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10.1146/annurev.neuro.24.1.167 | 83,551,177 | ▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of pat... | 10.1038/nrn.2017.111 | This study provides an explanation of the role of prefrontal cortex in cognitive control and flexibility. |
10.1126/science.1131295 | 104,439,072 | Despite evidence pointing to a ubiquitous tendency of human minds to wander, little is known about the neural operations that support this core component of human cognition. Using both thought sampling and brain imaging, the current investigation demonstrated that mind-wandering is associated with activity in a default... | 10.1038/nrn.2017.111 | This study shows that some brain regions, including the frontopolar cortex, show higher activation levels during rest periods, which correlates with the level of mind-wandering. |
10.1098/rstb.2013.0474 | 37,356,079 | The prefrontal cortex subserves executive control and decision-making, that is, the coordination and selection of thoughts and actions in the service of adaptive behaviour. We present here a computational theory describing the evolution of the prefrontal cortex from rodents to humans as gradually adding new inferential... | 10.1038/nrn.2017.111 | This paper contains the first theory formalizing the evolution of the prefrontal function in mammals from rodents to humans. |
10.1126/science.7886457 | 104,338,718 | The neurotrophins are signaling factors important for the differentiation and survival of distinct neuronal populations during development. To test whether the neurotrophins also function in the mature nervous system, the effects of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophic f... | 10.1038/nrn3505 | This is the first report to show, using rat hippocampal slices, a pharmacological effect of BDNF on synaptic transmission. |
10.1113/jphysiol.2003.052639 | 42,548,905 | The refinement and plasticity of neuronal connections require synaptic activity and neurotrophin signalling; their specific contributions and interplay are, however, poorly understood. We show here that brain‐derived neurotrophic factor (BDNF) increased spine density in apical dendrites of CA1 pyramidal neurones in org... | 10.1038/nrn3505 | An important study that clearly demonstrates the pharmacological effect of BDNF on synaptic growth; that is, it found an increase in the number of dendritic spines. |
10.1111/1467-8721.00137 | 122,592,704 | The fact that brain disorder can impair social interactions in different ways suggests that social competence has multiple components that have foundations in brain systems. The physiological basis of one aspect of social cognition, theory of mind, is just beginning to be understood. Brain-imaging studies suggest that ... | 10.1038/nrn844 | References 6–8 elegantly review the role of neural systems that are involved in mentalizing, with particular emphasis on the systems that underlie the detection and interpretation of biological motion. |
10.1126/science.290.5499.2155 | 20,569,144 | Class I major histocompatibility complex (class I MHC) molecules, known to be important for immune responses to antigen, are expressed also by neurons that undergo activity-dependent, long-term structural and synaptic modifications. Here, we show that in mice genetically deficient for cell surface class I MHC or for a ... | 10.1038/nrn1428 | Using mice deficient for most MHC class I genes, this study determined that MHC class I is required for normal activity-dependent refinement of developing visual projections as well as normal long-term potentiation and long-term depression in the adult hippocampus. |
10.1073/pnas.1735415100 | 23,812,778 | MHC class I proteins are cell-surface ligands that bind to T cell receptors and other immunoreceptors and act to regulate the activation state of immune cells. Recent work has shown that MHC class I genes and CD3ζ, an obligate component of T cell receptors, are expressed in neurons, are regulated by neuronal activity, ... | 10.1038/nrn1428 | This study found striking and dynamic expression of mRNA encoding an unrecombined β-subunit of the TCR in the developing and adult mouse CNS, including in the thalamic nuclei and deep layers of cortex. |
10.1126/science.7939663 | 79,440,186 | Interval mapping of data from two independent samples of sib pairs, at least one member of whom was reading disabled, revealed evidence for a quantitative trait locus (QTL) on chromosome 6. Results obtained from analyses of reading performance from 114 sib pairs genotyped for DNA markers localized the QTL to 6p21.3. An... | 10.1038/nrn1428 | This study was the first to show a strong genetic link between the MHC class I region and developmental dyslexia. |
10.1128/jvi.78.19.10793-10802.2004 | 59,701,451 | ABSTRACT The membrane glycoproteins (Gn and Gc) of Bunyamwera virus (BUN; family Bunyaviridae ) accumulate in the Golgi complex, where virion maturation occurs. The Golgi targeting and retention signal has previously been shown to reside within the Gn protein. A series of truncated Gn and glycoprotein precursor cDNAs w... | 10.1038/nrmicro3332 | This study shows that the Golgi-targeting signal is present in the transmembrane domain of the orthobunyavirus Gn protein. |
10.1128/jvi.00902-10 | 81,264,625 | ABSTRACT The virion glycoproteins Gn and Gc of Bunyamwera virus (BUNV), the prototype of the Bunyaviridae family and also of the Orthobunyavirus genus, are encoded by the medium (M) RNA genome segment and are involved in both viral attachment and entry. After their synthesis Gn and Gc form a heterodimer in the endoplas... | 10.1038/nrmicro3332 | This paper describes the generation of a recombinant BUNV in which the Gc glycoprotein is fused to GFP, which enables viral propagation to be monitored by light microscopy. |
10.1073/pnas.1302298110 | 122,324,387 | The nucleoprotein (NP) of segmented negative-strand RNA viruses such as Orthomyxo-, Arena-, and Bunyaviruses coats the genomic viral RNA and together with the polymerase forms ribonucleoprotein particles (RNPs), which are both the template for replication and transcription and are packaged into new virions. Here we des... | 10.1038/nrmicro3332 | References 47, 48, 49, 50 and 51 report crystal structures of orthobunyavirus nucleocapsid proteins. |
10.1128/jvi.00140-12 | 16,904,681 | ABSTRACT La Crosse virus (LACV) is a leading cause of pediatric encephalitis and aseptic meningitis in the midwestern and southern United States, where it is considered an emerging human pathogen. No specific therapies or vaccines are available for LACV or any other orthobunyaviruses. Inhibition of LACV entry into cell... | 10.1038/nrmicro3332 | This paper describes the entry mechanism of LACV into cells of the central nervous system. |
