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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10.1073/pnas.1400178111 | 62,190,843 | Significance Blood perfusion is a fundamental property of brain physiology and is known to be higher in adult females than in males. However, it is unknown when such a sex difference emerges during the lifespan, or what biological processes may cause it. In the largest study of brain perfusion yet reported, we establis... | 10.1038/s41386-018-0111-z | Identified marked sex differences in cerebral blood flow in 922 youth ages 8 to 22 years, where males show a relatively linear decline in cerebral blood flow, while females initially show a similar decline until mid-adolescence when cerebral perfusion begins to increase. |
10.1111/j.1365-2958.2011.07797.x | 82,468,764 | Summary The filamentous, heterocyst‐forming cyanobacteria are multicellular organisms in which two different cell types, the CO 2 ‐fixing vegetative cells and the N 2 ‐fixing heterocysts, exchange nutrients and regulators. In Anabaena sp. strain PCC 7120, inactivation of sepJ or genes in the fraC operon ( fraC , fraD a... | 10.1038/nrmicro3178 | This study clarifies the mechanistic basis of intercellular communication across cyanobacterial septa. |
10.1073/pnas.1115323109 | 102,409,644 | Multicellularity was one of the most significant innovations in the history of life, but its initial evolution remains poorly understood. Using experimental evolution, we show that key steps in this transition could have occurred quickly. We subjected the unicellular yeast Saccharomyces cerevisiae to an environment in ... | 10.1038/nrmicro3178 | This study shows the ease with which multicellular clusters can evolve de novo in S. cerevisiae under laboratory conditions. |
10.1073/pnas.191384198 | 125,166,784 | Spore formation by the bacterium Bacillus subtilis has long been studied as a model for cellular differentiation, but predominantly as a single cell. When analyzed within the context of highly structured, surface-associated communities (biofilms), spore formation was discovered to have heretofore unsuspected spatial or... | 10.1038/nrmicro3178 | This study is the first to recognize the complex multicellular behaviour of B. subtilis biofilms. |
10.1126/science.1086462 | 83,398,219 | Spore formation by the bacterium Bacillus subtilis is an elaborate developmental process that is triggered by nutrient limitation. Here we report that cells that have entered the pathway to sporulate produce and export a killing factor and a signaling protein that act cooperatively to block sister cells from sporulatin... | 10.1038/nrmicro3178 | This study shows that a subpopulation of B. subtilis communities can delay sporulation by PCD-mediated cannibalism of their siblings. |
10.1073/pnas.1216376110 | 104,157,696 | Many bacteria on earth exist in surface-attached communities known as biofilms. These films are responsible for manifold problems, including hospital-acquired infections and biofouling, but they can also be beneficial. Biofilm growth depends on the transport of nutrients and waste, for which diffusion is thought to be ... | 10.1038/nrmicro3178 | This paper reports on the importance of microchannels for the distribution of nutrients and the removal of waste products from biofilms. |
10.1128/jb.173.11.3318-3333.1991 | 19,315,319 | Myxococcus xanthus, a gram-negative bacterium, has a complex life cycle. In response to starvation, most cells in a population participate in the formation of multicellular aggregates (i.e., fruiting bodies) in which cells differentiate into spores. However, some cells do not enter aggregates. In this and the two accom... | 10.1038/nrmicro3178 | This study provides the first evidence that M. xanthus peripheral rods are a cell type that is distinct from vegetative cells and spores. |
10.1038/embor.2008.83 | 41,361,063 | Members of the soil‐dwelling prokaryotic genus Streptomyces produce many secondary metabolites, including antibiotics and anti‐tumour agents. Their formation is coupled with the onset of development, which is triggered by the nutrient status of the habitat. We propose the first complete signalling cascade from nutrient... | 10.1038/nrmicro3178 | This study provides the first evidence of a direct correlation between PCD and the onset of aerial growth and antibiotic production in S. coelicolor |
10.1111/j.1365-2958.1993.tb00955.x | 124,741,860 | Summaryf We report that the normally rod‐shaped bacterium Escherichia coli can form branched cells. These were found in strains in which chromosome replication or nucleoid segregation was disturbed, e.g. in minB mutants, intR1 strains, and in strains exhibiting stable DNA replication. Often, chromosome DNA was found to... | 10.1038/nrmicro3178 | This work shows that single mutations can introduce branching in populations of E. coli cells. |
10.1111/j.1365-2958.1994.tb01285.x | 124,783,985 | Summary A homologue of the bacterial cell division gene ftsZ was cloned from the filamentous bacterium Streptomyces coelicolor. The gene was located on the physical map of the chromosome at about ‘11 o'clock’ (in the vicinity of glkA, hisA and trpB). Surprisingly, a null mutant in which the 399‐codon ftsZ open reading ... | 10.1038/nrmicro3178 | This paper shows that ftsZ -null mutants of S. coelicolor are viable; this is the first example of a free-living bacterium that can grow without cell division. |
10.1073/pnas.72.5.1858 | 62,121,467 | A heat stable protein essentail for microtubule assembly has been isolated. This protein, which we designate tau (tau), is present in association with tubulin purified from porcine brain by repeated cycles of polymerization. Tau is separated from tubulin by ion exchange chromatography on phosphocellulose. In the absenc... | 10.1038/nrn.2015.1 | This study led to the discovery of tau protein as a microtubule-associated protein. |
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.2015.1 | This study demonstrates in a mouse model that tau is necessary for Aβ-induced excitotoxicity. |
10.1126/science.3122323 | 61,251,120 | Tau protein is a family of microtubule binding proteins, heterogeneous in molecular weight, that are induced during neurite outgrowth and are found prominently in neurofibrillary tangles in Alzheimer's disease. The predicted amino acid sequences of two forms of tau protein from mouse brain were determined from compleme... | 10.1038/nrn.2015.1 | This was the first study to sequence tau protein, highlighting its hydrophilic nature and the presence of pseudorepeats. |
