source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1126/science.1095862 | 83,230,197 | In the nervous system of vertebrates, myelination is essential for rapid and accurate impulse conduction. Myelin thickness depends on axon fiber size. We use mutant and transgenic mouse lines to show that axonal Neuregulin-1 (Nrg1) signals information about axon size to Schwann cells. Reduced Nrg1 expression causes hyp... | 10.1038/nrn1743 | Transgenic overexpression of the NRG1 type III protein in neurons regulates myelin thickness. |
10.1073/pnas.0901870106 | 20,103,042 | Fungi produce numerous low molecular weight molecules endowed with a multitude of biological activities. However, mining the full-genome sequences of fungi indicates that their potential to produce secondary metabolites is greatly underestimated. Because most of the biosynthesis gene clusters are silent under laborator... | 10.1038/nrmicro2916 | A report on the activation of a silent fungal secondary metabolism gene cluster by a distinct bacterium. |
10.1098/rstb.2007.2044 | 123,064,137 | We present the argument that the majority of low-molecular-weight organic compounds made and secreted by microbes play roles as cell-signalling molecules in the environment. Of the large number of compounds isolated to date, only a small fraction have been shown to possess useful therapeutic antibiotic activity. Howeve... | 10.1038/nrmicro2916 | A comprehensive review discussing possible functions of secondary metabolites in nature. |
10.1128/ec.3.2.527-535.2004 | 18,925,990 | ABSTRACT Secondary metabolites, or biochemical indicators of fungal development, are of intense interest to humankind due to their pharmaceutical and/or toxic properties. We present here a novel Aspergillus nuclear protein, LaeA, as a global regulator of secondary metabolism in this genus. Deletion of laeA ( Δ laeA ) b... | 10.1038/nrmicro2916 | The initial report about the identification of LaeA, which has a major influence on the regulation of secondary metabolism. |
10.1126/science.1155888 | 82,403,921 | Differentiation and secondary metabolism are correlated processes in fungi that respond to light. In Aspergillus nidulans , light inhibits sexual reproduction as well as secondary metabolism. We identified the heterotrimeric velvet complex VelB/VeA/LaeA connecting light-responding developmental regulation and control o... | 10.1038/nrmicro2916 | A comprehensive analysis of the velvet complex, showing that LaeA is part of the complex. |
10.1073/pnas.1103523108 | 41,360,733 | Sequence analyses of fungal genomes have revealed that the potential of fungi to produce secondary metabolites is greatly underestimated. In fact, most gene clusters coding for the biosynthesis of antibiotics, toxins, or pigments are silent under standard laboratory conditions. Hence, it is one of the major challenges ... | 10.1038/nrmicro2916 | A study finding that the modulation of histone chromatin modification by bacteria leads to the activation of silent fungal gene clusters. |
10.1083/jcb.200607098 | 101,573,635 | Transformation of a transected axonal tip into a growth cone (GC) is a critical step in the cascade leading to neuronal regeneration. Critical to the regrowth is the supply and concentration of vesicles at restricted sites along the cut axon. The mechanisms underlying these processes are largely unknown. Using online c... | 10.1038/nrn3176 | Live confocal microscope imaging documentation of the sequence of events leading to the polar reorientation of microtubules after axotomy and the ensuing accumulation of Golgi-derived vesicles and endocytic vesicles in separate traps. |
10.1002/cne.21522 | 101,747,730 | Abstract Following axotomy, both the proximal and distal cut axonal ends transform into growth cones (GCs). Whereas the GCs formed by the tip of the proximal segment branch to form neurites, the structure formed by the distal cut end fails to grow. The mechanisms underlying the formation of an aberrant GC by the distal... | 10.1038/nrn3176 | An analysis of the structural reorganization of the distal segment of a cut axon and the mechanisms underlying its failure to reassemble a competent growth cone. |
10.1126/science.1165527 | 82,909,582 | Regeneration of injured neurons can restore function, but most neurons regenerate poorly or not at all. The failure to regenerate in some cases is due to a lack of activation of cell-intrinsic regeneration pathways. These pathways might be targeted for the development of therapies that can restore neuron function after... | 10.1038/nrn3176 | A study showing that growth cone regeneration in C. elegans requires an MAPK signalling pathway. |
10.1126/science.1201148 | 62,130,491 | Taxol stimulates the capacity of axons to grow after spinal cord injury. | 10.1038/nrn3176 | This study shows that administration of the clinically approved drug taxol to rats with spinal cord injuries causes axon regeneration and improvement in gait by reducing scarring and inducing axon regeneration. |
10.1126/science.289.5477.310 | 40,699,515 | Although the diploid fungus Candida albicans , a human pathogen, has been thought to have no sexual cycle, it normally possesses mating-type–like orthologs ( MTL ) of both of the Saccharomyces cerevisiae mating-type genes ( MAT ) a and α. When strains containing only MTL a or MTL α were constructed by the loss of one h... | 10.1038/nrmicro752 | References 8 and 9 are the first reports of mating in C. albicans |
10.1126/science.285.5431.1271 | 18,509,256 | Candida albicans , the most prevalent fungal pathogen in humans, is thought to lack a sexual cycle. A set of C. albicans genes has been identified that corresponds to the master sexual cycle regulators a1, α1, and α2 of the Saccharomyces cerevisiae mating-type ( MAT ) locus. The C. albicans genes are arranged in a way ... | 10.1038/nrmicro752 | Description of the C. albicans mating-type-like ( MTL ) locus. |
10.1073/pnas.232566499 | 29,103,188 | Phase and antigenic variation are mechanisms used by microbial pathogens to stochastically change their cell surface composition. A related property, referred to as phenotypic switching, has been described for some pathogenic fungi. This phenomenon is best studied in Candida albicans , where switch phenotypes vary in m... | 10.1038/nrmicro752 | Description of several hundred genes differentially expressed in white versus opaque cells. |
