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 |
|---|---|---|---|---|
10.1126/science.1160033 | 62,110,888 | The bacterium Proteus mirabilis is capable of movement on solid surfaces by a type of motility called swarming. Boundaries form between swarming colonies of different P. mirabilis strains but not between colonies of a single strain. A fundamental requirement for boundary formation is the ability to discriminate between... | 10.1038/nrmicro3185 | This study identified a single genetic locus that is linked to self-recognition in P. mirabilis , which is an important bacterial model for social behaviour. |
10.1111/j.1365-2958.2004.04123.x | 45,319,810 | Summary Edwardsiella tarda is an important cause of haemorrhagic septicaemia in fish and also of gastro‐ and extraintestinal infections in humans. Using a combination of comparative proteomics and Tn phoA mutagenesis, we have identified five proteins that may contribute to E . tarda PPD130/91 pathogenesis. Lowered prot... | 10.1038/nrmicro3185 | This study reports for the first time that the export of Hcp depends on genes within a conserved cluster. |
10.1126/science.1115109 | 104,396,148 | Bacteria have developed mechanisms to communicate and compete with each other for limited environmental resources. We found that certain Escherichia coli , including uropathogenic strains, contained a bacterial growth-inhibition system that uses direct cell-to-cell contact. Inhibition was conditional, dependent upon th... | 10.1038/nrmicro3185 | This paper reports the discovery of CDI in E. coli |
10.1073/pnas.93.19.10268 | 80,117,087 | The recently sequenced genome of the parasitic bacterium Mycoplasma genitalium contains only 468 identified protein-coding genes that have been dubbed a minimal gene complement [Fraser, C.M., Gocayne, J.D., White, O., Adams, M.D., Clayton, R.A., et al. (1995) Science 270, 397-403]. Although the M. genitalium gene compl... | 10.1038/nrmicro751 | The first attempt to derive a minimal gene-set using a comparative-genomic computational approach (comparing the gene sets of H. influenzae and M. genitalium , the only two bacterial genomes sequenced at the time). |
10.1128/jb.185.19.5673-5684.2003 | 101,089,687 | ABSTRACT Defining the gene products that play an essential role in an organism's functional repertoire is vital to understanding the system level organization of living cells. We used a genetic footprinting technique for a genome-wide assessment of genes required for robust aerobic growth of Escherichia coli in rich me... | 10.1038/nrmicro751 | A thorough experimental and theoretical analysis of the essential genes of E. coli |
10.1126/science.286.5447.2165 | 41,459,533 | Mycoplasma genitalium with 517 genes has the smallest gene complement of any independently replicating cell so far identified. Global transposon mutagenesis was used to identify nonessential genes in an effort to learn whether the naturally occurring gene complement is a true minimal genome under laboratory growth cond... | 10.1038/nrmicro751 | The first attempt to identify essential genes at the whole-genome level. |
10.1073/pnas.95.12.6854 | 104,069,313 | A genetic annealing model for the universal ancestor of all extant life is presented; the name of the model derives from its resemblance to physical annealing. The scenario pictured starts when “genetic temperatures” were very high, cellular entities (progenotes) were very simple, and information processing systems wer... | 10.1038/nrmicro751 | A profound discussion of the nature of the last universal common ancestor. The two principal ideas are that the last universal common ancestor did not comprise a unique species, but rather a community of organisms that engaged in rampant gene exchange, and that the different cellular systems 'crystallized' asynchronous... |
10.1101/gr.176501 | 19,788,607 | In the course of evolution, genomes are shaped by processes like gene loss, gene duplication, horizontal gene transfer, and gene genesis (the de novo origin of genes). Here we reconstruct the gene content of ancestral Archaea and Proteobacteria and quantify the processes connecting them to their present day representat... | 10.1038/nrmicro751 | The first earnest attempt to construct evolutionary scenarios on the basis of genome comparisons, taking into account gene loss and HGT. |
10.1073/pnas.1632870100 | 18,578,736 | It has been suggested that horizontal gene transfer (HGT) is the “essence of phylogeny.” In contrast, much data suggest that this is an exaggeration resulting in part from a reliance on inadequate methods to identify HGT events. In addition, the assumption that HGT is a ubiquitous influence throughout evolution is ques... | 10.1038/nrmicro751 | A useful counterpoint to reference 46. Makes the argument that numerous apparent cases of HGT are artefacts. |
10.1091/mbc.e09-07-0596 | 62,630,258 | Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the... | 10.1038/nrn3445 | This paper is a detailed platinum replica electron microscopy study that characterizes the organization of the subsynaptic actin cytoskeleton in dendritic spines and dendritic filopodia using dissociated neuron cultures. |
10.1083/jcb.143.7.1899 | 59,302,826 | Unlike wild-type mouse melanocytes, where melanosomes are concentrated in dendrites and dendritic tips, melanosomes in dilute (myosin Va−) melanocytes are concentrated in the cell center. Here we sought to define the role that myosin Va plays in melanosome transport and distribution. Actin filaments that comprise a cor... | 10.1038/nrn3445 | Using myosin Va-deficient melanocytes, this study provides the first evidence for myosin Va regulating the peripheral accumulation of melanosomes by a mechanism known as the 'cooperative capture model'. |
10.1083/jcb.200410091 | 18,273,903 | Myosin VI (Myo6) is an actin-based motor protein implicated in clathrin-mediated endocytosis in nonneuronal cells, though little is known about its function in the nervous system. Here, we find that Myo6 is highly expressed throughout the brain, localized to synapses, and enriched at the postsynaptic density. Myo6-defi... | 10.1038/nrn3445 | This study shows that myosin VI forms a complex with AMPARs and that the myosin is important for stimulated AMPAR endocytosis and normal synapse numbers. |
10.1113/jphysiol.2013.265033 | 123,119,605 | Key points The temporal signals mediated by postsynaptic kainate receptors differ depending on subunit composition (GluK1–GluK5) and the presence of the auxiliary subunits Neto1 and Neto2. In ground squirrel retina, four anatomical types of Off bipolar cells can be divided into two functional groups, cb1a/b and cb3a/b,... | 10.1038/nrn3783 | A detailed dissection of how OFF bipolar cell types (in the ground squirrel) inherit different kinetic properties based on differential expression of glutamate receptor types on their dendrites. |
