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10.1073/pnas.1018214108 | 42,640,604 | Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, do... | 10.1038/nrn.2016.155 | This study provided the first evidence that glucocorticoid effects on memory can be used to enhance the outcome of extinction-based psychotherapy. |
10.1073/pnas.0401472101 | 26,824,923 | The cAMP-responsive transcription factor, CREB, is required for formation of long-term memory (LTM) in Drosophila melanogaster and regulates transcription of a circadian clock gene, period ( per ). Involvement of CREB both in LTM and circadian rhythm raises the possibility that per also plays a role in LTM. Assaying th... | 10.1038/nrn2881 | This study implicates a core clock gene in the regulation of LTM, reinforcing the pleiotropic nature of circadian genes in multiple behaviours, including memory. |
10.1126/science.1148564 | 78,040,288 | Memory processes are modulated by the biological clock, although the mechanisms are unknown. Here, we report that in the diurnal zebrafish both learning and memory formation of an operant conditioning paradigm occur better during the day than during the night. Melatonin treatment during the day mimics the nighttime sup... | 10.1038/nrn2881 | This study describes a time-of-day effect on memory formation in zebrafish, and shows that the hormone melatonin is necessary for the night-time suppression of memory. |
10.1073/pnas.2336172100 | 109,143,273 | As the mechanisms for learning and memory are elucidated, modulation of learning and memory becomes a central issue. We studied the modulation of learning and memory by investigating the circadian regulation of short- and long-term sensitization of the siphon withdrawal reflex in Aplysia . We found that Aplysia exhibit... | 10.1038/nrn2881 | This paper describes the circadian control of a form of non-associative learning observed in sea slugs, which suggests that the circadian effects on memory processes are evolutionarily conserved. |
10.1101/lm.1146009 | 101,030,080 | Endogenous biological clocks are widespread regulators of behavior and physiology, allowing for a more efficient allocation of efforts and resources over the course of a day. The extent that different processes are regulated by circadian oscillators, however, is not fully understood. We investigated the role of the cir... | 10.1038/nrn2881 | This study describes a time-of-day effect on olfactory avoidance-conditioning, and shows that this rhythm can be blocked by arrhythmic behaviour resulting from either clock mutants or constant lighting conditions. |
10.1126/science.1106215 | 122,981,223 | Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient rec... | 10.1038/nrneph.2016.127 | Seminal paper describing the discovery of the role of TRPC6 mechanosensation in podocytes and the role of TRPC6 mutations in the development of FSGS. |
10.1126/science.286.5438.312 | 83,032,825 | CD2-associated protein (CD2AP) is an 80-kilodalton protein that is critical for stabilizing contacts between T cells and antigen-presenting cells. In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomer... | 10.1038/nrneph.2016.127 | Milestone study elucidating the role of CD2AP in the maintenance of slit diaphragm structure and its role in the development of nephrotic syndrome. |
10.1523/jneurosci.2935-12.2013 | 19,247,915 | It is now accepted that glial cells actively interact with neurons and modulate their activity in many regions of the nervous system. Importantly, modulation of synaptic activity by glial cells depends on the proper detection and decoding of synaptic activity. However, it remains unknown whether glial cells are capable... | 10.1038/nrn3821 | By combining confocal calcium-imaging techniques and electrophysiological recordings at dually innervated mouse NMJs, this study shows that PSCs can differentially decode synaptic activity from competing nerve terminals at developing NMJs. |
10.1523/jneurosci.3339-13.2013 | 38,871,814 | The competitive processes that result in elimination/pruning of developing synapses are incompletely understood. Serial electron microscopy was used to image postnatal mouse neuromuscular junctions where elimination is well studied and events at every synaptic contact can be examined. Glial or Schwann cells (SCs) are s... | 10.1038/nrn3821 | This research shows that PSCs actively participate in axon removal during synaptic competition in the developing NMJ. |
10.1073/pnas.0504806102 | 59,307,653 | Synaptic organizing molecules and neurotransmission regulate synapse development. Here, we use the skeletal neuromuscular junction to assess the interdependence of effects evoked by an essential synaptic organizing protein, agrin, and the neuromuscular transmitter, acetylcholine (ACh). Mice lacking agrin fail to mainta... | 10.1038/nrn3821 | This elegant study uses double-mutant mice (lacking both ChAT and agrin) to show that synaptic transmission regulates NMJ maturation and counters the effects of agrin. |
10.1083/jcb.201108005 | 99,192,633 | Schwann cells (SCs), the glial cells of the peripheral nervous system, cover synaptic terminals, allowing them to monitor and modulate neurotransmission. Disruption of glial coverage leads to axon degeneration and synapse loss. The cellular mechanisms that establish and maintain this coverage remain largely unknown. To... | 10.1038/nrn3821 | This paper shows that following the ablation of individual SCs, changes in PSC-territory dynamics at developing and mature NMJs are under spatial constraints. |
10.1523/jneurosci.3165-10.2010 | 38,748,220 | In the nervous system, the induction of plasticity is coded by patterns of synaptic activity. Glial cells are now recognized as dynamic partners in a wide variety of brain functions, including the induction and modulation of various forms of synaptic plasticity. However, it appears that glial cells are usually activate... | 10.1038/nrn3821 | This study combines electrophysiological recordings, PSC Ca 2+ -imaging and alteration of the activity of specific PSCs using photo-activatable molecules to show that PSCs regulate synaptic plasticity by discerning patterns of motor nerve activity. |
10.1111/1467-9280.00221 | 20,240,140 | Studies reveal that when people are exposed to emotional facial expressions, they spontaneously react with distinct facial electromyographic (EMG) reactions in emotion-relevant facial muscles. These reactions reflect, in part, a tendency to mimic the facial stimuli. We investigated whether corresponding facial reaction... | 10.1038/nrn.2017.72 | This study is part of a series of studies on facial mimicry that first demonstrated the spontaneous nature of human empathic reactions. |
