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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10.1242/dev.01777 | 122,997,171 | Many oligodendrocytes in the spinal cord are derived from a region of the ventral ventricular zone (VZ) that also gives rise to motoneurons. Cell fate specification in this region depends on sonic hedgehog (Shh) from the notochord and floor plate. There have been suggestions of an additional source(s) of oligodendrocyt... | 10.1038/nrn1826 | This article from our own laboratory provides independent evidence, by Cre- lox fate mapping in transgenic mice, for dorsal production of OLPs (and astrocytes). It also shows that specification of the dorsal subset of OLPs is hedgehog-independent in culture but depends on FGF signalling. |
10.1242/dev.128.14.2723 | 62,232,988 | Oligodendrocytes are derived from glial precursors that arise from the ventral neural tube early in development. In the developing chicken CNS, oligodendrocyte progenitors selectively express Nkx2.2 homeodomain transcription factor, raising the possibility that Nkx2.2 may directly regulate oligogliogenesis. In this stu... | 10.1038/nrn1826 | Provides evidence that, in the mouse spinal cord, Nkx2.2 has an essential role in oligodendrocyte maturation, but not in initial lineage specification. |
10.1002/cne.10481 | 100,456,833 | Abstract Recent studies have suggested that the ependymal cells lining the central canal of postnatal spinal cord possess certain properties of neural stem cells. However, the embryonic origin and developmental potential of the postnatal spinal cord ependymal cells remain to be defined. In this report, we investigated ... | 10.1038/nrn1826 | Provides persuasive evidence that the postnatal ependymal layer that surrounds the lumen of the postnatal spinal cord is derived exclusively from neuroepithelial cells in the ventral (Nkx6.1-expressing) part of the embryonic spinal cord. The results of Cre- lox fate mapping (see reference 20) support this conclusion, w... |
10.1073/pnas.1121081109 | 104,118,507 | In light of the rising prevalence of Alzheimer’s disease (AD), new strategies to prevent, halt, and reverse this condition are needed urgently. Perturbations of brain network activity are observed in AD patients and in conditions that increase the risk of developing AD, suggesting that aberrant network activity might c... | 10.1038/nrn.2016.141 | This study shows that levetiracetam reduces network hypersynchrony, synaptic deficits and behavioural abnormalities in hAPP-J20 mice. |
10.1523/jneurosci.1195-14.2014 | 38,870,808 | The amyloid-β hypothesis of Alzheimer's Disease (AD) focuses on accumulation of amyloid-β peptide (Aβ) as the main culprit for the myriad physiological changes seen during development and progression of AD including desynchronization of neuronal action potentials, consequent development of aberrant brain rhythms releva... | 10.1038/nrn.2016.141 | This study shows that amyloid-β reduces gamma oscillations by desynchronizing the action potentials of hippocampal pyramidal cells. |
10.1073/pnas.1206171109 | 103,763,972 | Alzheimer’s disease (AD) is characterized by a progressive dysfunction of central neurons. Recent experimental evidence indicates that in the cortex, in addition to the silencing of a fraction of neurons, other neurons are hyperactive in amyloid-β (Aβ) plaque-enriched regions. However, it has remained unknown what come... | 10.1038/nrn.2016.141 | This study shows that amyloid-β increases hippocampal neuronal activity in vivo by calcium imaging. |
10.1126/science.1162844 | 20,751,873 | The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca 2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of laye... | 10.1038/nrn.2016.141 | This study shows that APP23xPS45 mice have hyperactive neurons and synchronized neuronal activity by calcium imaging. |
10.1126/science.1141736 | 100,515,169 | Many potential treatments for Alzheimer's disease target amyloid-β peptides (Aβ), which are widely presumed to cause the disease. The microtubule-associated protein tau is also involved in the disease, but it is unclear whether treatments aimed at tau could block Aβ-induced cognitive impairments. Here, we found that re... | 10.1038/nrn.2016.141 | This study shows that endogenous tau promotes APP-dependent network hypersynchrony and cognitive decline. |
10.1111/j.1528-1167.2006.00554.x | 45,350,853 | Summary: Purpose: To determine cumulative incidence and predictors of new‐onset seizures in mild Alzheimer's disease (AD) with a cohort followed prospectively. Limited information is available on the incidence of seizures, and no reports exist of seizure predictors in AD patients. Methods: Mild AD patients were prospec... | 10.1038/nrn.2016.141 | This study shows that early onset of AD is a risk factor for seizures. |
10.1523/jneurosci.0693-14.2014 | 38,871,584 | Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity... | 10.1038/nrn.2016.141 | This study shows that transplants of inhibitory interneurons restore learning and memory in APOE4 -KI mice. |
10.1523/jneurosci.2177-05.2005 | 62,261,759 | Alzheimer's disease (AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. In total, data from 764 participants were compared across five in vivo imaging methods. Conver... | 10.1038/nrn.2016.141 | This study shows that PiB + amyloid preferentially deposits in brain regions of the DMN. |
10.1002/art.1780200102 | 59,951,549 | Abstract An epidemic form of arthritis has been occurring in eastern Connecticut at least since 1972, with the peak incidence of new cases in the summer and early fall. Its identification has been possible because of tight geographic clustering in some areas, and because of a characteristic preceding skin lesion in som... | 10.1038/nrmicro2714 | An article describing the original epidemiological study of the outbreak of arthritis in and around Lyme, Connecticut. |
10.1126/science.7043737 | 20,395,140 | A treponema-like spirochete was detected in and isolated from adult Ixodes dammini , the incriminated tick vector of Lyme disease. Causally related to the spirochetes may be long-lasting cutaneous lesions that appeared on New Zealand White rabbits 10 to 12 weeks after infected ticks fed on them. Samples of serum from p... | 10.1038/nrmicro2714 | A classic paper that provides the first convincing evidence that Lyme disease is a tick-borne illness. |
