002/ana.22230 | 62,019,268 | Abstract Objective Prominent inflammation with formation of ectopic B‐cell follicle‐like structures in the meninges in secondary progressive multiple sclerosis (MS) (SPMS) is associated with extensive cortical pathology and an exacerbated disease course. Our objective was to evaluate the cellular substrates of the cort... | 10.1038/nrn3900 | A very interesting study demonstrating a direct relationship between meningeal inflammation, subpial demyelination and neuronal loss in multiple sclerosis. |
10.1002/ana.23882 | 124,212,395 | Objective Clinical and neuroimaging parameters predictive of the changing clinical course of multiple sclerosis (MS) from relapsing–remitting to secondary progressive have not been clarified yet. We specifically designed a prospective 5‐year longitudinal study aimed at assessing demographic, clinical, and magnetic reso... | 10.1038/nrn3900 | An interesting paper implicating grey matter damage in the progression of clinical disability during the course of multiple sclerosis. |
10.1126/science.1070824 | 132,875,837 | Neural crest cells, which generate peripheral nervous system and facial skeleton, arise at the neural plate/ectodermal border via an inductive interaction between these tissues. Wnts and bone morphogenetic proteins (BMPs) play roles in neural crest induction in amphibians and zebrafish. Here, we show that, in avians, W... | 10.1038/nrn1219 | Demonstration that Wnt is the neural crest-inducing signal from the non-neural ectoderm. |
10.1126/science.7513443 | 82,951,753 | Slug , a vertebrate gene encoding a zinc finger protein of the Snail family, is expressed in the neural crest and in mesodermal cells emigrating from the primitive streak. Early chick embryos were incubated with antisense oligonucleotides to chick Slug . These oligonucleotides specifically inhibit the normal change in ... | 10.1038/nrn1219 | The first description of the Slug expression pattern, providing a molecular marker for premigratory neural crest. |
10.1242/dev.00175 | 18,913,933 | The vertebrate neural crest is a migratory stem cell population that arises within the central nervous system. Here, we combine embryological techniques with array technology to describe 83 genes that provide the first gene expression profile of a newly induced neural crest cell. This profile contains numerous novel ma... | 10.1038/nrn1219 | The first molecular profile of a newly induced neural crest cell. |
10.1523/jneurosci.18-01-00411.1998 | 40,850,279 | Functional magnetic resonance imaging (fMRI) of the human brain was used to study whether the amygdala is activated in response to emotional stimuli, even in the absence of explicit knowledge that such stimuli were presented. Pictures of human faces bearing fearful or happy expressions were presented to 10 normal, heal... | 10.1038/nrn2889 | The first study reporting that fearful facial expressions that are masked still induce amygdala activity while activity in emotion-related cortical areas is suppressed. |
10.1162/jocn.2007.19.3.445 | 108,181,522 | Survival depends to some extent on the ability to detect salient signals and prepare an appropriate response even when attention is engaged elsewhere. Fearful body language is a salient signal of imminent danger, easily observable from a distance and indicating to the observer which adaptive action to prepare for. Here... | 10.1038/nrn2889 | This study showed that fearful body expressions can be processed pre-attentively in patients with hemispatial neglect, thereby reducing the attentional bias and increasing perceptual sensitivity to stimuli presented in the left side of the space. Similar effects were previously reported for schematic facial expressions... |
10.1073/pnas.96.4.1680 | 104,093,768 | Neuroimaging studies have shown differential amygdala responses to masked (“unseen”) emotional stimuli. How visual signals related to such unseen stimuli access the amygdala is unknown. A possible pathway, involving the superior colliculus and pulvinar, is suggested by observations of patients with striate cortex lesio... | 10.1038/nrn2889 | This study showed for the first time that non-conscious perception of emotions due to backward masking in healthy observers engages a subcortical pathway involving the superior colliculus, the pulvinar and the amygdala. |