10.1128/jvi.63.12.5166-5174.1989 | 123,557,605 | Within 24 to 48 h of La Crosse virus infection of mosquito cells, greater than 75% of the S mRNA was found to band in CsCl density gradients at the position of genome or antigenome nucleocapsids. The encapsidation of the S mRNA correlates with the repression of N protein synthesis in vivo, and the encapsidated S mRNA c... | 10.1038/nrmicro3332 | This study shows that the dsRNA panhandle structure in LACV nucleocapsids triggers the innate immune response by activating RIGI shortly after viral entry. |
10.1073/pnas.93.26.15400 | 105,409,957 | We provide the first report, to our knowledge, of a helper-independent system for rescuing a segmented, negative-strand RNA genome virus entirely from cloned cDNAs. Plasmids were constructed containing full-length cDNA copies of the three Bunyamwera bunyavirus RNA genome segments flanked by bacteriophage T7 promoter an... | 10.1038/nrmicro3332 | This paper describes the initial reverse genetics system for Bunyamwera virus, which was the first system used to generate a negative-sense RNA virus with a segmented genome from plasmid DNAs. |
10.1146/annurev-neuro-062012-170307 | 38,401,404 | To understand the organization and assembly of mammalian brain circuits, we need a comprehensive tool set that can address the challenges of cellular diversity, spatial complexity at synapse resolution, dynamic complexity of circuit operations, and multifaceted developmental processes rooted in the genome. Complementar... | 10.1038/nrn.2017.85 | This article summarizes the progress enabled by obtaining genetic access to specific cell types, which relied on molecular classification. |
10.1146/annurev-neuro-071714-034120 | 62,212,111 | In the retina, photoreceptors pass visual information to interneurons, which process it and pass it to retinal ganglion cells (RGCs). Axons of RGCs then travel through the optic nerve, telling the rest of the brain all it will ever know about the visual world. Research over the past several decades has made clear that ... | 10.1038/nrn.2017.85 | This article reviews the progress in classifying RGC types in mice. Remarkably, the estimated number has grown from ∼ 30 to >50 in the two years since its publication. |
10.1126/science.aaa6090 | 104,392,664 | Multiplexed RNA imaging in single cells The basis of cellular function is where and when proteins are expressed and in what quantities. Single-molecule fluorescence in situ hybridization (smFISH) experiments quantify the copy number and location of mRNA molecules; however, the numbers of RNA species that can be simulta... | 10.1038/nrn.2017.85 | This paper describes MERFISH, one of several highly multiplexed methods used for in situ hybridization. |
10.1126/science.aac9462 | 104,242,633 | A census of neocortical neurons Despite the importance of the brain's neocortex, we still do not completely understand the diversity and functional connections of its cell types. Jiang et al. recorded, labeled, and classified over 1200 interneurons and more than 400 pyramidal neurons in the mature mouse visual cortex. ... | 10.1038/nrn.2017.85 | Reports a large-scale electrophysiological and morphological characterization of adult neocortical neurons, revealing connectivity patterns among morphologically defined neuronal types. |
10.1126/science.1223616 | 20,370,106 | Generating the Cortex During development of the cerebral cortex, radial glial neural progenitor cells generate layer-specific subtypes of excitatory neurons in a defined temporal sequence, in which deep layers are formed before upper layers. The prevailing model for cortical neurogenesis over the last 20 years has been... | 10.1038/nrn3586 | Genetic fate-mapping of Cux2 -expressing cells enables the authors to establish that a subset of cortical progenitors, which are present from the earliest stages of corticogenesis, are committed to generating 'upper-layer' (commissural and associative) neurons. |
10.1002/cne.903360210 | 83,280,757 | Abstract We have previously shown that the density of dendritic spines on hippocampal CA1 pyramidal cells is dependent on circulating estradiol and progesterone and fluctuates naturally during the 5 day estrous cycle in the adult rat. To date, however, no detailed characterization of the roles that these hormones play ... | 10.1038/nrn1649 | Showed for the first time that dendritic spine density in the hippocampus can vary by as much as 30% across the oestrus cycle in adult female rats, bringing into question the relevance of spine density changes to memory storage. |
10.1146/annurev.neuro.051508.135600 | 83,552,304 | Glial cells were long considered end products of neural differentiation, specialized supportive cells with an origin very different from that of neurons. New studies have shown that some glial cells—radial glia (RG) in development and specific subpopulations of astrocytes in adult mammals—function as primary progenitor... | 10.1038/nrn.2016.70 | This review systematically summarizes the current state of knowledge of embryonic and adult neurogenesis. |
10.1126/science.1190485 | 125,112,847 | Location, Location, Location The genome receives epigenetic marks throughout development that regulate the activity of multiple genes. One such mark is methylation, which usually represses gene transcription. Methylation has generally been studied in the promoters of genes, where many regulatory signals coordinate to c... | 10.1038/nrn.2016.70 | This study uses Dnmt3a -conditional-knockout mice to reveal its critical role in neurogenesis through crosstalk with the repressive histone modification H3K27me3 and its modifiers, the PcG proteins. |
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.2016.70 | References 38 and 39 describe non-canonical CpH methylation in the mammalian genome. |
10.1126/science.1170116 | 125,255,278 | Methylation Mediation Methylation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role in mammalian genomes. Methylation patterns are often inherited across generations, but they can also be dynamic, suggesting that active DNA demethylation pathways exist. One such pathway, best characte... | 10.1038/nrn.2016.70 | This study, for the first time, identifies TET1 as a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyses the conversion of 5mC to 5hmC. |