10.1073/pnas.85.11.4051 | 103,643,489 | Screening of cDNA libraries prepared from the frontal cortex of an Alzheimer disease patient and from fetal human brain has led to isolation of the cDNA for a core protein of the paired helical filament of Alzheimer disease. The partial amino acid sequence of this core protein was used to design synthetic oligonucleoti... | 10.1038/nrn.2015.1 | This paper reveals the sequence of human tau protein and its presence in the core of tau filaments. |
10.1073/pnas.83.13.4913 | 20,681,934 | A monoclonal antibody to the microtubule-associated protein tau (tau) labeled some neurofibrillary tangles and plaque neurites, the two major locations of paired-helical filaments (PHF), in Alzheimer disease brain. The antibody also labeled isolated PHF that had been repeatedly washed with NaDodSO4. Dephosphorylation o... | 10.1038/nrn.2015.1 | This study demonstrates that tau protein is present in AD NFTs in a hyperphosphorylated state. |
10.1073/pnas.1504081112 | 83,416,468 | The structure, dynamic behavior, and spatial organization of microtubules are regulated by microtubule-associated proteins. An important microtubule-associated protein is the protein Tau, because its microtubule interaction is impaired in the course of Alzheimer’s disease and several other neurodegenerative diseases. H... | 10.1038/nrn.2015.1 | This paper found that tau binds at the interface between α-tubulin–β-tubulin heterodimers through residues including the motifs that are essential for the pathological aggregation of tau, suggesting that there is competition between physiological interaction and pathogenic misfolding. |
10.1111/j.1471-4159.2004.02611.x | 19,054,102 | Abstract Smearing from high‐molecular‐mass regions to low‐molecular‐mass regions on western blot is the most striking observation of the tau making up paired helical filaments in brain tissues affected by Alzheimer's disease. Because our previous study showed site‐specific deamidation/isomerization in the smeared tau i... | 10.1038/nrn.2015.1 | The authors show that site-specific deamidation or isomerization and non-enzymatic degradation of ageing tau facilitates tau aggregation and can cause the smearing of PHFs on western blot that is typical of AD-tau. |
10.1073/pnas.97.10.5129 | 20,782,813 | We have searched for a minimal interaction motif in τ protein that supports the aggregation into Alzheimer-like paired helical filaments. Digestion of the repeat domain with different proteases yields a GluC-induced fragment comprising 43 residues (termed PHF43), which represents the third repeat of τ plus some flankin... | 10.1038/nrn.2015.1 | This study identifies two hexapeptide motifs (VQIINK and VQIVYK) in tau R2 and R3, with high propensity for β-sheet structure responsible for tau aggregation. |
10.1073/pnas.0703676104 | 102,587,259 | Tau is a highly soluble protein, yet it aggregates abnormally in Alzheimer's disease. Here, we address the question of proteolytic processing of tau and the nucleation of aggregates by tau fragments. We show in neuronal cell models that fragments of the repeat domain of tau containing mutations of FTDP17 (frontotempora... | 10.1038/nrn.2015.1 | The authors show that truncation of tau can accelerate its aggregation in cells and that pro-aggregant truncated tau can seed the aggregation of endogenous tau. |
10.1126/science.1113694 | 103,827,988 | Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, ne... | 10.1038/nrn.2015.1 | This study describes a regulatable transgenic mouse line of tauopathy, showing that switching off the expression of the transgenic human tau can rescue cognitive deficits despite the continuing presence of tau aggregates, and implying that tau aggregates are not sufficient for neurodegeneration. |
10.1038/embor.2013.15 | 41,749,065 | Propagation of tau pathology is linked with progressive neurodegeneration, but the mechanism underlying trans‐synaptic spread of tau is unknown. We show that stimulation of neuronal activity, or AMPA receptor activation, induces tau release from healthy, mature cortical neurons. Notably, phosphorylation of extracellula... | 10.1038/nrn.2015.1 | This study demonstrates that the physiological release of tau can be stimulated by neuronal activity. |
10.1083/jcb.200707042 | 83,052,052 | Axon formation is the initial step in establishing neuronal polarity. We examine here the role of microtubule dynamics in neuronal polarization using hippocampal neurons in culture. We see increased microtubule stability along the shaft in a single neurite before axon formation and in the axon of morphologically polari... | 10.1038/nrn2631 | A key paper that described how local microtubule stabilization in one neurite is a crucial event in specifying neuronal polarization. |
10.1091/mbc.e07-09-0878 | 103,399,869 | Neurons express two different microtubule-severing proteins, namely P60-katanin and spastin. Here, we performed studies on cultured neurons to ascertain whether these two proteins participate differently in axonal branch formation. P60-katanin is more highly expressed in the neuron, but spastin is more concentrated at ... | 10.1038/nrn2631 | This study described different mechanisms used by microtubule severing proteins for regulating axon growth and collateral branching. |
10.1073/pnas.1316909110 | 62,211,962 | Significance Sex differences are of high scientific and societal interest because of their prominence in behavior of humans and nonhuman species. This work is highly significant because it studies a very large population of 949 youths (8–22 y, 428 males and 521 females) using the diffusion-based structural connectome o... | 10.1038/nrn.2017.61 | In this study, diffusion tensory imaging of nearly 1,000 human brains reveals sex differences in intra-hemispheric versus inter-hemispheric connectivity. |
10.1038/srep36916 | 20,363,801 | Abstract The mechanisms by which sex differences in the mammalian brain arise are poorly understood, but are influenced by a combination of underlying genetic differences and gonadal hormone exposure. Using a mouse embryonic neural stem cell (eNSC) model to understand early events contributing to sexually dimorphic bra... | 10.1038/nrn.2017.61 | This study shows that, in mouse embryonic stem cells, the transcriptional response to testosterone exposure is different in males versus females in both expression levels and numbers of genes responding. |