10.1128/jcm.25.3.557-558.1987 | 81,164,110 | Nymphal Ixodes dammini transmitted Borrelia burgdorferi to 1 of 14 rodents exposed for 24 h, 5 of 14 rodents exposed for 48 h, and 13 of 14 rodents exposed for greater than or equal to 72 h. Prompt removal of attached ticks is a prudent public health measure, especially in regions where Lyme disease is endemic. | 10.1038/nrmicro2714 | A classic study that defines the ∼ 48 hour window required for transmission of spirochaetes by feeding nymphs. |
10.1126/science.288.5471.1651 | 20,768,603 | A fundamental tenet of microbial pathogenesis is that bacterial pathogens must overcome host iron limitation to establish a successful infection. Surprisingly, the Lyme disease pathogen Borrelia burgdorferi has bypassed this host defense by eliminating the need for iron. B. burgdorferi grew normally and did not alter g... | 10.1038/nrmicro2714 | An article that provides evidence for one of the most unusual physiological properties of B. burgdorferi : its lack of a requirement for iron. |
10.1073/pnas.231442498 | 62,203,763 | RpoS and RpoN are two alternative sigma factors typically associated with general stress responses in bacteria. To date, there has been no experimental evidence that RpoS and RpoN can directly control the expression of one another. Herein, using a combined strategy of gene disruption and genetic complementation targeti... | 10.1038/nrmicro2714 | A ground-breaking demonstration of the unique control mechanism for rpoS transcription in B. burgdorferi and the role of this alternative σ-factor in controlling virulence gene expression. |
10.1073/pnas.1834315100 | 62,204,237 | Borrelia burgdorferi ( Bb ), the agent of Lyme disease, exists in nature through a complex enzootic life cycle that involves both ticks and mammals. As Bb transitions between its two diverse niches, profound adaptive changes occur that are reflected in differential patterns of gene expression, particularly involving li... | 10.1038/nrmicro2714 | An elegant use of mutagenesis to demonstrate the essentiality of Rrp2 for the induction of RpoS-dependent gene regulation. |
10.1111/j.1365-2958.2009.06951.x | 62,204,204 | Summary Borrelia burgdorferi , the Lyme disease spirochete, adapts as it moves between the arthropod and mammalian hosts that it infects. We hypothesize that BosR serves as a global regulator in B. burgdorferi to modulate the oxidative stress response and adapt to mammalian hosts. To test this hypothesis, a bosR mutant... | 10.1038/nrmicro2714 | One of the first investigations to demonstrate that the borrelial Fur–PerR orthologue, BosR, is required for expression of rpoS |
10.1111/j.1365-2958.2007.05716.x | 100,342,085 | Summary The alternative sigma factor RpoS (σ 38 or σ S ) plays a central role in the reciprocal regulation of the virulence‐associated major outer surface proteins OspC and OspA in Borrelia burgdorferi , the Lyme disease spirochete. Temperature is one of the key environmental signals controlling RpoS, but the molecular... | 10.1038/nrmicro2714 | The first paper to present evidence for post-transcriptional regulation of rpoS in B. burgdorferi |
10.1111/j.1365-2958.2011.07687.x | 123,172,798 | Summary Rrp1 is the sole c‐di‐GMP‐producing protein (diguanylate cyclase) of Borrelia burgdorferi . To test the hypothesis that Rrp1 regulates critical processes involved in the transmission of spirochetes between ticks and mammals, an rrp1 deletion mutant (B31‐Δ rrp1 ) and a strain that constitutively produces elevate... | 10.1038/nrmicro2714 | The finding that Rrp1 is required for adaptation of the spirochaete to the tick host. |
10.1084/jem.20031960 | 38,785,963 | The molecular basis of how Borrelia burgdorferi (Bb), the Lyme disease spirochete, maintains itself in nature via a complex life cycle in ticks and mammals is poorly understood. Outer surface (lipo)protein A (OspA) of Bb has been the most intensively studied of all borrelial molecular constituents, and hence, much has ... | 10.1038/nrmicro2714 | An elegant genetic demonstration that spirochaetes lacking OspA are virulent but unable to colonize larval midguts. |
10.1073/pnas.032667699 | 81,433,003 | DNA microarrays were used to survey the adaptive genetic responses of Borrelia burgdorferi ( Bb ) B31, the Lyme disease spirochete, when grown under conditions analogous to those found in unfed ticks (UTs), fed ticks (FTs), or during mammalian host adaptation ( Bb in dialysis membrane chambers implanted in rats). Micro... | 10.1038/nrmicro2714 | The first microarray analysis of the B. burgdorferi transcriptome, which cleverly uses in vitro conditions to emulate the tick and mammalian phases of the enzootic cycle. |
10.1073/pnas.92.7.2909 | 61,539,000 | Lyme disease spirochetes, Borrelia burgdorferi sensu lato, are maintained in zoonotic cycles involving ticks and small mammals. In unfed ticks, the spirochetes produce one outer surface protein, OspA, but not OspC. During infection in mammals, immunological data suggest that the spirochetes have changed their surface, ... | 10.1038/nrmicro2714 | The seminal demonstration of the induction of OspC during the nymphal blood meal and the importance of temperature as a stimulus for differential gene expression. |
10.1073/pnas.1131117100 | 18,750,288 | Borrelia burgdorferi , the agent of Lyme disease, expresses several adhesion molecules that are probably required for initial establishment of infection in mammalian hosts, and for colonization of various tissues within the host. The B. burgdorferi outer membrane protein P66 was previously identified as a ligand for β ... | 10.1038/nrmicro2714 | The first report to use targeted mutagenesis to show that a borrelial outer-membrane-spanning protein has a role in cytoadherence. |
10.1073/pnas.98.2.670 | 41,050,092 | The genome of Borrelia burgdorferi encodes a large number of lipoproteins, many of which are expressed only at certain stages of the spirochete's life cycle. In the current study we describe the B. burgdorferi population structure with respect to the production of two lipoproteins [outer surface protein A (OspA) and ou... | 10.1038/nrmicro2714 | A meticulous characterization of the expression profiles of OspA and OspC during tick dissemination. |
10.1073/pnas.0306845101 | 103,810,177 | Environmentally responsive synthesis of surface proteins represents a hallmark of the infectious cycle of the Lyme disease agent, Borrelia burgdorferi . Here we created and analyzed a B. burgdorferi mutant lacking outer-surface protein C (OspC), an abundant Osp that spirochetes normally synthesize in the tick vector du... | 10.1038/nrmicro2714 | A definitive demonstration that OspC is a borrelial virulence determinant following infection of mammals via needle or tick. |
