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10.1126/science.1194573 | 59,899,795 | Powdery mildews are phytopathogens whose growth and reproduction are entirely dependent on living plant cells. The molecular basis of this life-style, obligate biotrophy, remains unknown. We present the genome analysis of barley powdery mildew, Blumeria graminis f.sp. hordei ( Blumeria ), as well as a comparison with t... | 10.1038/nrmicro2790 | One of several papers published in recent years that describe repeat-driven expansions in the genomes of filamentous plant pathogens, in this case of powdery mildew fungi. |
10.1038/srep23701 | 6,417,034 | Abstract Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-... | 10.1038/nrn.2018.2 | This study shows little contribution of circulating bone-marrow-derived cells to the population of spinal microglia after PNI. |
10.1038/ncomms4771 | 41,564,834 | Abstract In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the purinergic P2X4 receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory... | 10.1038/nrn.2018.2 | This study provides evidence that the IRF8–IRF5 transcriptional cascade is necessary for producing P2X4-expressing microglia after PNI and in neuropathic pain. |
10.1038/ncomms12529 | 80,283,097 | Abstract Activation of purinergic receptors in the spinal cord by extracellular ATP is essential for neuropathic hypersensitivity after peripheral nerve injury (PNI). However, the cell type responsible for releasing ATP within the spinal cord after PNI is unknown. Here we show that PNI increases expression of vesicular... | 10.1038/nrn.2018.2 | This study reports that SDH neurons are the principal source of extracellular ATP in the spinal cord that causes PNI-induced pain hypersensitivity. |
10.1038/s41598-017-11506-4 | 71,665,665 | Abstract Fibromyalgia is a refractory disease characterized by chronic intractable pain and psychological suffering, the cause of which has not yet been elucidated due to its complex pathology. Activation of immune cells in the brain called microglia has attracted attention as a potential underlying pathological mechan... | 10.1038/nrn.2018.2 | This paper reports that induced microglia-like cells of fibromyalgia patients show an inflammatory phenotype that is correlated with pain severity. |
10.1146/annurev.neuro.30.051606.094328 | 41,689,735 | The ability to recognize a previously experienced stimulus is supported by two processes: recollection of the stimulus in the context of other information associated with the experience, and a sense of familiarity with the features of the stimulus. Although familiarity and recollection are functionally distinct, there ... | 10.1038/nrn3338 | This article reviews research on the roles of MTL subregions in recognition memory in rats, monkeys and humans. The authors propose that the PRC represents specific items, the PHC represents context information, and the hippocampus is crucial for associating item and context information (also see references 29, 30, 45,... |
10.1152/jn.00077.2008 | 17,633,971 | The hippocampus and adjacent cortical structures in the medial temporal lobe (MTL) contribute to memory through interactions with distributed brain areas. Studies of monkey and rodent anatomy suggest that parallel pathways converge on distinct subregions of the MTL. To explore the cortical areas linked to subregions of... | 10.1038/nrn3338 | This is the first study in which functional connectivity analysis of resting-state fMRI data was used to carefully characterize the connectivity of different MTL subregions in humans. The study demonstrated that the PHC and PRC show strikingly different functional connectivity profiles. |
10.1002/cne.20796 | 45,533,954 | Abstract Previous anatomical studies indicate that the orbital and medial prefrontal cortex (OMPFC) of monkeys is organized into an “orbital” network, which appears to be related to feeding and reward, and a “medial” network, related to visceral control and emotion. In this study, we examined the connections of the orb... | 10.1038/nrn3338 | This paper is an innovative synthesis of primate neuroanatomy data. The authors propose that the lateral orbitofrontal cortex is a component of an extended cortical network that also includes the PRC, whereas the medial prefrontal cortex is a component of a distributed network that also includes the PHC. |
10.1523/jneurosci.15-02-01090.1995 | 123,584,373 | Field potentials were recorded from intracranial electrodes in humans to study the role of the anterior medial temporal lobe (AMTL) in language-related processing. Subjects viewed lists of words in which orthography and word type varied, or in which words were primed by semantic associates. Large negative field potenti... | 10.1038/nrn3338 | Along with its companion paper, this study provided the first detailed characterization of the AMTL N400, demonstrating that field potentials recorded directly from the PRC are sensitive to semantic processing. |
10.1162/jocn.2008.21029 | 20,706,084 | A core brain network has been proposed to underlie a number of different processes, including remembering, prospection, navigation, and theory of mind [Buckner, R. L., & Carroll, D. C. Self-projection and the brain. Trends in Cognitive Sciences, 11, 49–57, 2007]. This purported network—medial prefrontal, medial-tem... | 10.1038/nrn3338 | This article is a meta-analysis of fMRI studies showing that the PHC, RSC, posterior hippocampus and default network are reliably recruited across autobiographical memory, virtual spatial navigation, theory of mind and episodic simulation tasks. |
10.1523/jneurosci.2542-07.2008 | 19,248,525 | Isolated feedforward networks (FFNs) of spiking neurons have been studied extensively for their ability to propagate transient synchrony and asynchronous firing rates, in the presence of activity independent synaptic background noise (Diesmann et al., 1999; van Rossum et al., 2002). In a biologically realistic scenario... | 10.1038/nrn2886 | The first study to show that asynchronous–irregular ongoing activity in a recurrent network facilitates propagation of both synchronous spiking and asynchronous firing rates in an embedded feedforward network. |
10.1126/science.286.5440.741 | 81,550,040 | The exuberant growth of neurites during development becomes markedly reduced as cortical neurons mature. In vitro studies of neurons from mouse cerebral cortex revealed that contact-mediated Notch signaling regulates the capacity of neurons to extend and elaborate neurites. Up-regulation of Notch activity was concomita... | 10.1038/nrn1847 | References 76 and 78 describe studies implicating Notch signals in events involving postmitotic, terminally differentiated neurons. |