10.1073/pnas.1307091111 | 40,038,376 | Significance Women are more susceptible to multiple sclerosis (MS), but men demonstrate a more progressive disease course. In the MS model, experimental autoimmune encephalomyelitis (EAE), XX as compared with XY, conferred greater encephalitogenic responses. Here, we examined effects of sex chromosomes in the CNS using... | 10.1038/nrn.2017.61 | This study shows that the impact of chromosome complement on disease progression in an animal model of multiple sclerosis is opposite in peripheral versus central nervous system tissues. |
10.1111/j.1471-4159.2011.07630.x | 20,766,612 | J. Neurochem. (2012) 120 , 948–963. Abstract Microglia are the resident immune cells within the brain and their production of immune molecules such as cytokines and chemokines is critical for the processes of normal brain development including neurogenesis, axonal migration, synapse formation, and programmed cell death... | 10.1038/nrn.2017.61 | This is the first report of a sex difference in microglia, showing that males have higher numbers of microglia that are more activated at early stages and that there is a switch to female preponderance around puberty. |
10.1073/pnas.0906293106 | 58,597,925 | Sexually dimorphic brain nuclei underlie gender-specific neural functions and susceptibility to disease, but the developmental basis of dimorphisms is poorly understood. In these studies, we focused on the anteroventral periventricular nucleus (AVPV), a nucleus that is larger in females and critical for the female-typi... | 10.1038/nrn.2017.61 | This study shows that the higher cell death in the developing male AVPV is mediated by the suppression of the TNF receptor-associated cell survival pathway. |
10.1210/en.2009-0458 | 40,290,506 | Abstract The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is larger in volume and contains more cells in male than female mice. These sex differences depend on testosterone and arise from a higher rate of cell death during early postnatal life in females. There is a delay of several days between... | 10.1038/nrn.2017.61 | In this study, treatment with the HDAC inhibitor valproic acid prevented the increased cell survival that normally occurs in males resulting in a BNST volume similar to that of females. |
10.1038/ncomms10717 | 122,989,364 | Abstract Autism spectrum disorder (ASD) is more prevalent in males, and the mechanisms behind this sex-differential risk are not fully understood. Two competing, but not mutually exclusive, hypotheses are that ASD risk genes are sex-differentially regulated, or alternatively, that they interact with characteristic sexu... | 10.1038/nrn.2017.61 | Re-analyses of existing transcriptomic data sets reveal sex differences in the fetal brain, including an increase in microglia-associated and activated astrocyte-associated genes in males. The same pattern was observed in adult males with ASD compared to neurotypic males. |
10.1126/science.1636089 | 79,440,114 | Stress has been shown to impair subsequent learning. To determine whether stress would impair classical conditioning, rats were exposed to inescapable, low-intensity tail shock and subsequently classically conditioned under freely moving conditions with a brief periorbital shock unconditioned stimulus and a white noise... | 10.1038/nrn849 | This study showed that stress that impairs LTP in the hippocampus enhances hippocampus-independent, but cerebellum-dependent, delay eyeblink conditioning in rats. |
10.1126/science.287.5451.248 | 38,447,845 | The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mec... | 10.1038/nrn849 | A review of the role of the amygdala and its neurochemical systems in modulating memory consolidation in extra-amygdalar structures such as the hippocampus. |
10.1113/jphysiol.1973.sp010273 | 20,750,040 | 1. The after‐effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro‐electrodes in rabbits anaesthetized with urethane. 2. In fifteen out of eighteen rabbits the population response recorded from granule cells in the den... | 10.1038/nrn849 | The first demonstration of activity-dependent, long-lasting enhancement of synaptic efficacy. This study provided a synaptic model of learning and memory. |
10.1126/science.3563512 | 102,573,557 | A new class of excitatory premotor interneurons that are important in the generation of locomotion in the lamprey has now been described. In the isolated spinal cord, these neurons act simultaneously with their postsynaptic motoneurons during fictive swimming. They are small and numerous, and they monosynaptically exci... | 10.1038/nrn.2016.9 | The first demonstration of excitatory locomotor-related neurons in the lamprey spinal cord. |
10.1113/jphysiol.2008.166942 | 104,214,973 | Electrical coupling is important in rhythm generating systems. We examine its role in circuits controlling locomotion in a simple vertebrate model, the young Xenopus tadpole, where the hindbrain and spinal cord excitatory descending interneurons (dINs) that drive and maintain swimming have been characterised. Using sim... | 10.1038/nrn.2016.9 | This study demonstrated the presence and connectivity of a network of excitatory neurons in the brainstem and spinal cord underlying rhythm generation in young tadpoles. |
10.1113/jphysiol.1985.sp015694 | 27,030,289 | The neuronal basis of the excitation received by motoneurones during swimming in curarized Xenopus embryos has been investigated further. Extracellular stimulation of axons in the fibre tracts of the spinal cord has been used to evoke unitary excitatory post‐synaptic potentials (p.s.p.s) in motoneurones. The p.s.p.s. h... | 10.1038/nrn.2016.9 | Electrophysiological demonstration of excitatory last-order neurons in the young tadpole spinal cord. |
10.1073/pnas.1115377109 | 16,793,937 | Neural circuits in the spinal cord transform instructive signals from the brain into well-coordinated locomotor movements by virtue of rhythm-generating components. Although evidence suggests that excitatory interneurons are the essence of locomotor rhythm generation, their molecular identity and the assessment of thei... | 10.1038/nrn.2016.9 | Using laser ablation of neurons in the larval zebrafish, this study show that the V2a neurons in zebrafish larvae are involved in producing swimming. |