10.4049/jimmunol.0901390 | 61,767,003 | Abstract Borrelia burgdorferi is the spirochetal agent of Lyme disease, a multisystemic disorder characterized by inflammation. Using global transcriptional profiling, we characterized the response of human PBMCs exposed to B. burgdorferi in an ex vivo coculture system. The expression profiles induced by B. burgdorferi... | 10.1038/nrmicro2714 | The first report to show that borreliae activate host immune responsesvia endosomal TLRs. |
10.1073/pnas.1013776108 | 28,078,123 | Phagocytosed Borrelia burgdorferi (Bb) induces inflammatory signals that differ both quantitatively and qualitatively from those generated by spirochetal lipoproteins interacting with Toll-like receptor (TLR) 1/2 on the surface of human monocytes. Of particular significance, and in contrast to lipoproteins, internalize... | 10.1038/nrmicro2714 | A paper confirming B. burgdorferi degradation in phagosomes as the principal mechanism for TLR signalling, and showing TLR2–TLR8 cooperativity. |
10.4049/jimmunol.181.12.8492 | 60,979,717 | Abstract Gene expression analysis previously revealed a robust IFN-responsive gene induction profile that was selectively up-regulated in Borrelia burgdorferi-infected C3H mice at 1 wk postinfection. This profile was correlated with arthritis development, as it was absent from infected, mildly arthritic C57BL/6 mice. I... | 10.1038/nrmicro2714 | A landmark paper calling attention to the involvement of type I IFNs in Lyme disease. |
10.1084/jem.20011870 | 103,465,506 | Borrelia burgdorferi, the Lyme disease spirochete, persistently infects mammalian hosts despite the development of strong humoral responses directed against the pathogen. Here we describe a novel mechanism of immune evasion by B. burgdorferi. In immunocompetent mice, spirochetes that did not express ospC (the outer-sur... | 10.1038/nrmicro2714 | An elegant study demonstrating that OspC-specific antibodies select for spirochaetes that have downregulated expression of the lipoprotein during early mouse infection. |
10.1098/rstb.1986.0056 | 62,265,988 | The structure and connectivity of the nervous system of the nematode Caenorhabditis elegans has been deduced from reconstructions of electron micrographs of serial sections. The hermaphrodite nervous system has a total complement of 302 neurons, which are arranged in an essentially invariant structure. Neurons with sim... | 10.1038/nrn897 | This paper documents the heroic efforts that were made in elucidating the complete neuronal wiring diagram of a metazoan organism. It is the first and still the only report of its kind, on which several generations of C. elegans researchers have now feasted. |
10.1073/pnas.87.15.6003 | 38,358,310 | The turnover and processing of the Alzheimer beta/A4 amyloid precursor protein (beta APP) has been studied in PC12 cells after treatment with agents that regulate protein phosphorylation. Phorbol 12,13-dibutyrate, an agent that stimulates protein kinase C, decreased the levels of mature beta APP and increased the level... | 10.1038/nrn2977 | This is the first study to demonstrate that proteolytic processing of APP involves a signal transduction cascade via activation of PKC. |
10.1126/science.1411529 | 122,701,709 | Altered processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease. To investigate whether cellular APP processing is controlled by cell-surface neurotransmitter receptors, human embryonic kidney (293) cell lines were t... | 10.1038/nrn2977 | This study and reference 21 were the first to demonstrate the effect of neurotransmitter receptor activation on the proteolysis of APP. Stimulation of the M1 mAChR and the M3 mAChR increases the PKC-mediated release of sAPP. |
10.1073/pnas.89.21.10075 | 58,474,270 | Activation of protein kinase C by phorbol esters is known to accelerate the processing and secretion of the beta/A4 amyloid protein precursor. We have now examined various first messengers that increase protein kinase C activity of target cells for their ability to affect beta/A4 amyloid protein precursor metabolism. A... | 10.1038/nrn2977 | Along with reference 20, this report demonstrates that activation of the M1 mAChR stimulates the release of sAPP. |
10.1073/pnas.92.17.8083 | 123,540,455 | Stimulation of muscarinic m1 or m3 receptors can, by generating diacylglycerol and activating protein kinase C, accelerate the breakdown of the amyloid precursor protein (APP) to form soluble, nonamyloidogenic derivatives (APPs), as previously shown. This relationship has been demonstrated in human glioma and neuroblas... | 10.1038/nrn2977 | This is the first study to demonstrate that the metabotropic glutamate receptors are involved in the proteolysis of APP and sAPP release. |
10.1126/science.1160649 | 103,585,177 | Deposition of the amyloid-β peptide is a pathological hallmark of Alzheimer's disease. A high-throughput functional genomics screen identified G protein–coupled receptor 3 (GPR3), a constitutively active orphan G protein–coupled receptor, as a modulator of amyloid-β production. Overexpression of GPR3 stimulated amyloid... | 10.1038/nrn2977 | This study demonstrates that the orphan GPCR GPR3 regulates the in vitro and in vivo amyloidogenic proteolysis of APP through modulation of the localization and/or activity of the γ-secretase complex in the absence of an effect on Notch processing. |
10.1126/science.1170116 | 125,255,278 | Methylation Mediation Methylation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role in mammalian genomes. Methylation patterns are often inherited across generations, but they can also be dynamic, suggesting that active DNA demethylation pathways exist. One such pathway, best characte... | 10.1038/nsmb.2489 | This work identifies TET proteins as mammalian homologs of trypanosome enzymes that are capable of oxidizing 5mC into 5hmC |
10.1146/annurev-genet-111212-133522 | 125,233,725 | The composition of the cellular proteome is commonly thought to strictly adhere to the genetic code. However, accumulating evidence indicates that cells also regulate the synthesis of mutant protein molecules that deviate from the genetic code. Production of mutant proteins generally occurs when cells are stressed or w... | 10.1038/nrmicro3568 | Excellent review on benefits of ambiguous decoding under stress conditions. |