10.1073/pnas.0912730107 | 62,420,150 | An essential step in intricate visual processing is the segregation of visual signals into ON and OFF pathways by retinal bipolar cells (BCs). Glutamate released from photoreceptors modulates the photoresponse of ON BCs via metabotropic glutamate receptor 6 (mGluR6) and G protein (Go) that regulates a cation channel. H... | 10.1038/nrn3783 | References 67 and 68 first showed that TRPM1 is the cation channel that lies downstream of the mGluR6 signalling cascade in mouse ON bipolar cells. |
10.1046/j.1460-9568.2000.00104.x | 83,081,769 | Abstract Functional properties of astrocytes were investigated with the patch‐clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco‐resistant temporal lobe epilepsy (TLE). In patients with significant neuronal cell loss, i.e. Ammon's horn sclerosis, the g... | 10.1038/nrn1870 | References 22 and 23 show the downregulation of inwardly rectifying K + currents and the impairment of Ba 2+ -sensitive K + -buffering in the sclerotic hippocampus from epilepsy patients. |
10.1073/pnas.0409308102 | 20,419,070 | An abnormal accumulation of extracellular K + in the brain has been implicated in the generation of seizures in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis. Experimental studies have shown that clearance of extracellular K + is compromised by removal of the perivascular pool of the wate... | 10.1038/nrn1870 | Reports that in patients with AHS the density of AQP4 water channels at perivascular end-feet is reduced. The perturbed water flux through astrocytes entails impaired buffering of extracellular potassium. |
10.1073/pnas.0437946100 | 79,782,597 | The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astrocytes. These membranes form the interface between the neuropil and extracerebral liquid spaces. AQP4 is anchored at these membranes by its carboxyl terminus to α-syntrophin, an adapter protein associated with dystrophin. T... | 10.1038/nrn1870 | Using a mouse model with defective anchoring of AQP4 to the cytoskeleton, the authors document the importance of proper subcellular segregation for aquaporin function in astrocytes under ischaemic stress in vivo |
10.1046/j.1528-1157.2002.38901.x | 103,734,634 | Summary: Purpose: Several findings suggest that energy metabolism and the glutamate–glutamine cycle may be impaired in epilepsy. Positron emission tomography often shows interictal hypometabolism of the epileptogenic hippocampus. In vivo microdialysis studies show that seizure‐associated glutamate release is doubled, a... | 10.1038/nrn1870 | References 39 and 40 indicate that in epilepsy in humans downregulation of astroglial glutamine synthetase disturbs the conversion of glutamate and its accumulation in the extracellular space. |
10.1002/ana.410380114 | 124,877,025 | Abstract The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is unknown, but defects in synaptosomal high‐affinity glutamate transport have been observed. In experimental models, chronic loss of glutamate transport can produce a loss of motor neurons and, therefore, could contribute to the disease. With th... | 10.1038/nrn1870 | References 54 and 55 describe the loss of glial glutamate transporters in ALS and identify astrocytes as crucial mediators of excitotoxicity and motor neuron loss. |
10.1046/j.1471-4159.2001.00198.x | 26,874,889 | Tamoxifen (TAM), a widely used non‐steroidal anti‐estrogen, has recently been shown to be neuroprotective in a rat model of reversible middle cerebral artery occlusion (rMCAo). Tamoxifen has several potential mechanisms of action including inhibition of the release of excitatory amino acids (EAA) and nitric oxide synth... | 10.1038/nrn1870 | Suggests that tamoxifen is an inhibitor of Ca 2+ /calmodulin-dependent NOS and the subsequent peroxynitrite production in transient focal cerebral ischaemia, which might represent one mechanism for the neuroprotective effect of tamoxifen. |
10.1126/science.279.5350.509 | 41,692,574 | The actin cytoskeleton mediates a variety of essential biological functions in all eukaryotic cells. In addition to providing a structural framework around which cell shape and polarity are defined, its dynamic properties provide the driving force for cells to move and to divide. Understanding the biochemical mechanism... | 10.1038/nrmicro2592 | A classical review about role of RHO-family proteins in regulation of the actin cytoskeleton. |
10.1083/jcb.111.3.1001 | 61,277,025 | The rho proteins, p21rho, are ubiquitously expressed guanine nucleotide binding proteins with approximately 30% amino acid homology to p21ras, but their biochemical function is unknown. We show here that microinjection of constitutively activated recombinant rho protein (Val14rho) into subconfluent cells induces dramat... | 10.1038/nrmicro2592 | An important early study on the role of RHO-family proteins in cytoskeleton regulation, and also the first usage of C3 as cell-biological tool. |
10.1126/science.1184557 | 82,130,933 | Tripartite Toxin Luminescent bacterial symbionts of nematode worms that attack insects have long stirred interest in their possibilities for biological control. The bacteria produce a family of toxins composed of at least three subunits that resemble a widely occurring class of bacterial toxins also produced by human p... | 10.1038/nrmicro2592 | A seminal paper about the molecular mechanism of P. luminescens Tc toxins. |
10.1073/pnas.0601562103 | 122,474,349 | Legionella pneumophila , the causal agent of Legionnaires' disease, is an intracellular parasite and invades and proliferates within different eukaryotic cells, including human alveolar macrophages. After several 100-fold multiplication within host cells, the pathogens are released for new invasion by induction of apop... | 10.1038/nrmicro2592 | The identification of EF1α as the target of L. pneumophila glucosyltransferases. |
10.1126/science.1166382 | 84,387,472 | The Vibrio parahaemolyticus type III effector VopS is implicated in cell rounding and the collapse of the actin cytoskeleton by inhibiting Rho guanosine triphosphatases (GTPases). We found that VopS could act to covalently modify a conserved threonine residue on Rho, Rac, and Cdc42 with adenosine 5′-monophosphate (AMP)... | 10.1038/nrmicro2592 | The discovery that adenylylation is the molecular mechanism of VopS, opening a new field in toxin studies. |