10.1126/science.1128322 | 82,882,328 | Empathy is thought to be unique to higher primates, possibly to humans alone. We report the modulation of pain sensitivity in mice produced solely by exposure to their cagemates, but not to strangers, in pain. Mice tested in dyads and given an identical noxious stimulus displayed increased pain behaviors with statistic... | 10.1038/nrn.2017.72 | This paper provides compelling evidence of emotional contagion in mice and set the stage for subsequent rodent research. |
10.1038/ncomms10904 | 26,879,618 | Abstract The anterior insula (AI) and mid-anterior cingulate cortex (mACC) have repeatedly been implicated in first-hand and vicarious experiences of pain, disgust and unfairness. However, it is debated whether these regions process different aversive events through a common modality-independent code, reflecting the sh... | 10.1038/nrn.2017.72 | In this study, the anterior insula and aMCC are engaged across pain, disgust and unfairness, showing that these regions are not pain specific but participate in various negative self and other experiences. |
10.1073/pnas.1307701110 | 41,519,080 | The Cyanobacteria Prochlorococcus and Synechococcus account for a substantial fraction of marine primary production. Here, we present quantitative niche models for these lineages that assess present and future global abundances and distributions. These niche models are the result of neural network, nonparametric, and p... | 10.1038/nrmicro3378 | This is an extensive synthesis of the global distributions of marine picocyanobacteria, including projections about how climate change may affect their abundance and habitats. |
10.1073/pnas.0600540103 | 103,193,719 | There is growing evidence that dissolved phosphorus can regulate planktonic production in the oceans’ subtropical gyres, yet there is little quantitative information about the biochemical fate of phosphorus in planktonic communities. We observed in the North Pacific Subtropical Gyre (NPSG) that the synthesis of membran... | 10.1038/nrmicro3378 | This study highlights the strong selective pressure that phosphorus limitation has imposed on the evolution of Prochlorococcus |
10.1128/aem.65.6.2585-2591.1999 | 28,043,565 | ABSTRACT The in situ community structure of Prochlorococcus populations in the eastern North Atlantic Ocean was examined by analysis of Prochlorococcus 16S rDNA sequences with three independent approaches: cloning and sequencing, hybridization to specific oligonucleotide probes, and denaturing gradient gel electrophore... | 10.1038/nrmicro3378 | This article provides the first description of how different Prochlorococcus ecotypes partition in the water column. |
10.1126/science.1118052 | 41,676,506 | Prochlorococcus is the numerically dominant phytoplankter in the oligotrophic oceans, accounting for up to half of the photosynthetic biomass and production in some regions. Here, we describe how the abundance of six known ecotypes, which have small subunit ribosomal RNA sequences that differ by less than 3%, changed a... | 10.1038/nrmicro3378 | This study showed that temperature correlated with the distribution of HL-adapted Prochlorococcus ecotypes along ocean gradients and provided evidence that the physiology of cells in culture is consistent with their distributions in the wild. |
10.1038/ismej.2010.60 | 41,096,618 | Abstract To better understand the temporal and spatial dynamics of Prochlorococcus populations, and how these populations co-vary with the physical environment, we followed monthly changes in the abundance of five ecotypes—two high-light adapted and three low-light adapted—over a 5-year period in coordination with the ... | 10.1038/nrmicro3378 | Using data from two long-term ocean time-series stations, this paper highlights the remarkable reproducibility of Prochlorococcus ecotype abundances over many years. |
10.1126/science.1248575 | 122,976,770 | Cyanobacterial Diversity What does it mean to be a global species? The marine cyanobacterium Prochlorococcus is ubiquitous and, arguably, the most abundant and productive of all living organisms. Although to our eyes the seas look uniform, to a bacterium the ocean's bulk is a plethora of microhabitats, and by large-sca... | 10.1038/nrmicro3378 | This study shows the vast genomic diversity of Prochorococcus cells in a single sample of seawater and argues that hundreds of diverse subpopulations contribute to the dynamics and stability of the global Prochlorococcus federation. |
10.1073/pnas.1009513107 | 59,068,373 | Prochlorococcus describes a diverse and abundant genus of marine photosynthetic microbes. It is primarily found in oligotrophic waters across the globe and plays a crucial role in energy and nutrient cycling in the ocean ecosystem. The abundance, global distribution, and availability of isolates make Prochlorococcus a ... | 10.1038/nrmicro3378 | This study shows the utility of metagenomic data for characterizing the distribution and key features of previously unknown and uncultured lineages of Prochlorococcus |
10.1126/science.1122050 | 81,046,168 | Prochlorococcus ecotypes are a useful system for exploring the origin and function of diversity among closely related microbes. The genetic variability between phenotypically distinct strains that differ by less that 1% in 16 S ribosomal RNA sequences occurs mostly in genomic islands. Island genes appear to have been a... | 10.1038/nrmicro3378 | This study reveals the importance of genomic islands as hot spots for the integration of ecologically important flexible genes into Prochlorococcus genomes. |
10.1073/pnas.0601301103 | 42,557,003 | The cyanobacterium Prochlorococcus is the numerically dominant phototroph in the oligotrophic oceans. This group consists of multiple ecotypes that are physiologically and phylogenetically distinct and occur in different abundances along environmental gradients. Here we examine adaptations to phosphate (P) limitation a... | 10.1038/nrmicro3378 | This article shows that phosphorus limitation is one of the strongest selective pressures shaping gene content of Prochlorococcus in the Atlantic versus the Pacific Ocean. |
