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10.1126/science.1178307
20,409,247
Subcortical Network Regulation Subcortical neuromodulatory centers dominate the motivational and emotional state–dependent control of cortical functions. Control of cortical circuits has been thought to involve a slow, diffuse neuromodulation that affects the excitability of large numbers of neurons relatively indiscri...
10.1038/nrn2969
This was the first paper providing direct evidence of in vivo glutamate release by CNS monoamine neurons, through the use of optogenetics.
10.1073/pnas.0910986107
81,133,883
The “One neuron-one neurotransmitter” concept has been challenged frequently during the last three decades, and the coexistence of neurotransmitters in individual neurons is now regarded as a common phenomenon. The functional significance of neurotransmitter coexistence is, however, less well understood. Several studie...
10.1038/nrn2969
This was the first report describing the behavioural consequences of the conditional deletion of a VGLUT in dopamine neurons. The knockout mice showed a blunted behavioural activation in response to amphetamine compared to controls.
10.1126/science.1240933
107,299,323
Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING ...
10.1038/nrmicro3449
This study identifies cGAS as an important sensor of HIV.
10.1111/j.1365-2958.2009.06938.x
26,839,591
Summary Attaching and effacing (A/E) lesions and actin polymerization, the hallmark of enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC) and Citrobacter rodentium (CR) infections, are dependent on the effector Tir. Phosphorylation of Tir EPEC/CR Y474/1 leads to recruitment of Nck and neural Wis...
10.1038/nrmicro3315
This study shows that the Tir signalling pathways that are triggered in cultured epithelial cells in vitro by EPEC, EHEC and C. rodentium are not required for A/E lesion formation in vivo
10.1126/science.1222195
41,754,251
Establishing an Enteric Infection Complex and highly regulated interactions are required to keep the peace between the bacteria that reside in our gut and the immune system. How do pathogenic bacteria, such as the strains of Escherichia coli that cause gastroenteritis, get a foothold to establish an infection, and what...
10.1038/nrmicro3315
This study suggests that temporal expression of the virulence factor Ler controls the ability of C. rodentium to outcompete the gut microbiota.
10.1002/cne.901870103
20,764,187
Abstract The efferent connections of the medial (MHb) and lateral (LHb) habenular nuclei in the rat were demonstrated autoradiographically following small injections of tritiated amino acids localized within various parts of the habenular complex. Comparison of individual cases led to the following conclusions. MHb eff...
10.1038/nrn2866
Together with a companion paper (reference 6) this comprehensive anatomical study on the rat habenula provides detailed axonal projection patterns to and from the lateral and medial habenula.
10.1046/j.1365-2958.2001.02428.x
17,698,189
The C‐signal is a morphogen that controls the assembly of fruiting bodies and the differentiation of myxospores. Production of this signal, which is encoded by the csg A gene, is regulated by the act operon of four genes that are co‐transcribed from the same start site. The act A and act B genes regulate the maximum le...
10.1038/nrmicro733
Provides evidence for a positive feedback circuit that increases the number of C-signal molecules that are displayed on the cell surface.
10.1046/j.1365-2958.1998.01113.x
122,146,333
During fruiting body morphogenesis in Myxococcus xanthus , the intercellular C‐signal induces aggregation, sporulation and developmental gene expression. To understand how a single signal system may induce temporally separated processes, we have focused on the class II gene, which codes for an essential component in th...
10.1038/nrmicro733
References 50 and 51 show that the fruA response-regulator links reception of the C-signal to the frz chemosensory pathway.
10.1073/pnas.042535699
18,556,694
In response to starvation, an unstructured population of identical Myxococcus xanthus cells rearranges into an asymmetric, stable pattern of multicellular fruiting bodies. Central to this pattern formation process are changes in organized cell movements from swarming to aggregation. Aggregation is induced by the cell s...
10.1038/nrmicro733
The first cell-tracking experiments of cells that are induced to stream by the C-signal.
10.1073/pnas.97.16.9098
18,506,351
Myxococcus xanthus develops species-specific multicellular fruiting bodies. Starting from a uniform mat of cells, some cells enter into nascent fruiting body aggregates, whereas other cells remain outside. The cells within the fruiting body differentiate from rods into spherical, heat-resistant spores, whereas the cell...
10.1038/nrmicro733
The first paper to show that the C-signal induces sporulation only inside of a fruiting body.
10.1073/pnas.1035720100
104,111,967
Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that wh...
10.1038/nrn.2017.156
The data in this study provide the first evidence that IMS exerts beneficial effects on the brain that are independent of overall energy intake.
10.1111/jnc.13868
103,182,288
Abstract During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3‐hydroxybutyrate (3 OHB ) occurs. Studies have shown that 3 OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained ...