10.1126/science.1241459 | 104,322,458 | Changing the Code Easily and efficiently expanding the genetic code could provide tools to genome engineers with broad applications in medicine, energy, agriculture, and environmental safety. Lajoie et al. (p. 357 ) replaced all known UAG stop codons with synonymous UAA stop codons in Escherichia coli MG1655, as well a... | 10.1038/nrmicro3568 | Created the first synthetic microorganism with complete removal of UAG stop codons. |
10.1073/pnas.1016460108 | 83,431,343 | Mycoplasma parasites escape host immune responses via mechanisms that depend on remarkable phenotypic plasticity. Identification of these mechanisms is of great current interest. The aminoacyl-tRNA synthetases (AARSs) attach amino acids to their cognate tRNAs, but occasionally make errors that substitute closely simila... | 10.1038/nrmicro3568 | Suggested that Mycoplasma spp. may use ambiguous decoding to defend against the host immune response. |
10.1073/pnas.1317580111 | 83,084,432 | Significance Although error rates in protein translation, particularly under stress, are high, it is not known if these errors are inherent to the system, or if they may have an adaptive function. Here, we provide evidence that specific mistranslation of mycobacterial proteins is important for phenotypic resistance to ... | 10.1038/nrmicro3568 | Demonstrated that ambiguous decoding increases resistance to an antibiotic in mycobacteria. |
10.1073/pnas.1420193111 | 37,391,278 | Significance Expanding the genetic code is an important aim of synthetic biology, but some organisms developed naturally expanded genetic codes over the course of evolution. To understand the selective advantage of genetically encoding more than 20 amino acids, we investigated the proteome-wide response to reducing the... | 10.1038/nrmicro3568 | Provided proteome-level view of the phenotypic impact of removing Pyl from the genetic code of M. acetivorans |
10.1073/pnas.1218613110 | 20,373,397 | Despite the fact that the genetic code is known to vary between organisms in rare cases, it is believed that in the lifetime of a single cell the code is stable. We found Acetohalobium arabaticum cells grown on pyruvate genetically encode 20 amino acids, but in the presence of trimethylamine (TMA), A. arabaticum dynami... | 10.1038/nrmicro3568 | Demonstrated natural Pyl decoding in bacteria and revealed first example of dynamic genetic code expansion. |
10.1146/annurev-biochem-060713-035737 | 41,374,416 | Genetic code expansion and reprogramming enable the site-specific incorporation of diverse designer amino acids into proteins produced in cells and animals. Recent advances are enhancing the efficiency of unnatural amino acid incorporation by creating and evolving orthogonal ribosomes and manipulating the genome. Incre... | 10.1038/nrmicro3568 | An excellent review on engineering protein synthesis for genetic code expansion in diverse expression systems. |
10.1126/science.1205822 | 38,450,553 | Template-mediated, genome construction and assembly created a strain with 80 precise codon changes. | 10.1038/nrmicro3568 | First example of a genome engineered with 62 codons by mutation of all TAGs to TAA. |
10.1523/jneurosci.10-04-01286.1990 | 20,105,269 | Gonadal steroids are known to influence hippocampal physiology in adulthood. It is presently unknown whether gonadal steroids influence the morphology of hippocampal neurons in the adult intact rat brain. In order to determine whether female sex hormones influence hippocampal morphology in the intact adult, we performe... | 10.1038/s41386-018-0208-4 | An early study indicating that phase of estrous cycle influence spine density in the CA1 region of the hippocampus |
10.1523/jneurosci.4437-15.2016 | 60,156,477 | Estradiol (E2) acutely potentiates glutamatergic synaptic transmission in the hippocampus of both male and female rats. Here, we investigated whether E2-induced synaptic potentiation occurs via presynaptic and/or postsynaptic mechanisms and which estrogen receptors (ERs) mediate E2's effects in each sex. Whole-cell vol... | 10.1038/s41386-018-0208-4 | This is the first study elucidating the cellular mechanism of enhancing effects of estradiol on neural excitability of the hippocampal neurons, in which estradiol enhances long-term potentiation through different estrogen receptors between males and females |
10.1126/science.1173215 | 29,293,637 | Neurogenesis and Spatial Memory The dentate gyrus of the hippocampus is one of two sites in the brain where new neurons are produced throughout life. Adult-born neurons integrate into the dentate gyrus circuitry and are thought to play a role in learning and memory. However, their contribution to hippocampal function r... | 10.1038/s41386-018-0208-4 | One of the first studies to show that adult neurogenesis in the hippocampus was required for pattern separation |
10.1126/science.1248903 | 41,762,604 | Forget It! When examining the relationship between the production of new neurons in the hippocampus and memory, studies have generally first manipulated hippocampal neurogenesis and afterward investigated memory formation and found that new neurons help to encode new memories. However, when investigating how similar ma... | 10.1038/s41386-018-0208-4 | The first direct evidence that adult neurogenesis in the hippocampus was related to forgetting |
10.1073/pnas.0809650106 | 87,897,341 | Learning increases the survival of new cells that are generated in the hippocampal formation before the training experience, especially if the animal learns to associate stimuli across time [Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Nat Neurosci 2:260–265]. All relevant studies have been conducted on male... | 10.1038/s41386-018-0208-4 | The first study to indicate that sex differences in learning was related to sex differences in the impact of that learning on neurogenesis in the hippocampus |
10.1523/jneurosci.1392-15.2015 | 45,464,878 | Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas m... | 10.1038/s41386-018-0208-4 | This is the first study indicating that elucidating the association between transcriptome analysis in the nucleus accumbens and sex differences in stress vulnerability |