10.1073/pnas.191355898 | 82,948,425 | We used positron emission tomography to study neural mechanisms underlying intensely pleasant emotional responses to music. Cerebral blood flow changes were measured in response to subject-selected music that elicited the highly pleasurable experience of “shivers-down-the-spine” or “chills.” Subjective reports of chill... | 10.1038/nrn3666 | This landmark paper was the first to show that music-evoked pleasure is associated with nucleus accumbens activity. |
10.1111/j.1756-8765.2012.01223.x | 18,451,713 | Abstract Implicit learning is a core process for the acquisition of a complex, rule‐based environment from mere interaction, such as motor action, skill acquisition, or language. A body of evidence suggests that implicit knowledge governs music acquisition and perception in nonmusicians and musicians, and that both exp... | 10.1038/nrn3666 | An authoritative review of studies investigating implicit learning with music. |
10.1525/mp.2012.29.5.479 | 122,291,249 | this research addressed the question: is musical memory preserved in dementia, specifically, dementia of the Alzheimer type (AD)? Six tests involving different aspects of melody and language processing were administered to each of five groups of participants: 50 younger adults, 100 older adults, and 50 AD older adults ... | 10.1038/nrn3666 | This article shows that long-term memory for music is spared through the mild and moderate stages of AD, and may even be preserved in some patients at the severe stage. |
10.1126/science.1134239 | 38,259,179 | People typically exhibit greater sensitivity to losses than to equivalent gains when making decisions. We investigated neural correlates of loss aversion while individuals decided whether to accept or reject gambles that offered a 50/50 chance of gaining or losing money. A broad set of areas (including midbrain dopamin... | 10.1038/nrn2357 | This fMRI study showed that the striatal-OFC network encodes a value signal at the time of the goal-directed choice that is consistent with the properties of PT. Furthermore, the study presented evidence that suggests that both the appetitive and the aversive aspects of goal-directed decisions might be encoded in a com... |
10.1126/science.1100907 | 83,055,769 | When humans are offered the choice between rewards available at different points in time, the relative values of the options are discounted according to their expected delays until delivery. Using functional magnetic resonance imaging, we examined the neural correlates of time discounting while subjects made a series o... | 10.1038/nrn2357 | This fMRI study argued that competing goal-directed valuation systems play a part in decisions that involve choosing between immediate small monetary payoffs and larger but delayed payoffs. |
10.1073/pnas.0706929105 | 103,619,020 | Despite the importance and pervasiveness of marketing, almost nothing is known about the neural mechanisms through which it affects decisions made by individuals. We propose that marketing actions, such as changes in the price of a product, can affect neural representations of experienced pleasantness. We tested this h... | 10.1038/nrn2357 | This paper showed that the level of “experienced pleasantness” encoded in the medial OFC at the time of consuming a wine is modulated by subjects' beliefs about the price of the wine that they are drinking. |
10.1126/science.275.5306.1593 | 41,713,287 | The capacity to predict future events permits a creature to detect, model, and manipulate the causal structure of its interactions with its environment. Behavioral experiments suggest that learning is driven by changes in the expectations about future salient events such as rewards and punishments. Physiological work h... | 10.1038/nrn2357 | This seminal paper proposed the connection between the prediction-error component of reinforcement-learning models and the behaviour of dopamine cells. |
10.1126/science.1102384 | 29,129,105 | Addictive drugs have been hypothesized to access the same neurophysiological mechanisms as natural learning systems. These natural learning systems can be modeled through temporal-difference reinforcement learning (TDRL), which requires a reward-error signal that has been hypothesized to be carried by dopamine. TDRL le... | 10.1038/nrn2357 | This paper showed how addiction can be conceptualized as a disease of the habit valuation system, using a simple modification of the reinforcement-learning model. |
10.1126/science.1228172 | 20,399,768 | Influenza Revealed Influenza virus, a single-stranded RNA virus, is responsible for substantial morbidity and mortality worldwide. The influenza ribonucleoprotein (RNP) complex, which carries out viral replication and transcription, is central to the virus life-cycle and to viral host adaptation (see the Perspective by... | 10.1038/nrmicro3367 | This paper describes the three-dimensional structure of native RNPs derived from influenza virions. |
10.1126/science.1227270 | 107,157,558 | Influenza Revealed Influenza virus, a single-stranded RNA virus, is responsible for substantial morbidity and mortality worldwide. The influenza ribonucleoprotein (RNP) complex, which carries out viral replication and transcription, is central to the virus life-cycle and to viral host adaptation (see the Perspective by... | 10.1038/nrmicro3367 | This paper describes the three-dimensional structure of native RNPs derived from cells expressing influenza RNP complex components. |
10.1128/jvi.65.1.232-244.1991 | 125,048,008 | Upon penetration of the influenza virus nucleocapsid into the host cell cytoplasm, the viral RNA and associated proteins are transported to the nucleus, where viral transcription and replication occur. By using quantitative confocal microscopy, we have found that over half of cell-associated nucleoprotein (NP) entered ... | 10.1038/nrmicro3367 | This paper was the first to show that influenza vRNPs enter the nucleus through the nuclear pore complex by an active mechanism. |
10.1073/pnas.0437772100 | 124,115,525 | The genome of influenza A virus is comprised of eight viral RNA (vRNA) segments. Although the products of all eight vRNA segments must be present for viral replication, little is known about the mechanism(s) responsible for incorporation of these segments into virions. Two models have been proposed for the generation o... | 10.1038/nrmicro3367 | This paper was the first to identify segment-specific packaging signals for an influenza vRNP, which supported the selective incorporation model of vRNP packaging. |