10.1523/jneurosci.1016-06.2006 | 61,830,622 | Many of the same regions of the human brain are activated during conscious attention to signals of fear and in the absence of awareness for these signals. The neural mechanisms that dissociate level of awareness from activation in these regions remain unknown. Using functional magnetic resonance imaging with connectivi... | 10.1038/nrn2889 | This study showed that the conscious versus non-conscious perception of fearful facial expressions is associated with distinct patterns of functional connectivity. Conscious perception of fearful facial expressions was associated with negative functional connectivity between the amygdala and related cortical and subcor... |
10.1073/pnas.0908994106 | 123,127,092 | The spontaneous tendency to synchronize our facial expressions with those of others is often termed emotional contagion. It is unclear, however, whether emotional contagion depends on visual awareness of the eliciting stimulus and which processes underlie the unfolding of expressive reactions in the observer. It has be... | 10.1038/nrn2889 | This study showed that spontaneous facial and pupillary reactions can be triggered by passive exposure to consciously and non-consciously perceived expressions of fear and happiness in patients with cortical blindness. Facial reactions were shown to be faster and pupil dilation higher for non-consciously than for consc... |
10.1038/ncomms12948 | 20,654,487 | Abstract Nicotinamide riboside (NR) is in wide use as an NAD + precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD + metabolism in humans. We report that human blood NAD + can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral... | 10.1038/nrneph.2017.5 | The first clinical study of nicotinamide riboside supplementation; shows a dose-dependent increase in NAD + with nicotinamide riboside, demonstrating the potential of NAD + boosting therapies in a clinical setting. |
10.1073/pnas.1519858113 | 123,163,870 | Cellular metabolites, such as acyl-CoA, can modify proteins, leading to protein posttranslational modifications (PTMs). One such PTM is lysine succinylation, which is regulated by sirtuin 5 (SIRT5). Although numerous proteins are modified by lysine succinylation, the physiological significance of lysine succinylation a... | 10.1038/nrneph.2017.5 | This study shows that SIRT5-knockout hearts have impaired fatty acid oxidation that contributes to cardiac hypertrophy with ageing. |
10.1126/science.272.5269.1791 | 83,012,323 | Substantial functional reorganization takes place in the motor cortex of adult primates after a focal ischemic infarct, as might occur in stroke. A subtotal lesion confined to a small portion of the representation of one hand was previously shown to result in a further loss of hand territory in the adjacent, undamaged ... | 10.1038/nrn2735 | An elegant illustration of cortical motor function remapping in non-human primates following stroke. This form of neuroplasticity requires use-dependent experience as a result of rehabilitation. |
10.1097/phm.0000000000001249 | 20,661,048 | Abstract A 56-yr-old woman with chronic stroke and gait dysfunction was recruited for this study. A lower-extremity constraint-induced movement therapy protocol was given consisting of 3.5 hrs/d of supervised intervention activities on 10 consecutive weekdays. Motor training was intensive and involved shaping. In addit... | 10.1038/nrn2735 | The original description of constraint-induced movement therapy, which has been shown to be perhaps the most effective method for producing functional gains months or years after the initial stroke injury. |
10.1126/science.1192430 | 107,369,879 | Stop, No-Go The decoding of messenger RNA (mRNA) into protein by eukaryotic ribosomes is constantly monitored to prevent errors. As well as mechanisms that detect and degrade messages with premature stop codons, no-go decay (NGD) results in the degradation of mRNA with inhibitory secondary structure or chemical damage.... | 10.1038/nsmb.3147 | This study together with ref. 37 provides rigorous biochemical evidence that the Dom34–Hbs1 complex mediates the splitting of translationally stalled ribosomes |
10.1126/science.1259724 | 123,032,147 | In Eukarya, stalled translation induces 40 S dissociation and recruitment of the ribosome quality control complex (RQC) to the 60 S subunit, which mediates nascent chain degradation. Here we report cryo–electron microscopy structures revealing that the RQC components Rqc2p (YPL009C/Tae2) and Ltn1p (YMR247C/Rkr1) bind t... | 10.1038/nsmb.3147 | This study determined the structure of the 60S–RQC by cryo-EM, discovered CAT tails, and demonstrated their synthesis by an mRNA- and 40S-independent Rqc2-driven process |