10.1101/gad.1908710 | 122,019,819 | In plants and invertebrates, viral-derived siRNAs processed by the RNaseIII Dicer guide Argonaute (AGO) proteins as part of antiviral RNA-induced silencing complexes (RISC). As a counterdefense, viruses produce suppressor proteins (VSRs) that inhibit the host silencing machinery, but their mechanisms of action and cell... | 10.1038/nrmicro3120 | References 21, 22 and 29 detail genetic work with subtle viral mutations that disrupt silencing suppressors |
10.1073/pnas.1209329109 | 41,475,496 | Regulation of gene expression by DNA methylation is crucial for defining cellular identities and coordinating organism-wide developmental programs in many organisms. In plants, modulation of DNA methylation in response to environmental conditions represents a potentially robust mechanism to regulate gene expression net... | 10.1038/nrmicro3120 | With Reference 4, first demonstration that RdDM represses plant defence |
10.1073/pnas.1005635107 | 39,167,325 | In the antennal lobe of Drosophila , information about odors is transferred from olfactory receptor neurons (ORNs) to projection neurons (PNs), which then send axons to neurons in the lateral horn of the protocerebrum (LHNs) and to Kenyon cells (KCs) in the mushroom body. The transformation from ORN to PN responses can... | 10.1038/nrn3136 | This study explored the benefits of normalization in the fly olfactory system (see also REF. 27) in terms of coding for different odours |
10.1073/pnas.1003109107 | 38,278,948 | Intrinsic or resting state functional connectivity MRI and structural covariance MRI have begun to reveal the adult human brain's multiple network architectures. How and when these networks emerge during development remains unclear, but understanding ontogeny could shed light on network function and dysfunction. In thi... | 10.1038/nrn3465 | This paper tracks the development of seed-based structural co-variance networks from 5 to18 years of age. |
10.3389/fragi.2022.916336 | 142,297,282 | Introduction: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. While genetics are important in the development of AD, environment and lifestyle are also important factors influencing AD. One such lifestyle factor is alcohol consumption. Unhealthy and excessive chronic alcohol consumption is associa... | 10.1038/nrn.2017.130 | This review discusses the bidirectional interactions between energy homeostasis signals and neural circuits that control motivation and food intake, with a focus on the activity of specific cell types in these networks. |
10.1126/science.1085028 | 125,149,669 | The KirBac1.1 channel belongs to the inward-rectifier family of potassium channels. Here we report the structure of the entire prokaryotic Kir channel assembly, in the closed state, refined to a resolution of 3.65 angstroms. We identify the main activation gate and structural elements involved in gating. On the basis o... | 10.1038/nrn1244 | The first X-ray crystal structure of a Kir channel, showing both the transmembrane and cytoplasmic regions of the same K + channel. |
10.1523/jneurosci.15-05-04102.1995 | 101,113,877 | Whether amphetamine acts principally at the plasma membrane or at synaptic vesicles is controversial. We find that d-amphetamine injection into the Planorbis giant dopamine neuron causes robust dopamine release, demonstrating that specific amphetamine uptake is not required. Arguing for action at vesicles, whole-cell c... | 10.1038/nrn983 | The first report to show that amphetamine promotes reverse transport of dopamine through the plasma-membrane dopamine transporter after its redistribution from vesicles to the cytosol. |
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/nrn983 | The first study to link mutations in the α-synuclein gene to familial Parkinson's disease. |
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/nrn983 | The first study to show that both α-synuclein mutations increase the protein's ability to form oligomers, key intermediates in the aggregation process. |
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/nrn983 | This was the first α-synuclein transgenic mouse to be created; it overexpresses human wild-type α-synuclein under the control of the platelet-derived growth factor-β promoter. This is the only paper so far to report a nigrostriatal defect in mice that overexpress any form of α-synuclein. |
10.1523/jneurosci.20-09-03214.2000 | 81,814,212 | α-, β-, and γ-Synuclein, a novel family of neuronal proteins, has become the focus of research interest because α-synuclein has been increasingly implicated in the pathogenesis of Parkinson's and Alzheimer's disease. However, the normal functions of the synucleins are still unknown. For this reason, we characterized α-... | 10.1038/nrn983 | A study showing that deletion of wild-type α-synuclein using antisense oligonucleotide technology reduces the number of vesicles in the reserve pool, indicating that α-synuclein might regulate vesicle biogenesis. |
10.1146/annurev.cellbio.17.1.463 | 20,783,455 | ▪ Abstract The matrix metalloproteinases (MMPs) constitute a multigene family of over 25 secreted and cell surface enzymes that process or degrade numerous pericellular substrates. Their targets include other proteinases, proteinase inhibitors, clotting factors, chemotactic molecules, latent growth factors, growth fact... | 10.1038/nrn1807 | A very thorough review on the many roles of metalloproteinases. |
10.1126/science.289.5483.1360 | 40,526,561 | Contact-mediated axon repulsion by ephrins raises an unresolved question: these cell surface ligands form a high-affinity multivalent complex with their receptors present on axons, yet rather than being bound, axons can be rapidly repelled. We show here that ephrin-A2 forms a stable complex with the metalloprotease Kuz... | 10.1038/nrn1807 | Using in vitro systems, the authors showed a role for metalloproteinases in axonal guidance. |
10.1242/jcs.01324 | 102,363,311 | The central nervous system myelin components oligodendrocyte-myelin glycoprotein, myelin-associated glycoprotein and the Nogo-66 domain of Nogo-A inhibit neurite outgrowth by binding the neuronal glycosyl-phosphatidylinositol-anchored Nogo-66 receptor (NgR) that transduces the inhibitory signal to the cell interior via... | 10.1038/nrn1807 | Lays the foundation for considering the involvement of metalloproteinases in overcoming inhibition of axonal regrowth by Nogos. |