10.1073/pnas.1314419110 | 82,991,862 | Significance Influenza A viruses cause annual influenza epidemics and occasional severe pandemics. Their genome is segmented into eight RNA fragments, which offers evolutionary advantages but complicates genomic packaging. The existence of a selective mechanism ensuring specific packaging of one copy of each RNA into e... | 10.1038/nrmicro3367 | This paper provides an intriguing set of experiments that suggest the existence of a bona fide inter-segment vRNA–vRNA interaction that occurs in IAV-infected cells. |
10.1046/j.0953-816x.2001.01472.x | 59,772,134 | Abstract To determine the cortical areas controlling memory‐guided sequences of saccadic eye movements, we performed functional magnetic resonance imaging (fMRI) in six healthy adults. Subjects had to perform a memorized sequence of three saccades in darkness, after a triple‐step stimulus of successively flashed laser ... | 10.1038/nrn1005 | An important functional imaging study localizing areas that are related to trans-saccadic updating of spatial representation. |
10.1126/science.1097434 | 125,244,082 | MicroRNAs (miRNAs) are endogenous ∼22-nucleotide RNAs, some of which are known to play important regulatory roles in animals by targeting the messages of protein-coding genes for translational repression. We find that miR-196, a miRNA encoded at three paralogous locations in the A, B, and C mammalian HOX clusters, has ... | 10.1038/nrn2037 | Deepened interest in an important feature of the HOX gene loci, specifically the relationship between the physical location of a gene and its function. |
10.1126/science.1116502 | 122,983,213 | Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 ( SLITRK1 ) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrel... | 10.1038/nrn2037 | Presents a novel and provocative basis for a poorly understood syndrome. |
10.1073/pnas.0511041103 | 80,893,688 | MicroRNAs (miRNAs) are implicated in both tissue differentiation and maintenance of tissue identity. In most cases, however, the mechanisms underlying their regulation are not known. One brain-specific miRNA, miR-124a, decreases the levels of hundreds of nonneuronal transcripts, such that its introduction into HeLa cel... | 10.1038/nrn2037 | Opens the way to a network approach to the acquisition and maintenance of cell identity. |
10.1084/jem.20040634 | 102,877,350 | Primary infection with varicella-zoster virus (VZV) causes the characteristic syndrome of varicella, or chickenpox. Experiments in severe combined immunodeficiency mice with human skin grafts (SCIDhu mice) indicate that VZV infection of T cells can mediate transfer of infectious virus to skin. VZV-infected T cells reac... | 10.1038/nrmicro3215 | This paper shows the role of T cells in the transport of VZV and the control of replication by the potent innate response of skin cells. |
10.1128/jvi.01693-08 | 40,484,889 | ABSTRACT The varicella-zoster virus (VZV) major transactivator, IE62, is involved in the expression of all kinetic classes of VZV genes and can also activate cellular promoters, promoters from heterologous viruses, and artificial promoters containing only TATA elements. A key component of the mechanism of IE62 transact... | 10.1038/nrmicro3215 | This paper documents the VZV takeover of the host cell gene transcription complex for viral gene transcription in combination with the IE62 major viral transactivator. |
10.1128/jvi.80.4.1710-1723.2006 | 60,894,928 | ABSTRACT IE62, the major transcriptional regulatory protein encoded by varicella-zoster virus (VZV), is nuclear at early times of VZV infection but then becomes predominantly cytoplasmic as a result of expression of the protein kinase encoded by open reading frame 66 (ORF66). Cytoplasmic forms of IE62 are required for ... | 10.1038/nrmicro3215 | This paper shows the role of the ORF66 viral kinase in activating the transcriptional function of IE62. |
10.1128/jvi.02137-08 | 26,880,305 | ABSTRACT Varicella-zoster virus (VZV) is a human alphaherpesvirus that is highly cell associated in cell culture. Because cell-free virus yields are too low to permit the synchronous infections needed for time-resolved analyses, information is lacking about the sequence of events during the VZV replication cycle. To ad... | 10.1038/nrmicro3215 | This study documents the dynamics of VZV protein expression, genome replication and progeny virus assembly in newly infected cells from entry to virion release. |
10.1073/pnas.1111333108 | 120,654,284 | Enveloped viruses require membrane fusion for cell entry and replication. For herpesviruses, this event is governed by the multiprotein core complex of conserved glycoproteins (g)B and gH/gL. The recent crystal structures of gH/gL from herpes simplex virus 2, pseudorabies virus, and Epstein–Barr virus revealed distinct... | 10.1038/nrmicro3215 | This study maps the functional domains in the gH ectodomain that are required for replication and skin infection. |
10.1073/pnas.1216985110 | 78,685,827 | Herpesvirus entry functions of the conserved glycoproteins gB and gH–gL have been delineated, but their role in regulating cell–cell fusion is poorly understood. Varicella-zoster virus (VZV) infection provides a valuable model for investigating cell–cell fusion because of the importance of this process for pathogenesis... | 10.1038/nrmicro3215 | This paper shows that the gB cytoplasmic domain has a previously unrecognized motif that mimicks cellular ITIMs and that must be phosphorylated to control the fusogenic properties of gB and the detrimental effects of exaggerated cell fusion on VZV infection of skin. |
10.1128/jvi.72.2.965-974.1998 | 103,158,394 | ABSTRACT The SCID-hu mouse implanted with human fetal tissue is a novel model for investigating human viral pathogenesis. Infection of human skin implants was used to investigate the basis for the clinical attenuation of the varicella-zoster virus (VZV) strain, V-Oka, from which the newly licensed vaccine is made. The ... | 10.1038/nrmicro3215 | This study is the first report to model VZV pathogenesis using T cell and skin xenografts in SCID mice. |
10.1073/pnas.0501045102 | 109,118,877 | Varicella-zoster virus (VZV) causes varicella and establishes latency in sensory ganglia. VZV reactivation results in herpes zoster. We developed a model using human dorsal root ganglion (DRG) xenografts in severe combined immunodeficient (SCID) mice to investigate VZV infection of differentiated neurons and satellite ... | 10.1038/nrmicro3215 | This paper is the first report to model the neurotropism of VZV using DRG xenografts in SCID mice. |