10.1126/science.1192276 | 80,316,398 | Legionella Hijacks Rab Legionella pneumophila can infect eukaryotic cells and takes up residence within intracellular vacuoles, where it multiplies. In order to produce and maintain this intracellular niche, the pathogen must manipulate membrane trafficking within the host cell. Now, Müller et al. (p. 946 , published o... | 10.1038/nrmicro2592 | The characterization of DrrA as an adenylylating enzyme acting on RAB proteins. |
10.1073/pnas.75.6.2669 | 101,186,639 | Treatment of pigeon erythrocyte membranes with cholera toxin and NAD + enhanced the GTP stimulation and suppressed the F - activation of the adenylate cylase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. In the presence of NAD + labeled with 32 P in the AMP moiety the toxin catalyzed the covalent incorporation of ... | 10.1038/nrmicro2592 | A classical paper on the molecular mechanism of cholera toxin. |
10.1073/pnas.0900160106 | 47,748,898 | Pasteurella multocida toxin is a major virulence factor of Pasteurella multocida , which causes pasteurellosis in men and animals and atrophic rhinitis in rabbits and pigs. The ≈145 kDa protein toxin stimulates various signal transduction pathways by activating heterotrimeric G proteins of the Gα q , Gα i , and Gα 12/1... | 10.1038/nrmicro2592 | A seminal paper on the identification of Pmt as a deamidase. |
10.1146/annurev.biochem.66.1.639 | 122,598,355 | This review is concerned with the structures and mechanisms of a superfamily of regulatory GTP hydrolases (G proteins). G proteins include Ras and its close homologs, translation elongation factors, and heterotrimeric G proteins. These proteins share a common structural core, exemplified by that of p21 ras (Ras), and s... | 10.1038/nrmicro2592 | An excellent early review on structure–function analyses of G proteins. |
10.1073/pnas.1002199107 | 18,510,045 | Clostridium difficile toxins A and B are members of an important class of virulence factors known as large clostridial toxins (LCTs). Toxin action involves four major steps: receptor-mediated endocytosis, translocation of a catalytic glucosyltransferase domain across the membrane, release of the enzymatic moiety by aut... | 10.1038/nrmicro2592 | An impressive study on the power of negative-stain microscopy and three-dimensional restructuring for the structure–function analysis of clostridial toxins. |
10.1073/pnas.89.12.5675 | 19,011,702 | Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive ... | 10.1038/nrn1929 | This seminal paper describes the theory and phenomenon of fMRI, supported by a compelling series of experiments. A methods paper that is almost unrivalled for completeness and clarity in this young field. |
10.1073/pnas.222536799 | 20,586,988 | Movement of an affected hand after stroke is associated with increased activation of ipsilateral motor cortical areas, suggesting that these motor areas in the undamaged hemisphere may adaptively compensate for damaged or disconnected regions. However, this adaptive compensation has not yet been demonstrated directly. ... | 10.1038/nrn1929 | Illustrates, with the analysis of ipsilateral motor cortical activity in recovery after a motor stroke, the potential for transcranial magnetic stimulation to be used as a way of testing the functional significance of activity associated with a behaviour assessed by fMRI. |
10.1073/pnas.071582498 | 62,367,389 | Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (... | 10.1038/nrn1929 | An elegant demonstration of how spontaneous activity can be imaged in the brain, using fMRI to better define the relationship between neurophysiological changes and symptoms in migraine. |
10.1073/pnas.0504935102 | 122,957,970 | Our objective was to evaluate the brain regions showing increased and decreased metabolism in patients at the time of generalized bursts of epileptic discharges in order to understand their mechanism of generation and effect on brain function. By recording the electroencephalogram during the functional MRI, changes in ... | 10.1038/nrn1929 | This paper makes the compelling argument that central generators for primary generalized epilepsy are localized in the thalamus on the basis of combined EEG and fMRI studies: a striking example of the application of this new integration of technology for exciting new clinical neuroscience. |
10.1073/pnas.111134598 | 19,021,807 | Abnormalities of prefrontal cortical function are prominent features of schizophrenia and have been associated with genetic risk, suggesting that susceptibility genes for schizophrenia may impact on the molecular mechanisms of prefrontal function. A potential susceptibility mechanism involves regulation of prefrontal d... | 10.1038/nrn1929 | One of a series of papers illustrating how imaging can be used as an endophenotype for the characterization of genes that influence complex disease expression. The Weinberger laboratory has pioneered this approach for psychiatric disease. |
10.1073/pnas.85.21.8335 | 62,166,947 | We have analyzed the polarity orientation of microtubules in the axons and dendrites of cultured rat hippocampal neurons. As previously reported of axons from other neurons, microtubules in these axons are uniform with respect to polarity; (+)-ends are directed away from the cell body toward the growth cone. In sharp c... | 10.1038/nrn.2017.100 | This study analysed microtubule orientation in hippocampal neurons and demonstrated uniform plus-end-outward orientation in axons and mixed orientation in dendrites. |
10.1083/jcb.200606077 | 101,992,302 | The small GTPase Rab7 controls late endocytic transport by the minus end–directed motor protein complex dynein–dynactin, but how it does this is unclear. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein–related protein 1L (ORP1L) are two effectors of Rab7. We show that GTP-bound Rab7 simultaneous... | 10.1038/nrn.2017.100 | This study characterized the assembly of a late-endosomal dynein-adaptor complex via the scaffolding proteins and adaptors RILP and ORP1L. |
10.1126/science.1232251 | 62,302,011 | Axonal Actin How actin is organized in the axons and dendrites of neurons is largely unknown. Xu et al. (p. 452 , published online 13 December) imaged actin in axons and dendrites using stochastic optical reconstruction microscopy. Surprisingly, while actin in dendrites formed long filaments, the actin in axons was org... | 10.1038/nrn.2017.100 | This study discovered and characterized periodic actin-spectrin ring structures in axons using super-resolution microscopy. |