10.1073/pnas.1413882111 | 103,994,422 | Significance All organisms have systems in place to ensure that aberrant nascent polypeptide chains are promptly dealt with before being released from ribosomes and posing harm to the cell. The ribosome-associated quality control complex (RQC), composed of the Ltn1 E3 ubiquitin ligase catalytic subunit and cofactors, h... | 10.1038/nsmb.3147 | This study reports the cryo-EM structure of the 60S–RQC, in which the position of Rqc2 was first identified at the 60S interface bound to a P-site tRNA |
10.1098/rstb.2006.1852 | 122,541,067 | Complementary neurophysiological recordings in macaques and functional neuroimaging in humans show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature and texture (including viscosity and fat texture) of food in the... | 10.1038/nrn3105 | An excellent overview of the neurocircuitries that regulate the perception of food palatability. |
10.1126/science.1135926 | 29,300,727 | A number of brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. We found that smokers with brain damage involving the insula, a region implicated in conscious urges, were more likely than smokers with brain damage not... | 10.1038/nrn3105 | An important paper suggesting that the insula may be involved in drug addiction. |
10.1126/science.1195701 | 20,464,913 | The consumption of a food typically leads to a decrease in its subsequent intake through habituation—a decrease in one’s responsiveness to the food and motivation to obtain it. We demonstrated that habituation to a food item can occur even when its consumption is merely imagined. Five experiments showed that people who... | 10.1038/nrn3105 | An intriguing finding suggesting that mental representations of consuming a particular food item may be sufficient to trigger satiety in the absence of actually eating the food item. The paper highlights the importance of higher-order cortical brain sites in regulating the relative incentive value of particular food it... |
10.1126/science.1144599 | 20,667,105 | Studies of the fat-derived hormone leptin have provided key insights into the molecular and neural components of feeding behavior and body weight regulation. An important challenge lies in understanding how the rewarding properties of food interact with, and can override, physiological satiety signals and promote overe... | 10.1038/nrn3105 | An elegant demonstration that leptin can influence activity in brain reward systems and may thereby control food intake. |
10.7551/mitpress/4928.001.0001 | 4,827,945 | This book brings together an international group of neuroscientists and philosophers who are investigating how the content of subjective experience is correlated with events in the brain. The fundamental methodological problem in consciousness research is the subjectivity of the target phenomenon—the fact that consciou... | 10.1038/nrn783 | A collection of expert views on conceptual and empirical aspects of contemporary consciousness studies, with an important focus on bringing together different areas of inquiry. |
10.1126/science.280.5371.1930 | 102,372,685 | When dissimilar images are presented to the two eyes, perception alternates spontaneously between each monocular view, a phenomenon called binocular rivalry. Functional brain imaging in humans was used to study the neural basis of these subjective perceptual changes. Cortical regions whose activity reflected perceptual... | 10.1038/nrn783 | The first in a series of recent brain-imaging studies in humans that report fluctuations in BOLD signal either time-locked to transitions between different bistable states (see also references 87 and 88 ), or associated with specific conscious states during binocular rivalry (see also references 26 27 and 56 |
10.1126/science.279.5347.91 | 102,432,687 | Positron emission tomography was used to measure cerebral activity and to evaluate regional interrelationships within visual cortices and their projections during rapid eye movement (REM) sleep in human subjects. REM sleep was associated with selective activation of extrastriate visual cortices, particularly within the... | 10.1038/nrn783 | An important early positron emission tomography (PET) study indicating that during REM sleep, visual association cortices operate independently as a closed system dissociated from frontal regions that are associated with the control of behaviour. |