10.1073/pnas.1221775110 | 103,295,434 | Prochlorococcus is responsible for a significant part of CO 2 fixation in the ocean. Although it was long considered an autotrophic cyanobacterium, the uptake of organic compounds has been reported, assuming they were sources of limited biogenic elements. We have shown in laboratory experiments that Prochlorococcus can... | 10.1038/nrmicro3378 | This article shows the potential for Prochlorococcus photoheterotrophic growth in the wild. |
10.1126/science.1173205 | 103,472,930 | Sensorin Reporter Long-term memory and synaptic plasticity require changes in gene expression and yet can occur in a synapse-specific manner. Messenger RNA (mRNA) localization and regulated translation at synapses have been proposed as mechanisms for spatially restricting gene expression during transcription-dependent,... | 10.1038/nrn2763 | This study uses imaging of photoconvertible reporter genes to demonstrate regulated local translation at A. californica sensorimotor synapses during long-term synaptic plasticity. |
10.1083/jcb.200209124 | 20,439,928 | We find that Bax, a proapoptotic member of the Bcl-2 family, translocates to discrete foci on mitochondria during the initial stages of apoptosis, which subsequently become mitochondrial scission sites. A dominant negative mutant of Drp1, Drp1K38A, inhibits apoptotic scission of mitochondria, but does not inhibit Bax t... | 10.1038/nrn2417 | References 52 and 53 were two of the first studies to describe the relationship between mitochondrial fission and cell death. |
10.1126/science.276.5321.2045 | 83,454,674 | Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromoso... | 10.1038/nrn1199 | The first report showing that a missense mutation in the α-synuclein gene (A53T) causes an early-onset, familial form of PD. This was the first study to identify a genetic cause of PD. |
10.1073/pnas.97.2.571 | 62,088,366 | The Parkinson's disease (PD) substantia nigra is characterized by the presence of Lewy bodies containing fibrillar α-synuclein. Early-onset PD has been linked to two point mutations in the gene that encodes α-synuclein, suggesting that disease may arise from accelerated fibrillization. However, the identity of the path... | 10.1038/nrn1199 | This seminal study indicated that both α-synuclein mutations responsible for familial PD increase the rate of protofibril formation during the process of fibrillization. |
10.1073/pnas.172514599 | 122,408,657 | Parkinson's disease (PD) is most commonly a sporadic illness, and is characterized by degeneration of substantia nigra dopamine (DA) neurons and abnormal cytoplasmic aggregates of α-synuclein. Rarely, PD may be caused by missense mutations in α-synuclein. MPTP, a neurotoxin that inhibits mitochondrial complex I, is a p... | 10.1038/nrn1199 | These authors were the first to show that α-synuclein- knockout mice, and neuronal cultures derived from these mice, are resistant to the neurotoxin MPTP. |
10.1126/science.287.5456.1265 | 62,117,853 | To elucidate the role of the synaptic protein α-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human α-synuclein were generated. Neuronal expression of human α-synuclein resulted in progressive accumulation of α-synuclein—and ubiquitin-immunoreactive inclusions in neurons in the neocorte... | 10.1038/nrn1199 | These authors were the first to develop α-synuclein transgenic mice. These mice were created using the PDGFβ promoter, and exhibited a loss of striatal dopaminergic terminals. |
10.1073/pnas.0737556100 | 20,591,175 | Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Several lines of evidence strongly implicate mitochondrial dysfunction as a major causative factor in PD, although the molecular mechanisms responsible for mitochondrial dysfunction are... | 10.1038/nrn1199 | The first deletion of the parkin gene in Drosophila . The parkin-null flies exhibited muscle degeneration but no defects in the dopaminergic system. |
10.1073/pnas.0536383100 | 62,188,405 | We used a high-titer recombinant adeno-associated virus (rAAV) vector to express WT or mutant human α-synuclein in the substantia nigra of adult marmosets. The α-synuclein protein was expressed in 90–95% of all nigral dopamine neurons and distributed by anterograde transport throughout their axonal and dendritic projec... | 10.1038/nrn1199 | The first study attempting to create a primate model overexpressing the α-synuclein gene. These primates exhibited nigrostriatal degeneration, but lacked a motor phenotype resembling PD. |
10.1126/science.1063522 | 103,236,645 | The substantia nigra in Parkinson's disease (PD) is depleted of dopaminergic neurons and contains fibrillar Lewy bodies comprising primarily α-synuclein. We screened a library to identify drug-like molecules to probe the relation between neurodegeneration and α-synuclein fibrilization. All but one of 15 fibril inhibito... | 10.1038/nrn1199 | This prominent work showed that DA stabilizes the protofibrillary conformation of α-synuclein. |
10.1101/lm.69204 | 18,429,166 | A profound loss of cortical cholinergic innervation is a nearlyinvariant feature of advanced Alzheimer's disease (AD). The temporal course of this lesion and its relationship to other aspects of the disease have not yet been fully clarified. Despite assertions to the contrary, a review of the evidence suggests that a p... | 10.1038/nrn1588 | This paper provides an up-to-date and balanced review of the evidence concerning the role of the cholinergic system in the cognitive decline of Alzheimer's disease. |
10.1083/jcb.200402100 | 38,960,376 | The Escherichia coli YidC protein belongs to the Oxa1 family of membrane proteins that have been suggested to facilitate the insertion and assembly of membrane proteins either in cooperation with the Sec translocase or as a separate entity. Recently, we have shown that depletion of YidC causes a specific defect in the ... | 10.1038/nrmicro3595 | References 32 and 39 show that YidC is sufficient to promote the membrane insertion of Sec-independent proteins. |
10.1126/science.1110647 | 104,394,772 | Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells... | 10.1038/nrn1905 | References 4 and 5 are the first reports to illustrate the remarkable in vivo dynamics of microglia cells in the brain. |
10.1073/pnas.1232232100 | 20,580,675 | Two-photon calcium imaging is a powerful means for monitoring the activity of distinct neurons in brain tissue in vivo . In the mammalian brain, such imaging studies have been restricted largely to calcium recordings from neurons that were individually dye-loaded through microelectrodes. Previous attempts to use membra... | 10.1038/nrn1905 | Introduces the 'multicell bolus loading' technique that is used widely to label neurons and glial cells with calcium indicators in vivo |