10.1073/pnas.1419045111 | 123,874,789 | Significance Terrestrial locomotion is thought to be generated by the actions of a circuit of interconnected interneurons (central pattern generator) in the spinal cord that drive the patterned activity of pools of motor neurons, causing sequential contraction of dozens of leg muscles. Sensory feedback exerts a strong ... | 10.1038/nrn.2016.9 | This study shows that mouse locomotor patterns are significantly changed after genetic elimination of proprioceptive feedback from muscle spindles and GTOs. Activity in muscle spindles alone affects swing-stance transition and the combination of muscle spindles and GTOs affects stance-swing phase transitions. |
10.1073/pnas.1324118111 | 38,452,773 | Significance To investigate the organizational principles of human brain development, we analyzed cerebral structural connectivity in the period leading up to the time of normal birth. We found that a “rich club” of interconnected cortical hubs previously reported in adults is present by 30 wk gestation. From mid to la... | 10.1038/nrn.2018.1 | This paper presents an early study of the white-matter connectome in preterm and term infants, demonstrating that major hubs are already present at 30 weeks gestational age. |
10.1126/science.1077066 | 122,410,560 | Human infants begin to acquire their native language in the first months of life. To determine which brain regions support language processing at this young age, we measured with functional magnetic resonance imaging the brain activity evoked by normal and reversed speech in awake and sleeping 3-month-old infants. Left... | 10.1038/nrn.2018.1 | This is an important early task-based functional imaging study that demonstrated that adult language areas are already active in 2-month-olds to 3 month-olds. |
10.1073/pnas.0704380104 | 103,811,414 | In the absence of any overt task performance, it has been shown that spontaneous, intrinsic brain activity is expressed as systemwide, resting-state networks in the adult brain. However, the route to adult patterns of resting-state activity through neuronal development in the human brain is currently unknown. Therefore... | 10.1038/nrn.2018.1 | This study delineates resting-state functional networks in human infants through the use of a cohort of sedated premature infants. |
10.1073/pnas.95.7.3943 | 38,282,554 | Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes vir... | 10.1038/nrmicro884 | First detailed description of how specific loss of genetic information enhances bacterial virulence. |
10.1046/j.1462-2920.2003.00515.x | 23,655,521 | Summary We screened a Thermotoga sp. strain RQ2 lambda library for genes present in that strain but absent from the closely related completely sequenced relative Thermotoga maritima strain MSB8, by using probes generated in an earlier genomic subtraction study. Five lambda insert fragments were sequenced, containing, r... | 10.1038/nrmicro884 | Describes the analysis of genome variability in the hyperthermophilic organism Thermotoga maritima by the identification of strain-specific genomic regions using genomic subtraction. |
10.1046/j.1462-2920.2003.00400.x | 40,552,679 | Summary The genetic structure of two Ralstonia spp., strain JS705 and strain JS745, isolated from the same groundwater aquifer, was characterized with respect to the degradation capacities for toluene and chlorobenzene degradation. Cosmid library construction, cloning, DNA sequencing and mating experiments indicated th... | 10.1038/nrmicro884 | Describes how metabolic pathway evolution can occur under natural conditions in a few steps through the activity of IS elements and formation of a genomic island. |
10.1242/dev.127.20.4383 | 41,774,794 | The development of the enteric nervous system is dependent upon the actions of glial cell line-derived neurotrophic factor (GDNF) on neural crest-derived precursor cells in the embryonic gut. GDNF treatment of cultured enteric precursor cells leads to an increase in the number of neurons that develop and/or survive. He... | 10.1038/nrn812 | The first demonstration of endogenous soluble GFRα1, which is released by cultured gut cells in a developmentally regulated manner. |
10.1101/gad.205001 | 82,969,419 | The RET receptor tyrosine kinase has a critical role in kidney organogenesis and the development of the enteric nervous system. Two major isoforms, RET9 and RET51, differ in the amino acid sequence of the C-terminal tail as a result of alternative splicing. To determine the roles of these isoforms in vivo, we used targ... | 10.1038/nrn812 | Using a knock-in approach, this study shows that the short RET isoform mediates most of the biological activities of RET in vivo |
10.1242/dev.127.22.4877 | 83,366,794 | The neurotrophic factors that influence the development and function of the parasympathetic branch of the autonomic nervous system are obscure. Recently, neurturin has been found to provide trophic support to neurons of the cranial parasympathetic ganglion. Here we show that GDNF signaling via the RET/GFR(alpha)1 compl... | 10.1038/nrn812 | Together with reference 39 , this paper indicates an early role for GDNF in parasympathetic precursor development. |
10.1126/science.287.5457.1489 | 62,152,775 | The molecular control of self-renewal and differentiation of stem cells has remained enigmatic. Transgenic loss-of-function and overexpression models now show that the dosage of glial cell line–derived neurotrophic factor (GDNF), produced by Sertoli cells, regulates cell fate decisions of undifferentiated spermatogonia... | 10.1038/nrn812 | The first demonstration that GDNF regulates spermatogonia differentiation in vivo |
10.1126/science.290.5489.124 | 59,249,239 | Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line–derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathi... | 10.1038/nrn812 | Shows that GDNF supresses neuropathic pain, possibly by preventing the upregulation of Na + channel subunits. |
10.1261/rna.041178.113 | 20,697,460 | N 6 -methyladenosine (m 6 A) is the most abundant modification in mammalian mRNA and long noncoding RNA (lncRNA). Recent discoveries of two m 6 A demethylases and cell-type and cell-state-dependent m 6 A patterns indicate that m 6 A modifications are highly dynamic and likely play important biological roles for RNA aki... | 10.1038/nsmb.3162 | Probed the m 6 A status at single-nucleotide resolution and revealed fractional m 6 A modification in mRNA and lncRNA |