10.1113/jphysiol.2003.058701 | 125,076,789 | For much of the 20th century, lactate was largely considered a dead‐end waste product of glycolysis due to hypoxia, the primary cause of the O 2 debt following exercise, a major cause of muscle fatigue, and a key factor in acidosis‐induced tissue damage. Since the 1970s, a ‘lactate revolution’ has occurred. At present,... | 10.1038/nrn.2018.19 | A broad overview of lactate metabolism and intercellular lactate shuttling in different tissues, with an emphasis on the brain. |
10.1073/pnas.91.22.10625 | 83,038,395 | Glutamate, released at a majority of excitatory synapses in the central nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly via Na(+)-dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in add... | 10.1038/nrn.2018.19 | This article presents the first study of the ANLS model, demonstrating that glutamate uptake by astrocytes promotes aerobic glycolysis and lactate release. |
10.1126/science.aaa1299 | 104,392,679 | Targeting metabolism to tackle seizures About 1% of us suffer from epilepsy. Unfortunately, presently available drugs do not work for a third of epileptic patients. Sada et al. wanted to develop compounds to treat drug-resistant epilepsy (see the Perspective by Scharfman). They focused on a metabolic pathway in the bra... | 10.1038/nrn.2018.19 | This study demonstrates that lactate shuttling from astrocytes to neurons controls the excitability of excitatory neurons in the subthalamic nucleus and the hippocampus. |
10.1073/pnas.1322912111 | 103,814,999 | Significance The transfer of lactate, a product of aerobic glycolysis, from astrocytes to neurons was recently shown to be necessary for the establishment of long-term memory and for the maintenance of in vivo long-term potentiation. Here, we report that lactate induces the expression of plasticity genes such as Arc, c... | 10.1038/nrn.2018.19 | This study provides evidence that lactate stimulates expression of synaptic-plasticity-related genes in neurons through a mechanism involving redox changes and potentiation of NMDAR activity and its downstream signalling cascade through extracellular signal-regulated kinase 1and 2 (ERK1/2). |
10.1038/sj.jcbfm.9600256 | 102,678,504 | The metabolic response to brain activation in exercise might be expressed as the cerebral metabolic ratio (MR; uptake O 2 /glucose + 1/2 lactate). At rest, brain energy is provided by a balanced oxidation of glucose as MR is close to 6, but activation provokes a ‘surplus’ uptake of glucose relative to that of O 2 . Whe... | 10.1038/nrn.2018.19 | This review article provides an overview of in vivo evidence that increasing blood lactate levels through physical exercise leads to its utilization by the brain at the expense of glucose utilization. |
10.1113/jphysiol.2005.091355 | 124,943,061 | Physiological activation increases glucose uptake locally in the brain. However, it is not known how high intensity exercise affects regional and global brain glucose uptake. The effect of exercise intensity and exercise capacity on brain glucose uptake was directly measured using positron emission tomography (PET) and... | 10.1038/nrn.2018.19 | This human study provides evidence that increasing blood lactate levels through (moderate-to-vigorous) exercise linearly shifts cerebral metabolism from using glucose to using other energy substrates. |
10.1038/mp.2016.179 | 124,861,347 | Abstract In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l -lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are a... | 10.1038/nrn.2018.19 | This study demonstrates that peripheral administration of lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. |
10.1126/science.1093155 | 123,005,476 | The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibilitythat, for influenz... | 10.1038/nrmicro3362 | References 29, 30 and 31 provide a structural explanation for the receptor-binding shift of H1 subtype viruses. |
10.1073/pnas.0906849106 | 120,269,847 | The viruses that caused the three influenza pandemics of the twentieth century in 1918, 1957, and 1968 had distinct hemagglutinin receptor binding glycoproteins that had evolved the capacity to recognize human cell receptors. We have determined the structure of the H2 hemagglutinin from the second pandemic, the “Asian ... | 10.1038/nrmicro3362 | This paper provides the structural basis of the receptor-binding shift of H2 subtype viruses. |