10.1523/jneurosci.23-03-00876.2003 | 41,654,401 | Recently it was demonstrated that exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors or drugs that potentiate GABA A receptors can trigger widespread apoptotic neurodegeneration. All currently used general anesthetic agents have either NMDA receptor-blockin... | 10.1038/nrn.2016.128 | This paper is the first to demonstrate that exposure to anaesthesia in the early postnatal period can induce histological, functional and behavioural alterations in the developing brain. |
10.1097/aln.0000000000000851 | 82,890,771 | Abstract Background Retrospective studies in humans have shown a higher prevalence of learning disabilities in children that received multiple exposures to general anesthesia before the age of 4 yr. Animal studies, primarily in rodents, have found that postnatal anesthetic exposure causes neurotoxicity and neurocogniti... | 10.1038/nrn.2016.128 | This publication demonstrates that exposure of NHP infants to the commonly used anaesthetic agent sevoflurane can induce lasting alterations in emotional reactivity. |
10.1126/science.287.5455.1056 | 62,623,854 | The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N -methyl- d -aspartate (NMDA) glutamate receptors and excessive activation of GABA A receptors], triggers widespread apoptotic neurodegeneration in the devel... | 10.1038/nrn.2016.128 | This work can be considered as the one that provided the biological rational to evaluate the effect of anaesthesia on the developing brain. |
10.1002/ana.23892 | 18,944,196 | Objective Anesthetics have been linked to widespread neuronal cell death in neonatal animals. Epidemiological human studies have associated early childhood anesthesia with long‐term neurobehavioral abnormalities, raising substantial concerns that anesthetics may cause similar cell death in young children. However, key ... | 10.1038/nrn.2016.128 | This paper and reference 44 demonstrate that the neuronal vulnerability to anaesthetics depends on the developmental stage of individual neurons. |
10.1097/aln.0b013e318221fbbd | 20,512,107 | Background Recent observations demonstrate that anesthetics rapidly impair synaptogenesis during neuronal circuitry development. Whether these effects are lasting and depend on the developmental stage at which these drugs are administered remains, however, to be explored. Methods Wistar rats received propofol anesthesi... | 10.1038/nrn.2016.128 | This work shows that the administration of GAs in the early postnatal period can induce lasting changes in the number of dendritic spines and synapses, and demonstrates that the direction of these changes depends on the developmental stage at drug exposure. |
10.1097/aln.0b013e318289bc9b | 104,434,252 | Abstract Background: General anesthetics induce apoptotic neurodegeneration in the developing mammalian brain. General anesthesia (GA) also causes significant disturbances in mitochondrial morphogenesis during intense synaptogenesis. Mitochondria are dynamic organelles that undergo remodeling via fusion and fission. Th... | 10.1038/nrn.2016.128 | This publication describes anaesthesia exposure-induced mitochondrial dysfunction as a plausible cause of anaesthesia neurotoxicity. |
10.1002/ana.21548 | 107,322,210 | Abstract Objective An estimated 200 million patients worldwide have surgery each year. Anesthesia and surgery have been reported to facilitate emergence of Alzheimer's disease. The commonly used inhalation anesthetic isoflurane has previously been reported to induce apoptosis, and to increase levels and aggregation of ... | 10.1038/nrn.2016.128 | This is the first publication to show that anaesthesia exposure in vivo can induce pathological features of AD in experimental animals. |
10.1097/00000542-200409000-00019 | 19,684,161 | Background The majority of surgical patients receive inhaled anesthetics, principally small haloalkanes and haloethers. Long-term cognitive problems occur in the elderly subsequent to anesthesia and surgery, and previous surgery might also be a risk factor for neurodegenerative disorders like Alzheimer and Parkinson di... | 10.1038/nrn.2016.128 | This in vitro work is the first to demonstrate that anaesthetics can increase pathological events that are associated with AD. |
10.1002/ana.22082 | 83,026,848 | Abstract Objective: Although postoperative cognitive dysfunction (POCD) often complicates recovery from major surgery, the pathogenic mechanisms remain unknown. We explored whether systemic inflammation, in response to surgical trauma, triggers hippocampal inflammation and subsequent memory impairment, in a mouse model... | 10.1038/nrn.2016.128 | This seminal work demonstrates a role for systemic inflammation in the pathogenesis of postoperative cognitive dysfunction. |
10.1126/science.2296719 | 18,981,708 | Priming is a nonconscious form of human memory, which is concerned with perceptual identification of words and objects and which has only recently been recognized as separate from other forms of memory or memory systems. It is currently under intense experimental scrutiny. Evidence is converging for the proposition tha... | 10.1038/nrn1534 | Argues for the view that priming reflects the operation of a perceptual representation system that can function separately from other memory systems, such as episodic, semantic and procedural memory. |
10.1073/pnas.89.5.1837 | 29,112,237 | We studied regional cerebral blood flow using the H2(15)O method while normal subjects performed four similar tasks involving three-letter word beginnings (stems). Prior to each task, subjects studied a list of words. Local blood flow was then monitored during a 40-sec period while subjects (i) silently viewed word ste... | 10.1038/nrn1534 | The first neuroimaging study to provide evidence for a priming-related reduction in activity in extrastriate occipital cortex. |
10.1101/gad.227902 | 122,930,531 | Many regulons controlled by alternative ς factors, including ς S and ς 32 , are poorly induced in cells lacking the alarmone ppGpp. We show that ppGpp is not absolutely required for the activity of ς S -dependent promoters because underproduction of ς 70 , specific mutations in rpoD ( rpoD40 and rpoD35 ), or overproduc... | 10.1038/nrmicro2720 | Genetic and biochemical studies that establish the concept of σ-factor competition. |