10.1038/nrn.2017.156
This study shows that the ketone BHB can act directly on neurons to induce transcription of the gene encoding BDNF by a mechanism involving NF-κB.
10.1073/pnas.012605299
125,069,579
Many forms of long-lasting behavioral and synaptic plasticity require the synthesis of new proteins. For example, long-term potentiation (LTP) that endures for more than an hour requires both transcription and translation. The signal-transduction mechanisms that couple synaptic events to protein translational machinery...
10.1038/nrn.2017.156
This study demonstrates a role for the nutrient-sensing mTOR pathway in hippocampal synaptic plasticity.
10.1002/jnr.21628
18,406,087
Abstract To determine the neuroprotective effect of fasting after traumatic brain injury (TBI) and to elucidate the potential underlying mechanisms, we used a controlled cortical impact (CCI) injury model to induce either a moderate or a severe injury to adult male Sprague Dawley rats. Tissue‐sparing assessments were u...
10.1038/nrn.2017.156
This study shows that when initiated after traumatic brain injury, fasting and ketone administration reduce neuronal loss in rats.
10.1073/pnas.0405831102
83,143,722
We report that a low-calorie diet can lessen the severity of neurochemical deficits and motor dysfunction in a primate model of Parkinson's disease. Adult male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30% caloric restriction (CR)] or an ad libitum control diet after which they were subject...
10.1038/nrn.2017.156
This study demonstrates that daily CR lessens motor deficits and dopamine depletion and elevates striatal levels of glial-cell-line-derived neurotrophic factor in a nonhuman primate model of PD.
10.1126/science.2858126
122,683,507
Hemorrhagic fever with renal syndrome (HFRS) comprises a variety of clinically similar diseases of viral etiology that are endemic to and sporadically epidemic throughout the Eurasian continent and Japan. Although HFRS has not been reported in North America, viruses that are antigenically similar to HFRS agents were re...
10.1038/nrmicro3066
This pioneering article establishes hantaviruses as a separate genus in the Bunyaviridae family.
10.1128/jvi.00057-10
100,557,634
ABSTRACT Hantaviruses (family Bunyaviridae ) are rodent-borne emerging viruses that cause a serious, worldwide threat to human health. Hantavirus diseases include hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Virions are enveloped and contain a tripartite single-stranded negative-sense ...
10.1038/nrmicro3066
This work obtains the first solved structure of the hantavirus spike.
10.1160/th09-09-0640
125,090,264
Summary Hantaviruses cause two vascular permeability-based diseases and primarily infect endothelial cells which form the primary fluid barrier of the vasculature. Since hantavirus infections are not lytic, the mechanisms by which hantaviruses cause haemorrhagic fever with renal syndrome (HFRS) or Hantavirus Pulmonary ...
10.1038/nrmicro3066
This report summarizes the concept that disrupted endothelial function is a crucial factor in disease mediated by hantaviruses.
10.1128/jvi.69.9.5754-5762.1995
62,405,798
We examined the 5' ends of Hantaan virus (HTN) genomes and mRNAs to gain insight into the manner in which these chains were initiated. Like those of all members of the family Bunyaviridae described so far, the HTN mRNAs contained 5' terminal extensions that were heterogeneous in both length and sequence, presumably bec...
10.1038/nrmicro3066
This article describes the prime-and-realign mechanism used in the initiation of hantavirus RNA synthesis.
10.1073/pnas.0707454104
59,647,342
Hantavirus cardiopulmonary syndrome is a zoonotic illness associated with a systemic inflammatory immune response, capillary leak, noncardiogenic pulmonary edema, and shock in humans. Cytokines, including TNF, IFN-γ, and lymphotoxin, are thought to contribute to its pathogenesis. In contrast, infected rodent reservoirs...
10.1038/nrmicro3066
References 58 and 59 are the first to describe the role of T cells in the reservoir hosts of hantaviruses.
10.1128/cvi.05187-11
57,470,085
ABSTRACT Major histocompatibility complex (MHC) class I and class II genes regulate the balance between appropriate aggressive responses and invading pathogens while minimizing the destruction of host tissue. Several studies have shown that in hemorrhagic fever with renal syndrome (HFRS) patients, the disease outcome i...
10.1038/nrmicro3066
This large study shows that the severities of DOBV-mediated HFRS and PUUV-mediated HFRS are associated with different HLA haplotypes.
10.1101/gr.1180903
61,652,332
We generated draft genome sequences for two cold-adapted Archaea, Methanogenium frigidum and Methanococcoides burtonii , to identify genotypic characteristics that distinguish them from Archaea with a higher optimal growth temperature (OGT). Comparative genomics revealed trends in amino acid and tRNA composition, and s...