10.1111/j.1365-2958.2011.07891.x | 60,872,696 | Summary Nickel is toxic to all forms of life, but the mechanisms of cell damage are unknown. Indeed, environmentally relevant nickel levels (8 µM) inhibit wild‐type Escherichia coli growth on glucose minimal medium. The same concentration of nickel also inhibits growth on fructose, but not succinate, lactate or glycero... | 10.1038/nrmicro3028 | A study that correlates bacteriostasis to Ni-dependent inhibition of a glycolytic enzyme in E. coli |
10.1073/pnas.0812808106 | 125,110,127 | Excess copper is poisonous to all forms of life, and copper overloading is responsible for several human pathologic processes. The primary mechanisms of toxicity are unknown. In this study, mutants of Escherichia coli that lack copper homeostatic systems ( copA cueO cus ) were used to identify intracellular targets and... | 10.1038/nrmicro3028 | Work which demonstrates that Cu abolishes the activity of sensitive enzymes with solvent-accessible Fe–S clusters and that this is responsible for growth inhibition of E. coli |
10.1111/j.1462-2920.2007.01448.x | 4,678,950 | Summary Growth in a biofilm modulates microbial metal susceptibility, sometimes increasing the ability of microorganisms to withstand toxic metal species by several orders of magnitude. In this study, a high‐throughput metal toxicity screen was initiated with the aim of correlating biological toxicity data in planktoni... | 10.1038/nrmicro3028 | A study that establishes statistical correlations between the microbiological toxicity of metal ions and their chemical properties. |
10.1128/jb.177.9.2305-2314.1995 | 122,870,778 | The Escherichia coli Fur protein, with its iron(II) cofactor, represses iron assimilation and manganese superoxide dismutase (MnSOD) genes, thus coupling iron metabolism to protection against oxygen toxicity. Iron assimilation is triggered by iron starvation in wild-type cells and is constitutive in fur mutants. We sho... | 10.1038/nrmicro3028 | A report that links Fe toxicity to lethal DNA damage in E. coli |
10.1086/502251 | 63,097,448 | Abstract Background and Objectives: Hospital-acquired legionnaires' disease can be prevented by disinfection of hospital water systems. This study assessed the long-term efficacy of copper-silver ionization as a disinfection method in controlling Legionella in hospital water systems and reducing the incidence of hospit... | 10.1038/nrmicro3028 | The results of field testing suggesting that the use of Cu–Ag ionization systems can eliminate hospital outbreaks of Legionnaires' disease. |
10.4049/jimmunol.163.2.913 | 139,046,435 | Abstract Recent publications have provided confusing information on the importance of the J chain for secretion of dimeric IgA at mucosal surfaces. Using J chain-deficient (J chain−/−) mice, we addressed whether a lack of J chain had any functional consequence for the ability to resist challenge with cholera toxin (CT)... | 10.1038/nrmicro2384 | A discussion about the role of the J chain in antibody secretion and the requirement for IgA in toxin neutralization. |
10.1084/jem.190.7.915 | 59,999,624 | Mucosal surfaces are protected specifically by secretory immunoglobulin A (SIgA) and SIgM generated through external translocation of locally produced dimeric IgA and pentameric IgM. Their active transport is mediated by the epithelial polymeric Ig receptor (pIgR), also called the transmembrane secretory component. Par... | 10.1038/nrmicro2384 | This work shows that mice that are deficient in pIgR are also deficient for IgA transport, confirming the in vitro models of SIg secretion. |
10.1073/pnas.0812681106 | 107,321,141 | A T cell receptor transgenic mouse line reactive to a microbiota flagellin, CBir1, was used to define mechanisms of host microbiota homeostasis. Intestinal IgA, but not serum IgA, was found to block mucosal flagellin uptake and systemic T cell activation in mice. Depletion of CD4 + CD25 + Tregs decreased IgA + B cells,... | 10.1038/nrmicro2384 | This article demonstrates the role of the intestinal microbiota in shaping both regulation of the mucosal immune system and antibody secretion. |
10.1126/science.1169152 | 4,604,933 | Most of the immunoglobulin A (IgA) in the gut is generated by B cells in the germinal centers of Peyer's patches through a process that requires the presence of CD4 + follicular B helper T(T FH ) cells. The nature of these T FH cells in Peyer's patches has been elusive. Here, we demonstrate that suppressive Foxp3 + CD4... | 10.1038/nrmicro2384 | The discovery of a pathway for the generation of T H cells from T Reg cells in the gut. |
10.1126/science.288.5474.2222 | 104,311,736 | The immunoglobulin A (IgA) is produced to defend mucosal surfaces from environmental organisms, but host defenses against the very heavy load of intestinal commensal microorganisms are poorly understood. The IgA against intestinal commensal bacterial antigens was analyzed; it was not simply “natural antibody” but was s... | 10.1038/nrmicro2384 | This study identified a T cell-independent secretory antibody that is generated in the gut in response to gut flora. |
10.1084/jem.20052093 | 61,343,679 | The production of IgA is induced in an antigen-unspecific manner by commensal flora. These secretory antibodies (SAbs) may bind multiple antigens and are thought to eliminate commensal bacteria and self-antigens to avoid systemic recognition. In this study, we addressed the role of “innate” SAbs, i.e., those that are c... | 10.1038/nrmicro2384 | This work elucidates the role of SIg in preventing both the natural transmission and the acquisition of a gastrointestinal pathogen. |
10.1046/j.1365-2958.2002.03265.x | 81,473,384 | Summary Although natural genetic transformation is a widely disseminated form of genetic exchange in prokaryotic species, the proficiencies with which DNA recognition, uptake and processing occur in nature vary greatly. However, the molecular factors and interactions underlying intra‐ and interspecies diversity in leve... | 10.1038/nrmicro844 | References 21 and 22 show that expression of two minor pilins can modulate the ability of Neisseria gonorrhoeae to bind and take up DNA; the role of PilT, the traffic NTPase responsible for pilus retraction and twitching motility, is also investigated. |
10.1046/j.1365-2958.1999.01170.x | 19,399,817 | Competent cells of Bacillus subtilis efficiently bind and internalize DNA. ComEA and the seven proteins encoded by the comG operon are required in vivo for the binding step. We show here that ComEA, a bitopic membrane protein, is itself capable of high‐affinity DNA binding. A domain necessary for DNA binding is located... | 10.1038/nrmicro844 | The authors show that ComEA, a conserved competence protein required for both DNA binding and uptake, is itself a non-sequence-specific double-strand-DNA-binding protein, acting as a cell-surface DNA receptor. |