10.1111/j.1365-2958.2009.06739.x | 100,342,512 | Summary Biofilms are communities of surface‐attached, matrix‐embedded microbial cells that can resist antimicrobial chemotherapy and contribute to persistent infections. Using an Escherichia coli biofilm model we found that exposure of bacteria to subinhibitory concentrations of ribosome‐targeting antibiotics leads to ... | 10.1038/nrmicro2720 | A genetic study demonstrating synergy between the ppGpp and c-di-GMP signalling pathways. |
10.1101/gad.1400306 | 39,480,681 | The σ S subunit of Escherichia coli RNA polymerase regulates the expression of stationary phase and stress response genes. σ S is highly unstable in exponentially growing cells, whereas its stability increases dramatically upon starvation or under certain stress conditions. The degradation of σ S is controlled by the p... | 10.1038/nrmicro2720 | A molecular genetics investigation which finds that stabilization of σ S during phosphate starvation is mediated by SpoT-induced activation of iraP transcription. |
10.1111/j.1365-2958.2007.06072.x | 100,314,539 | Summary One of the major signalling pathways responsible for intercompartmental communication between the cell envelope and cytoplasm in Escherichia coli is mediated by the alternative sigma factor, σ E . σ E has been studied primarily for its role in response to the misfolding of outer membrane porins. This response i... | 10.1038/nrmicro2720 | A biochemical experiment determining that ppGpp directly stimulates σ E activity, together with an in vivo analysis that indicates enhanced competition for RNAP also occurs. |
10.1073/pnas.0807071106 | 123,757,974 | We present a molecular mechanism for signal transduction that activates transcription of the SlyA regulon in Salmonella typhimurium . We demonstrate that SlyA mediates transcriptional activation in response to guanosine tetraphosphate, ppGpp, according to the following observations: ( i ) in vivo transcription of SlyA-... | 10.1038/nrmicro2720 | Genetic and biochemical experiments which demonstrate that ppGpp binds the transcription factor SlyA and promotes its dimerization, DNA binding and activity as a transcriptional activator. |
10.1111/j.1365-2958.2010.07240.x | 82,587,748 | Summary With the beginning of the idiophase the highly phosphorylated guanylic nucleotides guanosine 5′‐diphosphate 3′‐diphosphate (ppGpp) and guanosine 5′‐triphosphate 3′‐diphosphate (pppGpp), collectively referred to as (p)ppGpp, activate stress survival adaptation programmes and trigger secondary metabolism in actin... | 10.1038/nrmicro2720 | In vitro and in vivo experiments which establish that ppGpp binds and inhibits the activity of an enzyme that destabilizes mRNAs. |
10.1084/jem.20082874 | 58,616,254 | The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyc... | 10.1038/nrmicro2720 | The first work to demonstrate that treatment with cyclic nucleotides stimulates innate immune mechanisms of mammalian cells. |
10.1126/science.1189801 | 125,223,424 | Bacterial (Interferon)ce Intracellular bacterial pathogens, such as Listeria monocytogenes , are detected in the cytosol of host immune cells, where they induce a host response that is often dependent on microbial secretion systems. Woodward et al. (p. 1703 , published online 27 May) now show that L. monocytogenes prod... | 10.1038/nrmicro2720 | An investigation which uses bacterial genetics to establish that the production of cyclic nucleotides by an intracellular pathogen stimulates host innate immune defence pathways. |
10.1111/j.1365-2958.2010.07498.x | 82,468,747 | Summary Bacteria comprehensively reorganize their global gene expression when faced with starvation. The alarmone ppGpp facilitates this massive response by co‐ordinating the downregulation of genes of the translation apparatus, and the induction of biosynthetic genes and the general stress response. Such a large reori... | 10.1038/nrmicro2720 | A transcriptional profile analysis identifying genes that require different amounts of ppGpp for their induction, thus illustrating a dynamic range for this regulatory pathway. |
10.1126/science.7569895 | 84,481,224 | The behavioral and cognitive effects of nicotine suggest that nicotinic acetylcholine receptors (nAChRs) participate in central nervous system (CNS) function. Although nAChR subunit messenger RNA (mRNA) and nicotine binding sites are common in the brain, there is little evidence for synapses mediated by nAChRs in the C... | 10.1038/nrn1298 | An important study on the role of nanomolar nicotine concentrations in the enhancement of glutamatergic and cholinergic transmission through presynaptic α7–containing nAChRs. |
10.1126/science.1159775 | 62,295,623 | A long-standing conjecture in neuroscience is that aspects of cognition depend on the brain's ability to self-generate sequential neuronal activity. We found that reliably and continually changing cell assemblies in the rat hippocampus appeared not only during spatial navigation but also in the absence of changing envi... | 10.1038/nrn3827 | This study revealed the existence of hippocampal neurons that fire briefly in sequence as rats run in a running wheel between alternations on a T-maze. Different firing sequences distinguished left-turn and right-turn paths through the maze. |
10.1523/jneurosci.1537-13.2013 | 104,367,439 | Previous studies have revealed the existence of hippocampal “time cells,” principal neurons in CA1 that fire at specific moments in temporally organized experiences. However, in all these studies, animals were in motion; and so, temporal modulation might be due, at least in part, to concurrent or planned movement throu... | 10.1038/nrn3827 | This study revealed that time cells fire in sequence during the delay period in head-fixed rats performing a delayed matching-to-sample task, showing that time-cell sequences exist even when movement is completely prevented. Furthermore, the results showed that distinct time-cell sequences are associated with different... |
10.7554/elife.01982 | 59,519,280 | Animals can learn causal relationships between pairs of stimuli separated in time and this ability depends on the hippocampus. Such learning is believed to emerge from alterations in network connectivity, but large-scale connectivity is difficult to measure directly, especially during learning. Here, we show that area ... | 10.1038/nrn3827 | This study imaged calcium signals in hippocampal neurons of head-fixed mice during trace eye-blink classical conditioning. Hippocampal neural ensembles developed time-cell firing sequences, including during the trace period, associated with learning the conditioned response. |