10.1523/jneurosci.17-13-05046.1997 | 26,991,662 | The adult mammalian subventricular zone (SVZ) contains stem cells that give rise to neurons and glia. In vivo , SVZ progeny migrate 3–8 mm to the olfactory bulb, where they form neurons. We show here that the SVZ of the lateral wall of the lateral ventricles in adult mice is composed of neuroblasts, glial cells, and a ... | 10.1038/nrn2216 | Detailed account of the anatomy and cellular composition of the rodent SVZ. |
10.1073/pnas.1532244100 | 41,128,147 | Neurogenesis has recently been observed in the adult human brain, suggesting the possibility of endogenous neural repair. However, the augmentation of neurogenesis in the adult human brain in response to neuronal cell loss has not been demonstrated. This study was undertaken to investigate whether neurogenesis occurs i... | 10.1038/nrn2216 | The first demonstration of neurogenesis and progenitor cell proliferation in the human SVZ in response to neuropathology. |
10.1523/jneurosci.2344-04.2004 | 123,258,211 | We examined the cell proliferative, neurogenic, and behavioral effects of transforming growth factor α (TGFα) in a 6-OHDA Parkinson's disease model when compared with naive rats. Intrastriatal TGFα infusion induced significant proliferation, hyperplastic nodules, and substantial migratory waves of nestin-positive proge... | 10.1038/nrn2216 | Demonstrates how a mitogenic factor can cause remarkable proliferation and migration of progenitor cells bilaterally despite a unilateral administration. |
10.1161/01.str.0000166197.94147.59 | 82,662,449 | Background and Purpose— The subventricular zone in the adult brain is identified as an endogenous resource of neuronal precursors that can be recruited to adjacent lesioned areas. The hypothesis was tested that postischemic environmental enrichment might enhance subventricular zone cell genesis. Methods— A cortical inf... | 10.1038/nrn2216 | Shows that altering the living environment of the mammal has a neurogenic effect on its neurological outcome after a middle-cerebral-artery-occlusion-induced stroke. |
10.1002/cne.901240303 | 20,644,694 | Abstract In the autoradiograms of young rats injected with thymidine‐H 3 many of the granule cells of the dentate gyrus were found labeled. The number of labeled cells declined rapidly with increased age at the time of injection. Histological studies showed the presence in young rats of a large germinal matrix of mitot... | 10.1038/nrn2216 | One of the earliest studies on adult neurogenesis; important technique advances are displayed in which tritiated thymidine, together with histological techniques, reveal adult neurogenesis in the adult rodent brain. |
10.1177/1073858403252680 | 19,479,703 | The persistence of neurogenesis in the adult mammalian forebrain suggests that endogenous precursors may be a potential source for neuronal replacement after injury or neurodegeneration. Limited knowledge exists, however, regarding the normal function of neurogenesis in the adult and its alteration by brain injury. Neu... | 10.1038/nrn2216 | Review of stroke and epilepsy studies on proliferation in the germinal zones in rodent brains. |
10.1101/122648 | 112,395,280 | Abstract Cpf1 is a single RNA-guided endonuclease of class 2 type V CRISPR-Cas system, emerging as a powerful genome editing tool 1,2 . To provide insight into its DNA targeting mechanism, we have determined the crystal structure of Francisella novicida Cpf1 (FnCpf1) in complex with the triple strand R-loop formed afte... | 10.1038/nsmb.3486 | First structure of the R loop of Cpf1 after cleavage revealing the different paths taken by the two DNA strands toward the catalytic center |
10.1126/science.aad8282 | 39,325,672 | CRISPR Cas9 molecular scissors The CRISPR-associated (Cas) protein Cas9 is a molecular scissor for cutting DNA. The first step in the cutting reaction is the RNA-guided unwinding of the DNA double helix. Jiang et al. determined the structures of Cas9 bound to DNA unwound by the targeting RNA (see the Perspective by Che... | 10.1038/nsmb.3486 | Crystal structure of the Cas9 R loop before cleavage and cryo-EM structure of Cas9 in complex with a long DNA target revealing the position of the catalytic domains RuvC and HNH and the enter and exit point of the DNA in Cas9 |
10.1073/pnas.1018217108 | 45,477,324 | Evolutionarily conserved hedgehog proteins orchestrate the patterning of embryonic tissues, and dysfunctions in their signaling can lead to tumorigenesis. In vertebrates, Sonic hedgehog (Shh) is essential for nervous system development, but the mechanisms underlying its action remain unclear. Early electrical activity ... | 10.1038/nrn3154 | This study shows that the concentration of the morphogen SHH controls the frequency of calcium spikes that regulate neurotransmitter respecification. |
10.1152/jn.00762.2007 | 47,072,401 | Specification of neurotransmitter phenotype is critical for neural circuit development and is influenced by intrinsic and extrinsic factors. Recent findings in rat hypothalamus in vitro suggest the role of neurotransmitter glutamate in the regulation of cholinergic phenotype. Here we extended our previous studies on th... | 10.1038/nrn3154 | This paper demonstrated respecification of choline acetyltransferase expression in hypothalamic neurons following blockade or inactivation of NMDA receptors. |
10.1073/pnas.0607450104 | 18,615,555 | Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because a... | 10.1038/nrn3154 | This paper demonstrated the presence of non-cholinergic postsynaptic currents following activity-dependent neurotransmitter respecification in the embryonic spinal cord. |
10.1152/jn.2002.87.5.2562 | 113,581,722 | GABAergic transmission in the mossy fiber (MF) projection of the hippocampus is not normally detected in the rat. However, seizures induce simultaneous glutamatergic and GABAergic transmission in this projection, which coincides with an overexpression of GAD 67 and vesicular GABA transporter (VGAT) mRNA in the dentate ... | 10.1038/nrn3154 | This study demonstrated activity-dependent neurotransmitter switching in the adult rat brain. |