10.1155/2010/139891 | 103,831,529 | Memory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity underlying learning and memory. This study explored the temporal expression profiles of these proteins in the rat ... | 10.1038/s41386-018-0208-4 | This is one of few study reporting time courses of immediate early genes Arc and zif268 protein expression, which indicates zif268 expression reaches the peak earlier than Arc protein expression |
10.7554/elife.11352 | 20,579,956 | Traditional rodent models of Pavlovian fear conditioning assess the strength of learning by quantifying freezing responses. However, sole reliance on this measure includes the de facto assumption that any locomotor activity reflects an absence of fear. Consequently, alternative expressions of associative learning are r... | 10.1038/s41386-018-0208-4 | A study showing that female rats show distinctly different active responses to fear memory, unlike male rats |
10.1073/pnas.0811058106 | 61,488,547 | Processes as diverse as receptor binding and signaling, cytoskeletal dynamics, and programmed cell death are manipulated by mimics of host proteins encoded by pathogenic bacteria. We show here that the Salmonella virulence factor SspH2 belongs to a growing class of bacterial effector proteins that harness and subvert t... | 10.1038/nrmicro3259 | This study reports the crystal structure of Salmonella spp. SspH2 and shows that the LRR domain interacts with the E3 ligase domain to regulate its activity. |
10.1126/science.1193844 | 80,269,876 | Gee-Up, NEDD8 Diverse bacterial pathogens, such as Burkholderia pseudomallei and enteropathogenic Escherichia coli (EPEC), inject effector proteins into eukaryotic host cells to subvert host cell biology. Cui et al. (p. 1215 ; published online 5 August) show that certain bacterial effector proteins promoted the glutami... | 10.1038/nrmicro3259 | This study reveals that Cif and CHBP deamidate NEDD8 and interfere with its function, resulting in cell cycle arrest. |
10.1126/science.1212868 | 102,463,818 | The bacterial pathogen Legionella pneumophila ensures amino acid supplies by promoting degradation of target host proteins. | 10.1038/nrmicro3259 | This study shows that L. pneumophila AnkB assembles polyubiquitylated proteins on the LCV and promotes their proteasomal degradation to generate amino acids that contribute to intracellular bacterial proliferation and survival. |
10.1126/science.1227026 | 82,817,874 | Axing Autophagy When intracellular pathogens like Legionella pneumophila take up residence in mammalian host cells, they must combat the efforts of the host cell to attack them. Autophagy is a process by which cells digest their own constituents, often involved in response to starvation or pathogen attack. Choy et al. ... | 10.1038/nrmicro3259 | This study shows that the L. pneumophila T4SS effector RavZ uncouples the LC3–PE interaction — which is important for autophagosome maturation — via its proteolytic activity, thereby preventing autophagy. |
10.1111/j.1600-0854.2008.00847.x | 29,180,946 | Mutations in the gene encoding the microtubule (MT)‐severing protein spastin are the most common cause of hereditary spastic paraplegia, a genetic condition in which axons of the corticospinal tracts degenerate. We show that not only does endogenous spastin colocalize with MTs, but that it is also located on the early ... | 10.1038/nrn2946 | This paper showed that spastin is recruited to membrane sites in an isoform-specific fashion. Together with reference 30, it showed that spastin is required for the completion of cytokinesis. |
10.1038/ismej.2010.161 | 103,639,747 | Abstract Complex microbial populations are organized in relation to their environment. In the intestine, the inner lining (mucosa) is a potential focal point for such organization. The proximal murine colon contains mucosal folds that are known to be associated with morphologically distinct microbes. To identify these ... | 10.1038/nrmicro3552 | Laser capture microdissection and 16S sequencing are used to profile the microbiome of the inter-fold regions of the proximal colon, revealing a community distinct from that of the central lumen. |
10.1073/pnas.1219247110 | 102,291,388 | The animal and human intestinal mucosa secretes an assortment of compounds to establish a physical barrier between the host tissue and intestinal contents, a separation that is vital for health. Some pathogenic microorganisms as well as members of the commensal intestinal microbiota have been shown to be able to break ... | 10.1038/nrmicro3552 | Isotope labelling of mucosal proteins in the gut followed by nanoscale secondary ion mass spectrometry (nanoSIMS) detection in conjunction with FISH identifies mucosal bacteria that consume host-derived proteins. This powerful method provides in situ support for the theory that certain mucin-degrading bacteria largely ... |
10.1126/science.1109051 | 62,253,732 | Germ-free mice were maintained on polysaccharide-rich or simple-sugar diets and colonized for 10 days with an organism also found in human guts, Bacteroides thetaiotaomicron , followed by whole-genome transcriptional profiling of bacteria and mass spectrometry of cecal glycans. We found that these bacteria assembled on... | 10.1038/nrmicro3552 | Transcriptional profiling of B. thetaiotaomicron in the gut of gnotobiotic animals identifies genes involved in the utilization of diet-derived and host-derived nutrients. |
10.1126/science.1209791 | 62,593,960 | Innate immune signaling and antimicrobial peptide activity maintain separation of the microbiota and intestinal epithelium. | 10.1038/nrmicro3552 | Bacterial sensing by the epithelium and REGIIIγ secretion by Paneth cells are shown to be necessary for the prevention of microbial overgrowth on the epithelial surface in the small intestine. |
10.1073/pnas.1006451107 | 20,856,651 | The normal intestinal microbiota inhabits the colon mucus without triggering an inflammatory response. The reason for this and how the intestinal mucus of the colon is organized have begun to be unraveled. The mucus is organized in two layers: an inner, stratified mucus layer that is firmly adherent to the epithelial c... | 10.1038/nrmicro3552 | A detailed investigation of the protein content of colonic mucus finds distinguishing factors between the outer and inner layers. MUC2 is shown to be required to prevent bacterial overgrowth on the epithelial surface and invasion of tissue. |