10.1126/science.1210597 | 20,790,441 | 5-methylcytosine (5mC) in DNA plays an important role in gene expression, genomic imprinting, and suppression of transposable elements. 5mC can be converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) proteins. Here, we show that, in addition to 5hmC, the Tet proteins can generate 5-formylcy... | 10.1038/nrn.2016.70 | References 54 and 55 together reveal that TET proteins can further convert 5hmC to 5fC and then 5caC, with the latter being converted back to cytosine by thymine DNA glycosylase. |
10.1126/science.1166859 | 18,478,289 | The mammalian brain exhibits diverse types of neural plasticity, including activity-dependent neurogenesis in the adult hippocampus. How transient activation of mature neurons leads to long-lasting modulation of adult neurogenesis is unknown. Here we identify Gadd45b as a neural activity–induced immediate early gene in... | 10.1038/nrn.2016.70 | This study reveals that DNA demethylation plays a crucial part in controlling key neuronal gene expression. |
10.1073/pnas.96.20.11167 | 123,889,132 | Spinal muscular atrophy (SMA) is a common motor neuron degenerative disease and the leading genetic cause of death of young children. The survival of motor neurons ( SMN ) gene, the SMA disease gene, is homozygously deleted or mutated in more than 98% of SMA patients. The SMN protein interacts with itself, with SMN-int... | 10.1038/nrn2670 | Demonstrated that SMN needs to be oligomeric to efficiently bind Sm proteins. |
10.1073/pnas.0508947102 | 41,652,108 | Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by loss of spinal motor neurons. The gene encoding the survival of motor neurons (SMN) protein is mutated in >95% of SMA cases. SMN is the central component of a large oligomeric complex, including Gemins2–7, that is necessary and sufficient ... | 10.1038/nrn2670 | The first assay of the ability of a panel of SMN missense alleles to perform snRNP assembly. |
10.1083/jcb.200304128 | 28,222,704 | Spinal muscular atrophy (SMA), a common autosomal recessive form of motoneuron disease in infants and young adults, is caused by mutations in the survival motoneuron 1 (SMN1) gene. The corresponding gene product is part of a multiprotein complex involved in the assembly of spliceosomal small nuclear ribonucleoprotein c... | 10.1038/nrn2670 | In this work, cultured motor neurons from SMA mice showed altered axon length and altered transport of β-actin mRNA to axon tips. |
10.1073/pnas.94.18.9920 | 20,706,809 | Proximal spinal muscular atrophy is an autosomal recessive human disease of spinal motor neurons leading to muscular weakness with onset predominantly in infancy and childhood. With an estimated heterozygote frequency of 1/40 it is the most common monogenic disorder lethal to infants; milder forms represent the second ... | 10.1038/nrn2670 | The first demonstration that loss of SMN in mammals is an embryonic lethal phenotype, which showed that SMN is an essential gene. |
10.1083/jcb.200303168 | 18,549,048 | Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by a loss of α motoneurons in the spinal cord. SMA is caused by low levels of the ubiquitously expressed survival motor neuron (Smn) protein. As it is unclear how low levels of Smn specifically affect motoneurons, we have modeled SMA in zebr... | 10.1038/nrn2670 | Demonstrated that knockdown of SMN in zebrafish causes a cell-autonomous defect in motor axons that can be corrected with SMN expression, allowing the crucial pathways in SMA to be assayed. |
10.1146/annurev.psych.49.1.289 | 83,541,683 | ▪ Abstract Numerous empirical and theoretical observations point to the constructive nature of human memory. This paper reviews contemporary research pertaining to two major types of memory distortions that illustrate such constructive processes: (a) false recognition and (b) intrusions and confabulations. A general in... | 10.1038/nrn1179 | Review on the mechanisms that supervise memory retrieval and interpretation of confabulations as a defect of constructive processes. |
10.1002/hipo.450030307 | 125,121,675 | Abstract Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroer cephalograph theta pattern of rhythmical waves (7–12 Hz) is better correlated with a class of movements that change ... | 10.1038/nrn.2016.21 | This study describes the discovery of theta phase precession in hippocampal place cells. |
10.7554/elife.03061 | 123,921,173 | Assessing the behavioral relevance of the hippocampal theta rhythm has proven difficult, due to a shortage of experiments that selectively manipulate phase-specific information processing. Using closed-loop stimulation, we triggered inhibition of dorsal CA1 at specific phases of the endogenous theta rhythm in freely be... | 10.1038/nrn.2016.21 | This study shows that memory encoding and memory retrieval are differentially affected depending on the theta phase at which CA1 is inhibited. Optogenetic techniques were used to inhibit CA1 activity at particular phases of theta. |
10.1523/jneurosci.2614-14.2015 | 81,794,763 | Theta sequences are circuit-level activity patterns produced when groups of hippocampal place cells fire in sequences that reflect a compressed behavioral order of place fields within each theta cycle. The high temporal coordination between place cells exhibited in theta sequences is compatible with the induction of sy... | 10.1038/nrn.2016.21 | This study reveals that theta phase precession is present immediately in a novel environment but that theta sequences develop with experience. |
10.1126/science.1217230 | 104,166,790 | Spatial Memory Perturbation The hippocampus is important for learning and memory. However, it is not clear which patterns of neural activity in the hippocampus support specific mnemonic functions. Jadhav et al. (p. 1454 , published online 3 May) developed a real-time analysis system to detect and selectively interrupt ... | 10.1038/nrn.2016.21 | This study disrupts sharp wave–ripples in rats while they carry out a spatial memory task and shows that task performance is impaired, suggesting that sharp wave–ripples in awake animals have a role in memory-guided trajectory planning. |
10.1146/annurev.immunol.19.1.253 | 102,652,126 | ▪ Abstract HIV-1 particles are decorated with a network of densely arranged envelope spikes on their surface. Each spike is formed of a trimer of heterodimers of the gp120 surface and the gp41 transmembrane glycoproteins. These molecules mediate HIV-1 entry into target cells, initiating the HIV-1 replication cycle. The... | 10.1038/nrmicro729 | A review on the structure and function of the HIV-1 envelope glycoproteins that puts the activity of Env-targeting inhibitors into context. |