10.1128/jvi.75.13.6183-6192.2001 | 80,432,534 | ABSTRACT During primary varicella-zoster virus (VZV) infection, it is presumed that virus is transmitted from mucosal sites to regional lymph nodes, where T cells become infected. The cell type responsible for VZV transport from the mucosa to the lymph nodes has not been defined. In this study, we assessed the suscepti... | 10.1038/nrmicro3215 | This paper shows the capacity of VZV to infect dendritic cells in skin and their capacity to transfer the virus into T cells. |
10.1073/pnas.1114232109 | 18,060,277 | Varicella-zoster virus (VZV) is a human α-herpesvirus that causes varicella (chickenpox) during primary infection and zoster (shingles) upon reactivation. Like other viruses, VZV must subvert the intrinsic antiviral defenses of differentiated human cells to produce progeny virions. Accordingly, VZV inhibits the activat... | 10.1038/nrmicro3215 | This paper shows that VZV, which is a lytic herpesvirus, induces STAT3 activation — leading to survivin expression, which was previously associated with oncogenic herpesviruses — and that takeover of this cellular pathway is necessary for VZV skin infection. |
10.1073/pnas.0912373107 | 36,512,403 | Varicella-zoster virus (VZV) is an alphaherpesvirus that infects skin, lymphocytes, and sensory ganglia. VZV glycoprotein E (gE) has a unique N-terminal region (aa1-188), which is required for replication and includes domains involved in secondary envelopment, efficient cell-cell spread, and skin infection in vivo. The... | 10.1038/nrmicro3215 | This study identifies a large non-conserved region of gE and maps its functions in skin infection. |
10.1128/jvi.77.1.489-498.2003 | 40,558,729 | ABSTRACT Varicella-zoster virus (VZV) glycoprotein I is dispensable in cell culture but necessary for infection of human skin and T cells in SCIDhu mice in vivo. The gI promoter contains an activating upstream sequence that binds the cellular transactivators specificity factor 1 (Sp1) and upstream stimulatory factor (U... | 10.1038/nrmicro3215 | This paper reports that cell transcription factors have an essential role as determinants of VZV pathogenesis. |
10.1128/jvi.00281-11 | 20,635,509 | ABSTRACT Autophagy is a recently recognized component of the life cycle of varicella-zoster virus (VZV). We have documented abundant autophagosome formation in skin vesicles (final site of virion assembly) from randomly selected cases of varicella and zoster. The fact that autophagy was an early event in the VZV replic... | 10.1038/nrmicro3215 | This paper shows the role of autophagy in the intrinsic response of skin cells to VZV infection. |
10.1128/jvi.01020-10 | 100,670,261 | ABSTRACT Varicella-zoster virus (VZV) causes varicella (chicken pox) and establishes latency in ganglia, from where it reactivates to cause herpes zoster (shingles), which is often followed by postherpetic neuralgia (PHN), causing severe neuropathic pain that can last for years after the rash. Despite the major impact ... | 10.1038/nrmicro3215 | This paper shows the prominent characteristics of the host immune cell response to VZV reactivation in ganglia. |
10.1128/jvi.02592-07 | 18,991,056 | ABSTRACT Varicella-zoster virus (VZV) is a human alphaherpesvirus that infects sensory ganglia and reactivates from latency to cause herpes zoster. VZV replication was examined in human dorsal root ganglion (DRG) xenografts in mice with severe combined immunodeficiency using multiscale correlative immunofluorescence an... | 10.1038/nrmicro3215 | This paper reports that the capacity of VZV to induce cell fusion includes the fusion of satellite cells and neurons in infected DRG in addition to polykaryocte formation in skin. |
10.1073/pnas.0706023104 | 100,670,140 | Varicella-zoster virus (VZV) causes varicella, establishes latency in sensory ganglia, and reactivates as herpes zoster. Human dorsal root ganglia (DRGs) xenografts in immunodeficient mice provide a model for evaluating VZV neuropathogenesis. Our investigation of the role of glycoprotein I (gI), which is dispensable in... | 10.1038/nrmicro3215 | This study documents the unexpected finding that the mutation of VZV proteins can result in chronic infectious processes in DRG. |
10.1073/pnas.90.15.7376 | 28,091,460 | Four overlapping cosmid clones were constructed that contain the complete genome of the attenuated Oka strain of VZV. Transfection of human melanoma cells with the four cosmids resulted in production of infectious VZV. A double-stranded oligonucleotide, encoding a stop codon in all three open reading frames, was insert... | 10.1038/nrmicro3215 | This paper reports the first use of VZV cosmids for generating mutant viruses. |
10.1128/jvi.01148-07 | 26,880,196 | ABSTRACT In order to facilitate the generation of mutant viruses of varicella-zoster virus (VZV), the agent causing varicella (chicken pox) and herpes zoster (shingles), we generated a full-length infectious bacterial artificial chromosome (BAC) clone of the P-Oka strain. First, mini-F sequences were inserted into a pr... | 10.1038/nrmicro3215 | This paper reports the first use of a VZV bacterial artificial chromosome (BAC) for generating mutant viruses. |
10.1111/j.1460-9568.2008.06358.x | 62,377,150 | Abstract Neurons in primary visual cortex exhibit well documented centre–surround receptive field organization, whereby the centre is dominated by excitatory influences and the surround is generally dominated by inhibitory influences. These effects have largely been established by measuring the output of neurons, i.e. ... | 10.1038/nrn3599 | Using LFPs recorded from the primary visual cortex during the presentation of visual stimuli of variable size, the authors show that the neural generators of bands of the extracellular signal that are highly correlated in most conditions (such as gamma oscillations and spiking activity) can be dissociated by careful st... |
10.1073/pnas.92.17.7612 | 81,781,834 | We report the results of two studies examining the genetic overlap between schizophrenia and velocardiofacial syndrome. In study A, we characterize two interstitial deletions identified on chromosome 22q11 in a sample of schizophrenic patients. The size of the deletions was estimated to be between 1.5 and 2 megabases. ... | 10.1038/nrn2841 | A seminal paper that provided the first evidence to support the importance of CNVs in schizophrenia vulnerability. |
10.1073/pnas.0905696106 | 38,737,449 | The 22q11 deletion (or DiGeorge) syndrome (22q11DS), the result of a 1.5- to 3-megabase hemizygous deletion on human chromosome 22, results in dramatically increased susceptibility for “diseases of cortical connectivity” thought to arise during development, including schizophrenia and autism. We show that diminished do... | 10.1038/nrn2841 | This paper provided evidence that diminished dosage of 22q11.2 genes subtly compromises neurogenesis and subsequent neuronal differentiation in the cerebral cortex. |