10.1073/pnas.0500530102 | 102,682,986 | Acetylcholine is the main neurotransmitter at the mammalian neuromuscular junction (NMJ) where nicotinic acetylcholine receptors mediate the signaling between nerve terminals and muscle fibers. We show that under glutamatergic transmission, rat NMJ switches from cholinergic type synapse to glutamatergic synapse. Connec... | 10.1038/nrn3154 | This study illustrated the plasticity of neurotransmitter receptor expression at the adult mammalian neuromuscular junction. |
10.1038/jcbfm.1987.127 | 18,801,886 | We have tested whether small intraischemic variations in brain temperature influence the outcome of transient ischemia. To measure brain temperature, a thermocouple probe was placed stereotaxically into the left dorsolateral striatum of rats prior to 20 min of four-vessel occlusion. Rectal temperature was maintained at... | 10.1038/nrn3174 | This study was the first to show that relatively small decreases in temperature resulted in remarkable neuroprotection and led to a resurgence of interest in the field of therapeutic hypothermia. |
10.1097/00004647-199907000-00003 | 124,341,309 | Considerable controversy exists about whether postischemic hypothermia can permanently salvage hippocampal CA 1 neurons or just postpone injury. Studies of very brief cooling in rat have found transient benefit, whereas experiments in gerbil using protracted hypothermia report lasting protection. This discrepancy might... | 10.1038/nrn3174 | This study demonstrated remarkable and durable neuroprotection by therapeutic cooling in a global cerebral ischaemia model, even when cooling was started as late as 6 h from ischaemia onset. |
10.1038/sj.jcbfm.9600540 | 101,086,481 | Mild or moderate hypothermia is generally thought to block all changes in signaling events that are detrimental to ischemic brain, including ATP depletion, glutamate release, Ca 2+ mobilization, anoxic depolarization, free radical generation, inflammation, blood—brain barrier permeability, necrotic, and apoptotic pathw... | 10.1038/nrn3174 | This paper provides a comprehensive description of the protective mechanisms of hypothermia from laboratory data to facilitate clinical translation of therapeutic hypothermia. |
10.1038/jcbfm.2011.33 | 121,920,886 | Therapeutic hypothermia promotes protection after traumatic brain injury (TBI). The mechanisms underlying hypothermic protection are multifactorial and may include the modulation of microRNA (miRNA) expression after trauma. We utilized microarrays to examine the effects of posttraumatic hypothermia on the expression of... | 10.1038/nrn3174 | This paper demonstrated that several miRNAs are also extremely temperature sensitive (in addition to many well-known temperature-sensitive mRNAs). |
10.1038/jcbfm.2011.25 | 121,916,692 | Delayed hypothermia salvages CA1 neurons from global ischemic injury. However, the effects of this potent neuroprotectant on endogenous repair mechanisms, such as neurogenesis, have not been clearly examined. In this study, we quantified and phenotyped newly generated cells within the hippocampus following untreated an... | 10.1038/nrn3174 | This paper showed that prolonged hypothermia positively interacts with post-ischaemic repair processes, such as neurogenesis, resulting in improved functional outcome. |
10.2217/14796708.2.4.435 | 21,743,590 | Therapeutic hypothermia has gained considerable interest, given that it appears to improve neurological outcomes in patients who have suffered cardiac arrest. In spite of its remarkable beneficial effect, the mechanism of protection by brain cooling is still unclear. Hypothermia is known to alter gene expression; thus,... | 10.1038/nrn3174 | This review covers the spectrum of gene expression changes resulting from hypothermia, including temperature-sensitive RNAs. |
10.1073/pnas.051633998 | 67,570,932 | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the pro-apoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuronal apoptosis. In adult ... | 10.1038/nrn1100 | Direct evidence indicating that the pro-PCD protein Bax is essential in MPTP-induced neurodegeneration. |
10.1002/ana.10350 | 82,280,742 | Abstract Drugs currently used for patients with Parkinson's disease provide temporary relief of symptoms but do not halt or slow the underlying neurodegenerative disease process. Increasing evidence suggests that neurons die in Parkinson's disease by a process called apoptosis, which may be triggered by mitochondrial i... | 10.1038/nrn1100 | This study demonstrates that intraperitoneal injections of two p53 inhibitors attenuates Bax upregulation, improves motor function, reduces damage to nigrostriatal DA neurons and reduces depletion of DA and its metabolites in MPTP-treated mice. |
10.1073/pnas.181182298 | 59,680,387 | Increasing evidence suggests that apoptosis may be the underlying cell death mechanism in the selective loss of dopaminergic neurons in Parkinson's disease. Because the inhibition of caspases provides only partial protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP + ) m... | 10.1038/nrn1100 | Direct evidence of the involvement of the JNK/Jun pathway in MPTP-induced apoptotic cell death. |
10.1073/pnas.191107398 | 65,345,993 | Adeno-associated virus (AAV) vector delivery of an Apaf-1-dominant negative inhibitor was tested for its antiapoptotic effect on degenerating nigrostriatal neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. The wild-type caspase recruitment domain of Apaf-1 was used as a domi... | 10.1038/nrn1100 | Using viral vectors to deliver an Apaf1 inhibitor, this paper shows the instrumental role of the mitochondrial PCD pathway in MPTP-mediated neurodegeneration. |
10.1126/science.277.5325.559 | 67,570,575 | Mutations in the gene encoding copper/zinc superoxide dismutase enzyme produce an animal model of familial amyotrophic lateral sclerosis (FALS), a fatal disorder characterized by paralysis. Overexpression of the proto-oncogene bcl-2 delayed onset of motor neuron disease and prolonged survival in transgenic mice express... | 10.1038/nrn1100 | Demonstration that overexpression of Bcl2 mitigates neurodegeneration and prolongs survival in a transgenic mouse model of familial ALS. |
10.1126/science.288.5464.335 | 38,370,814 | Mutations in the copper/zinc superoxide dismutase (SOD1) gene produce an animal model of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a subst... | 10.1038/nrn1100 | Demonstration that the irreversible broad-caspase inhibitor zVAD-fmk attenuates mutant SOD1-mediated cell death in a transgenic mouse model of ALS, resulting in a delayed disease onset and mortality. |