10.1073/pnas.252469399 | 41,562,929 | HIV entry inhibitors include coreceptor antagonists and the fusion inhibitor T-20. T-20 binds the first helical region (HR1) in the gp41 subunit of the viral envelope (Env) protein and prevents conformational changes required for membrane fusion. HR1 appears to become accessible to T-20 after Env binds CD4, whereas cor... | 10.1038/nrmicro729 | References 59 and 60 review the HIV-1 fusion process and outline many of the parameters that affect the efficiency of entry-inhibitor action. |
10.1128/jvi.69.11.6609-6617.1995 | 20,829,209 | We have tested three human monoclonal antibodies (MAbs) IgG1b12, 2G12, and 2F5) to the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1), and a tetrameric CD4-IgG molecule (CD4-IgG2), for the ability to neutralize primary HIV-1 isolates from the genetic clades A through F and from group O. Each of t... | 10.1038/nrmicro729 | An early paper that showed that selected human mAbs and a CD4-based agent can have broad neutralizing activity against diverse primary isolates in vitro |
10.1126/science.280.5371.1884 | 83,554,107 | The human immunodeficiency virus–type 1 (HIV-1) envelope glycoproteins interact with receptors on the target cell and mediate virus entry by fusing the viral and cell membranes. The structure of the envelope glycoproteins has evolved to fulfill these functions while evading the neutralizing antibody response. An unders... | 10.1038/nrmicro729 | An overview of the structure of the HIV-1 envelope glycoproteins, with an emphasis on the core of the gp120 subunit. |
10.1523/jneurosci.4902-09.2010 | 42,558,968 | As human life expectancy continues to rise, financial decisions of aging investors may have an increasing impact on the global economy. In this study, we examined age differences in financial decisions across the adult life span by combining functional neuroimaging with a dynamic financial investment task. During the t... | 10.1038/nrn3917 | This study identifies a novel measure of neural signal variability that mediates age differences in risky choice during a financial investment task. |
10.1111/j.1749-6632.2011.06200.x | 82,925,605 | Does risk taking change as a function of age? We conducted a systematic literature search and found 29 comparisons between younger and older adults on behavioral tasks thought to measure risk taking ( N = 4,093). The reports relied on various tasks differing in several respects, such as the amount of learning required ... | 10.1038/nrn3917 | This quantitative meta-analysis implies that there are age-related performance decrements in learning-dependent compared with non-learning-dependent tasks. |
10.1523/jneurosci.5756-11.2012 | 123,258,918 | Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for... | 10.1038/nrn3917 | This study shows that the structural connectivity of frontostriatal projections mediates age differences in reward learning. |
10.1523/jneurosci.2888-14.2014 | 103,560,600 | Everyday consumer choices frequently involve memory, as when we retrieve information about consumer products when making purchasing decisions. In this context, poor memory may affect decision quality, particularly in individuals with memory decline, such as older adults. However, age differences in choice behavior may ... | 10.1038/nrn3917 | This study shows that increased mPFC activity in older adults promotes improved decision making in cognitively demanding decision tasks. |
10.1353/eca.0.0067 | 62,538,081 | Many consumers make poor financial choices, and older adults are particularly vulnerable to such errors. About half of the population between ages 80 and 89 have a medical diagnosis of substantial cognitive impairment. We study life-cycle patterns in financial mistakes using a proprietary database with information on 1... | 10.1038/nrn3917 | This study adapts classic findings on age differences in fluid and crystallized abilities to explain adult age differences in optimal financial decisions in the real world. |
10.1016/j.febslet.2011.12.024 | 40,544,473 | Using comparative genomics and functional analysis, this work summarises how the cell's genome is organised, with emphasis on the importance of the cell's chassis. Some discrete but important engineering constraints are reviewed, beginning with the need for scaffolds, as well as the question posed by the difficult task... | 10.1038/nrmicro3253 | This paper provides an enlightening discussion on the neglected issue of choosing an appropriate chassis for synthetic biology applications. |
10.1046/j.1462-2920.2002.00370.x | 20,261,254 | Summary Analysis of the catabolic potential of Pseudomonas putida KT2440 against a wide range of natural aromatic compounds and sequence comparisons with the entire genome of this microorganism predicted the existence of at least four main pathways for the catabolism of central aromatic intermediates, that is, the prot... | 10.1038/nrmicro3253 | A comprehensive survey of the many biochemical mechanisms that enable P. putida to grow on diverse carbon substrates. |
10.1186/1752-0509-2-79 | 123,076,094 | Abstract Background Pseudomonas putida is the best studied pollutant degradative bacteria and is harnessed by industrial biotechnology to synthesize fine chemicals. Since the publication of P. putida KT2440's genome, some in silico analyses of its metabolic and biotechnology capacities have been published. However, glo... | 10.1038/nrmicro3253 | This paper reports on the development of the first genome-wide metabolic model of strain KT2440, which has enabled the identification of this bacterium as a useful microbial cell factory. |
10.1111/j.1462-2920.2011.02538.x | 100,628,292 | Summary The genome of the soil bacterium Pseudomonas putida strain KT2440 has been erased of various determinants of resistance to antibiotics encoded in its extant chromosome. To this end, we employed a coherent genetic platform that allowed the precise deletion of multiple genomic segments in a large variety of Gram‐... | 10.1038/nrmicro3253 | This paper presents a method for the seamless deletion of genetic elements in Pseudomonas spp. and other Gram-negative bacteria. |
10.1080/14640747508400525 | 41,489,122 | The selective impairment of semantic memory is described in three patients with diffuse cerebrallesions. These patients, selected on the basis of a failure to recognize or identify common objects (agnosia for objects), were investigated in detail. In particular, their perceptual, language and memory functions were asse... | 10.1038/nrn1076 | Classic paper first reporting the syndrome that is now known as semantic dementia. |