10.1126/science.1098439 | 104,197,981 | Neurons in the human central nervous system (CNS) are unable to regenerate, as a result of both an inhibitory environment and their inherent inability to regrow. In contrast, the CNS environment in fish is permissive for growth, yet some neurons still cannot regenerate. Fish thus offer an opportunity to study molecules... | 10.1038/nrn1905 | Shows that in vivo imaging can help to document axonal regeneration and functional reconnection in the CNS of zebrafish. |
10.1038/ncomms10536 | 28,254,649 | Abstract There is concern that the stresses of inducing pluripotency may lead to deleterious DNA mutations in induced pluripotent stem cell (iPSC) lines, which would compromise their use for cell therapies. Here we report comparative genomic analysis of nine isogenic iPSC lines generated using three reprogramming metho... | 10.1038/nrneurol.2017.45 | Mutagenicity of three reprogramming approaches were compared: retroviral vectors, Sendai virus and synthetic mRNAs. No significant differences were detected. |
10.1146/annurev.neuro.24.1.1041 | 122,555,394 | ▪ Abstract The developmental steps required to build a brain have been recognized as a distinctive sequence since the turn of the twentieth century. As marking tools for experimental embryology emerged, the cellular events of cortical histogenesis have been intensively scrutinized. On this rich backdrop, molecular gene... | 10.1038/nrn845 | A review of studies that point to neuronal migration disorders in human brain malformations. |
10.1126/science.1411527 | 41,457,151 | During early development of the mammalian cerebral cortex, young neurons migrate outward from the site of their final mitosis in the ventricular zone into the cortical plate, where they form the adult cortex. Time-lapse confocal microscopy was used to observe directly the dynamic behaviors of migrating cells in living ... | 10.1038/nrn845 | The first direct evidence of tangential movement of cortical neurons in vitro. |
10.1073/pnas.101122598 | 82,886,196 | Lissencephaly is a severe brain malformation in humans. To study the function of the gene mutated in lissencephaly ( LIS1 ), we deleted the first coding exon from the mouse Lis1 gene. The deletion resulted in a shorter protein (sLIS1) that initiates from the second methionine, a unique situation because most LIS1 mutat... | 10.1038/nrn845 | References 47 and 48 provided the first evidence for an involvement of LIS1 in neuronal migration. |
10.1146/annurev.neuro.24.1.1005 | 83,425,375 | ▪ Abstract The neurological mutant mouse reeler has played a critical role in the evolution of our understanding of normal brain development. From the earliest neuroanatomic studies of reeler, it was anticipated that the characterization of the gene responsible would elucidate important molecular and cellular principle... | 10.1038/nrn845 | References 65 and 66 are comprehensive reviews of the role of reelin and its signalling pathways in the developing nervous system. |
10.1073/pnas.1000081107 | 125,323,192 | The colonization process of the infant gut microbiome has been called chaotic, but this view could reflect insufficient documentation of the factors affecting the microbiome. We performed a 2.5-y case study of the assembly of the human infant gut microbiome, to relate life events to microbiome composition and function.... | 10.1038/nrmicro2746 | A study of microbiota formation in a single human child over the first 3 years of life, using 16S rRNA genes and metagenomic approaches to correlate changes in the microbiota with life events such as diet shifts, illness and antibiotics. |
10.1126/science.1109051 | 62,253,732 | Germ-free mice were maintained on polysaccharide-rich or simple-sugar diets and colonized for 10 days with an organism also found in human guts, Bacteroides thetaiotaomicron , followed by whole-genome transcriptional profiling of bacteria and mass spectrometry of cecal glycans. We found that these bacteria assembled on... | 10.1038/nrmicro2746 | The first in vivo transcriptomics-based study of a human gut symbiont ( B. thetaiotaomicron ) in the intestines of gnotobiotic mice consuming diets with varying glycan content. |
10.1073/pnas.1005963107 | 83,539,810 | Gut microbial composition depends on different dietary habits just as health depends on microbial metabolism, but the association of microbiota with different diets in human populations has not yet been shown. In this work, we compared the fecal microbiota of European children (EU) and that of children from a rural Afr... | 10.1038/nrmicro2746 | An investigation that analyses the composition of the microbiota in two populations of children (one in Africa and the other in Europe) that consume different diets. |
10.1038/ismej.2010.118 | 62,587,127 | Abstract The populations of dominant species within the human colonic microbiota can potentially be modified by dietary intake with consequences for health. Here we examined the influence of precisely controlled diets in 14 overweight men. Volunteers were provided successively with a control diet, diets high in resista... | 10.1038/nrmicro2746 | A human volunteer study that tracks the changes in the microbiota following a shift to a low-carbohydrate diet, then to an RS-containing diet and finally to a diet that is rich in non-starch polysaccharides. |
10.1126/scitranslmed.3000322 | 104,315,850 | A translational medicine pipeline is described where human gut microbial communities and diets are re-created in gnotobiotic mice and the impact on microbe and host is defined using metagenomics. | 10.1038/nrmicro2746 | An investigation that uses culture-independent methods to monitor alterations in the microbiota of humanized mice in response to rapid diet shift. |
10.1126/stke.3352006re5 | 100,498,332 | Over the millennia, pathogens have coevolved with their hosts and acquired the ability to intercept, disrupt, mimic, and usurp numerous signaling pathways of those hosts. The study of host/pathogen interactions thus not only teaches us about the intricate biology of these parasitic invaders but also provides interestin... | 10.1038/nrmicro2574 | A comprehensive review on how pathogen infection affects signalling mechanisms. |