10.1038/nrmicro773
This is the first comparison using genome data from Archaea spanning the growth temperature extremes from psychrophiles to hyperthermophiles.
10.1073/pnas.95.19.11476
45,530,495
To elucidate mechanisms of enzymatic adaptation to extreme cold, we determined kinetic properties, thermal stabilities, and deduced amino acid sequences of lactate dehydrogenase A 4 (A 4 -LDH) from nine Antarctic (−1.86 to 1°C) and three South American (4 to 10°C) notothenioid teleosts. Higher Michaelis–Menten constant...
10.1038/nrmicro773
This landmark paper indicates that localized increases in flexibility around the active site improve the k cat of cold-active enzymes at the expense of K m
10.1073/pnas.95.13.7406
60,862,500
3-Isopropylmalate dehydrogenase (IPMDH, E.C. 1.1.1.85) from the thermophilic bacterium Thermus thermophilus HB8 is homologous to IPMDH from the mesophilic Escherichia coli , but has an approximately 17°C higher melting temperature. Its temperature optimum is 22–25°C higher than that of the E. coli enzyme; however, it i...
10.1038/nrmicro773
The title of this paper clearly indicates the importance of flexibility in temperature adapation, which is probed here by biophysical methods.
10.1073/pnas.0810185106
67,454,818
The proteasomal degradation of β-catenin mediated by the glycogen synthase kinase 3β (GSK3β) and destruction complex is the central step in the canonical Wnt signaling pathway. However, that there are branches of Wnt signaling pathways that do not depend on β-catenin/Tcf-mediated transcription activation has long been ...
10.1038/nrn2870
This study, to our knowledge, is the first attempt to discover additional GSK3 substrates using an unbiased screening approach. Identification of new GSK3 substrates will help to reveal novel functions of GSK3 signalling in the nervous system.
10.1242/jcs.03159
59,391,951
An essential step during the development of hippocampal neurons is the polarised outgrowth of a single axon. Recently, it has been suggested that inhibition of glycogen synthase kinase-3β (GSK-3β) via Akt/PKB-dependent phosphorylation of Ser9, specifically at the tip of the presumptive axon, is required for selective a...
10.1038/nrn2870
Using neurons from the GSK3α-Ser21A/GSK3β-Ser29A double knock-in mice, this study shows clearly that phosphorylation of GSK3s at their N-terminal serine residues is not necessary for neuronal polarization, although inactivation of GSK3s is still required.
10.1083/jcb.121.6.1409
100,773,900
We have previously shown that the neural adhesion molecules L1 and NCAM interact with each other to form a complex which binds more avidly to L1 than L1 to L1 alone (Kadmon, G., A. Kowitz, P. Altevogt, and M. Schachner. 1990a. J. Cell Biol. 110:193-208). This cis-association between L1 and NCAM is carbohydrate-dependen...
10.1038/nrn1349
This study provides the first evidence of a functional cis -interaction between adhesion molecules mediated by a glycan (see also references 39 and 48).
10.1046/j.1471-4159.2003.01537.x
41,089,385
Abstract Recognition molecules that carry carbohydrate structures regulate cell interactions during development and play important roles in synaptic plasticity and regeneration in the adult. Glycans appear to be involved in these interactions. We have searched for binding proteins for oligomannosidic structures using t...
10.1038/nrn1349
Description of an unconventional approach to identify receptors for glycans.
10.1046/j.1471-4159.2001.00042.x
109,155,377
Lecticans, a family of chondroitin sulfate proteoglycans, represent the largest group of proteoglycans expressed in the nervous system. We previously showed that the C‐type lectin domains of lecticans bind two classes of sulfated cell surface glycolipids, sulfatides and HNK‐1‐reactive sulfoglucuronylglycolipids (SGGLs)...
10.1038/nrn1349
An important contribution to the function of the HNK1 glycan in proteoglycan-mediated neuronal interactions.
10.1046/j.1471-4159.2002.01247.x
105,405,147
Abstract The L2/HNK‐1 carbohydrate is carried by many neural recognition molecules and is involved in neural cell interactions during development, regeneration in the peripheral nervous system, synaptic plasticity, and autoimmune‐based neuropathies. Its key structure consists of a sulfated glucuronic acid linked to lac...
10.1038/nrn1349
This study provides a basis for the identification of peptide mimics for the functions of the HNK1 glycan.
10.1126/science.1072699
62,247,072
In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of t...
10.1038/nrn1349
An important study on the role of chondroitin sulphate as a regulator of synaptic plasticity.
10.1146/annurev.biochem.72.121801.161809
83,294,514
▪ Abstract The four essential building blocks of cells are proteins, nucleic acids, lipids, and glycans. Also referred to as carbohydrates, glycans are composed of saccharides that are typically linked to lipids and proteins in the secretory pathway. Glycans are highly abundant and diverse biopolymers, yet their functi...