10.1073/pnas.0504640102 | 59,512,561 | The molecular mechanisms contributing to the normal age-related decline of cognitive functions or to pathological learning and memory impairment are largely unknown. We demonstrate here that young mice (6–7 weeks) with a genetic deletion of the cannabinoid CB1 receptor performed as well as WT mice, or often better, in ... | 10.1038/nrn3876 | This paper shows that brain ageing is accelerated in mice lacking cannabinoid CB1 receptors. |
10.1073/pnas.0504187103 | 82,768,414 | The endogenous cannabinoids bind to and activate two G protein-coupled receptors, the predominantly central cannabinoid receptor type 1 (CB1) and peripheral cannabinoid receptor type 2 (CB2). Whereas CB1 mediates the cannabinoid psychotropic, analgesic, and orectic effects, CB2 has been implicated recently in the regul... | 10.1038/nrn3876 | This paper demonstrates that mice lacking cannabinoid CB2 receptors have an age-related osteoporosis phenotype. |
10.1073/pnas.1219485110 | 81,282,323 | Significance Endocannabinoids act retrogradely at presynaptic sites to activate cannabinoid receptor type 1 (CB 1 ) receptors, thereby inhibiting neurotransmitter release and fine-tuning synaptic transmission. In murine models of obesity with leptin deficiency, we report that orexin-A neurons undergo a shift from predo... | 10.1038/nrn3876 | The first paper describing endocannabinoid-mediated mechanisms through which the orexinergic control of basic functions can be disrupted in obesity. |
10.1126/science.1209200 | 124,117,204 | A new tissue-specific pathway for the synthesis of proinflammatory prostaglandins is described. | 10.1038/nrn3876 | This study identifies COX2 as a major metabolism pathway of the endocannabinoid 2-AG that mediates neuroinflammation and neuronal loss in a mouse model of Parkinson's disease, suggesting that COX2 inhibitors might represent promising therapeutic approaches for this neurodegenerative disease. |
10.1111/jnc.12137 | 83,055,155 | Abstract Type 1 cannabinoid receptor (CB1) is expressed in different neuronal populations in the mammalian brain. In particular, CB1 on GABAergic or glutamatergic neurons exerts different functions and display different pharmacological properties in vivo . This suggests the existence of neuron‐type specific signalling ... | 10.1038/nrn3876 | This study shows that CB1 receptor coupling efficacy in glutamatergic neurons is greater than in GABAergic neurons, providing evidence for an additional level of complexity in the differential signalling measured for this GPCR depending on the cell type. |
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/nrmicro866 | Recognition of the Archaea as a distinct Domain with many molecular properties resembling Eukaryotes. |
10.1128/jb.176.19.6148-6152.1994 | 28,261,458 | Thermophilic organisms from each of the three phylogenetic domains (Bacteria, Archaea, and Eucarya) acquired thermotolerance after heat shock. Bacillus caldolyticus grown at 60 degrees C and heat shocked at 69 degrees C for 10 min showed thermotolerance at 74 degrees C, Sulfolobus shibatae grown at 70 degrees C and hea... | 10.1038/nrmicro866 | Pioneering work recognizing the major components of heat-shock regulation in all Domains. |
10.1073/pnas.2136795100 | 41,349,825 | Chaperonins are protein complexes that are believed to function as part of a protein folding system in the cytoplasm of the cell. We observed, however, that the group II chaperonins known as rosettasomes in the hyperthermophilic archaeon Sulfolobus shibatae , are not cytoplasmic but membrane associated. This associatio... | 10.1038/nrmicro866 | Identification of membrane-bound chaperonins in a hyperthermophile. Introduces the idea of cellular functions beyond protein folding. |
10.1073/pnas.89.21.10449 | 125,310,517 | The alpha-crystallins (alpha A and alpha B) are major lens structural proteins of the vertebrate eye that are related to the small heat shock protein family. In addition, crystallins (especially alpha B) are found in many cells and organs outside the lens, and alpha B is overexpressed in several neurological disorders ... | 10.1038/nrmicro866 | First recognition of the protein stabilization role of the α-crystallins. |
10.1073/pnas.95.16.9129 | 122,370,433 | Small heat shock proteins (sHSPs) belong to a family of 12- to 43-kDa proteins that are ubiquitous and are conserved in amino acid sequence among all organisms. A sHSP homologue of Methanococcus jannaschii , a hyperthermophilic Archaeon, forms a homogeneous multimer comprised of 24 monomers with a molecular mass of 400... | 10.1038/nrmicro866 | Groundbreaking paper describing the cloning and expression of an sHsp from a hyperthermophile. |
10.1126/science.1065057 | 18,439,663 | Neurotrophins are growth factors that promote cell survival, differentiation, and cell death. They are synthesized as proforms that can be cleaved intracellularly to release mature, secreted ligands. Although proneurotrophins have been considered inactive precursors, we show here that the proforms of nerve growth facto... | 10.1038/nrn1726 | A milestone paper showing that proneurotrophins are secreted and cleaved by extracellular proteases such as plasmin and MMPs. This study also shows that proneurotrophins bind p75 NTR with high affinity to mediate apoptosis and that mature neurotrophins preferentially activate Trk receptors to promote survival. |
10.1523/jneurosci.19-06-02069.1999 | 42,606,278 | Nerve growth factor (NGF) is released through the constitutive secretory pathway from cells in peripheral tissues and nerves where it can act as a target-derived survival factor. In contrast, brain-derived neurotrophic factor (BDNF) appears to be processed in the regulated secretory pathway of brain neurons and secrete... | 10.1038/nrn1726 | Used various approaches to show that BDNF is sorted primarily into the regulated secretory pathway, whereas the bulk of NGF is secreted constitutively. It seems that NGF is secreted mainly in the mature form, whereas proBDNF is the major form secreted from hippocampal neurons. |
10.1523/jneurosci.5123-04.2005 | 20,811,413 | Brain-derived neurotrophic factor (BDNF) is best characterized for critical roles in neuronal survival, differentiation, and synaptic modulation mediated by the TrkB receptor tyrosine kinase. Developmentally regulated death signaling by BDNF has also been demonstrated via activation of p75 NTR . Because recent studies ... | 10.1038/nrn1726 | This study, along with reference 11, shows that endogenous proBDNF is secreted from neuronal cells through the constitutive or regulated pathways. |