10.1083/jcb.56.2.412 | 106,777,488 | A comparison is made of the ultrastructure of the cell periphery in three cloned cell lines: untransformed Balb/c 3T3 cells, SV40-transformed Balb/c 3T3 cells, and revertant cells obtained from the transformed cell line by a selection technique utilizing concanavalin A. Both thin-section and surface replication techniq... | 10.1038/nrmicro2574 | The earliest report on SV40-induced cell transformation and morphological changes. |
10.1073/pnas.73.11.4065 | 122,920,729 | A series of morphological changes occurred when chick embryo fibroblasts infected with the NY68 mutant of Rous sarcoma virus were shifted from nonpermissive temperature (41degrees) to permissive temperature (37 degrees). We observed three distinct stages in cell morphology and surface topography that were correlated wi... | 10.1038/nrmicro2574 | The earliest demonstration of the gradual changes in cell morphology that occur as a result of cell transformation. |
10.1083/jcb.200503059 | 38,200,815 | Viruses have often been observed in association with the dense microvilli of polarized epithelia as well as the filopodia of nonpolarized cells, yet whether interactions with these structures contribute to infection has remained unknown. Here we show that virus binding to filopodia induces a rapid and highly ordered la... | 10.1038/nrmicro2574 | The earliest description of viral surfing as it relates to viral entry and infection. |
10.1084/jem.188.11.2113 | 60,878,136 | After interaction of human immunodeficiency virus type 1 (HIV-1) virions with cell surface receptors, a series of poorly characterized events results in establishment of a viral reverse transcription complex in the host cell cytoplasm. This process is coordinated in such a way that reverse transcription is initiated sh... | 10.1038/nrmicro2574 | A biochemical analysis of the association between actin and HIV particles at different stages post-entry. |
10.1073/pnas.0409099102 | 103,579,797 | The US3 protein is a viral kinase that is conserved among the Alphaherpesvirinae . Here, we show that US3 of the swine alphaherpesvirus pseudorabies virus causes dramatic alterations in the cytoskeleton, resulting in the formation of long actin- and microtubule-containing cell projections in infected and transfected ce... | 10.1038/nrmicro2574 | An investigation that demonstrates the direct induction of cytoskeletal extensions by a herpesvirus protein kinase. |
10.1126/science.1183173 | 103,803,188 | Viral Superspreaders Viruses are thought to spread across a lawn of cells by an iterative process of infection, replication, and release. If this were the case, the rate of spread would be limited by the viral replication kinetics. Now, Doceul et al. (p. 873 , published online 21 January; see the Perspective by Pickup ... | 10.1038/nrmicro2574 | A report that connects the history of VV-mediated actin modulation with long-distance viral spread and the observable phenomenon of plaque formation. |
10.1126/science.1105654 | 84,385,218 | We show that the specific subcellular distribution of H- and Nras guanosine triphosphate–binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi apparatus. Depalmitoylation redistributes far... | 10.1038/nrn2788 | This study showed that constitutive palmitate cycling on HRAS and NRAS regulates their shuttling between the plasma membrane and the Golgi complex, contributing to spatiotemporal segregation of Ras signalling. |
10.1083/jcb.200206120 | 40,344,653 | Protein palmitoylation has been long appreciated for its role in tethering proteins to membranes, yet the enzymes responsible for this modification have eluded identification. Here, experiments in vivo and in vitro demonstrate that Akr1p, a polytopic membrane protein containing a DHHC cysteine-rich domain (CRD), is a p... | 10.1038/nrn2788 | Using genetic screening in yeast, references 16, 18 and 19 identified proteins containing a DHHC CRD as palmitoylating enzymes. |
10.1523/jneurosci.2171-08.2008 | 42,507,382 | During development of the nervous system, short- and long-range signals cooperate to promote axonal growth, guidance, and target innervation. Particularly, a short-range signal transducer, the neural cell adhesion molecule (NCAM), stimulates neurite outgrowth via mechanisms that require posttranslational modification o... | 10.1038/nrn2788 | This study showed that DHHC7 palmitoylates NCAMs downstream of FGF signalling and plays a crucial part in FGF-mediated neurite outgrowth. |
10.1083/jcb.200903101 | 80,031,619 | Protein palmitoylation is the most common posttranslational lipid modification; its reversibility mediates protein shuttling between intracellular compartments. A large family of DHHC (Asp-His-His-Cys) proteins has emerged as protein palmitoyl acyltransferases (PATs). However, mechanisms that regulate these PATs in a p... | 10.1038/nrn2788 | This paper was the first to document differential regulation of the large DHHC protein family members and showed that activity-sensitive DHHC2 translocation enhances synaptic PSD95 palmitoylation and mediates AMPAR homeostasis. |
10.1523/jneurosci.2464-07.2007 | 19,248,971 | Palmitoylation affects the trafficking, stability, aggregation, and/or functional activity of a substantial number of neuronal proteins. We identified mutations in dHIP14, the Drosophila homolog of the human palmitoyl transferase, Huntingtin-interacting protein 14 (HIP14). HIP14 was previously reported to localize prim... | 10.1038/nrn2788 | References 59 and 60 showed that DHHC17 has an essential role in synaptic transmission by palmitoylating SNAP25 and CSP. |
10.1111/j.2044-8295.1986.tb02199.x | 83,329,829 | The aim of this paper is to develop a theoretical model and a set of terms for understanding and discussing how we recognize familiar faces, and the relationship between recognition and other aspects of face processing. It is suggested that there are seven distinct types of information that we derive from seen faces; t... | 10.1038/nrn1724 | A theoretical paper that proposes a multiroute model of face perception in which different facial attributes are processed by distinct functional routes. |
10.1207/s15516709cog2301_1 | 123,002,006 | Research in face recognition has largely been divided between those projects concerned with front‐end image processing and those projects concerned with memory for familiar people. These perceptual and cognitive programmes of research have proceeded in parallel, with only limited mutual influence. In this paper we pres... | 10.1038/nrn1724 | Presents a model of facial identity recognition in which the front end is implemented as a PCA, and the subsequent cognitive processes are implemented as an interactive activation and competition architecture. |