10.1073/pnas.0600206103 | 38,879,343 | About 35% of patients with 22q11 deletion syndrome (22q11DS), which includes DiGeorge and velocardiofacial syndromes, develops psychiatric disorders, mainly schizophrenia and bipolar disorder. We previously reported that mice carrying a multigene deletion ( Df1 ) that models 22q11DS have reduced prepulse inhibition (PP... | 10.1038/nrn2841 | This paper described the first traditional deletion-mapping approach to dissect genotype–phenotype relationships in the 22q11.2 locus. |
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/nrn1078 | The precursor forms of neurotrophins have been implicated in the folding and processing of the mature proteins. This paper indicates that the pro-sequence of NGF preferentially binds to the p75 receptor. |
10.1083/jcb.200202010 | 17,819,826 | Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. The receptor for MAG or signals that elicit morphological changes in neurons remained to be established. Here we show that the neurotrophin receptor p75 (p75NTR) is the signal transducing element for MAG. Adult do... | 10.1038/nrn1078 | An important link is made between the ability of MAG to block axonal growth and Rho activity through the p75 receptor. The results led to the experiments showing that the p75 and Nogo receptors act in a complex. |
10.1523/jneurosci.23-13-05425.2003 | 40,229,231 | The 75 kDa neurotrophin receptor (p75 NTR ) and two neurotrophin receptor homologs (NRH1, NRH2) constitute a subfamily of the nerve growth factor/tumor necrosis factor receptor superfamily. NRH1 coexists with p75 NTR in fish, amphibians, and birds but is absent in mammals, whereas NRH2 exists only in mammals. Unlike p7... | 10.1038/nrn1078 | Intramembranous cleavage of Notch, the amyloid precursor protein and ErbB4 receptors generates intracellular cytoplasmic fragments that produce marked changes in signalling and transcriptional activities. The cleavage of p75 by a γ-secretase reveals a new mechanism for transmitting neurotrophin signals from the cell su... |
10.1126/science.280.5360.69 | 83,368,665 | The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K + channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the ... | 10.1038/nrn1559 | The first X-ray structure of a potassium channel. The KcsA potassium channel is a prokaryotic channel from Streptomyces lividans that was crystallized in a closed conformation. |
10.1085/jgp.109.5.527 | 61,911,445 | Small organic molecules, like quaternary ammonium compounds, have long been used to probe both the permeation and gating of voltage-dependent K+ channels. For most K+ channels, intracellularly applied quaternary ammonium (QA) compounds such as tetraethylammonium (TEA) and decyltriethylammonium (C10) behave primarily as... | 10.1038/nrn1559 | This paper clearly shows the trapping of quaternary ammonium compounds in the intracellular pore of the Shaker potassium channel. |
10.1085/jgp.200308993 | 4,269,365 | Positively charged voltage sensors of sodium and potassium channels are driven outward through the membrane's electric field upon depolarization. This movement is coupled to channel opening. A recent model based on studies of the KvAP channel proposes that the positively charged voltage sensor, christened the “voltage-... | 10.1038/nrn1559 | A recent paper that examines where in S4 the addition of charged MTS moieties contributes to the total gating charge per channel. The results indicate that only the positions that are charged in the wild-type channel are capable of contributing to gating charge. |
10.1126/science.271.5246.213 | 41,458,601 | In response to membrane depolarization, voltage-gated ion channels undergo a structural rearrangement that moves charges or dipoles in the membrane electric field and opens the channel-conducting pathway. By combination of site-specific fluorescent labeling of the Shaker potassium channel protein with voltage clamping,... | 10.1038/nrn1559 | This was the first study that investigated S4 movements using fluorescence spectroscopy. |
10.1126/science.1101373 | 67,101,449 | We have analyzed the local structure and dynamics of the prokaryotic voltage-dependent K + channel (KvAP) at 0 millivolts, using site-directed spin labeling and electron paramagnetic resonance spectroscopy. We show that the S4 segment is located at the protein/lipid interface, with most of its charges protected from th... | 10.1038/nrn1559 | A timely EPR study investigating the mobility and environmental exposure (water vs lipid) of spin labels attached to specific positions throughout S1–S4. |
10.1146/annurev-arplant-043014-115619 | 17,306,133 | A major challenge for biology is to extend our understanding of molecular regulation from the simplified conditions of the laboratory to ecologically relevant environments. Tractable examples are essential to make these connections for complex, pleiotropic regulators and, to go further, to link relevant genome sequence... | 10.1038/nsmb.3327 | This recent review provides a comprehensive discussion of plant circadian timekeeping circuits in the context of ecologically relevant environments |
10.1126/science.1061320 | 20,452,522 | The interactive regulation between clock genes is central for oscillator function. Here, we show interactions between the Arabidopsis clock genes LATE ELONGATED HYPOCOTYL ( LHY ), CIRCADIAN CLOCK ASSOCIATED 1 ( CCA1 ), and TIMING OF CAB EXPRESSION 1 ( TOC1 ). The MYB transcription factors LHY and CCA1 negatively regula... | 10.1038/nsmb.3327 | This work proposed the first plant clock transcriptional feedback loop |
10.1126/science.290.5499.2110 | 62,032,863 | Like most organisms, plants have endogenous biological clocks that coordinate internal events with the external environment. We used high-density oligonucleotide microarrays to examine gene expression in Arabidopsis and found that 6% of the more than 8000 genes on the array exhibited circadian changes in steady-state m... | 10.1038/nsmb.3327 | This paper describes early genome-wide approaches that uncovered the pervasive regulation of gene expression by the clock and characterized the EE as a crucial motif for rhythmicity |
10.1126/science.1219075 | 59,289,816 | In many organisms, the circadian clock is composed of functionally coupled morning and evening oscillators. In Arabidopsis , oscillator coupling relies on a core loop in which the evening oscillator component TIMING OF CAB EXPRESSION 1 (TOC1) was proposed to activate a subset of morning-expressed oscillator genes. Here... | 10.1038/nsmb.3327 | Genome-wide approaches indicate that TOC1 functions as a repressor of clock-gene expression. This paper, together with refs. 49 and 50, has prompted the revision of the prevailing model of the Arabidopsis core circuit |