10.1073/pnas.0305755101 | 100,515,049 | The unprocessed precursor of the neurotrophin nerve growth factor (NGF), proNGF, has been suggested to be a death-inducing ligand for the neurotrophin receptor p75. Whether proNGF is a true pathophysiological ligand that is secreted, binds p75, and activates cell death in vivo , however, has remained unknown. Here, we ... | 10.1038/nrn1726 | Internal-capsule lesion triggers the secretion of endogenous proNGF, which binds p75 NTR in vivo to induce the death of corticospinal neurons. |
10.1523/jneurosci.1017-05.2005 | 4,775,015 | Brain-derived neurotrophic factor (BDNF), after activity-dependent secretion from neurons, modulates critical nervous system functions. Recently, a variant in the human bdnf gene, resulting in a valine to methionine substitution in the prodomain, has been shown to lead to defective regulated secretion from neurons and ... | 10.1038/nrn1726 | Shows that the interaction of sortilin with the pro-domain contributes to the regulated secretion of BDNF. This report also shows that Val to Met conversion prevents binding of the pro-domain to sortilin. |
10.1126/science.1100135 | 62,623,777 | Long-term memory is thought to be mediated by protein synthesis–dependent, late-phase long-term potentiation (L-LTP). Two secretory proteins, tissue plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF), have been implicated in this process, but their relationship is unclear. Here we report that tPA,... | 10.1038/nrn1726 | This study shows that tPA, by activating the extracellular protease plasmin, converts proBDNF to mature BDNF, and that such conversion is required for the expression of late-phase LTP. |
10.1126/science.8332899 | 19,771,903 | Nerve growth factor (NGF) binding to cellular receptors is required for the survival of some neural cells. In contrast to TrkA, the high-affinity NGF receptor that transduces NGF signals for survival and differentiation, the function of the low-affinity NGF receptor, p75 NGFR , remains uncertain. Expression of p75 NGFR... | 10.1038/nrn1726 | This and the following three papers show that p75 NTR activation can lead to cell death in certain cell populations independently of TrkA signalling. |
10.1073/pnas.0502460102 | 29,305,829 | Neurotrophins are involved in the modulation of synaptic transmission, including the induction of long-term potentiation (LTP) through the receptor TrkB. Because previous studies have revealed a bidirectional mode of neurotrophin action by virtue of signaling through either the neurotrophin receptor p75 NTR or the Trk ... | 10.1038/nrn1726 | Shows that p75 NTR is important for hippocampal LTD but not LTP. |
10.1113/jphysiol.2003.052639 | 42,548,905 | The refinement and plasticity of neuronal connections require synaptic activity and neurotrophin signalling; their specific contributions and interplay are, however, poorly understood. We show here that brain‐derived neurotrophic factor (BDNF) increased spine density in apical dendrites of CA1 pyramidal neurones in org... | 10.1038/nrn1726 | An important study showing that BDNF promotes dendritic spine growth. |
10.1073/pnas.0910672106 | 123,002,044 | Protein coding genes constitute only approximately 1% of the human genome but harbor 85% of the mutations with large effects on disease-related traits. Therefore, efficient strategies for selectively sequencing complete coding regions (i.e., “whole exome”) have the potential to contribute to the understanding of rare a... | 10.1038/nrneph.2017.167 | This article is among the first papers published showing the utility of WES to achieve a specific diagnosis for patients presenting with nondiagnostic phenotypes. |
10.1111/ctr.12408 | 60,930,643 | Abstract Background Patients with a rare genetic disease may receive renal transplantation ( KT x) without a correct diagnosis of causal nephropathy and therefore develop unexpected and even severe complications. The aim of the study was to describe the cases of rare genetic disorders diagnosed after KT x, in order to ... | 10.1038/nrneph.2017.167 | This retrospective study of 911 renal transplant recipients highlights the fact that many patients who progress to ESRD have no clear clinical diagnosis of their renal disease and that rare monogenic forms of nephropathy may be found in a notable fraction of these patients. These findings highlight the potential utilit... |
10.1146/annurev-genom-091416-035222 | 122,338,712 | In addition to genetic data, precision medicine research gathers information about three factors that modulate gene expression: lifestyles, environments, and communities. The relevant research tools—epidemiology, environmental assessment, and socioeconomic analysis—are those of public health sciences rather than molecu... | 10.1038/nrneph.2017.167 | This review examines central ELSIs of expanding genetic testing to a population-wide scale and highlights the need for study of both genetic and environmental determinants of health. |
10.1073/pnas.1009445107 | 20,637,735 | The pressing need for broad-spectrum antivirals could be met by targeting host rather than viral processes. Cholesterol biosynthesis within the infected cell is one promising target for a large number of viral systems, including hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV. Liposomes developed for intracell... | 10.1038/nrmicro3475 | An important paper which advances the concept that modulating the lipids and the sterol levels in membranes can have antiviral effects. |
10.1126/science.1136237 | 103,818,244 | A mutualistic association between a fungal endophyte and a tropical panic grass allows both organisms to grow at high soil temperatures. We characterized a virus from this fungus that is involved in the mutualistic interaction. Fungal isolates cured of the virus are unable to confer heat tolerance, but heat tolerance i... | 10.1038/nrmicro2491 | This paper describes a very novel mutualistic symbiosis that allows plants and endophytic fungi to survive harsh geothermal soils. |
10.1207/s15516709cog2601_1 | 123,087,448 | Abstract We address how listeners perceive temporal regularity in music performances, which are rich in temporal irregularities. A computational model is described in which a small system of internal self‐sustained oscillations, operating at different periods with specific phase and period relations, entrains to the rh... | 10.1038/nrn2152 | This paper synthesizes the authors' empirical studies to develop both a theoretical framework and a mathematical model for the way listeners perceive temporal regularity in musical performance. |