10.1126/science.285.5435.1870 | 62,065,416 | Long-term potentiation of synaptic transmission in the hippocampus is the leading experimental model for the synaptic changes that may underlie learning and memory. This review presents a current understanding of the molecular mechanisms of this long-lasting increase in synaptic strength and describes a simple model th... | 10.1038/nrn753 | Summarizes extensive work that points to a postsynaptic site for the expression of LTP in the CA1 pyramidal cells of the hippocampus. |
10.1073/pnas.95.8.4732 | 81,511,934 | The molecular mechanisms underlying long-term potentiation in the hippocampus have received much attention because of the likely functional importance of synaptic plasticity for information storage and the development of neuronal connectivity. Surprisingly, it remains unclear whether activity modifies the strength of i... | 10.1038/nrn753 | The only report, so far, of synaptic plasticity at a single hippocampal synapse. It shows that plasticity occurs as a large and discrete change, supporting the idea that a switch-like process controls plasticity. |
10.1126/science.276.5321.2042 | 38,394,704 | Long-term potentiation (LTP), a cellular model of learning and memory, requires calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32 labeling of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)–type glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic transmission... | 10.1038/nrn753 | An elegant study showing changes in CaMKII during LTP and consequent changes in AMPA receptors. |
10.1126/science.279.5352.870 | 103,695,198 | The calcium-calmodulin–dependent kinase II (CaMKII) is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)–dependent activity, CaMKII can undergo autophosphorylation, resulting in CaM-independent activity. A point mutation was introduced into the αCaMK... | 10.1038/nrn753 | Shows the powerful physiological and behavioural effects of a single amino-acid change in CaMKII that prevents Thr286 phosphorylation. |
10.1073/pnas.92.24.11175 | 20,389,684 | Ca(2+)-sensitive kinases are thought to play a role in long-term potentiation (LTP). To test the involvement of Ca2+/calmodulin-dependent kinase II (CaM-K II), truncated, constitutively active form of this kinase was directly injected into CA1 hippocampal pyramidal cells. Inclusion of CaM-K II in the recording pipette ... | 10.1038/nrn753 | A classic paper that shows the close correspondence of LTP to the potentiation that can be produced by CaMKII. |
10.1126/science.274.5289.972 | 60,330,325 | Whole-cell recordings from optic tectal neurons in Xenopus tadpoles were used to study the maturation of a glutamatergic synapse. The first glutamatergic transmission is mediated only by N -methyl-D-aspartate (NMDA) receptors and is silent at resting potentials. More mature synapses acquire transmission by α-amino-3-hy... | 10.1038/nrn753 | The first in vivo demonstration of silent synapses and their maturation by the addition of AMPA-receptor-mediated responses through a CaMKII-dependent mechanism. |
10.1126/science.279.5348.222 | 38,238,701 | Calcium-calmodulin–dependent protein kinase II (CaMKII) promotes the maturation of retinotectal glutamatergic synapses in Xenopus . Whether CaMKII activity also controls morphological maturation of optic tectal neurons was tested using in vivo time-lapse imaging of single neurons over periods of up to 5 days. Dendritic... | 10.1038/nrn753 | This and the following paper provide clear evidence for CaMKII-mediated structural plasticity during circuit development. |
10.1126/science.1321493 | 19,706,332 | Although long-term potentiation (LTP) has been studied as the mechanism for hippocampus-dependent learning and memory, evidence for this hypothesis is still incomplete. The mice with a mutation in the α-calcium-calmodulin-dependent kinase II (α-CaMKII), a synaptic protein enriched in the hippocampus, are appropriate fo... | 10.1038/nrn753 | This groundbreaking paper established the field of mouse behavioural genetics and, together with work in flies, showed a role for CaMKII in complex animal behaviour. |
10.1126/science.274.5293.1678 | 123,191,992 | One of the major limitations in the use of genetically modified mice for studying cognitive functions is the lack of regional and temporal control of gene function. To overcome these limitations, a forebrain-specific promoter was combined with the tetracycline transactivator system to achieve both regional and temporal... | 10.1038/nrn753 | The first attempt to regulate the expression of CaMKII shows that CaMKII activity is required for both learning and recall. |
10.1073/pnas.0500136102 | 83,161,831 | The histone code hypothesis holds that covalent posttranslational modifications of histone tails are interpreted by the cell to yield a rich combinatorial transcriptional output. This hypothesis has been the subject of active debate in the literature. Here, we investigated the combinatorial complexity of the acetylatio... | 10.1038/nsmb.2470 | This work shows that cumulative lysine charge neutralization is the predominant determinant of transcriptional effects mediated by histone H4 tail acetylation. |
10.1101/gr.136366.111 | 83,285,482 | Gene regulation at functional elements (e.g., enhancers, promoters, insulators) is governed by an interplay of nucleosome remodeling, histone modifications, and transcription factor binding. To enhance our understanding of gene regulation, the ENCODE Consortium has generated a wealth of ChIP-seq data on DNA-binding pro... | 10.1038/nsmb.2470 | This work shows that there are notably few patterns of histone modifications around transcription factor binding sites in the human genome. |
10.1126/science.2937147 | 104,149,216 | Human color vision is based on three light-sensitive pigments. The isolation and sequencing of genomic and complementary DNA clones that encode the apoproteins of these three pigments are described. The deduced amino acid sequences show 41 ± 1 percent identity with rhodopsin. The red and green pigments show 96 percent ... | 10.1038/nrn2094 | A genetic analysis of human photopigments that underpins our knowledge of the evolution of colour vision. |