10.1038/nrn1349
A scholarly compilation of the functional consequences of glycosyltransferase deficiencies.
10.1186/1742-2094-9-151
82,959,572
Abstract Background Alzheimer’s disease (AD) is the most prevalent form of age-related dementia, and its effect on society increases exponentially as the population ages. Accumulating evidence suggests that neuroinflammation, mediated by the brain’s innate immune system, contributes to AD neuropathology and exacerbates...
10.1038/nrn3880
This study shows that unspecific immune activation maternally and postnatally in wild-type mice can induce full-blown AD pathology, thus causally linking (early) immune stimulation and the development of AD pathology.
10.1084/jem.20142322
104,394,971
Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2’s involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myel...
10.1038/nrn3880
These two publications show the importance and function of TREM2 in AD mouse models; that is, to promote the survival of activated microglia and myeloid cells, to recruit these cells to A β plaques through sensing for A β -associated lipids, and to modulate hippocampal A β burden.
10.1002/0471142700.nc0301s00
46,073,014
Abstract This unit begins with a discussion of the advantages and disadvantages of oligonucleotide synthesis using solid supports. The physical and chemical properties of solid‐phase supports are discussed in terms of their suitability for oligonucleotide synthesis. In addition, the unit outlines the properties of link...
10.1038/nrmicro841
A good account of some of the most exciting recent developments in diagnostic technology.
10.1101/gad.1256405
103,783,892
Our brain serves as a center for cognitive function and neurons within the brain relay and store information about our surroundings and experiences. Modulation of this complex neuronal circuitry allows us to process that information and respond appropriately. Proper development of neurons is therefore vital to the ment...
10.1038/nrn2056
An excellent review that extensively describes a variety of signalling cascades that mediate Rho GTPases and the associating factors.
10.1186/1749-8104-1-2
103,696,658
Abstract In the absence of external cues, neurons in vitro polarize by using intrinsic mechanisms. For example, cultured hippocampal neurons extend arbitrarily oriented neurites and then one of these, usually the one nearest the centrosome, begins to grow more quickly than the others. This neurite becomes the axon as i...
10.1038/nrn2056
An important paper showing the morphological and molecular differences between retinal ganglion cells in vivo and in vitro
10.1126/science.161.3837.186
20,387,591
We have found marked anatomical asymmetries between the upper surfaces of the human right and left temporal lobes. The planum temporale (the area behind Heschl's gyrus) is larger on the left in 65 percent of brains; on the right it is larger in only 11 percent. The left planum is on the average one-third longer than th...
10.1038/nrn1009
This seminal report observed anatomical asymmetries in perisylvian brain structures that are involved in language. It ignited the interest in anatomical asymmetry, using post-mortem and imaging methods.
10.1098/rstb.2001.0915
62,233,745
Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four–dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being c...
10.1038/nrn1009
This paper describes the efforts of an international consortium to build an image database of the human brain that encodes statistical information on anatomical and functional variation. The resulting reference system stores brain maps from multiple imaging devices, and can be used to assess group differences in brain ...
10.1017/s1355617701245123
62,679,946
A few years ago, at the end of a lecture on handedness, a neuropsychology graduate student asked, “Why should I care about handedness? Left-handedness is not a disease.” She had missed the main point of the lecture, namely that left-handedness is an exciting experiment of nature. In the left-hander we find the opportun...
10.1038/nrn1009
This book provides an overview of studies that assess sex differences in brain structure and function.
10.1085/jgp.59.1.1
4,507,724
A cross-correlation technique has been applied to quantify the dependence of the dynamic characteristics of retinal ganglion cell responses in goldfish on intensity, wavelength, spatial configuration, and spot size. Both theoretical and experimental evidence justify the use of the cross-correlation procedure which allo...
10.1038/nrn1668
This paper provided experimental evidence for a positive role of noise in sensory systems, which was largely overlooked until the idea was re-examined recently in references 24 and 25.
10.1126/science.1070291
62,031,278
Three-dimensional (3D) movement of neuroprosthetic devices can be controlled by the activity of cortical neurons when appropriate algorithms are used to decode intended movement in real time. Previous studies assumed that neurons maintain fixed tuning properties, and the studies used subjects who were unaware of the mo...
10.1038/nrn1668
This paper showed that, with a learning algorithm, relatively few cortical neurons in a monkey could generate improved real-time control of movements in three dimensions. It provided a proof-of-principle for the implantation of electrode arrays in the motor cortex of severely disabled humans, as mentioned in the text.