10.1111/j.1460-9568.2006.04960.x | 20,154,049 | Abstract Learning a musical piece requires the development of a strong linkage between sensory and motor representations. Audition plays a central role and a tight cortical auditory–motor corepresentation is a characteristic feature of music processing. Recent works have indicated the establishment of a functional conn... | 10.1038/nrn2152 | TMS study demonstrating differential changes in short- and long-term motor cortical excitability in musicians during music perception. |
10.1146/annurev.neuro.27.070203.144230 | 125,317,048 | ▪ Abstract A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is ano... | 10.1038/nrn2152 | A review of the mirror neuron system and presentation of an idea for the evolution of echo mirror neurons. |
10.1152/jn.01126.2005 | 63,093,797 | We examined neuronal activity in the dorsal and ventral premotor cortex (PMd and PMv, respectively) to explore the role of each motor area in processing visual signals for action planning. We recorded neuronal activity while monkeys performed a behavioral task during which two visual instruction cues were given success... | 10.1038/nrn2152 | The latest in a series of excellent electrophysiological studies on the premotor cortex in monkeys; presents a well-supported hypothesis for how the ventral and dorsal premotor cortex are involved in sensory–motor integration. |
10.1126/science.1162253 | 83,013,057 | Transcription initiation by RNA polymerase II (RNAPII) is thought to occur unidirectionally from most genes. Here, we present evidence of widespread divergent transcription at protein-encoding gene promoters. Transcription start site–associated RNAs (TSSa-RNAs) nonrandomly flank active promoters, with peaks of antisens... | 10.1038/nsmb.2428 | Refs. 21,22 describe the presence of widespread divergent transcription at the promoters of active protein-coding genes |
10.1101/gad.455708 | 60,826,043 | Expression of Snail1 in epithelial cells triggers an epithelial–mesenchymal transition (EMT). Here, we demonstrate that the synthesis of Zeb2, a transcriptional repressor of E-cadherin, is up-regulated after Snail1-induced EMT. Snail1 does not affect the synthesis of Zeb2 mRNA, but prevents the processing of a large in... | 10.1038/nsmb.2428 | One of the better-studied cases in which an antisense transcript interferes with processing by splicing of the sense protein-coding gene |
10.1146/annurev-cellbio-101512-122326 | 62,662,146 | In the 1980s, exosomes were described as vesicles of endosomal origin secreted from reticulocytes. Interest increased around these extracellular vesicles, as they appeared to participate in several cellular processes. Exosomes bear proteins, lipids, and RNAs, mediating intercellular communication between different cell... | 10.1038/nrn.2015.29 | An important review of the current understanding of EV biogenesis and secretion, including protocols for EV isolation and current challenges for the field. |
10.1002/glia.22558 | 41,641,440 | Axonal regeneration in the peripheral nervous system is greatly supported by Schwann cells (SCs). After nerve injury, SCs dedifferentiate to a progenitor‐like state and efficiently guide axons to their original target tissues. Contact and soluble factors participate in the crosstalk between SCs and axons during axonal ... | 10.1038/nrn.2015.29 | An important study documenting the role of EVs liberated from Schwann cells during axonal regeneration. |
10.1083/jcb.57.2.315 | 41,383,229 | When the nerves of isolated frog sartorius muscles were stimulated at 10 Hz, synaptic vesicles in the motor nerve terminals became transiently depleted. This depletion apparently resulted from a redistribution rather than disappearance of synaptic vesicle membrane, since the total amount of membrane comprising these ne... | 10.1038/nrn1583 | This seminal paper describes vesicle cycling at the frog NMJ under conditions of strong stimulation. The roles of endocytic intermediates and clathrin are emphasized; endosomal sorting is proposed as a stage during recycling. |
10.1083/jcb.133.6.1237 | 80,119,722 | Strong evidence implicates clathrin-coated vesicles and endosome-like vacuoles in the reformation of synaptic vesicles after exocytosis, and it is generally assumed that these vacuoles represent a traffic station downstream from clathrin-coated vesicles. To gain insight into the mechanisms of synaptic vesicle budding f... | 10.1038/nrn1583 | The authors describe vesicle reformations through bulk endocytosis. Membrane retrieved through bulk uptake is broken down by clathrin-coated-vesicle formation; new synaptic vesicles are generated by uncoating. |
10.1083/jcb.81.2.275 | 101,039,467 | We describe the design and operation of a machine that freezes biological tissues by contact with a cold metal block, which incorporates a timing circuit that stimulates frog neuromuscular junctions in the last few milliseconds before thay are frozen. We show freeze-fracture replicas of nerve terminals frozen during tr... | 10.1038/nrn1583 | By use of elegant rapid-freezing methods, frog motor nerve terminal ultrastructure within ∼ 2 ms of electrical stimulation is investigated, providing direct morphological evidence for the location of synaptic vesicle fusion. |
10.1083/jcb.108.1.111 | 105,360,074 | We have examined the cytoskeletal architecture and its relationship with synaptic vesicles in synapses by quick-freeze deep-etch electron microscopy (QF.DE). The main cytoskeletal elements in the presynaptic terminals (neuromuscular junction, electric organ, and cerebellar cortex) were actin filaments and microtubules.... | 10.1038/nrn1583 | Ultrastructural (freeze-fracture, deep-etch) study of vesicle clusters shows different types of filaments, some of which interlink vesicles, some of which attach vesicles to actin, and some of which link vesicles to the surface membrane. |
10.1083/jcb.135.3.797 | 29,103,414 | In this paper, evidence is presented that two distinct synaptic vesicle recycling pathways exist within a single terminal. One pathway emanates from the active zone, has a fast time course, involves no intermediate structures, and is blocked by exposure to high Mg2+/low Ca2+ saline, while the second pathway emanates at... | 10.1038/nrn1583 | Describes two recycling pathways in Drosophila adult nerve terminals, which might be used by two distinct vesicle pools. |
10.1523/jneurosci.2808-07.2007 | 20,472,799 | Cocaine produces a persistent reduction in cystine–glutamate exchange via system x c − in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System x c − influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens, which, ... | 10.1038/nrn2515 | This excellent paper provides definitive evidence that the capacity of N -acetylcysteine to regulate drug-seeking behaviour results from actions on the cystine–glutamate exchanger and is associated with preventing the large release of glutamate in the accumbens during drug seeking. |