10.1126/science.1598577 | 58,373,022 | How does the brain represent objects in the world? A proportion of cells in the temporal cortex of monkeys responds specifically to objects, such as faces, but the type of coding used by these cells is not known. Population analysis of two sets of such cells showed that information is carried at the level of the popula... | 10.1038/nrn1724 | Shows that face-responsive cells in the inferotemporal cortex of monkeys code visual properties, whereas face-responsive cells in the STS code nonvisual properties, such as familiarity or social status. |
10.1152/jn.1996.76.1.109 | 41,441,699 | 1. Processing of visual information in primates is believed to occur in at least two separate cortical pathways, commonly labeled the "form" and "motion" pathways. This division lies in marked contrast to our everyday visual experience, in which we have a unified percept of both the form and motion of objects, implying... | 10.1038/nrn1724 | Reports evidence from cell recording in monkeys that the STS is involved in the integration of visual form and motion components of biological motion. |
10.1046/j.0956-7976.2003.psci_1479.x | 81,667,134 | There is good reason to believe that gaze direction and facial displays of emotion share an information value as signals of approach or avoidance. The combination of these cues in the analysis of social communication, however, has been a virtually neglected area of inquiry. Two studies were conducted to test the predic... | 10.1038/nrn1724 | Presents evidence that gaze direction affects the perception of emotion from faces. |
10.1152/jn.00325.2001 | 17,851,977 | The primary olfactory brain center, the antennal lobe (AL) in insects or the olfactory bulb in vertebrates, is a notable example of a neural network for sensory processing. While physiological properties of the input, the olfactory receptor neurons, have become clearer, the operation of the network itself remains crypt... | 10.1038/nrn1074 | This is a good example of the new level of analysis provided by calcium imaging and is very informative about processing in the antennal lobe. |
10.1126/science.1070502 | 60,045,943 | In the insect olfactory system, oscillatory synchronization is functionally relevant and reflects the coherent activation of dynamic neural assemblies. We examined the role of such oscillatory synchronization in information transfer between networks in this system. The antennal lobe is the obligatory relay for olfactor... | 10.1038/nrn1074 | Although this work is on locust, which has an atypical olfactory system, it systematically investigates for the first time the data transfer from projection neurons to Kenyon cells. |
10.1126/science.288.5466.672 | 41,297,708 | Memories are thought to be due to lasting synaptic modifications in the brain. The search for memory traces has relied predominantly on determining regions that are necessary for the process. However, a more informative approach is to define the smallest sufficient set of brain structures. The rutabaga adenylyl cyclase... | 10.1038/nrn1074 | This paper and reference 39 emphasize the distinction between necessary and sufficient structures, heralding the power of reconstruction as opposed to dissection. |
10.1126/science.1062622 | 20,566,596 | The mushroom bodies of the Drosophila brain are important for olfactory learning and memory. To investigate the requirement for mushroom body signaling during the different phases of memory processing, we transiently inactivated neurotransmission through this region of the brain by expressing a temperature-sensitive al... | 10.1038/nrn1074 | References 38 and 39 show that output from the mushroom bodies is required for olfactory memory only during retrieval but not during acquisition. |
10.1126/science.1064200 | 38,581,770 | The mushroom bodies, substructures of the Drosophila brain, are involved in olfactory learning and short-term memory, but their role in long-term memory is unknown. Here we show that the alpha-lobes-absent ( ala ) mutant lacks either the two vertical lobes of the mushroom body or two of the three median lobes which con... | 10.1038/nrn1074 | The first link of long-term olfactory memory to the mushroom bodies. |
10.1126/science.1058237 | 16,751,720 | We studied the underlying neural mechanism of a simple choice behavior between competing alternatives in Drosophila . In a flight simulator, individual flies were conditioned to choose one of two flight paths in response to color and shape cues; after the training, they were tested with contradictory cues. Wild-type fl... | 10.1038/nrn1074 | A fascinating, new non-olfactory function of the mushroom bodies in 'decisions'. |
10.1126/science.1138140 | 20,870,775 | Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or ... | 10.1038/nrn.2015.2 | This work provides the first experimental demonstration of the adaptive immune function of the CRISPR–Cas9 system in bacteria. |
10.1126/science.1232033 | 125,274,783 | Genome Editing Clustered regularly interspaced short palindromic repeats (CRISPR) function as part of an adaptive immune system in a range of prokaryotes: Invading phage and plasmid DNA is targeted for cleavage by complementary CRISPR RNAs (crRNAs) bound to a CRISPR-associated endonuclease (see the Perspective by van d... | 10.1038/nrn.2015.2 | References 24 and 25 describe the successful harnessing of the CRISPR–Cas9 system for editing the mammalian genome in cell lines. |
10.1038/ncomms8391 | 20,398,608 | Abstract In vivo functional investigation of oncogenes using somatic gene transfer has been successfully exploited to validate their role in tumorigenesis. For tumour suppressor genes this has proven more challenging due to technical aspects. To provide a flexible and effective method for investigating somatic loss-of-... | 10.1038/nrn.2015.2 | This paper describes methods for delivering Cas9 and guide RNA into the brains of newborn mice and embryos. By targeting multiple tumour-suppressor genes, the development of the medulla and glioblastoma was induced. |