10.1126/science.1189801 | 125,223,424 | Bacterial (Interferon)ce Intracellular bacterial pathogens, such as Listeria monocytogenes , are detected in the cytosol of host immune cells, where they induce a host response that is often dependent on microbial secretion systems. Woodward et al. (p. 1703 , published online 27 May) now show that L. monocytogenes prod... | 10.1038/nrmicro3069 | The original paper demonstrating that c-di-AMP is synthesized by bacterial cells and that it can activate a human innate immune response. |
10.1038/embor.2011.77 | 83,471,474 | The bacterium Bacillus subtilis produces the DNA integrity scanning protein (DisA), a checkpoint protein that delays sporulation in response to DNA damage. DisA scans the chromosome and pauses at sites of DNA lesions. Structural analysis showed that DisA synthesizes the small molecule cyclic diadenosine monophosphate (... | 10.1038/nrmicro3069 | A study which establishes that c-di-AMP is produced by B. subtilis and that YybT functions in vivo as a PDE for c-di-AMP. |
10.1128/mbio.00018-13 | 104,311,618 | ABSTRACT STING ( s t i mulator of interfero n [IFN] g enes) initiates type I IFN responses in mammalian cells through the detection of microbial nucleic acids. The membrane-bound obligate intracellular bacterium Chlamydia trachomatis induces a STING-dependent type I IFN response in infected cells, yet the IFN-inducing ... | 10.1038/nrmicro3069 | The first evidence that c-di-AMP is also produced by a Gram-negative bacterium. |
10.1126/science.1229963 | 41,621,469 | DNA Sensing Is a (c)GAS DNA is normally localized to the nucleus, and so its cytoplasmic localization sends off alarm bells to the immune system because it indicates that a virus may have entered. But how does the immune system actually detect the DNA (see the Perspective by O'Neill )? Sun et al. (p. 786 , published on... | 10.1038/nrmicro3069 | The first demonstration that the cyclic hybrid dinucleotide cGAMP(2′–5′) is produced by eukaryotic cells. |
10.1126/science.1232458 | 41,740,034 | DNA Sensing Is a (c)GAS DNA is normally localized to the nucleus, and so its cytoplasmic localization sends off alarm bells to the immune system because it indicates that a virus may have entered. But how does the immune system actually detect the DNA (see the Perspective by O'Neill )? Sun et al. (p. 786 , published on... | 10.1038/nrmicro3069 | A report detailing the discovery of the enzyme responsible for cGAMP(2′–5′) production in eukaryotic cells. |
10.1073/pnas.1018949108 | 81,793,678 | Interactions of proteins with low-molecular-weight ligands, such as metabolites, cofactors, and allosteric regulators, are important determinants of metabolism, gene regulation, and cellular homeostasis. Pharmaceuticals often target these interactions to interfere with regulatory pathways. We have developed a rapid, pr... | 10.1038/nrmicro3069 | A paper describing a novel and rapid method for the detection of small-molecule protein interactions; this procedure is ideally suited for high-throughput screening assays. |
10.1093/clinchem/48.1.121 | 80,637,192 | Abstract Background: Progress in robotic printing technology has allowed the development of high-density nucleic acid and protein arrays that have increased the throughput of a variety of assays. We generated protein microarrays by printing microbial antigens to simultaneously determine in human sera antibodies directe... | 10.1038/nrmicro820 | A pioneering work on antigenic microarrays for the serological analysis of infectious diseases. |
10.1126/science.1216166 | 80,219,594 | Cells use both deterministic and stochastic mechanisms to generate cell-to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is deterministic heterogeneity in elongation rate that arises because mycobacteria gr... | 10.1038/nrmicro3299 | This study presents a model for asymmetric mycobacterial polar growth and division and finds that the poles elongate at different rates throughout the cell cycle. |
10.1073/pnas.0610634104 | 45,517,334 | Mycobacterium tuberculosis synthesizes specific polyketide lipids that interact with the host and are required for virulence. Using a mass spectrometric approach to simultaneously monitor hundreds of lipids, we discovered that the size and abundance of two lipid virulence factors, phthiocerol dimycocerosate (PDIM) and ... | 10.1038/nrmicro3299 | This paper reports the discovery that the cell wall lipids of M. tuberculosis change in relation to the anabolism of host carbon sources. |
10.1126/science.1229858 | 104,412,729 | Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing “persisters.” Using microfluidic cultures and time-lapse microscopy, we found that Mycobacter... | 10.1038/nrmicro3299 | This study shows that, in addition to deterministic processes, stochastic processes generate population heterogeneity in mycobacteria and contribute to mycobacterial persistence. |
10.1126/scisignal.2002525 | 28,099,187 | Structure-function studies in mycobacteria reveal how a Ser-Thr protein kinase and pseudokinase work together to regulate the synthesis of the bacterial cell wall. | 10.1038/nrmicro3299 | This study identifies MviN as an essential transporter of peptidoglycan subunits in mycobacteria and describes a unique phosphorylation network that regulates its activity. |
10.1101/gad.1311105 | 41,279,825 | The Mycobacterium tuberculosis genome contains 11 serine/threonine kinase genes including two, pknA and pknB , that are part of an operon encoding genes involved in cell shape control and cell wall synthesis. Here we demonstrate that pknA and pknB are predominantly expressed during exponential growth, and that overexpr... | 10.1038/nrmicro3299 | This paper describes the essential role of the serine/threonine kinases PknA and PknB in the regulation of cell morphogenesis in mycobacteria. |
10.1126/science.1163885 | 125,151,041 | The protein modifier ubiquitin is a signal for proteasome-mediated degradation in eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin-like protein, Pup (Rv2111c), which was specifically conjugated to proteasome ... | 10.1038/nrmicro3299 | This paper describes the discovery of a prokaryotic version of the eukaryotic ubiquitin system, which is known as pupylation. Pupylation seems to be analogous, but not homologous, to ubiquitylation, as not all pupylated proteins are targeted to the proteasome. |