10.1046/j.1365-2958.2001.02502.x | 40,530,234 | Helicobacter pylori ( Hp ), a Gram‐negative bacterial pathogen and aetiologic agent of gastroduodenal disease in humans, is naturally competent for genetic transformation. Natural competence in bacteria is usually correlated with the presence of type IV pili or type IV pilin‐like proteins, which are absent in Hp . Inst... | 10.1038/nrmicro844 | References 84 and 85 show that transformation in Helicobacter pylori is mediated by proteins related to components of type IV secretion systems, in contrast to other competence systems, which use type-II-secretion-related proteins. |
10.1084/jem.79.2.137 | 45,414,581 | 1. From Type III pneumococci a biologically active fraction has been isolated in highly purified form which in exceedingly minute amounts is capable under appropriate cultural conditions of inducing the transformation of unencapsulated R variants of Pneumococcus Type II into fully encapsulated cells of the same specifi... | 10.1038/nrmicro844 | A seminal paper in the history of modern genetics, demonstrating that the 'transforming principle' is DNA. |
10.1162/jocn.2009.21185 | 122,008,945 | Parietal cortex contributes to body representations by integrating visual and somatosensory inputs. Because mirror neurons in ventral premotor and parietal cortices represent visual images of others' actions on the intrinsic motor representation of the self, this matching system may play important roles in recognizing ... | 10.1038/nrn2833 | This single-cell recording study in macaques provides the first systematic evidence of the existence in monkeys of single neurons that respond both when the monkey is being touched and when it sees someone else being touched. |
10.1126/science.1089506 | 83,021,240 | To what extent do all brains work alike during natural conditions? We explored this question by letting five subjects freely view half an hour of a popular movie while undergoing functional brain imaging. Applying an unbiased analysis in which spatiotemporal activity patterns in one brain were used to “model” activity ... | 10.1038/nrn2833 | By analysing the degree of synchrony among the brain activity of many viewers of the same western movie, this methodologically pioneering study shows that BA2 is active while the hand–object interactions of other people are being observed. |
10.1126/science.283.5398.70 | 83,411,675 | Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. Blockade of N -methyl- d -aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal ... | 10.1038/nrn2911 | This study provided an elegant demonstration of the widespread vulnerability of the developing nervous system to NMDAR blockade. Subsequent studies would characterize the effect of NMDAR blockade in the mature CNS and the extent to which NMDAR blockade exacerbates neuronal loss following injury of metabolic inhibition. |
10.1126/science.8097060 | 60,078,228 | Calcium ions (Ca 2+ ) act as an intracellular second messenger and can enter neurons through various ion channels. Influx of Ca 2+ through distinct types of Ca 2+ channels may differentially activate biochemical processes. N -Methyl-D-aspartate (NMDA) receptors and L-type Ca 2+ channels, two major sites of Ca 2+ entry ... | 10.1038/nrn2911 | This was the first paper to show that Ca 2+ regulation of gene expression can depend on the site of Ca 2+ entry in neurons. Membrane depolarization, inducing Ca 2+ influx through voltage-gated Ca 2+ channels, was shown to activate overlapping but different promoter elements compared to Ca 2+ influx triggered by bath-gl... |
10.1146/annurev.neuro.24.1.167 | 83,551,177 | ▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of pat... | 10.1038/nrn2538 | An explanation of the role of the PFC in cognitive control and flexibility. |
10.1126/science.1089910 | 20,869,692 | Conflict monitoring by the anterior cingulate cortex (ACC) has been posited to signal a need for greater cognitive control, producing neural and behavioral adjustments. However, the very occurrence of behavioral adjustments after conflict has been questioned, along with suggestions that there is no direct evidence of A... | 10.1038/nrn2538 | An fMRI study that showed the role of the ACC and the DLPFC in the conflict detection–resolution process. |
10.1146/annurev.nutr.20.1.627 | 19,703,156 | ▪ Abstract Mammalian iron homeostasis is maintained through the concerted action of sensory and regulatory networks that modulate the expression of proteins of iron metabolism at the transcriptional and/or post-transcriptional levels. Regulation of gene transcription provides critical developmental, cell cycle, and cel... | 10.1038/nrn1537 | A recent review of the translational control of iron homeostasis. |
10.1073/pnas.0403495101 | 103,972,449 | In this study, a comparative analysis of metal-related neuronal vulnerability was performed in two brainstem nuclei, the locus coeruleus (LC) and substantia nigra (SN), known targets of the etiological noxae in Parkinson's disease and related disorders. LC and SN pars compacta neurons both degenerate in Parkinson's dis... | 10.1038/nrn1537 | This is the first study on iron, neuromelanin and ferritin in the locus coeruleus that provides an accurate comparison with iron in the substantia nigra. The age trend and cellular distribution in the locus coeruelus and substantia nigra is reported. |
10.1111/j.1471-4159.1989.tb09150.x | 103,722,237 | Abstract: The regional distributions of iron, copper, zinc, magnesium, and calcium in parkinsonian brains were compared with those of matched controls. In mild Parkinson's disease (PD), there were no significant differences in the content of total iron between the two groups, whereas there was a significant increase in... | 10.1038/nrn1537 | This paper describes the first systematic determination of iron concentrations, GSH, vitamin C and ferritin in the substantia nigra in individuals with PD. |
10.1111/j.1471-4159.1991.tb11444.x | 125,306,444 | Abstract: A selective increase in content of iron in the pars compacta of the substantia nigra has been implicated in the biochemical pathology of Parkinson's disease. Iron is thought to induce oxidative stress by liberation of oxygen free radicals from H 2 O 2 . Because 6‐hydroxydopamine (6‐OHDA) is thought to induce ... | 10.1038/nrn1537 | This paper describes the first use of an iron chelator, desferal, as a neuroprotective drug in a model of PD. |