10.1002/hipo.450030307
125,121,675
Abstract Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroer cephalograph theta pattern of rhythmical waves (7–12 Hz) is better correlated with a class of movements that change ...
10.1038/nrn1668
This paper described how the relationship between spike and slow rhythms could be used to code information about the place of an animal with respect to a preferred location.
10.1126/science.274.5292.1527
103,816,661
Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in...
10.1038/nrn1429
The first study to associate a polymorphism in the 5-HTT gene with anxiety traits in a healthy population.
10.1126/science.1083968
20,668,598
In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depre...
10.1038/nrn1429
A longitudinal population study showing that a gene–environment interaction between probable assessments of early childhood maltreatment or life stressors and the short 5-HTT promoter polymorphism influences the incidence of depression in adulthood. This was the first study to implicate a specific gene–environment inte...
10.1073/pnas.95.9.5335
104,392,429
The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantial...
10.1038/nrn1429
This research revealed a correlation between levels of maternal care and anxiety-related behaviour of adult rats.
10.1083/jcb.200110108
103,481,264
Trophic factor deprivation (TFD)-induced apoptosis in sympathetic neurons requires macromolecular synthesis–dependent BAX translocation, cytochrome c (cyt c) release, and caspase activation. Here, we report the contributions of other intrinsic and extrinsic pathway signals to these processes. Sympathetic neurons expres...
10.1038/nrn1477
Analysis of intrinsic apoptosis of trophic-factor-deprived neonatal sympathetic neurons, and potassium-deprived cerebellar granule neurons from BAX −/− , BAK −/− , BIM −/− , BID −/− and BAD −/− mice. The authors propose that BAX exists in an equilibrium between a cytosolic state in the presence of trophic factors, and ...
10.1083/jcb.147.5.1049
58,551,663
About 50% of spinal motoneurons undergo programmed cell death (PCD) after target contact, but little is known about how this process is initiated. Embryonic motoneurons coexpress the death receptor Fas and its ligand FasL at the stage at which PCD is about to begin. In the absence of trophic factors, many motoneurons d...
10.1038/nrn1477
Shows actively triggered FAS–FASL-mediated cell death of motor neurons during PCD, and neurotrophin-mediated supression of FAS/FASL death by FLIP.
10.1111/j.1471-4159.2004.02357.x
83,133,863
Abstract Reactive astrocytes frequently surround degenerating motor neurons in patients and transgenic animal models of amyotrophic lateral sclerosis (ALS). We report here that reactive astrocytes in the ventral spinal cord of transgenic ALS‐mutant G93A superoxide dismutase (SOD) mice expressed nerve growth factor (NGF...
10.1038/nrn1477
p75 NTR expression in spinal motor neurons of mice with ALS, and blocking antibodies to p75 NTR suppressed NGF-mediated motor neuron death in vitro
10.1083/jcb.200307130
19,463,477
In sympathetic neurons, unlike most nonneuronal cells, growth factor withdrawal–induced apoptosis requires the development of competence in addition to cytochrome c release to activate caspases. Thus, although most nonneuronal cells die rapidly with cytosolic cytochrome c alone, sympathetic neurons are remarkably resis...
10.1038/nrn1477
This paper demonstrates that XIAP functions as a 'safety brake' in sympathetic neurons and is a key player in the resistance (or competence pathway) of sympathetic neurons to apoptotic death. Neuronal cell death fails to occur on endogenous mitochondrial SMAC and cytochrome c release, unless XIAP levels are reduced, in...
10.1046/j.1365-2958.1998.00706.x
122,715,281
Pili, which are assembled from protein subunits called pilin, are indispensable for the adhesion of capsulated Neisseria meningitidis (MC) to eukaryotic cells. Both MC and Neisseria gonorrhoeae (GC) pilins are glycosylated, but the effect of this modification is unknown. In GC, a galactose α‐1,3‐ N ‐acetyl glucosamine ...
10.1038/nrmicro885
The authors identify the MC pilin glycosylation site at Ser63 and show that glycosylation does not have an important role in pilus assembly or adhesion but is required for expression of S pilin.
10.1046/j.1365-2958.1999.01184.x
122,660,836
Understanding the structural biology of type IV pili, fibres responsible for the virulent attachment and motility of numerous bacterial pathogens, requires a detailed understanding of the three‐dimensional structure and chemistry of the constituent pilin subunit. X‐ray crystallographic refinement of Neisseria gonorrhoe...
10.1038/nrmicro885
The covalently linked phosphate at Ser63 of GC pilin was removed by mutation (Ser to Ala), producing pili that were functionally indistinguishable from the wild type in vitro , but were less straight and more bundled, indicating that the phosphate might have a minor role in pilus assembly.