10.1073/pnas.1218841110 | 122,681,277 | The hemagglutinin (HA) of influenza A(H3N2) virus responsible for the 1968 influenza pandemic derived from an avian virus. On introduction into humans, its receptor binding properties had changed from a preference for avian receptors (α2,3-linked sialic acid) to a preference for human receptors (α2,6-linked sialic acid... | 10.1038/nrmicro3362 | References 40 and 41 describe the structural basis of the receptor-binding shift of H3 subtype viruses. |
10.1126/science.1124514 | 103,086,806 | Numerous human diseases are associated with the chronic expression of misfolded and aggregation-prone proteins. The expansion of polyglutamine residues in unrelated proteins is associated with the early onset of neurodegenerative disease. To understand how the presence of misfolded proteins leads to cellular dysfunctio... | 10.1038/nrn2474 | In this article the authors reported that the expression of one aggregation-prone polyQ protein can destabilize the genome and lead to the aggregation of other proteins. |
10.1126/science.1083701 | 104,186,175 | The Caenorhabditis elegans transcription factor HSF-1, which regulates the heat-shock response, also influences aging. Reducing hsf-1 activity accelerates tissue aging and shortens life-span, and we show that hsf-1 overexpression extends lifespan. We find that HSF-1, like the transcription factor DAF-16, is required fo... | 10.1038/nrn2474 | This paper showed that HSF-1 is crucial for enabling reduced IIS to extend lifespan. |
10.1073/pnas.152161099 | 62,334,159 | Studies of the mutant gene in Huntington's disease, and for eight related neurodegenerative disorders, have identified polyglutamine (polyQ) expansions as a basis for cellular toxicity. This finding has led to a disease hypothesis that protein aggregation and cellular dysfunction can occur at a threshold of approximate... | 10.1038/nrn2474 | This seminal study indicated that the minimal number of polyQ repeats that is needed to enable aggregation declines with age. It also showed that a reduction in IIS protects worms from polyQ aggregation. |
10.1073/pnas.0705467105 | 60,014,239 | Rather than being a passive, haphazard process of wear and tear, lifespan can be modulated actively by components of the insulin/insulin-like growth factor I (IGFI) pathway in laboratory animals. Complete or partial loss-of-function mutations in genes encoding components of the insulin/IGFI pathway result in extension ... | 10.1038/nrn2474 | This report indicated that reduced IGF signalling is typical in the offspring of centenarians and suggested that the regulation of lifespan by IGF signalling is conserved in humans. It also showed that high IGF plasma levels can lead to reduced IGF signalling, supporting the idea that feedback loops regulate the IIS pa... |
10.1212/wnl.50.1.164 | 104,149,430 | Patients with Alzheimer's disease (AD) have elevations of fasting plasma insulin that are hypothesized to be associated with disrupted brain insulin metabolism. We examined paired fasted plasma and CSF insulin levels in 25 patients with AD and 14 healthy age-matched adults and determined whether insulin levels were rel... | 10.1038/nrn2474 | This study indicated that insulin levels can vary in the plasma and in the CSF, and it correlated these levels with severity of dementia in Alzheimer's disease. |
10.1523/jneurosci.18-01-00251.1998 | 123,691,908 | The transport of mRNAs into developing dendrites and axons may be a basic mechanism to localize cytoskeletal proteins to growth cones and influence microfilament organization. Using isoform-specific antibodies and probes for in situ hybridization, we observed distinct localization patterns for β- and γ-actin within cul... | 10.1038/nrn2593 | Demonstration of β-actin mRNA transport to, and localization of translational components in, the axonal growth cone. |
10.1242/jcs.022442 | 58,408,413 | Similar to most differentiated cells, both neurons and epithelial cells elaborate distinct plasma membrane domains that contain different membrane proteins. We have previously shown that the axonal cell-adhesion molecule L1/NgCAM accumulates on the axonal surface by an indirect transcytotic pathway via somatodendritic ... | 10.1038/nrn2593 | This study demonstrated transcytotic targeting of L1 in hippocampal neurons. |