10.1146/annurev.neuro.23.1.217 | 19,192,750 | A growing number of neurodegenerative diseases have been found to result from the expansion of an unstable trinucleotide repeat. Over the past 6 years, researchers have focused on identifying the mechanism by which the expanded polyglutamine tract renders a protein toxic to a subset of vulnerable neurons. In this revie... | 10.1038/nrn1537 | This review discusses the consequences of too many glutamine repeats. |
10.1111/j.1365-2958.2005.04609.x | 82,540,724 | Summary Deletion of gene Rv3676 in Mycobacterium tuberculosis coding for a transcription factor belonging to the cAMP receptor protein (CRP) family caused growth defects in laboratory medium, in bone marrow‐derived macrophages and in a mouse model of tuberculosis. Transcript profiling of M. tuberculosis grown in vitro ... | 10.1038/nrmicro2688 | This is the first study to implicate a cAMP signalling pathway in M. tuberculosis virulence. |
10.1073/pnas.94.1.265 | 38,715,845 | Insertion mutations in two Vibrio cholerae genes, cya and crp , which encode adenylate cyclase and the cyclic AMP (cAMP) receptor protein (CRP), respectively, derepressed the expression of a chromosomal cholera toxin (CT) promoter– lacZ fusion at the nonpermissive temperature of 37°C. In the classical biotype strain O3... | 10.1038/nrmicro2688 | This paper describes some of the earliest evidence that cAMP has a role in virulence gene expression in V. cholerae . Recent studies have revealed just how extensive this role is. |
10.1101/gr.10.2.204 | 60,315,787 | We have analyzed the cyclic nucleotide (cNMP)-binding protein and nucleotide cyclase superfamilies using Bayesian computational methods of protein family identification and classification. In addition to the known cNMP-binding proteins (cNMP-dependent kinases, cNMP-gated channels, cAMP-guanine nucleotide exchange facto... | 10.1038/nrmicro2688 | This investigation is the first to identify an unusually large number of putative AC-encoding genes and cAMP-binding proteins in M. tuberculosis , suggesting that cAMP signalling constitutes a potentially key (but overlooked) signal transduction system in mycobacteria. |
10.1083/jcb.200505117 | 67,515,029 | The host hormone melatonin increases cytoplasmic Ca2+ concentration and synchronizes Plasmodium cell cycle (Hotta, C.T., M.L. Gazarini, F.H. Beraldo, F.P. Varotti, C. Lopes, R.P. Markus, T. Pozzan, and C.R. Garcia. 2000. Nat. Cell Biol. 2:466–468). Here we show that in Plasmodium falciparum melatonin induces an increas... | 10.1038/nrmicro2688 | This article indicates that the synchronization of the blood stage cell cycle of Plasmodium spp. by melatonin is mediated through the interplay of cAMP and Ca 2+ signalling in the parasite. |
10.1242/jcs.110.21.2661 | 41,612,701 | Differentiation of African trypanosomes from replicating slender bloodstream forms to nondividing stumpy forms limits the parasite population size, allowing survival of the mammalian host and establishment of a stable host-parasite relationship. Using a novel in vitro culture system we have shown that slender to stumpy... | 10.1038/nrmicro2688 | This study shows that cell cycle-mediated regulation of bloodstream forms of African trypanosomes is controlled by cAMP signalling. |
10.1126/science.1087919 | 83,541,565 | Adaptive behavior is optimized in organisms that maintain flexible representations of the value of sensory-predictive cues. To identify central representations of predictive reward value in humans, we used reinforcer devaluation while measuring neural activity with functional magnetic resonance imaging. We presented tw... | 10.1038/nrn1747 | A demonstration of how predictive reward value is encoded in the human brain in the orbitofrontal cortex and amygdala. |
10.1126/science.1067176 | 20,666,574 | It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomogr... | 10.1038/nrn1747 | An elegant demonstration of placebo mechanisms in the human brain in which the pain relief in placebo-responders is correlated with activity in lateral orbitofrontal and anterior cingulate cortices. |
10.1111/j.1460-9568.2004.03589.x | 45,386,064 | Abstract The motivation to eat in humans is a complex process influenced by intrinsic mechanisms relating to the hunger and satiety cascade, and extrinsic mechanisms based on the appetitive incentive value of individual foods, which can themselves induce desire. This study was designed to investigate the neural basis o... | 10.1038/nrn1747 | Demonstrates that the extrinsic incentive value of foods is located in mid-anterior parts of the orbitofrontal cortex. |
10.1152/jn.00669.2002 | 16,766,099 | Umami taste stimuli, of which an exemplar is monosodium glutamate (MSG) and which capture what is described as the taste of protein, were shown using functional MRI (fMRI) to activate similar cortical regions of the human taste system to those activated by a prototypical taste stimulus, glucose. These taste regions inc... | 10.1038/nrn1747 | Shows that the subjective synergistic enhancement of umami taste is represented in mid-anterior parts of the orbitofrontal cortex. |
10.1139/z04-163 | 104,058,213 | Amphioxus neuroanatomy is important not just in its own right but also for the insights it provides regarding the evolutionary origin and basic organization of the vertebrate nervous system. This review summarizes the overall layout of the central nervous system (CNS), peripheral nerves, and nerve plexuses in amphioxus... | 10.1038/nrn2703 | This comprehensive review covers the anatomy of the central and peripheral nervous systems of both larval and adult amphioxus at the levels of both circuitry and cell types, and discusses homologies with vertebrates. |
10.1111/j.1525-142x.2009.00315.x | 100,630,037 | SUMMARY In amphioxus embryos, the early development of the type 1 sensory neurons was followed by Tlx gene expression and scanning electron microscopy. At the early neurula stage, AmphiTlx transcription is first detectable in a ventral zone of epidermis. In later embryos, expression is also seen in differentiating type... | 10.1038/nrn2703 | This study demonstrated that in amphioxus, ectodermal sensory neurons that originate in the ventral ectoderm begin to be specified at the late gastrula stage and subsequently lose their cilia, delaminate into the subepidermal space, develop pseudopodia and migrate dorsally. |