10.1073/pnas.1121161109 | 16,127,017 | Intracellular vesicular trafficking is regulated by approximately 60 members of the Rab subfamily of small Ras-like GDP/GTP binding proteins. Rab proteins cycle between inactive and active states as well as between cytosolic and membrane bound forms. Membrane extraction/delivery and cytosolic distribution of Rabs is me... | 10.1038/nrmicro3520 | This study investigates how PTMs of RAB GTPases affect their biochemical response to host cell regulators. |
10.1126/science.1244705 | 83,085,476 | Persistent Survival The role of persister cells—dormant cells that survive multidrug treatment—in the context of bacterial pathogenesis has not been explored in depth. Using a single-cell fluorescent dilution technique, Helaine et al. (p. 204 ) examined Salmonella Typhimurium persister-cell formation in vitro and in in... | 10.1038/nrmicro3520 | This study uncovers a novel function of the Doc–Phd module in favouring the appearance of Salmonella enterica subsp. enterica serovar Typhimurium persisters. |
10.1523/jneurosci.3009-07.2007 | 42,606,919 | Synaptic glutamate transients resulting from vesicular exocytosis are superimposed on a low baseline concentration of glutamate in the extracellular space. Reported values of baseline glutamate concentrations range up to 4 μ m . If glutamate were present tonically at low micromolar concentrations, many receptors, espec... | 10.1038/nrn2274 | Using NMDA receptors as a 'sniffer', this article provided a quantitative measurement of the glutamate concentration in the extracellular space. |
10.1523/jneurosci.18-21-08751.1998 | 38,417,726 | The role of transporters in shaping the glutamate concentration in the extracellular space after synaptic release is controversial because of their slow cycling and because diffusion alone gives a rapid removal. The transporter densities have been measured electrophysiologically, but these data are from immature brains... | 10.1038/nrn2274 | This rigorous study used quantitative immunoblotting to determine the number of glial and neuronal transporters in different regions of the brain. The authors concluded that the number of glial transporters is sufficiently high to clear the number of glutamate molecules released per vesicle. |
10.1523/jneurosci.19-21-09663.1999 | 123,584,065 | Transporters are thought to assist in the termination of synaptic transmission at some synapses by removing neurotransmitter from the synapse. To investigate the role of glutamate transport in shaping the time course of excitatory transmission at the mossy fiber–granule cell synapse, the effects of transport impairment... | 10.1038/nrn2274 | This paper provided an early demonstration of how glutamate transporters limit the extent of glutamate spillover during repetitive synaptic stimulation. |
10.1113/jphysiol.1983.sp014478 | 104,259,595 | 1. The effects of excitatory amino acids and some antagonists applied by ionophoresis to stratum radiatum in the CA1 region of rat hippocampal slices were examined on the locally recorded field e.p.s.p. evoked by stimulation of the Schaffer collateral‐commissural projection. 2. L‐glutamate, L‐aspartate and the more pot... | 10.1038/nrn1385 | The first demonstration that long-term potentiation in the hippocampus is NMDAR-dependent. |
10.1098/rstb.1971.0078 | 38,451,254 | It is proposed that the most important characteristic of archicortex is its ability to perform a simple kind of memorizing task. It is shown that rather general numerical constraints roughly determine the dimensions of memorizing models for the mammalian brain, and from these is derived a general model for archicortex.... | 10.1038/nrn1385 | A seminal work that laid the foundation of much of our current understanding of hippocampal computation. Marr's models include a discussion of partial-cue-based recall and experience-dependent modifications of synaptic strength. |
10.1126/science.1071795 | 39,425,017 | Pattern completion, the ability to retrieve complete memories on the basis of incomplete sets of cues, is a crucial function of biological memory systems. The extensive recurrent connectivity of the CA3 area of hippocampus has led to suggestions that it might provide this function. We have tested this hypothesis by gen... | 10.1038/nrn1385 | This study combines regionally restricted genetic modification with in vivo physiology and behaviour to provide strong evidence that NMDARs in region CA3 are required for memory recall by pattern completion. |
10.1126/science.8351520 | 103,640,479 | Ensemble recordings of 73 to 148 rat hippocampal neurons were used to predict accurately the animals' movement through their environment, which confirms that the hippocampus transmits an ensemble code for location. In a novel space, the ensemble code was initially less robust but improved rapidly with exploration. Duri... | 10.1038/nrn1385 | Utilizing multiple recording tetrodes, these authors monitored the simultaneous activity of more than one-hundred CA1 neurons as a rat explored the environment. This study was the first to look at hippocampal spatial activity on the level of a network and also the first to demonstrate the establishment of a spatial cod... |
10.1126/science.280.5372.2121 | 20,683,439 | Hippocampal pyramidal cells are called place cells because each cell tends to fire only when the animal is in a particular part of the environment—the cell's firing field. Acute pharmacological blockade of N -methyl- d -aspartate (NMDA) glutamate receptors was used to investigate how NMDA-based synaptic plasticity part... | 10.1038/nrn1385 | Combining pharmacology and in vivo recording, the authors show that acute blockade of the NMDAR during the exploration of a novel environment impairs the long-term stability of the newly encoded place fields. |
10.1111/j.1469-7793.1998.289br.x | 104,149,466 | The responsiveness of the rat hypothalamo‐pituitary‐adrenal (HPA) axis and hypothalamo‐neurohypophysial system (HNS) to emotional (elevated plus‐maze) and physical (forced swimming) stressors and to administration of synthetic corticotrophin‐releasing hormone (CRH) was investigated during pregnancy and lactation. In ad... | 10.1038/nrn2280 | This study provided the first detailed analysis of reduced HPA-axis responses to stress in pregnant rats. |
10.1523/jneurosci.0866-05.2005 | 20,097,642 | In late pregnant rats, the hypothalamic-pituitary-adrenal (HPA) axis is hyporesponsive to psychogenic stressors. Here, we investigated attenuated HPA responses to an immune challenge and a role for endogenous opioids. ACTH and corticosterone were assayed in blood samples from virgin and 21 d pregnant rats before and af... | 10.1038/nrn2280 | This study used an immune challenge to demonstrate that suppressed HPA-axis responses in late pregnancy result from endogenous-opioid inhibition of noradrenergic input to the CRH neurons. |