10.1523/jneurosci.08-04-01454.1988 | 38,399,639 | By the end of the first week in culture, hippocampal neurons have established a single axon and several dendrites. These 2 classes of processes differ in their morphology, in their molecular composition, and in their synaptic polarity (Bartlett and Banker, 1984a, b; Caceres et al., 1984). We examined the events during ... | 10.1038/nrn2593 | This classic paper describes the stages of axon versus dendrite outgrowth during neuronal differentiation. |
10.1523/jneurosci.23-15-06188.2003 | 104,284,270 | Organelles of the neuronal secretory pathway are critical for the addition of membrane that accompanies neuronal development, as well as for the proper localization of plasma membrane proteins necessary for polarity, synaptic transmission, and plasticity. Here, we demonstrate that two organizations of the secretory pat... | 10.1038/nrn2593 | This paper and reference 82 provided key evidence for the roles of Golgi outposts in dendritic vesicular trafficking and outgrowth. |
10.1083/jcb.150.4.849 | 40,400,570 | Cellularization of the Drosophila embryo is a specialized form of cytokinesis that results in the formation of a polarized epithelium. The mechanisms of membrane growth during cytokinesis are largely unknown. It is also unclear whether membrane growth and polarization represent distinct processes that occur simultaneou... | 10.1038/nrn2593 | A striking demonstration of highly polarized, specifically targeted membrane expansion in non-neuronal cells. |
10.1073/pnas.0902362106 | 103,986,686 | Many plant pathogens secrete toxins that enhance microbial virulence by killing host cells. Usually, these toxins are produced by particular microbial taxa, such as bacteria or fungi. In contrast, many bacterial, fungal and oomycete species produce necrosis and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) th... | 10.1038/nrmicro3118 | The three-dimensional structure of an NLP from an oomycete pathogen, which showed structural similarities between NLPs and pore-forming toxins produced by marine organisms. |
10.1073/pnas.1733690100 | 122,353,140 | Polygalacturonase-inhibiting proteins (PGIPs) are plant cell wall proteins that protect plants from fungal invasion. They interact with endo polygalacturonases secreted by phytopathogenic fungi, inhibit their enzymatic activity, and favor the accumulation of oligogalacturonides, which activate plant defense responses. ... | 10.1038/nrmicro3118 | This article shows the crystal structure of PGIP2 from the common bean. This was the first structure of a plant LRR protein and remains one of the few cases in which the crystallized protein was purified from plants. |
10.1126/science.1218867 | 59,350,701 | Dissecting Chitin Binding The chitin in fungal cells walls serves as a trigger to initiate plant defenses against pathogenic fungi. Arabidopsis detects these signals through a cell surface chitin receptor whose intracellular kinase domain initiates a signaling cascade in response to chitin that activates the plant's re... | 10.1038/nrmicro3118 | This article shows the crystal structure of the extracellular LysM domains of A. thaliana CERK1 in both ligand-free and chitin-bound forms, which provides evidence for ligand-induced dimerization of CERK1. The paper assesses the relevance of this dimerization for signal transduction. |
10.1126/science.1120131 | 123,634,147 | The Pseudomonas syringae protein AvrPtoB is translocated into plant cells, where it inhibits immunity-associated programmed cell death (PCD). The structure of a C-terminal domain of AvrPtoB that is essential for anti-PCD activity reveals an unexpected homology to the U-box and RING-finger components of eukaryotic E3 ub... | 10.1038/nrmicro3118 | This is a structure determination of a previously uncharacterized C-terminal domain of AvrPtoB, which shows that it adopts the fold of eukaryotic U-box ubiquitin E3 ligases. E3 ligase activity is required for both effector-triggered susceptibility and interference with NB-LRR-mediated immunity. |
10.1105/tpc.109.066878 | 39,563,531 | Abstract Resistance to bacterial speck disease in tomato (Solanum lycopersicum) is activated upon recognition by the host Pto kinase of either one of two sequence-unrelated effector proteins, AvrPto or AvrPtoB, from Pseudomonas syringae pv tomato (Pst). Pto induces Pst immunity by acting in concert with the Prf protein... | 10.1038/nrmicro3118 | This article shows the crystal structure of a complex between the first four-helix bundle of AvrPtoB and Pto, which reveals contact with the P + 1 loop of the kinase. |
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