10.1126/science.1088525 | 104,264,258 | Semiconductor quantum dots (QDs) are nanometer-sized fluorescent probes suitable for advanced biological imaging. We used QDs to track individual glycine receptors (GlyRs) and analyze their lateral dynamics in the neuronal membrane of living cells for periods ranging from milliseconds to minutes. We characterized multi... | 10.1038/nrn1827 | First major work showing the application of functionalized quantum dots to target neurons in the investigation of a specific neurophysiological process. The authors took advantage of the physical properties of quantum dots to achieve single-particle tracking of glycine receptors. |
10.1126/science.1093783 | 83,493,060 | Neural progenitor cells were encapsulated in vitro within a three-dimensional network of nanofibers formed by self-assembly of peptide amphiphile molecules. The self-assembly is triggered by mixing cell suspensions in media with dilute aqueous solutions of the molecules, and cells survive the growth of the nanofibers a... | 10.1038/nrn1827 | First major work describing the application of a nanoengineered material designed specifically for neural regeneration that had multiple, functional properties, including in vitro self-assembly under physiological conditions and preferential differentiation of neurons over astrocytes. |
10.1128/jb.177.22.6625-6629.1995 | 101,104,883 | Transmission electron microscopy was used to investigate the ultrastructural features of diverse cellulase and cellulase-xylanase multiprotein complexes that are components of the cellulase-xylanase system of Clostridium papyrosolvens C7. The multiprotein complexes were separated by anion-exchange chromatography into s... | 10.1038/nrmicro925 | One of the best structural studies showing the subpopulations of cellulosomes. |
10.1073/pnas.1936124100 | 123,183,557 | The utilization of organized supramolecular assemblies to exploit the synergistic interactions afforded by close proximity, both for enzymatic synthesis and for the degradation of recalcitrant substrates, is an emerging theme in cellular biology. Anaerobic bacteria harness a multiprotein complex, termed the “cellulosom... | 10.1038/nrmicro925 | A structural analysis of the interaction between cohesins and dockerins. |
10.1046/j.1365-2958.2003.03860.x | 28,219,445 | Summary The enzymatic composition of the cellulosomes produced by Clostridium cellulolyticum was modified by inhibiting the synthesis of Cel48F that is the major cellulase of the cellulosomes. The strain ATCC 35319 (pSOS asrF ) was developed to over‐produce a 469 nucleotide‐long antisense‐RNA (asRNA) directed against t... | 10.1038/nrmicro925 | Anti-sense RNA technology was used to illustrate the importance of exoglucanase Cel48F in the full expression of cellulosome activity. |
10.1046/j.1365-2958.2003.03859.x | 46,104,101 | Summary Progress towards understanding the molecular basis of cellulolysis by Clostridium cellulolyticm was obtained through the study of the first cellulolysis defective mutant strain, namely cipC Mut1. In this mutant, a 2 659 bp insertion element, disrupts the cipC gene at the sequence encoding the seventh cohesin of... | 10.1038/nrmicro925 | Shows the importance of the expression of the scaffoldin gene in the expression of downstream genes of cipC and the enzymes in the cipC gene cluster for full expression of the cellulosome activity. |
10.1046/j.1365-2958.2002.03049.x | 86,112,856 | Summary Enhancement of enzyme thermostability by protein engineering gives us information about the thermostabilization mechanism as well as advantages for industrial use of enzymes. In this study, we enhanced the thermostability of endoglucanase EngB, one component of the cellulase complex (cellulosome) from Clostridi... | 10.1038/nrmicro925 | The DNA-shuffling technique was used to form a more heat-stable endoglucanase from two mesophilic enzymes. |
10.1126/science.1059581 | 83,494,423 | Huntingtin is a 350-kilodalton protein of unknown function that is mutated in Huntington's disease (HD), a neurodegenerative disorder. The mutant protein is presumed to acquire a toxic gain of function that is detrimental to striatal neurons in the brain. However, loss of a beneficial activity of wild-type huntingtin m... | 10.1038/nrn1806 | Together with reference 16, this paper shows that wild-type but not mutant huntingtin contributes to the transcription of the BDNF gene. Cortex taken from HD mice and patients with HD has reduced BDNF mRNA and protein. |
10.1046/j.1471-4159.2003.01980.x | 45,272,134 | Abstract Huntington's disease (HD) is caused by a mutation in the gene encoding for huntingtin resulting in selective neuronal degeneration. Because HD is an autosomal dominant disorder, affected individuals have one copy of the mutant and one copy of the wild‐type allele. Huntingtin has antiapoptotic properties and is... | 10.1038/nrn1806 | Levels of full-length huntingtin are reduced in the brains of transgenic mouse models of HD, ischaemia and trauma, and in the spinal cord after injury. Wild-type huntingtin protects against neurodegeneration after ischaemia. |
10.1126/science.1092194 | 59,310,323 | Huntington's disease (HD) is characterized by the accumulation of a pathogenic protein, Huntingtin (Htt), that contains an abnormal polyglutamine expansion. Here, we report that a pathogenic fragment of Htt (Httex1p) can be modified either by small ubiquitin-like modifier (SUMO)–1 or by ubiquitin on identical lysine re... | 10.1038/nrn1806 | Sumoylation of an N-terminal fragment of huntingtin reduces the ability of the protein to form aggregates, therefore exacerbating its toxicity. Aggregated huntingtin is considered less pathogenic than soluble huntingtin. |
10.1073/pnas.1133382100 | 61,989,285 | NeuroD (ND) is a basic helix–loop–helix transcription factor important for neuronal development and survival. By using a yeast two-hybrid screen, we identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2), both of which are known to interact with huntingti... | 10.1038/nrn1806 | The authors propose that huntingtin, together with HAP1, functions as a scaffold protein for the activation of the transcription factor NeuroD by mixed-linage kinase 2 (MLK2). |
10.1083/jcb.128.1.185 | 3,428,295 | The structure of rat brain-derived neurotrophic factor (BDNF) gene is complex; four 5' exons are linked to separate promoters and one 3' exon is encoding the BDNF protein. To analyze the relative importance of the regulatory regions in vivo, we have generated transgenic mice with six different promoter constructs of th... | 10.1038/nrn1806 | Analyses the activity of BDNF regulatory regions, and shows that a tissue-specific activation of the different BDNF promoter exons occurs in the brain and the periphery. |