10.1126/science.1206773 | 41,347,605 | Structures of the medial temporal lobe provide distinct but complementary signals to encode temporal-order information. | 10.1038/nrn3827 | This study identifies time cells that fire as head-fixed monkeys learn the temporal order of pairs of visual stimuli separated by a delay. Notably, in this task, hippocampal neurons encoded elapsed time but not the visual stimuli, whereas neurons in upstream areas (entorhinal cortex, perirhinal cortex and inferotempora... |
10.1073/pnas.0910834107 | 57,717,506 | Memory formation requires the placement of experienced events in the same order in which they appeared. A large body of evidence from human studies indicates that structures in the medial temporal lobe are critically involved in forming and maintaining such memories, and complementing evidence from lesion and electroph... | 10.1038/nrn3827 | This study revealed the emergence of a gradually changing representation of events with repeated exposures to specific film clips in humans. These patterns, similar to those observed in rats (reference 12), emerged only in the hippocampus and not in other medial temporal areas. |
10.1046/j.1460-9568.2002.02026.x | 121,878,999 | Abstract The growth‐associated protein GAP‐43 (or neuromodulin or B‐50) plays a critical role during development in mechanisms of axonal growth and formation of synaptic networks. At later times, GAP‐43 has also been implicated in the regulation of synaptic transmission and properties of plasticity such as long‐term po... | 10.1038/nrn1647 | Showed that overexpression of a mutated form of neuromodulin that mimics the protein phosphorylated at Ser41 enhances CA1 LTP. This paper supports the hypothesis that phosphorylation of neuromodulin at Ser41 by PKC releases CaM and enhances synaptic efficacy. |
10.1126/science.1378648 | 20,389,402 | As a first step in a program to use genetically altered mice in the study of memory mechanisms, mutant mice were produced that do not express the α-calcium-calmodulin-dependent kinase II (α-CaMKII). The α-CaMKII is highly enriched in postsynaptic densities of hippocampus and neocortex and may be involved in the regulat... | 10.1038/nrn1647 | References 38 and 39 were the first studies to use gene disruption technology to implicate CaMKII in LTP and memory. |
10.1073/pnas.2237201100 | 100,748,732 | The late, transcription- and translation-dependent phase of long-term synaptic potentiation (L-LTP) at the Schaffer collateral synapse of the hippocampus is an experimental model of the synaptic plasticity underlying long-lasting memory formation. L-LTP is typically induced by homosynaptic tetanic stimulation; but asso... | 10.1038/nrn1647 | This paper reports that heterosynaptically induced LTP requires PKA activity as well as protein synthesis. Transgenic mice that express a dominant-negative CREB inhibitor in the hippocampus have impaired heterosynaptic L-LTP. |
10.1523/jneurosci.20-12-04446.2000 | 123,584,145 | Long-term potentiation (LTP) has several different phases, and there is general agreement that the late phase of LTP requires the activation of adenylyl cyclase (AC) and cAMP-dependent protein kinase (PKA). In contrast, several studies indicate that the early LTP is not affected by interfering with the cAMP pathway. We... | 10.1038/nrn1647 | References 87 and 88 provide the first evidence that CaM-stimulated adenylyl cyclases and cAMP signalling are required for E-LTP. |
10.1002/ana.410360404 | 81,031,504 | Abstract The classic concept of the viability thresholds of ischemia differentiates between two critical flow rates, the threshold of electrical failure and the threshold of membrane failure. These thresholds mark the upper and lower flow limits of the ischemic penumbra which is thought ot suffer only functional but no... | 10.1038/nrn1387 | This paper provides an appraisal of the effects of reduction in CBF on brain metabolism and function. |
10.1038/jcbfm.2014.217 | 99,814,035 | Sex differences are well known in cerebral ischemia and may impact the effect of stroke treatments. In male rats, the MEK1/2 inhibitor U0126 reduces ischemia-induced endothelin type B (ET B ) receptor upregulation, infarct size and improves acute neurologic function after experimental stroke. However, responses to this... | 10.1038/nrn1387 | A comprehensive source addressing the main aspects of the structure and function of the cerebral circulation. |
10.1073/pnas.2133652100 | 83,054,420 | Analysis of the spatiotemporal coupling between neuronal activity and cerebral blood flow requires the precise measurement of the dynamics of RBC flow in individual capillaries that irrigate activated neurons. Here, we use two-photon microscopy in vivo to image individual RBCs in glomerular capillaries in the rat dorsa... | 10.1038/nrn1387 | This paper provides striking evidence of the spatial accuracy of the changes in CBF produced by neural activity. |
10.1152/physrev.1998.78.1.53 | 81,040,057 | Faraci, Frank M., and Donald D. Heistad. Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels. Physiol. Rev. 78: 53–97, 1998. — Several new concepts have emerged in relation to mechanisms that contribute to regulation of the cerebral circulation. This review focuses on some physiological m... | 10.1038/nrn1387 | This review provides a detailed account of the endothelial regulation of the cerebral circulation. |
10.1073/pnas.97.17.9735 | 82,899,221 | Peptides derived from proteolytic processing of the β-amyloid precursor protein (APP), including the amyloid-β peptide (Aβ), play a critical role in the pathogenesis of Alzheimer's dementia. We report that transgenic mice overexpressing APP and Aβ have a profound attenuation in the increase in neocortical blood flow el... | 10.1038/nrn1387 | This paper provided the first demonstration that Aβ inhibits functional hyperaemia in mice overexpressing App. |
10.1126/science.280.5366.1089 | 29,201,851 | Ataxia telangiectasia (AT) is characterized by progressive neurodegeneration that results from mutation of the ATM gene. However, neither the normal function of ATM in the nervous system nor the biological basis of the degeneration in AT is known. Resistance to apoptosis in the developing central nervous system (CNS) o... | 10.1038/nrn2559 | Together with reference 60, this study showed that ATM function is required for DNA damage-induced apoptosis in immature differentiating neural cells but not in proliferating cells. |
10.1073/pnas.0536856100 | 124,976,865 | In addition to neurological deficits, Huntington's disease (HD) patients and transgenic mice expressing mutant human huntingtin exhibit reduced levels of brain-derived neurotrophic factor, hyperglycemia, and tissue wasting. We show that the progression of neuropathological (formation of huntingtin inclusions and apopto... | 10.1038/nrn1386 | This study shows improvement with dietary restriction in the N171-82Q HD mice. |