10.1046/j.1365-2958.2000.01764.x
38,398,146
The toxin‐co‐regulated pilus (TCP), a type 4 pilus that is expressed by epidemic strains of Vibrio cholerae O1 and O139, is required for colonization of the human intestine. The TCP structure is assembled as a polymer of repeating subunits of TcpA pilin that form long fibres, which laterally associate into bundles. Pre...
10.1038/nrmicro885
Discrete functional domains are identified in the D-region of V. cholerae TcpA. The first two-thirds of the D-region are required for pilin folding and/or pilus assembly and are predicted to be buried in the TCP filament, and the last third of the D-region is involved in pilus–pilus interactions and predicted to be sur...
10.1111/j.1365-2958.1994.tb00348.x
41,735,210
Summary Pili are one of the adhesins of Pseudomonas aeruginosa that mediate adherence to epithelial cell‐surface receptors. The pili of P. aeruginosa strains PAK and PAO were examined and found to bind gangliotetraosyl ceramide (asialo‐GM 1 ) and, to a lesser extend, ll 3 N ‐acetylneuraminosylgangliotetraosyl ceramide ...
10.1038/nrmicro885
The authors present strong evidence that the receptor-binding region of PAK pilin is buried along the length of the pilus filament and only exposed at its tip.
10.1046/j.1365-2958.1997.4841857.x
18,820,534
Pili of Neisseria gonorrhoeae and Neisseria meningitidis mediate binding of the bacteria to human cell‐surface receptors. We found that purified pili bound to a 55‐ to 60‐kDa doublet band on SDS–PAGE of separated human epithelial cell extracts. This is a migration pattern typical of membrane cofactor protein (MCP or CD...
10.1038/nrmicro885
Identified the cell surface receptor for N. gonorrhoeae and established a direct interaction between GC pili and CD46.
10.1073/pnas.121171698
82,949,695
Type IV pili are thin filaments that extend from the poles of a diverse group of bacteria, enabling them to move at speeds of a few tenths of a micrometer per second. They are required for twitching motility, e.g., in Pseudomonas aeruginosa and Neisseria gonorrhoeae , and for social gliding motility in Myxococcus xanth...
10.1038/nrmicro885
A direct demonstration that twitching motility is driven by type IV pilus retraction. Total internal reflection microscopy was used to record extension and retraction of fluorescently labelled type IV pili at rates of 0.5 μm s −1 in P. aeruginosa , and showed that pilus retraction propelled cells forward.
10.1046/j.1365-2958.2002.03193.x
102,730,091
Summary The mechanisms by which DNA is taken up into the bacterial cell during natural genetic transformation are poorly understood. Although related components essential to the uptake of DNA during transforma‐tion have been defined in Gram‐negative species, it remains unclear whether DNA binding and uptake are dissoci...
10.1038/nrmicro885
Demonstrated that DNA binding and uptake occur in two discrete steps, with DNA binding requiring type IV pili and ComP, and DNA uptake requiring functional PilT.
10.1126/science.272.5270.1910
62,359,437
Vibrio cholerae , the causative agent of cholera, requires two coordinately regulated factors for full virulence: cholera toxin (CT), a potent enterotoxin, and toxin-coregulated pili (TCP), surface organelles required for intestinal colonization. The structural genes for CT are shown here to be encoded by a filamentous...
10.1038/nrmicro885
Identified the filamentous phage CTXφ, which carries the structural genes for cholera toxin, and showed that CTXφ uses the V. cholerae TCP as its receptor.
10.1523/jneurosci.13-05-01862.1993
81,798,070
The gymnotiform fish Eigenmannia generates weakly electric signals for electrolocation and communication. The signals are produced by electric organ discharges (EODs) that are driven by a medullary pacemaker nucleus. To avoid jamming by neighboring conspecifics with similar frequencies, a fish raises its own EOD freque...
10.1038/nrn1558
Previously, it was thought that JAR-related increases and decreases in the pacemaker frequency were controlled by a single region, the prepacemaker nucleus. This study showed that a second region, the sublemniscal prepacemaker nucleus, is important for controlling frequency decreases.
10.1002/cne.11041
100,446,292
Abstract Phase‐locking neurons in the electrosensory lateral line lobe (ELL) of a weakly electric fish, Gymnarchus niloticus , fire an action potential in response to each cycle of the sinusoidal electrosensory signal (350–500 Hz) created by the fish's own electric organ. The exact firing times of the phase‐locking neu...
10.1038/nrn1558
This investigation showed that sign-selective neurons are present in the midbrain of this African electric fish. This finding, predicted by behavioural studies, makes the case that concurrent analysis of amplitude and phase difference information served as a preadaptation for the evolution of JARs.