10.1073/pnas.0401827101 | 125,134,852 | The completion of whole genome sequencing projects has provided the genetic instructions of life. However, whereas the identification of gene coding regions has progressed, the mapping of transcriptional regulatory motifs has moved more slowly. To understand how distinct expression profiles can be established and maint... | 10.1038/nrn1806 | A report on in silico and biochemical approaches that revealed the presence of 1,892 RE1/NRSE sites in the human genome. |
10.1126/science.284.5423.2168 | 61,017,492 | Segmentation of the hindbrain and branchial region is a conserved feature of head development, involving the nested expression of Hox genes. Although it is presumed that vertebrate Hox genes function as segment identifiers, responsible for mediating registration between elements of diverse embryonic origin, this assump... | 10.1038/nrn1702 | Complements reference 22 by showing that Hoxb1 is sufficient to induce r4 character ectopically in r2. Taken together, the two studies indicate that Hoxb1 functions as a selector gene for r4 identity. |
10.1242/dev.01862 | 20,383,820 | The vertebrate hindbrain is subdivided into segments, termed neuromeres,that are units of gene expression, cell differentiation and behavior. A key property of such segments is that cells show a restricted ability to mix across segment borders – termed lineage restriction. In order to address segmentation in the midbra... | 10.1038/nrn1702 | This study exploits the advantages of the zebrafish embryo — transparency and the comparably small number of cells for characterizing cell lineage restriction at the MHB. |
10.1242/dev.129.1.83 | 83,427,808 | Regionalization of the embryonic brain is achieved through multi-step processes that operate sequentially and/or simultaneously. Localized sources of various signaling molecules act as organizing centers that pattern neighboring fields to create molecularly distinct domains. We investigated the mechanisms underlying th... | 10.1038/nrn1702 | Shows that the transcription factors SIX3 and IRX3 are sufficient to define anterior and posterior domains of competence to respond to signals from the anterior neural border, the MHB and the floor plate. |
10.1073/pnas.91.1.206 | 19,194,605 | The sorting-out of embryonic cells from a cell mixture and the selective spreading of one cell population over the surface of another have been attributed to various causes. These include differentials in chemotaxis, in cellular adhesiveness, in cell surface contractility, in speed of cell movement, and in the timing o... | 10.1038/nrn1702 | Shows that mere differences in expression levels of cadherins are sufficient to render cell populations immiscible. |
10.1073/pnas.97.16.8841 | 104,089,887 | This review summarizes recent evidence from knock-out mice on the role of reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in mammalian immunity. Reflections on redundancy in immunity help explain an apparent paradox: the phagocyte oxidase and inducible nitric oxide synthase are each nonredundant... | 10.1038/nrmicro3391 | This excellent review summarizes evidence for the role of ROS and RNS in protection against microbial infections. |
10.1073/pnas.94.10.5243 | 82,972,182 | Mutagenesis of the host immune system has helped identify response pathways necessary to combat tuberculosis. Several such pathways may function as activators of a common protective gene: inducible nitric oxide synthase (NOS2). Here we provide direct evidence for this gene controlling primary Mycobacterium tuberculosis... | 10.1038/nrmicro3391 | This study provides direct evidence for the protective role of the host nitric oxide synthase against TB. |
10.1073/pnas.2134250100 | 62,567,222 | Despite the importance of tuberculosis as a public health problem, we know relatively little about the molecular mechanisms used by the causative organism, Mycobacterium tuberculosis , to persist in the host. To define these mechanisms, we have mutated virtually every nonessential gene of M. tuberculosis and determined... | 10.1038/nrmicro3391 | By screening a mutant library, this study identified 194 genes that are important for mycobacterial growth in vivo |
10.4049/jimmunol.174.6.3658 | 29,003,780 | Abstract Helicobacter pylori (Hp) infection triggers a chronic influx of polymorphonuclear leukocyte neutrophils (PMNs) into the gastric mucosa. Although Hp reside in a neutrophil-rich environment, how these organisms evade phagocytic killing is largely unexplored. We now show that live Hp (strains 11637, 60190, DT61A,... | 10.1038/nrmicro3391 | This study shows that H. pylori disrupts targeting by NADPH oxidase in the phagosome and redirects superoxide for release to the extracellular environment. |
10.1073/pnas.0337641100 | 83,488,500 | Helicobacter pylori elicits an oxidative stress during host colonization. This oxidative stress is known to cause lesions in the host DNA. Here we addressed the question as to whether the pathogen DNA is subject to lethal or mutational damage by the host-generated oxidative response. H. pylori Hpnth mutants unable to r... | 10.1038/nrmicro3391 | This study provides evidence for host-induced oxidative DNA damage of the H. pylori genome during colonization. |
10.1128/iai.01176-06 | 81,766,637 | ABSTRACT Chronic infection of the human stomach by Helicobacter pylori leads to a variety of pathological sequelae, including peptic ulcer and gastric cancer, resulting in significant human morbidity and mortality. Several genes have been implicated in disease related to H. pylori infection, including the vacuolating c... | 10.1038/nrmicro3391 | This study screened a library of H. pylori mutants in a mouse model of infection to identify genes that are important for gastric colonization. |
10.1111/j.1365-2958.2012.07989.x | 4,800,705 | Summary Although oxidative stress is a key aspect of innate immunity, little is known about how host‐restricted pathogens successfully repair DNA damage. Base excision repair is responsible for correcting nucleobases damaged by oxidative stress, and is essential for bloodstream infection caused by the human pathogen, N... | 10.1038/nrmicro3391 | This study highlights that BER in N. meningitidis consists of a flexible network of enzymes with both overlapping and distinct activities. |