10.1073/pnas.182426599 | 122,519,677 | Preventing the formation of insoluble polyglutamine containing protein aggregates in neurons may represent an attractive therapeutic strategy to ameliorate Huntington's disease (HD). Therefore, the ability to screen for small molecules that suppress the self-assembly of huntingtin would have potential clinical and sign... | 10.1038/nrn1386 | Description of a high throughput assay to identify inhibitors of huntingtin aggregation. |
10.1126/science.1072613 | 83,339,614 | Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine tract in the huntingtin protein. Transcriptional dysregulation has been implicated in HD pathogenesis. Here, we report that huntingtin interacts with the transcriptional activator Sp1 and coactivator TAFII130. Coe... | 10.1038/nrn1386 | An important paper showing that both SP1 and TAF II 130 transcription is impaired in HD, and that SP1 overexpression protects against toxic effects of mutant huntingtin. |
10.1073/pnas.0437870100 | 81,577,360 | Huntington's disease (HD) is an inherited, progressive neurological disorder that is caused by a CAG/polyglutamine repeat expansion and for which there is no effective therapy. Recent evidence indicates that transcriptional dysregulation may contribute to the molecular pathogenesis of this disease. Supporting this view... | 10.1038/nrn1386 | A study showing inproved rotarod performance with the HDAC inhibitor SAHA. This was the first demonstration that SAHA, and which has benefits in yeast and D. melanogaster , also shows benefits in a transgenic mouse model of HD. |
10.1212/wnl.57.3.397 | 18,067,736 | Objectives: To determine whether chronic treatment with coenzyme Q 10 or remacemide hydrochloride slows the functional decline of early Huntington’s disease (HD). Methods: The authors conducted a multicenter, parallel group, double-blind, 2 × 2 factorial, randomized clinical trial. Research participants with early HD (... | 10.1038/nrn1386 | A controlled clinical trial of remacemide and CoQ 10 in HD. |
10.1073/pnas.2628045100 | 38,526,979 | The formation of polyglutamine-containing aggregates and inclusions are hallmarks of pathogenesis in Huntington's disease that can be recapitulated in model systems. Although the contribution of inclusions to pathogenesis is unclear, cell-based assays can be used to screen for chemical compounds that affect aggregation... | 10.1038/nrn1386 | A study showing that cell-based high throughput screening for aggregation inhibitors identifies compounds that show efficacy in D. melanogaster |
10.1073/pnas.061629598 | 101,111,829 | We report here the construction, characterization, and application of a bacterial bioreporter for fructose and sucrose that was designed to monitor the availability of these sugars to microbial colonizers of the phyllosphere. Plasmid pP fruB - gfp [AAV] carries the Escherichia coli fruB promoter upstream from the gfp [... | 10.1038/nrmicro2910 | A seminal paper showing the heterogeneity of available fructose and/or sucrose on leaf surfaces. |
10.1073/pnas.0905240106 | 125,205,442 | Aerial plant surfaces represent the largest biological interface on Earth and provide essential services as sites of carbon dioxide fixation, molecular oxygen release, and primary biomass production. Rather than existing as axenic organisms, plants are colonized by microorganisms that affect both their health and growt... | 10.1038/nrmicro2910 | A paper describing the application of a metaproteogenomic approach to the analysis of complex bacterial communities in the phyllosphere of three different model plants. The paper reveals a high consistency among the communities, suggesting that there are unifying adaptive mechanisms among commonly found bacteria. |
10.1073/pnas.051633898 | 41,544,969 | Phyllosphere microbial communities were evaluated on leaves of field-grown plant species by culture-dependent and -independent methods. Denaturing gradient gel electrophoresis (DGGE) with 16S rDNA primers generally indicated that microbial community structures were similar on different individuals of the same plant spe... | 10.1038/nrmicro2910 | The first cultivation-independent study to demonstrate that the diversity of phyllosphere bacteria is complex. |
10.1038/ismej.2010.9 | 20,591,690 | Abstract The plant phyllosphere constitutes a habitat for numerous microorganisms; among them are members of the genus Methylobacterium. Owing to the ubiquitous occurrence of methylobacteria on plant leaves, they represent a suitable target for studying plant colonization patterns. The influence of the factor site, hos... | 10.1038/nrmicro2910 | A comprehensive cultivation-independent study showing the importance of plant species and site for the community composition of ubiquitous methylobacteria. |
10.1111/j.1462-2920.2010.02258.x | 41,469,750 | Summary Large populations of bacteria live on leaf surfaces and these phyllosphere bacteria can have important effects on plant health. However, we currently have a limited understanding of bacterial diversity on tree leaves and the inter‐ and intra‐specific variability in phyllosphere community structure. We used a ba... | 10.1038/nrmicro2910 | An article providing evidence that there is a predictable bacterial phyllosphere community pattern which is dependent on the relatedness of trees. |
10.1146/annurev-phyto-073009-114436 | 103,821,249 | This review examines the many ways in which water influences the relations between foliar bacterial pathogens and plants. As a limited resource in aerial plant tissues, water is subject to manipulation by both plants and pathogens. A model is emerging that suggests that plants actively promote localized desiccation at ... | 10.1038/nrmicro2910 | A review that provides an integrated summary of the various aspects and consequences of water availability for microorganisms in the phyllosphere. |
10.1073/pnas.2436560100 | 19,646,274 | The survival of individual Pseudomonas syringae cells was determined on bean leaf surfaces maintained under humid conditions or periodically exposed to desiccation stress. Cells of P. syringae strain B728a harboring a GFP marker gene were visualized by epifluorescence microscopy, either directly in situ or after recove... | 10.1038/nrmicro2910 | An investigation that uses epifluorescence microscopy to demonstrate that aggregate formation by a phyllosphere bacterium is important for tolerating environmental stresses. |