10.1242/dev.02886 | 79,404,316 | Neurogenic placodes are specialized regions of embryonic ectoderm that generate the majority of the neurons of the cranial sensory ganglia. Here we examine in chick the mechanism underlying the delamination of cells from the epibranchial placodal ectoderm. We show that the placodal epithelium has a distinctive morpholo... | 10.1038/nrn2703 | This study showed that cells migrating from the neurogenetic placodes do not express genes required for the epithelial–mesenchymal transition (as occurs in delamination of neural crest cells) and do not adopt a mesenchymal morphology as they migrate. |
10.1242/dev.01803 | 100,784,883 | Neurotrophins (Nt) and their tyrosine kinase Trk receptors play an essential role in the development and maintenance of the complex vertebrate nervous system. Invertebrate genome sequencing projects have suggested that the Nt/Trk system is a vertebrate innovation. We describe the isolation and characterisation of the a... | 10.1038/nrn2703 | This study demonstrated the ventral-to-dorsal migration of presumed ectodermal sensory cells in amphioxus and the expression of the neurotrophin receptor Trk in these cells. It also presents evidence for the evolution of the Trk receptor by exon shuffling. |
10.1073/pnas.0611223104 | 84,386,966 | At least 5% of the human genome predating the mammalian radiation is thought to have evolved under purifying selection, yet protein-coding and related untranslated exons occupy at most 2% of the genome. Thus, the majority of conserved and, by extension, functional sequence in the human genome seems to be nonexonic. Rec... | 10.1038/nrn2703 | This analysis of over 10,000 transposable elements in the human genome shows that they are concentrated near developmental genes and those involved in the regulation of transcription. |
10.1111/imr.12479 | 40,225,902 | Summary Endothelium is strategically located at the interface between blood and interstitial tissues, placing thus endothelial cell as a key player in vascular homeostasis. Endothelial cells are in a dynamic equilibrium with their environment and constitute concomitantly a source, a barrier, and a target of defensive m... | 10.1038/nrneph.2017.156 | This review describes the intricate relationship between humoral host defence systems, such as complement and coagulation, and endothelial cells, with a particular focus on aHUS and other diseases. |
10.1126/science.aad8373 | 104,395,153 | Too much cleaning up The complement system and microglia seek out and destroy unwanted cellular debris for the peripheral immune system as well as excess synapses in the developing brain. Hong et al. now show how the system may go haywire in adults early in the progression toward Alzheimer's disease (AD). Aberrant syna... | 10.1038/nrneph.2017.156 | This seminal paper on synaptic pruning by the complement system provides an excellent example of the immunoediting role of complement in physiological and pathophysiological situations. |
10.1073/pnas.92.19.8955 | 42,522,357 | Activated components of the complement system are potent mediators of inflammation that may play an important role in numerous disease states. For example, they have been implicated in the pathogenesis of inflammatory joint diseases including rheumatoid arthritis (RA). To target complement activation in immune-mediated... | 10.1038/nrneph.2017.156 | This seminal proof-of-concept study demonstrates the therapeutic benefit of anti-C5 therapy. |
10.1111/bjh.12347 | 20,633,912 | Summary Paroxysmal nocturnal haemoglobinuria ( PNH ) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events ( TE s) and chronic kidney disease ( CKD ). The long... | 10.1038/nrneph.2017.156 | This study contributes to the regained confidence in complement-targeting strategies by providing further evidence of a beneficial safety profile of therapeutic complement inhibition at the level of C5 in a chronic disease setting. |
10.1182/blood-2016-08-732800 | 40,751,769 | Key Points Strong complement activation overrides the terminal pathway inhibition by the anti-C5 antibody eculizumab. The more powerful complement is activated, the less effective is terminal pathway inhibition by diverse anti-C5 agents. | 10.1038/nrneph.2017.156 | This landmark study provides the first mechanistic insight into the clinical observation that anti-C5 therapies can be exhausted under conditions of extensive complement activation, leading to pharmacodynamic breakthrough. |
10.1126/science.1195821 | 28,091,670 | A Safety Catch on Immune Response The complement system is an integral part of the innate immune system. When triggered, it initiates a cascade that marks intruders for elimination and stimulates immune responses. The key amplification step is cleavage of a complex comprising the complement fragment C3b and factor B (C... | 10.1038/nrneph.2017.156 | This seminal study provides structural insight into the formation and functional determinants of the alternative pathway C3 convertase and facilitated the development of convertase-targeted therapeutics. |
10.4049/jimmunol.157.2.884 | 139,038,767 | Abstract We have screened a phage-displayed random peptide library for binding to C3b, the proteolytically activated form of complement component C3, and have identified a novel peptide that suppresses complement activation. This phage-displayed peptide bound to C3, C3b, and C3c, but not to C3d, indicating that it bind... | 10.1038/nrneph.2017.156 | This paper provides the first description of C3 inhibitors of the compstatin family, of which several derivatives are currently in clinical development and evaluation. |
10.1126/science.1248943 | 82,778,825 | Hexing Complement Complement activation is an immediate and potent immune defense mechanism, but how immunoglobulin G (IgG) antibodies activate complement at the molecular level is poorly understood. Using high-resolution crystallography, Diebolder et al. (p. 1260 ) show that human IgGs form hexameric structures by int... | 10.1038/nrneph.2017.156 | In this landmark paper, the researchers describe the structural base of antibody recognition by complement on cell surfaces; their findings have important implications for the design of therapeutic antibodies that induce complement-mediated cytotoxicity. |
10.1182/blood-2017-05-781450 | 81,290,460 | Key Points Eculizumab, an anti–complement C5 mAb, blocked killing of meningococci by whole blood from healthy immunized adults. Blocking the AP with ACH-4471, a small molecule in development for PNH, had much less of an effect on meningococcal killing. | 10.1038/nrneph.2017.156 | This article provides insight into the mechanisms by which neisserial infections might occur in vaccinated patients receiving anti-C5 treatment and specifically into why targeting alternative pathway activation might confer advantages in this context. |