10.1128/jb.00161-07 | 81,242,709 | ABSTRACT The current increase in the incidence and severity of infectious diseases mandates improved understanding of the basic biology and DNA repair profiles of virulent microbes. In our studies of the major pathogen and model organism Neisseria meningitidis , we constructed a panel of mutants inactivating genes invo... | 10.1038/nrmicro3391 | This study provides evidence for interactions between DNA repair pathways in N. meningitidis |
10.1073/pnas.1400335111 | 41,744,513 | Significance Research on Pavlovian fear conditioning has been very successful in revealing what has come to be called the brain’s fear system. The field has now matured to the point where a sharper conceptualization of what is being studied could be very useful as we go forward. Terms like “fear conditioning” and “fear... | 10.1038/nrn.2018.22 | This article provides a summary of the issues related to describing defensive behaviour in terms of fear versus threat processing. |
10.1073/pnas.1619316114 | 38,327,677 | Emotional states of consciousness, or what are typically called emotional feelings, are traditionally viewed as being innately programmed in subcortical areas of the brain, and are often treated as different from cognitive states of consciousness, such as those related to the perception of external stimuli. We argue th... | 10.1038/nrn.2018.22 | This paper proposes an extension of the higher-order theory of consciousness to emotional consciousness. |
10.31234/osf.io/mn6ea | 127,967,696 | Discrepancies in views of the Self are suggested to be negatively related to well-being (Higgins, 1987). In the present study, we used a novel concept, Personality Estimation Discrepancy (PED), to test this classic idea. PED is defined as the computed difference between how one view oneself (Self-Perceived Personality)... | 10.1038/nrn.2018.22 | This article makes the case for a more generous view of the importance of subjective experience in the clinical treatment of anxiety disorders. |
10.1111/j.1600-065x.2012.01138.x | 123,072,938 | Summary: Neural reflex circuits regulate cytokine release to prevent potentially damaging inflammation and maintain homeostasis. In the inflammatory reflex, sensory input elicited by infection or injury travels through the afferent vagus nerve to integrative regions in the brainstem, and efferent nerves carry outbound ... | 10.1038/nrn3946 | This review discusses the effects of the sympathetic nervous system on immune function. |
10.1073/pnas.1411032111 | 80,145,442 | Significance Asthma is an inflammatory airway disease characterized by acute attacks in which airway constriction impedes breathing. The variable success of anti-inflammatory treatments in managing asthma attacks suggests that additional mechanisms contribute to this symptom. Here, we used a mouse model of acute asthma... | 10.1038/nrn3946 | This paper discusses the role of nociceptors in the asthmatic-like disorders. |
10.1073/pnas.81.7.1971 | 79,758,112 | Three prokaryotic-derived probes to identify and study the temporal expression of polysialosyl units in neuronal tissue have been developed. A polyclonal antibody, a bacteriophage-derived endo-neuraminidase, and an Escherichia coli K1 sialyltransferase are all specific for either recognizing or synthesizing poly(sialic... | 10.1038/nrn2285 | This paper described the use of a phage-derived, PSA-specific endoneuraminidase, which made definitive functional studies of PSA possible. |
10.1523/jneurosci.18-10-03757.1998 | 19,247,847 | The mossy fiber axons of both the developing and adult dentate gyrus express the highly polysialylated form of neural cell adhesion molecule (NCAM) as they innervate the proximal apical dendrites of pyramidal cells in the CA3 region of the hippocampus. The present study used polysialic acid (PSA)-deficient and NCAM mut... | 10.1038/nrn2285 | This study demonstrated an insulative mode of action for PSA in regulating the interactions of axons with complex targets. |
10.1002/dvdy.20094 | 82,107,948 | Abstract Expression of polysialic acid (PSA) promotes migration of progenitor cells from the subventricular zone (SVZ) to the olfactory bulb, where they differentiate into interneurons. This differentiation has been found to coincide with a loss of PSA. Moreover, specific removal of PSA from the mouse SVZ by endoneuram... | 10.1038/nrn2285 | This report provided evidence that PSA can suppress the differentiation of neural progenitors. |
10.1523/jneurosci.1851-04.2004 | 102,372,626 | The neocortical GABAergic network consists of diverse interneuron cell types that display distinct physiological properties and target their innervations to subcellular compartments of principal neurons. Inhibition directed toward the soma and proximal dendrites is crucial in regulating the output of pyramidal neurons,... | 10.1038/nrn2285 | The ability of PSA to regulate activity-dependent changes in neural circuitry is established in this study. |
10.1046/j.1460-9568.2001.01427.x | 17,228,079 | Abstract The large quantities of polysialic acid (PSA) characterizing highly sialylated isoform of the neural cell adhesion molecule (PSA‐NCAM), greatly reduce cell adhesion and render this particular cell surface adhesion molecule a likely candidate to intervene in dynamic neuronal phenomena, such as synaptic plastici... | 10.1038/nrn2285 | This report documented the effects of PSA on the hormone-dependent morphology of synapses in the CNS. |
10.1073/pnas.0504718102 | 62,185,393 | Under chronic conditions of neuropathic pain, nociceptive C terminals are lost from their target region in spinal lamina II, leading to reduced thermal hyperalgesia. This region of the spinal cord expresses high levels of polysialic acid (PSA), a cell surface carbohydrate known to weaken cell–cell interactions and prom... | 10.1038/nrn2285 | This study presented evidence that the presence of PSA can allow the modification or uncoupling of spinal cord synapses in response to chronic pain. |
10.1002/jnr.490310315 | 62,342,821 | Abstract Synaptic connectivity change is a consistent anatomical feature of memory formation and the possibility that this is mediated by a replay of neurodevelopmental events has been investigated by measuring change in neural cell adhesion molecule sialylalion state during the acquisition and consolidation of a passi... | 10.1038/nrn2285 | This study provided the first evidence that PSA function is associated with learning and memory. |
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