10.1152/jn.1976.39.4.713
109,418,501
A signal associated with the neural command to discharge the electric organ is recorded in cells of the lateral line lobe. Responses of cells activated by medium receptor inputs are facilitated or less frequently inhibited during this command-associated signal. Only responses to disynaptic inputs are affected, the mono...
10.1038/nrn1558
The first evidence that mormyrid electric fish use corollary discharge information to evaluate electrosensory information, showing that sensory input was blocked if it was timed to the fish's command to produce an EOD.
10.1126/science.7291985
109,170,776
In electric fish of the mormyrid family, an efference copy is present in the brain region that receives afferent input from ampullary electroreceptors. The efference copy is elicited by the motor command to fire the electric organ. Its effect is always opposite that of ampullary afferents responding to the electric org...
10.1038/nrn1558
This study showed that mormyrids can construct a 'negative image' of the expected reafferent (self induced) ampullary-type electrosensory information, and that this 'efference copy' is plastic; it can be modified, based on experience, to precisely cancel the sensory effects of its own electric organ discharges.
10.1681/asn.v10122569
125,284,284
Abstract . An increase in Na + /glucose cotransport upstream to the macula densa might contribute to the increase in single nephron GFR (SNGFR) in early diabetes mellitus by lowering the signal of the tubuloglomerular feedback, i.e. , the luminal Na + , Cl - , and K + concentration sensed by the macula densa. To examin...
10.1038/nrneph.2016.75
Using an experimental diabetic model this study demonstrates that an increase in proximal tubular reabsorption of sodium leads to increased GFR by deactivation of tubuloglomerular feedback.
10.1152/ajprenal.00333.2011
61,605,877
Metabolic syndrome (MetS) is associated with glomerular hyperfiltration and is a risk factor for chronic kidney disease, but the underlying mechanisms are poorly defined. This study tested the hypothesis that increased glomerular filtration rate (GFR) in early MetS is associated with renal adiposity and microvascular p...
10.1038/nrneph.2016.75
This experimental study is the first to link renal triglycerides to functional and microvascular hyperfiltration.
10.2337/db06-1642
29,346,222
OBJECTIVE—Recent studies indicate an important role for nuclear receptors in regulating lipid and carbohydrate metabolism, fibrosis, and inflammation. Farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily. FXR is highly expressed in the liver, intestine, adrenal gland, and kidney. The prima...
10.1038/nrneph.2016.75
This study is the first to show regulation and beneficial effects of FXR in the diabetic kidney.
10.1126/science.283.5398.80
103,170,286
The genome of the human immunodeficiency virus (HIV) is packaged within an unusual conical core particle located at the center of the infectious virion. The core is composed of a complex of the NC (nucleocapsid) protein and genomic RNA, surrounded by a shell of the CA (capsid) protein. A method was developed for assemb...
10.1038/nrmicro3503
This paper established the first molecular models to explain the fullerene-cone structure of the HIV-1 core.
10.1186/1742-4690-10-20
61,826,209
Abstract Background Despite intensive investigation the mechanism by which HIV-1 reaches the host cell nucleus is unknown. TNPO3, a karyopherin mediating nuclear entry of SR-proteins, was shown to be required for HIV-1 infectivity. Some investigators have reported that TNPO3 promotes HIV-1 nuclear import, as would be e...
10.1038/nrmicro3503
An elegant molecular study establishing an assay to differentiate between 2-LTR circles and auto-integrants that is critical for understanding the roles of cellular factors and the stages in the lifecycle at which they act.
10.1073/pnas.93.23.13239
102,451,974
The proneural genes encode basic-helix–loop–helix (bHLH) proteins and promote the formation of distinct types of sensory organs. In Drosophila , two sets of proneural genes, atonal ( ato ) and members of the achaete–scute complex ( ASC ), are required for the formation of chordotonal (ch) organs and external sensory (e...
10.1038/nrn874
By analysing the properties of chimeric genes of ato and sc , this paper provided the first indication that the specificity of proneural gene function might depend on interactions with cofactors.
10.1242/dev.126.3.525
41,743,367
Previous studies have shown that mice mutant for the gene Mash1 display severe neuronal losses in the olfactory epithelium and ganglia of the autonomic nervous system, demonstrating a role for Mash1 in development of neuronal lineages in the peripheral nervous system. Here, we have begun to analyse Mash1 function in th...
10.1038/nrn874
References 43 and 46 first showed the importance of proneural gene activity for the development of the vertebrate CNS.
10.1101/gad.14.1.67
128,851,054
Neurogenin1 ( Ngn1 ), Neurogenin2 ( Ngn2 ), and Mash1 encode bHLH transcription factors with neuronal determination functions. In the telencephalon, the Ngns and Mash1 are expressed at high levels in complementary dorsal and ventral domains, respectively. We found that Ngn function is required to maintain these two sep...