10.1073/pnas.1010082108 | 103,695,855 | Small RNAs (sRNAs) regulate diverse pathways, including stress responses, virulence, and metabolism in Escherichia coli . At the center of this large sRNA regulatory network is the Hfq protein. Hfq mediates the binding of sRNAs to their target mRNAs; without Hfq, most sRNAs cannot efficiently regulate target mRNA expre... | 10.1038/nrmicro2615 | This paper demonstrates the effects of limiting intracellular Hfq concentrations on sRNA-mediated responses. Competition for Hfq binding is important for the organization of networks and for crosstalk between signalling pathways; these findings imply that Hfq–RNA effector complexes need to assemble or to act through ch... |
10.1073/pnas.0908744106 | 41,036,839 | Hfq is a small, highly abundant hexameric protein that is found in many bacteria and plays a critical role in mRNA expression and RNA stability. As an “RNA chaperone,” Hfq binds AU-rich sequences and facilitates the trans annealing of small RNAs (sRNAs) to their target mRNAs, typically resulting in the down-regulation ... | 10.1038/nrmicro2615 | A report and insightful interpretation of the crystal structure of Hfq in complex with RNA bound through the distal face of Hfq. This structure provides a rationalization of many other studies, including the findings that the proximal and distal faces of Hfq have different binding preferences. |
10.1101/gad.591310 | 38,277,120 | Hfq, a protein required for small RNA (sRNA)-mediated regulation in bacteria, binds RNA with low-nanomolar K d values and long half-lives of complexes (>100 min). This cannot be reconciled with the 1- 2-min response time of regulation in vivo. We show that RNAs displace each other on Hfq on a short time scale by RNA... | 10.1038/nrmicro2615 | An elegant work proposing active cycling of RNA on the Hfq molecules, and probing this model with a variety of methods. |
10.1111/j.1365-2958.2010.07342.x | 100,339,461 | Summary Prokaryotic regulatory small RNAs act by a conserved mechanism and yet display a stunning structural variability. In the present study, we used mutational analysis to dissect the functional anatomy of RybB, a σ E ‐dependent sRNA that regulates the synthesis of major porins in Escherichia coli and Salmonella . M... | 10.1038/nrmicro2615 | References 46 and 47 investigate the modular structure of a prototypical Hfq-associated sRNA. |
10.1073/pnas.1004435107 | 104,119,116 | Bacterial small noncoding RNAs carry out both positive and negative regulation of gene expression by pairing with mRNAs; in Escherichia coli , this regulation often requires the RNA chaperone Hfq. Three small regulatory RNAs (sRNAs), DsrA, RprA, and ArcZ, positively regulate translation of the sigma factor RpoS, each p... | 10.1038/nrmicro2615 | This investigation combines in vitro and in vivo experiments which suggest that Hfq increases RNA duplex strength in cognate sRNA–mRNA pairs. |
10.1101/gad.14.9.1109 | 132,269,678 | The adaptation of mRNA stability to environmental changes is a means of cells to adjust the level of gene expression. The Escherichia coli ompA mRNA has served as one of the paradigms for regulated mRNA decay in prokaryotes. The stability of the transcript is known to be correlated inversely with the bacterial growth r... | 10.1038/nrmicro2615 | A study providing evidence that Hfq can also regulate some mRNAs without the requirement of a cognate sRNA. |
10.1101/gad.1127103 | 62,189,772 | RyhB is a small antisense regulatory RNA that is repressed by the Fur repressor and negatively regulates at least six mRNAs encoding Fe-binding or Fe-storage proteins in Escherichia coli . When Fe is limiting, RyhB levels rise, and target mRNAs are rapidly degraded. RyhB is very stable when measured after treatment of ... | 10.1038/nrmicro2615 | The clear demonstration of a functional link between Hfq and RNase E in sRNA-mediated regulation. |
10.1101/gad.1330405 | 103,696,376 | Hfq-binding antisense small RNAs of Escherichia coli , SgrS and RyhB, mediate the destabilization of target mRNAs in an RNase E-dependent manner. SgrS, whose expression is induced in response to phosphosugar stress, act on the ptsG mRNA encoding a major glucose transporter, while RyhB, whose expression is induced in re... | 10.1038/nrmicro2615 | This article proposes a direct protein interaction between Hfq and RNase E, resulting in specialized complexes that are mutually exclusive with the larger RNase E-based degradosome. |
10.1111/j.1365-2958.2010.07374.x | 38,277,090 | Summary Hfq is a global regulatory RNA‐binding protein. We have identified and characterized an atypical Hfq required for gene regulation and infectivity in the Lyme disease spirochete Borrelia burgdorferi . Sequence analyses of the putative B. burgdorferi Hfq protein revealed only a modest level of similarity with the... | 10.1038/nrmicro2615 | A fascinating example of the conservation of Hfq and its function in conjunction with sRNA in a bacterium that is evolutionarily distant from E. coli |
10.1111/j.1365-2958.1994.tb00400.x | 45,315,007 | Summary The region immediately downstream from the miaA tRNA modification gene at 94.8 min contains the hfq gene and the hflA region, which are important in the bacteriophage Qβ and lambda life cycles. The roles of these genes in bacteria remain largely unknown. We report here the characterization of two chromosomal hf... | 10.1038/nrmicro2615 | A seminal paper identifying a broad set of physiological functions for Hfq in E. coli |
10.1128/jb.178.13.3763-3770.1996 | 62,543,148 | The RpoS transcription factor (also called sigma Sor sigma 38) is required for the expression of a number of stationary-phase and osmotically inducible genes in Escherichia coli. RpoS is also a virulence factor for several pathogenic bacteria, including Salmonella typhimurium. The activity of RpoS is regulated in respo... | 10.1038/nrmicro2615 | References 143 and 144 describe the first studies to identify an endogenous mRNA as a target of Hfq. |