10.1073/pnas.1208507109 | 62,549,560 | Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide adaptive immunity against viruses and plasmids in bacteria and archaea. The silencing of invading nucleic acids is executed by ribonucleoprotein complexes preloaded with small, interfering CRISPR RNAs (crRNAs) t... | 10.1038/nrn.2015.2 | This paper, along with reference 37, characterizes Cas9-mediated DNA cleavage in vitro |
10.1073/pnas.0601277103 | 20,526,656 | The factors that enhance the waterborne spread of bacterial epidemics and sustain the epidemic strain in nature are unclear. Although the epidemic diarrheal disease cholera is known to be transmitted by water contaminated with pathogenic Vibrio cholerae , routine isolation of pathogenic strains from aquatic environment... | 10.1038/nrmicro3433 | This study demonstrates that the ingestion of metabolically quiescent V. cholerae cells can lead to the formation of in vivo biofilms that are hyperinfective when excreted in patient stool. |
10.1073/pnas.0705599104 | 107,173,415 | Vibrio cholerae persists in aquatic environments predominantly in a nonculturable state. In this study coccoid, nonculturable V. cholerae O1 in biofilms maintained for 495 days in Mathbaria, Bangladesh, pond water became culturable upon animal passage. Culturability, biofilm formation, and the wbe , ctxA , and rstR2 ge... | 10.1038/nrmicro3433 | This report reveals the crucial role of biofilms in maintaining environmental reservoirs between epidemics as well as the role of host passage in the activation of metabolically quiescent cells. |
10.1073/pnas.0237386100 | 45,524,841 | Based on results of ecological studies demonstrating that Vibrio cholerae , the etiological agent of epidemic cholera, is commensal to zooplankton, notably copepods, a simple filtration procedure was developed whereby zooplankton, most phytoplankton, and particulates >20 μm were removed from water before use. Effect... | 10.1038/nrmicro3433 | This work shows that simple filtration to remove particulates >20 μm could reduce cholera outbreaks by 48%, suggesting that the removal of biofilms can significantly reduce V. cholerae infections. |
10.1126/science.1222981 | 29,228,170 | Biofilms Up Close Many bacterial infections involve biofilm formation. Cells within a biofilm are significantly more resistant to immune clearance and antibiotics compared to unattached, planktonic cells. Berk et al. (p. 236 ) applied superresolution optical methods to image living bacteria with nanometer-scale precisi... | 10.1038/nrmicro3433 | This study uses an in vivo labelling strategy to visualize and characterize the spatial and temporal organization of the major V. cholerae biofilm components — VPS, RbmA, Bap1 and RbmC — revealing unique roles for each within the biofilm. |
10.1073/pnas.1403683111 | 17,417,490 | Significance Identifying proteins localized on the surface and envelope of Gram-negative bacterial cells is an important problem in vaccine development and antibiotic target discovery. We show that the characterization of proteins associated with outer membrane vesicles (OMVs) released by Gram-negative cells provides a... | 10.1038/nrmicro3433 | This research shows that all three major biofilm matrix proteins are associated with OMVs, which implies that OMVs may have an as-yet- uncharacterized role in biofilm formation. |
10.1126/science.1181185 | 123,534,024 | Decoding a Second-Messenger's Message Biofilms are aggregates of bacteria on a surface often associated with increased resistance to antibiotics and stress. In Vibrio cholerae , the bacterial species that causes cholera, biofilm formation is promoted by the bacterial second-messenger cyclic diguanylate (c-di-GMP) and i... | 10.1038/nrmicro3433 | This article reports the crystal structure of VpsT and demonstrates that VpsT dimerizes and directly binds a c-di-GMP dimer to activate the transcriptional regulation of genes involved in biofilm regulation. |
10.1111/j.1365-2958.2004.04155.x | 83,029,736 | Summary While studying virulence gene regulation in Vibrio cholerae during infection of the host small intestine, we identified VieA as a two‐component response regulator that contributes to activating expression of cholera toxin. Here we report that VieA represses transcription of Vibrio exopolysaccharide synthesis ( ... | 10.1038/nrmicro3433 | This report identifies and characterizes the phosphodiesterase VieA, and is the first study to demonstrate the significant role c-di-GMP in regulating biofilm formation. |
10.2217/fvl.09.62 | 121,295,683 | Most α-herpesviruses are pantropic, neuroinvasive pathogens that establish a reactivateable, latent infection in the PNS of their natural hosts. Various manifestations of herpes disease rely on extent and direction of the spread of infection between the surface epithelia and the nervous system components that innervate... | 10.1038/nrn3029 | A comprehensive article on molecular mechanisms for the spread of various strains of herpesviruses in retrograde and anterograde directions in axons. |
10.1084/jem.189.4.657 | 28,014,371 | N-formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific receptors on mammalian phagocytes. Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N-formylpeptide receptor signaling in vivo may be important in antimicrobial host defense, althou... | 10.1038/nrmicro3390 | This publication confirms a crucial role for FPR1 in bacterial infection. |
10.1073/pnas.72.3.1059 | 81,453,030 | Leucocytes such as neutrophils are attracted by N-formylmethionine, but not by methionine. Di- and tripeptides containing formylmethionine are strong attractants for both neutrophils and macrophages, whereas the corresponding nonacylated compounds are not chemotactic. The formylated peptides may be related to an incomp... | 10.1038/nrmicro3390 | This publication reports the discovery of synthetic formylated peptides with chemoattractant activity. |
10.1073/pnas.87.1.66 | 28,063,666 | Bacteria produce a heterogeneous mixture of neutrophil chemotactic agents in culture filtrates. Formylmethionyl peptides have been shown to comprise a significant portion of the chemotactic activity in bacterial culture filtrates; however, not all of the chemotactic agents in bacterial culture filtrates are formylated ... | 10.1038/nrmicro3390 | This study reports on the neutrophil-attractant activity of enterococcal pheromone peptides. |
10.4049/jimmunol.177.11.8017 | 104,084,470 | Abstract Bacteria have developed mechanisms to escape the first line of host defense, which is constituted by the recruitment of phagocytes to the sites of bacterial invasion. We previously described the chemotaxis inhibitory protein of Staphylococcus aureus, a protein that blocks the activation of neutrophils via the ... | 10.1038/nrmicro3390 | This study presents the FPR2 inhibitory S. aureus protein FLIPr. |