10.1523/jneurosci.23-03-00788.2003 | 95,443,287 | In this study, we investigate how neurosteroid sensitivity of GABA A receptors (GABA A Rs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABA A Rs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the b... | 10.1038/nrn2280 | This intriguing study shows how oxytocin acts on oxytocin neurons to desensitize GABA A receptors to allopregnanolone at the end of pregnancy. |
10.1113/jphysiol.1995.sp020806 | 4,617,971 | 1. Electrophysiological recordings were undertaken to compare bursting characteristics of oxytocin (OT) neurones at four reproductive stages: day 20 pregnancy, day 22 of pregnancy (expected day of parturition), day 7‐11 of lactation, and day 5‐6 after weaning. 2. Each OT neurone was recorded for 1 h of suckling, combin... | 10.1038/nrn2280 | This paper describes the emergence, in late pregnancy, of the burst-firing responses of oxytocin neurons to suckling. These responses are classically associated with the milk-ejection reflex in lactation. |
10.1177/1534582306288790 | 82,933,588 | A theoretical neural model is developed, along with supportive evidence, to explain how the medial preoptic area (MPOA) of the hypothalamus can regulate maternal responsiveness toward infant-related stimuli. It is proposed that efferents from a hormone-primed MPOA (a) depress a central aversion system (composed of neur... | 10.1038/nrn2280 | This review synthesizes a large body of research on the details of the neural circuitry that is involved in different components of maternal behaviour, including motivation and reward. |
10.1210/en.2005-0194 | 16,668,486 | Abstract Pregnancy in the rat is a state of leptin resistance associated with impaired leptin signal transduction in the hypothalamus. The aim of this study was to determine whether this leptin-resistant state is mediated by a change in the level of leptin receptors in the hypothalamus. Real-time RT-PCR was used to det... | 10.1038/nrn2280 | Addressing the problem of the causes of leptin resistance in pregnancy, this paper provides evidence for changes in leptin signalling in the ventromedial nucleus (the satiety centre). |
10.1126/science.8036518 | 41,774,521 | Several paradigms of perceptual learning suggest that practice can trigger long-term, experience-dependent changes in the adult visual system of humans. As shown here, performance of a basic visual discrimination task improved after a normal night's sleep. Selective disruption of rapid eye movement (REM) sleep resulted... | 10.1038/nrn2737 | The first study to indicate that deprivation of REM sleep abolished VPL established by training before the sleep. The result suggests an important role of sleep in perceptual learning. |
10.1073/pnas.88.11.4966 | 103,782,850 | In terms of functional anatomy, where does learning occur when, for a basic visual discrimination task, performance improves with practice (perceptual learning)? We report remarkable long-term learning in a simple texture discrimination task where learning is specific for retinal input. This learning is (i) local (in a... | 10.1038/nrn2737 | A seminal study indicating a high specificity for location and the trained feature in VPL and suggesting the involvement of early visual stages in VPL. |
10.1073/pnas.95.23.13988 | 20,236,103 | To investigate the nature of plasticity in the adult visual system, perceptual learning was measured in a peripheral orientation discrimination task with systematically varying amounts of external (environmental) noise. The signal contrasts required to achieve threshold were reduced by a factor or two or more after tra... | 10.1038/nrn2737 | Proposes one of the most influential models of VPL. In this model, VPL occurs in association with changes in connectivity between areas for visual representation and for decision making, rather than with changes in visual representation in early areas. |
10.1046/j.1365-2958.2001.02646.x | 42,636,183 | The mechanism of pathogenicity in Shigella and enteroinvasive Escherichia coli (EIEC) requires the co‐ordinated expression of several genes located on both the virulence plasmid and the chromosome. We found that cells lacking a functional FIS protein (factor for inversion stimulation) are partially impaired in expressi... | 10.1038/nrmicro883 | Provides a molecular explanation of the subtleties of Fis–H-NS antagonism at the virF promoter that may have implications for other genes that are subject to conflicting regulatory influences. |
10.1128/iai.71.1.384-392.2003 | 27,947,823 | ABSTRACT The genome of enteropathogenic Escherichia coli (EPEC) encodes a global regulator, Ler (locus of enterocyte effacement [LEE]-encoded regulator), which activates expression of several polycistronic operons within the 35.6-kb LEE pathogenicity island, including the LEE2 - LEE3 divergent operon pair containing ov... | 10.1038/nrmicro883 | Describes a model for Ler–H-NS antagonism at promoters within the LEE pathogenicity island. Should be read in conjunction with reference 105. |
10.1128/jb.184.3.629-635.2002 | 19,315,355 | ABSTRACT Escherichia coli nucleoid-associated H-NS protein interacts with the Hha protein, a member of a new family of global modulators that also includes the YmoA protein from Yersinia enterocolitica . This interaction has been found to be involved in the regulation of the expression of the toxin α-hemolysin. In this... | 10.1038/nrmicro883 | Shows that Hha shows homology throughout its length to the oligomerization domain of H-NS. |
10.1046/j.1365-2958.2003.03701.x | 87,199,047 | Summary H‐NS is an abundant bacterial protein involved in transcriptional silencing of a variety of environmentally responsive genes during growth under non‐permissive conditions. We have previously demonstrated a direct role for H‐NS in the negative modulation of expression of several genes within the ToxR virulence r... | 10.1038/nrmicro883 | Discusses evidence that the H-NS protein of the pathogen Vibrio cholerae has an additional oligomerization motif in the extreme amino terminus of the protein. |
10.1046/j.1365-2958.2001.02209.x | 79,676,393 | Secretion of effector proteins in enteropathogenic Escherichia coli (EPEC) is mediated by a specialized type III secretion system whose components are encoded in the LEE1, LEE2 and LEE3 operons. Using cat transcriptional fusions and primer extension analysis, we determined that the LEE2 and LEE3 operons are expressed f... | 10.1038/nrmicro883 | Describes the antagonism of H-NS-mediated transcriptional repression by Ler, a protein that shares the DNA-binding domain of H-NS but not its oligomerization region. See also reference 48. |
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