10.1152/jn.1998.79.2.555 | 38,437,700 | Vicini, Stefano, Jian Feng Wang, Jin Hong Li, Wei Jian Zhu, Yue Hua Wang, Jian Hong Luo, Barry B. Wolfe, and Dennis R. Grayson. Functional and pharmacological differences between recombinant N-methyl-d-aspartate receptors. J. Neurophysiol. 79: 555–566, 1998. N-methyl-d-aspartic acid (NMDA) receptors transiently transfe... | 10.1038/nrn.2017.24 | This is a complete functional characterization of molecularly pure NMDAR subtypes in a recombinant system that definitively revealed subtype-specific kinetics and pharmacological properties. |
10.1002/ajmg.a.32232 | 102,964,269 | Abstract The goal of this study was to expand the description of the cognitive development phenotype in boys with Klinefelter syndrome (47,XXY). We tested neuropsychological measures of memory, attention, visual‐spatial abilities, visual‐motor skills, and language. We examined the influence of age, handedness, genetic ... | 10.1038/s41386-018-0153-2 | One of the only studies to systematically assess ADHD symptoms in males with KS. |
10.1542/peds.2011-0719 | 62,064,949 | OBJECTIVE: To contrast the behavioral and social phenotypes including a screen for autistic behaviors in boys with 47,XYY syndrome (XYY) or 47,XXY Klinefelter syndrome (KS) and controls and investigate the effect of prenatal diagnosis on the phenotype. METHODS: Patients included 26 boys with 47,XYY, 82 boys with KS, an... | 10.1038/s41386-018-0153-2 | A well-designed study comparing ASD, ADHD and other behavioral traits in KS and XYY syndrome. |
10.1111/j.1469-7610.2012.02573.x | 78,571,283 | Background: Supernumerary sex chromosome aneuploidies (X/Y‐aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of chil... | 10.1038/s41386-018-0153-2 | This systematic study compares the effects of the Y chromosome and the effects of X-chromosome dose on social functioning in various supernumerary SCAs. |
10.1002/jnr.23884 | 62,476,122 | A general theory of mammalian sexual differentiation is proposed. All biological sex differences are the result of the inequality in effects of the sex chromosomes, which are the only factors that differ in XX vs. XY zygotes. This inequality leads to male‐specific effects of the Y chromosome, including expression of th... | 10.1038/s41386-018-0153-2 | A comprehensive view of mammalian sexual differentiation accounting for the effects of the sex-chromosomes and their downstream hormonal influences on male versus female phenotype. |
10.1126/sciimmunol.aap8855 | 125,270,725 | Biallelic TLR7 expression in immune cells may contribute to increased autoimmune disease risk in women. | 10.1038/s41386-018-0153-2 | A recent study which examines the link between escape from X chromosome inactivation and increased prevalence of SLE in KS. |
10.1083/jcb.200310055 | 38,307,981 | We have previously shown that the seemingly static paracrystalline actin core of hair cell stereocilia undergoes continuous turnover. Here, we used the same approach of transfecting hair cells with actin–green fluorescent protein (GFP) and espin-GFP to characterize the turnover process. Actin and espin are incorporated... | 10.1038/nrn1828 | Shows treadmilling of actin along the stereocilia at a rate proportional to their length and proposes that myosin XVa that is localized at stereociliary tips regulates treadmilling rate and stereociliary length. |
10.1152/physrev.2001.81.3.1305 | 38,428,524 | In mammals, environmental sounds stimulate the auditory receptor, the cochlea, via vibrations of the stapes, the innermost of the middle ear ossicles. These vibrations produce displacement waves that travel on the elongated and spirally wound basilar membrane (BM). As they travel, waves grow in amplitude, reaching a ma... | 10.1038/nrn1828 | Comprehensive review of the measurements and mechanisms of the mechanical frequency tuning of the basilar membrane. |
10.1113/jphysiol.1987.sp016617 | 4,617,828 | 1. Outer hair cells from the cochlea of the guinea‐pig were isolated and their motile properties studied in short‐term culture by the whole‐cell variant of the patch recording technique. 2. Cells elongated and shortened when subjected to voltage steps. Cells from both high‐ and low‐frequency regions of the cochlea resp... | 10.1038/nrn1828 | Detailed description of the voltage-dependent somatic contractility of isolated OHCs and evidence for a novel mechanism resident in the cell cortex. |
10.1113/jphysiol.1985.sp015750 | 82,475,968 | The mechanical behaviour of the ciliary bundles of hair cells in the turtle cochlea was examined by deflecting them with flexible glass fibres of known compliance during simultaneous intracellular recording of the cell's membrane potential. Bundle motion was monitored through the attached fibre partially occluding a li... | 10.1038/nrn1828 | Used photodiode imaging to show both active and spontaneous motion of the hair bundle driven by changes in membrane potential |
10.1162/jocn.1994.6.2.99 | 38,411,316 | Cells have been found in the superior temporal polysensory area (STPa) of the macaque temporal cortex that are selectively responsive to the sight of particular whole body movements (e.g., walking) under normal lighting. These cells typically discriminate the direction of walking and the view of the body (e.g., left pr... | 10.1038/nrn1057 | References 8–10 present electrophysiological studies in macaque monkeys with recordings in different parts of the STS during presentation of biological movement stimuli. In different areas, neurons were found that seemed to respond selectively for biological movements of normal and point-light stimuli. |
10.1073/pnas.191374198 | 83,021,517 | We used whole brain functional MRI to investigate the neural network specifically engaged in the recognition of “biological motion” defined by point-lights attached to the major joints and head of a human walker. To examine the specificity of brain regions responsive to biological motion, brain activations obtained dur... | 10.1038/nrn1057 | An fMRI study that shows an involvement of the opponent motion-selective area KO in biological motion recognition, and an influence of the task on the identified biological motion-sensitive areas. |
10.1068/p3064 | 18,666,505 | A technique for the construction of exaggerated human movements was developed and its effectiveness tested for the case of categorising tennis serves as flat, slice, or topspin. The technique involves treating movements as points in a high-dimensional space and uses average movements as the basis for constructing exagg... | 10.1038/nrn1057 | A psychophysical experiment using morphing to generate exaggerations of biological movements. The recognition of spatially exaggerated patterns is improved. |
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