10.1073/pnas.93.18.9926 | 40,647,639 | Hippocampal neuron loss is widely viewed as a hallmark of normal aging. Moreover, neuronal degeneration is thought to contribute directly to age-related deficits in learning and memory supported by the hippocampus. By taking advantage of improved methods for quantifying neuron number, the present study reports evidence... | 10.1038/nrn1809 | Similar to findings in humans, this stereologically controlled experiment reveals that aged rats have no neuronal loss and so cell death cannot account for age-related behavioural impairments. |
10.1126/science.6494926 | 79,648,005 | The possibility that calcium is elevated in brain neurons during aging was examined by quantifying afterhyperpolarizations induced by spike bursts in CA1 neurons of hippocampal slices from young and aged rats. The afterhyperpolarizations result from Ca 2+ -dependent K + conductance increases and are blocked in medium l... | 10.1038/nrn1809 | The first report of a significant increase in the K + -dependent afterhyperpolarization of aged hippocampal CA1 pyramidal cells that is blocked by low concentrations of Ca 2+ |
10.1126/science.272.5264.1017 | 101,608,084 | Voltage-activated calcium (Ca 2+ ) influx is increased in mammalian CA1 hippocampal neurons during aging. However, the molecular basis for this elevation is not known. The partially dissociated hippocampal (“zipper'') slice preparation was used to analyze single Ca 2+ channel activity in CA1 neurons of adult and aged r... | 10.1038/nrn1809 | The first evidence that the increase in voltage-activated Ca 2+ influx in aged CA1 hippocampal neurons is due to an age-related increase in L-type Ca 2+ channels. |
10.1002/hipo.450030106 | 40,923,766 | Abstract The effect of two types of electrical stimulation designed to induce long‐lasting plasticity of the Schaffer/commissural inputs to CA1 pyramidal neurons was investigated using in vitro hippocampal slices made from young (3–6 month) and old (24–27 month) Fischer 344 rats. The first stimulation paradigm, primed ... | 10.1038/nrn1809 | In contrast to earlier reports of intact hippocampal LTP induction (see references 38 and 83), the results of this study suggest that engaging plasticity-inducing mechanisms around threshold becomes more difficult with age. |
10.1073/pnas.0400285101 | 103,496,582 | The hippocampal formation contains a distinct population of neurons organized into separate anatomical subregions. Each hippocampal subregion expresses a unique molecular profile accounting for their differential vulnerability to mechanisms of memory dysfunction. Nevertheless, it remains unclear which hippocampal subre... | 10.1038/nrn1809 | The authors used different imaging methods in rats and monkeys and report a cross-species consensus that the dentate gyrus of the hippocampus is particularly vulnerable to the impact of ageing. These results are consistent with a previous report in humans. |
10.1126/science.1206938 | 20,520,051 | Multidimensional RNA structures can act as scaffolds for the spatial organization of bacterial metabolism. | 10.1038/nrmicro3244 | This study describes synthetic scaffolding ncRNA devices that mediate protein localization and protein–protein interactions. |
10.1126/science.1160311 | 18,132,924 | The engineering of biological systems is anticipated to provide effective solutions to challenges that include energy and food production, environmental quality, and health and medicine. Our ability to transmit information to and from living systems, and to process and act on information inside cells, is critical to ad... | 10.1038/nrmicro3244 | This study demonstrates the rational design of ligand-sensing ncRNA modules into higher-order logic gates. |
10.1073/pnas.1015741108 | 82,299,985 | The widespread natural ability of RNA to sense small molecules and regulate genes has become an important tool for synthetic biology in applications as diverse as environmental sensing and metabolic engineering. Previous work in RNA synthetic biology has engineered RNA mechanisms that independently regulate multiple ta... | 10.1038/nrmicro3244 | This study describes the rational engineering of orthogonally acting transcriptional ncRNA devices that can form logics and signalling cascades. |
10.1126/science.1205527 | 19,282,132 | Engineered biological systems that integrate multi-input sensing, sophisticated information processing, and precisely regulated actuation in living cells could be useful in a variety of applications. For example, anticancer therapies could be engineered to detect and respond to complex cellular conditions in individual... | 10.1038/nrmicro3244 | This study reports a complex RNAi genetic circuit that can sense multiple microRNA signals for the identification of cancer cell types. |
10.1126/science.1235005 | 60,313,166 | Toward Synthetic Biology The detection of an appropriate point to intervene in a cellular pathway and minimize off-target effects on other cellular processes present problems for the design of circuits that control cellular signaling pathways and thus direct cell function. Galloway et al. (p. 1358 , published online 15... | 10.1038/nrmicro3244 | This study demonstrates the use of ligand-sensing ncRNA devices as tools to study the dynamic signalling networks that are important for cell fate determination. |
10.1073/pnas.1203808109 | 80,377,819 | A key next step in synthetic biology is to combine simple circuits into higher-order systems. In this work, we expanded our synthetic riboregulation platform into a genetic switchboard that independently controls the expression of multiple genes in parallel. First, we designed and characterized riboregulator variants t... | 10.1038/nrmicro3244 | This study demonstrates that ncRNA devices can be programmed as genetic switchboards to regulate multiple metabolic genes for controlling carbon flow through glucose-utilization pathways in E. coli |
10.1126/science.1212209 | 124,232,497 | Evidence is presented for the feasibility of computer-aided design of biological circuits for regulation of gene expression. | 10.1038/nrmicro3244 | This paper reports a model-based method to engineer ligand-sensing RNA devices that enable quantitative control of gene expression. |
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