10.1126/science.1074192 | 4,697,166 | Transgenic mice expressing a stabilized β-catenin in neural precursors develop enlarged brains with increased cerebral cortical surface area and folds resembling sulci and gyri of higher mammals. Brains from transgenic animals have enlarged lateral ventricles lined with neuroepithelial precursor cells, reflecting an ex... | 10.1038/nrn3707 | These authors demonstrate that expression of continuously activated β-catenin causes expansion of cortical NPs and folding of the cortex using mouse genetic tools. This paper suggests that cell cycle regulation of NPs is crucial for cortical growth and folding. |
10.1242/dev.040410 | 107,155,479 | Microcephaly affects ∼1% of the population and is associated with mental retardation, motor defects and, in some cases, seizures. We analyzed the mechanisms underlying brain size determination in a mouse model of human microcephaly. The Hertwig's anemia (an) mutant shows peripheral blood cytopenias, spontaneous aneuplo... | 10.1038/nrn3707 | References 124, 126 and 127 demonstrate molecular mechanisms of dysregulation of the centrosome cycle caused by altered expression of MCPH1 and CDK5RAP2 in mice, indicating the genetic basis of microcephaly in humans. |
10.1186/1749-8104-4-4 | 36,733,523 | Abstract Background Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. How... | 10.1038/nrn3707 | This paper shows in mice that an activating mutation in Fgfr3 , which is identical to the mutation in humans with thanatophoric dysplasia, causes selective tangential expansion of the occipitotemporal cortex, thus mimicking the human condition. In mice, however, the overgrowth is not sufficient to induce the formation ... |
10.1126/science.1128134 | 20,675,393 | Years of intensive investigation have yielded a sophisticated understanding of long-term potentiation (LTP) induced in hippocampal area CA1 by high-frequency stimulation (HFS). These efforts have been motivated by the belief that similar synaptic modifications occur during memory formation, but it has never been shown ... | 10.1038/nrn2738 | This study shows that the use of a one-trial inhibitory-avoidance learning task in rats produced the same changes in hippocampal glutamate receptors as induction of LTP with HFS. |
10.1523/jneurosci.2834-05.2006 | 123,585,319 | One of the brain sites more directly related with learning and memory processes is the hippocampus. We recorded, in conscious mice, the activity-dependent changes taking place at the hippocampal CA3–CA1 synapse during the acquisition, extinction, recall, and reconditioning of an associative task. Mice were classically ... | 10.1038/nrn2738 | This study made a significant advance by showing an LTP-like increase in hippocampal synaptic responses in behaving mice. |
10.1126/science.1152864 | 107,176,399 | Long-term potentiation (LTP) at glutamatergic synapses is considered to underlie learning and memory and is associated with the enlargement of dendritic spines. Because the consolidation of memory and LTP require protein synthesis, it is important to clarify how protein synthesis affects spine enlargement. In rat brain... | 10.1038/nrn2738 | This study shows that physiological synaptic signals induce the postsynaptic release of endogenous BDNF at the single-cell level. |
10.1101/lm.428307 | 15,749,308 | Previous in vitro studies have characterized the electrophysiological properties and molecular events associated with long-term potentiation (LTP), but as yet there are no in vivo data from molecular-level dissection that directly identify LTP as the biological substrate for learning and memory. Understanding whether t... | 10.1038/nrn2738 | Provided the first evidence that a TrkB–PLCγ site-activated molecular pathway underlies both associative learning and LTP triggered at the CA3–CA1 hippocampal synapse. |
10.1126/science.1455232 | 18,715,250 | To examine the basis for the evolutionary selection for codirectionality of replication and transcription in Escherichia coli , electron microscopy was used to visualize replication from an inducible ColE1 replication origin inserted into the Escherichia coli chromosome upstream (5′) or downstream (3′) of rrnB , a ribo... | 10.1038/nsmb.2543 | This is the first in vivo study of transcription-replication encounters, showing that RNA polymerases are dislodged from a bacterial rRNA operon when a replication fork passes from either the same or the opposite direction |
10.1242/jcs.082230 | 79,693,781 | Typically, only a fraction of the ≥600 ribosomal RNA (rRNA) gene copies in human cells are transcriptionally active. Expressed rRNA genes coalesce in specialized nuclear compartments – the nucleoli – and are believed to replicate during the first half of S phase. Paradoxically, attempts to visualize replicating rDNA du... | 10.1038/nsmb.2543 | This study shows that on active rDNA loci, replication initiates randomly throughout the early-replicating rDNA, whereas silent rDNA replicates inside the nucleoli during mid and late S phase, which ensures efficient replication and reduces the risk of chromosome breaks and rDNA hyper-recombination |
10.1101/gr.121830.111 | 20,729,174 | In metazoans, thousands of DNA replication origins (Oris) are activated at each cell cycle. Their genomic organization and their genetic nature remain elusive. Here, we characterized Oris by nascent strand (NS) purification and a genome-wide analysis in Drosophila and mouse cells. We show that in both species most CpG ... | 10.1038/nsmb.2543 | By performing a genome-scale purification of DNA replication origins, the authors show that replication-initiation events are most frequent at CpG island–containing promoters in mice and at CpG island–like regions in Drosophila |
10.1098/rspb.1977.0085 | 20,601,874 | Of the many possible functions of the macaque monkey primary visual cortex (striate cortex, area 17) two are now fairly well understood. First, the incoming information from the lateral geniculate bodies is rearranged so that most cells in the striate cortex respond to specifically oriented line segments, and, second, ... | 10.1038/nrn2741 | A classic review of the functional responses and organization of V1 neurons, and how these V1 responses and architectural properties emerge during postnatal development. |
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