10.1073/pnas.0810291106 | 15,290,554 | Bacteria have evolved regulatory traits to rapidly adapt to changing conditions. Two principal regulatory mechanisms to modulate gene expression consist of regulation via alternative sigma factors and phosphorylation-dependent response regulators. PhyR represents a recently discovered protein family combining parts of ... | 10.1038/nrmicro2910 | Together with reference 61, this report describes the discovery of the PhyR–NepR–σ EcfG signaling cascade, which is crucial for epiphytic fitness of phyllosphere bacteria and governs the general stress response in alphaproteobacteria. |
10.1073/pnas.0711723105 | 59,499,434 | The paradigm of bacterial quorum sensing (QS), which mediates cell-density-dependent gene expression, usually has been studied in high-cell-density planktonic liquid cultures or in biofilms in which signal concentrations accumulate to sufficiently high levels to induce QS. Presumably under conditions with restricted di... | 10.1038/nrmicro2910 | An article showing that induction of the quorum sensing system under in situ conditions is dependent on aggregate size. |
10.1523/jneurosci.3547-03.2004 | 20,511,416 | Reactive astrocytes are prominent in the cellular response to spinal cord injury (SCI), but their roles are not well understood. We used a transgenic mouse model to study the consequences of selective and conditional ablation of reactive astrocytes after stab or crush SCI. Mice expressing a glial fibrillary acid protei... | 10.1038/nrn3898 | This transgenic loss-of-function study shows that newly proliferated, scar-forming astrocytes have important functions in protecting adjacent neural tissue and thereby help to improve outcome after CNS injury. |
10.1523/jneurosci.6221-11.2012 | 62,602,706 | Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after in... | 10.1038/nrn3898 | This study provides evidence for large-scale differences in transcriptome profiles of reactive astrocytes responding to different stimuli such as stroke or the bacterial protein LPS. |
10.4049/jimmunol.181.4.2683 | 59,340,813 | Abstract Toxoplasma gondii infects astrocytes, neurons and microglia cells in the CNS and, after acute encephalitis, persists within neurons. Robust astrocyte activation is a hallmark of Toxoplasma encephalitis (TE); however, the in vivo function of astrocytes is largely unknown. To study their role in TE we generated ... | 10.1038/nrn3898 | This transgenic loss-of-function study shows that astrocytes have important functions in restricting the spread of CNS infections. |
10.1073/pnas.1103833108 | 82,813,757 | Estrogen has well-documented neuroprotective effects in a variety of clinical and experimental disorders of the CNS, including autoimmune inflammation, traumatic injury, stroke, and neurodegenerative diseases. The beneficial effects of estrogens in CNS disorders include mitigation of clinical symptoms, as well as atten... | 10.1038/nrn3898 | This transgenic loss-of-function study shows that reactive astrocytes can reduce CNS inflammation in autoimmune encephalomyelitis via an ERα-dependent mechanism. |
10.1084/jem.20050304 | 104,305,751 | Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serv... | 10.1038/nrn3898 | This study identifies the astrocyte protein AQP4 as the target of autoimmune antibodies in NMO, thereby providing both a diagnostic tool and a mechanistic target that have revolutionized understanding of this disorder. |
10.1073/pnas.0400285101 | 103,496,582 | The hippocampal formation contains a distinct population of neurons organized into separate anatomical subregions. Each hippocampal subregion expresses a unique molecular profile accounting for their differential vulnerability to mechanisms of memory dysfunction. Nevertheless, it remains unclear which hippocampal subre... | 10.1038/nrn3085 | This study applied a high-resolution variant of fMRI in ageing rhesus monkeys to show that the dentate gyrus is differentially affected by normal ageing, and that the entorhinal cortex is relatively preserved. |
10.1073/pnas.95.4.1834 | 104,375,867 | MRI was extended to the measurement of changes in oxidative metabolism in the normal human during functionally induced changes in cellular activity. A noninvasive MRI method that is model-independent calibrates the blood oxygen level dependent (BOLD) signal of functional MRI (fMRI) against perfusion-sensitive MRI, usin... | 10.1038/nrn3085 | This is a landmark study that established that, if uncalibrated, BOLD cannot reliably map brain metabolism. |
10.1002/hbm.20426 | 20,620,411 | Abstract Objective: A large number of studies with considerably variable methods have been performed to investigate brain regions involved in the pathophysiology of major depressive disorder. The aim of this study was to use a quantitative meta‐analytic technique to synthesise the results of much of this research. Meth... | 10.1038/nrn3085 | This meta-analysis shows that when antidepressants are effective they typically cause a reduction in hippocampal metabolism. |
10.1002/ana.20667 | 62,113,874 | Abstract Although, in principle, gene expression profiling is well suited to isolate pathogenic molecules associated with Alzheimer's disease (AD), techniques such as microarray present unique analytic challenges when applied to disorders of the brain. Here, we addressed these challenges by first constructing a spatiot... | 10.1038/nrn3085 | This paper relied on the pattern of hippocampal dysfunction observed in Alzheimer's disease to identify a novel defect in intracellular sorting and trafficking, illustrating the utility of the pathophysiological framework. |
10.1083/jcb.95.2.598 | 16,698,939 | The distribution of newly synthesized proteolipid protein (PLP, 23 kdaltons) and myelin basic proteins (MBPs, 14-21.5 kdaltons) was determined in microsomal and myelin fractions prepared from the brainstems o1 10-30 d-old rats sacrificed at different times after an intracranial injection of 35S-methionine. Labeled MBPs... | 10.1038/nrn1743 | One of the first demonstrations of local mRNA translation in a eukaryotic cell. |
10.1091/mbc.e04-08-0709 | 124,825,740 | In neural cells, such as oligodendrocytes and neurons, transport of certain RNAs along microtubules is mediated by the cis-acting heterogeneous nuclear ribonucleoprotein A2 response element (A2RE) trafficking element and the cognate trans-acting heterogeneous nuclear ribonucleoprotein (hnRNP) A2 trafficking factor. Usi... | 10.1038/nrn1743 | Provides a molecular mechanism for transporting RNA granules in oligodendrocytes. |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.