10.1113/jphysiol.1984.sp015499 | 124,931,995 | This paper introduces a new technique for the analysis of the chromatic properties of neurones, and applies it to cells in the lateral geniculate nucleus (l.g.n.) of macaque. The method exploits the fact that for any cell that combines linearly the signals from cones there is a restricted set of lights to which it is e... | 10.1038/nrn2094 | A quantitative analysis of responses of LGN neurons to chromatic modulation shows two distinct chromatically opponent groups. |
10.1523/jneurosci.10-02-00649.1990 | 124,166,161 | We measured the responses of 305 neurons in striate cortex to moving sinusoidal gratings modulated in chromaticity and luminance about a fixed white point. Stimuli were represented in a 3-dimensional color space defined by 2 chromatic axes and a third along which luminance varied. With rare exceptions the chromatic pro... | 10.1038/nrn2094 | A comparison of chromatic properties of V1 neurons with those in the LGN, showing how colour signals are transformed. |
10.1523/jneurosci.07-11-03416.1987 | 62,511,551 | Physiological and anatomical findings in the primate visual system, as well as clinical evidence in humans, suggest that different components of visual information processing are segregated into largely independent parallel pathways. Such a segregation leads to certain predictions about human vision. In this paper we d... | 10.1038/nrn2094 | Outlines the strong hypothesis of vision as a serial, parallel and hierarchical process. |
10.1073/pnas.86.24.10148 | 60,513,338 | By using antibodies directed against gap junction proteins of liver (connexins 26 and 32) and heart (connexin 43), we have localized immunoreactivity to specific cell types in frozen sections of adult rodent brains. Connexin 32 reactivity was found in oligodendrocytes and also in a few neurons, whereas reactivity to co... | 10.1038/nrn2757 | The first immunological and developmental study of the distribution of three connexins in the various cell populations of the rodent brain. |
10.1126/science.1164022 | 19,583,599 | Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucos... | 10.1038/nrn2757 | Demonstration of the role of gap junctions in metabolic supply of neurons by astrocytes. |
10.1523/jneurosci.22-01-00183.2002 | 104,238,683 | Protoplasmic astrocytes are increasingly thought to interact extensively with neuronal elements in the brain and to influence their activity. Recent reports have also begun to suggest that physiologically, and perhaps functionally, diverse forms of these cells may be present in the CNS. Our current understanding of ast... | 10.1038/nrn2757 | Demonstration of the true morphology of protoplasmic astrocytes by three-dimensional analysis of dye injection in fixed tissue and definition of individual astrocytic domains. |
10.1126/science.1169096 | 83,038,042 | Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium... | 10.1038/nrn2757 | In vivo demonstration of the propagation of intercellular Ca 2+ waves in astrocytes studied in a mouse model of Alzheimer's disease. |
10.1523/jneurosci.3827-07.2008 | 81,795,344 | Preconditioning is an endogenous mechanism in which a nonlethal exposure increases cellular resistance to subsequent additional severe injury. Here we show that connexin 43 (Cx43) plays a key role in protection afforded by preconditioning. Cx43 null mice were insensitive to hypoxic preconditioning, whereas wild-type li... | 10.1038/nrn2757 | Demonstration of the role of Cx43 hemichannels in the neuroprotection afforded by hypoxic preconditioning. |
10.1073/pnas.91.3.836 | 21,960,358 | The atomic force microscope has the potential to monitor structural changes of a biological system in its native environment. To correlate them with the biological function at a molecular level, high lateral and vertical resolution are required. Here we demonstrate that the atomic force microscope is capable of imaging... | 10.1038/nrmicro905 | Early work showing that high-resolution AFM images of native proteins correlate remarkably well with 3-D models determined by established structural methods. |
10.1128/jb.181.17.5350-5354.1999 | 101,176,949 | ABSTRACT Atomic force microscopy (AFM) has been used to probe, under physiological conditions, the surface ultrastructure and molecular interactions of spores of the filamentous fungus Phanerochaete chrysosporium . High-resolution images revealed that the surface of dormant spores was uniformly covered with rodlets hav... | 10.1038/nrmicro905 | The surface of hydrated P. chrysosporium spores was viewed by AFM to a resolution of a few nanometres. |
10.1128/jb.186.11.3286-3295.2004 | 45,570,314 | ABSTRACT The growth and division of Staphylococcus aureus was monitored by atomic force microscopy (AFM) and thin-section transmission electron microscopy (TEM). A good correlation of the structural events of division was found using the two microscopies, and AFM was able to provide new additional information. AFM was ... | 10.1038/nrmicro905 | A combination of AFM imaging of samples in aqueous solution and thin-section transmission electron microscopy was used to investigate the changes in the bacterial cell wall as the cells grow and divide. |
10.1128/jb.178.11.3106-3112.1996 | 122,704,886 | We describe a technique for probing the elastic properties of biological membranes by using an atomic force microscope (AFM) tip to press the biological material into a groove in a solid surface. A simple model is developed to relate the applied force and observed depression distance to the elastic modulus of the mater... | 10.1038/nrmicro905 | A pioneering work that uses AFM to quantitatively measure the elastic properties of a bacterial sheath in relation to its function. |
10.1126/science.275.5304.1295 | 40,663,353 | Recent developments in piconewton instrumentation allow the manipulation of single molecules and measurements of intermolecular as well as intramolecular forces. Dextran filaments linked to a gold surface were probed with the atomic force microscope tip by vertical stretching. At low forces the deformation of dextran w... | 10.1038/nrmicro905 | Pioneering study demonstrating how the AFM tip can be used in the force spectroscopy mode to pull on single macromolecules, providing new insights into their mechanical and conformational properties. |
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