10.1038/nrn874
This paper and reference 59 showed that proneural genes are involved in the specification of neuronal identity in the forebrain and spinal cord, respectively, and that distinct neuroepithelial domains of proneural gene expression are established through cross-inhibition.
10.1242/dev.125.4.609
41,595,376
We have investigated the genetic circuitry underlying the determination of neuronal identity, using mammalian peripheral autonomic neurons as a model system. Previously, we showed that treatment of neural crest stem cells (NCSCs) with bone morphogenetic protein-2 (BMP-2) leads to an induction of MASH1 expression and co...
10.1038/nrn874
References 130 and 131 show by complementary LOF and GOF approaches that Mash1 is a determinant of noradrenergic neuron identity.
10.1073/pnas.0705837104
41,333,572
West Nile virus (WNV) has emerged as a significant cause of epidemic viral encephalitis and flaccid limb paralysis, yet the mechanism by which it enters the CNS remains uncertain. We used compartmentalized neuron cultures to demonstrate that WNV spreads in both retrograde and anterograde directions via axonal transport...
10.1038/nrmicro2395
This study uses a combination of in vivo and in vitro techniques to characterize axonal transport of WNV and the subsequent flaccid paralysis.
10.1083/jcb.136.5.1007
123,224,115
Herpes simplex virus 1 fuses with the plasma membrane of a host cell, and the incoming capsids are efficiently and rapidly transported across the cytosol to the nuclear pore complexes, where the viral DNA genomes are released into the nucleoplasm. Using biochemical assays, immunofluorescence, and immunoelectron microsc...
10.1038/nrmicro2395
This is one of the first mechanistic investigations of the molecular mechanism used by HSV-1 to reach the nucleus.
10.1073/pnas.061029798
123,535,537
Alpha herpesviruses infect the vertebrate nervous system resulting in either mild recurrent lesions in mucosal epithelia or fatal encephalitis. Movement of virions within the nervous system is a critical factor in the outcome of infection; however, the dynamics of individual virion transport have never been assessed. H...
10.1038/nrmicro2395
This article reports a detailed analysis of the bidirectional transport dynamics of herpesviruses. This paper and reference 78 are two of the first studies to image live transport of herpesviruses and to identify the potential viral proteins involved in this process.
10.1073/pnas.0404686101
103,285,331
The core structures of many viruses move within cells by association with host cytoskeletal motor proteins; however, the mechanisms by which intracellular viral particles are transported toward sites of replication or the cell periphery at distinct stages of infection remain to be understood. The regulation of herpesvi...
10.1038/nrmicro2395
This study shows the different velocities of entering versus egressing herpesviruses. Axonal transport of the viruses is shown to occur outside endosomes.
10.1073/pnas.1315710110
20,421,745
Significance Using 3D culture of human ES cells, we show new self-organizing aspects of human corticogenesis: spontaneous development of intracortical polarity, curving morphology, and complex zone separations. Moreover, this culture generates species-specific progenitors, outer radial glia, which are abundantly presen...
10.1038/nrn.2017.107
This study provided a detailed exploration of brain organoid tissue including the temporal and spatial organization of cell type diversity and patterning.
10.1152/physrev.00030.2007
125,267,537
The calcium ion (Ca 2+ ) is the simplest and most versatile intracellular messenger known. The discovery of Ca 2+ sparks and a related family of elementary Ca 2+ signaling events has revealed fundamental principles of the Ca 2+ signaling system. A newly appreciated “digital” subsystem consisting of brief, high Ca 2+ co...
10.1038/nrn3168
A comprehensive review of calcium sparks in different cell types that emphasizes results from cardiac myocytes. A good starting point for exploring this field.
10.1152/jn.1996.76.1.554
95,477,463
1. Ca2+ imaging and simultaneous intracellular recording were performed on CA3 pyramidal neurons in hippocampal slice cultures and standard acute slices. Both fura-2 and a dextran conjugate of fura-2 (MW = 10,000) were used in the Ca2+ measurements to control for compartmentalization artifacts. Experiments were perform...
10.1038/nrn3168
This is the first description of synaptically activated calcium release in neurons in a brain slice preparation.
10.1113/jphysiol.2002.020362
17,793,057
Postsynaptic [Ca 2+ ] i increases result from Ca 2+ entry through ligand‐gated channels, entry through voltage‐gated channels, or release from intracellular stores. We found that these sources have distinct spatial distributions in hippocampal CA1 pyramidal neurons. Large amplitude regenerative release of Ca 2+ from IP...
10.1038/nrn3168
An interesting paper that emphasizes that synaptically activated calcium entry through NMDA receptors and synaptically activated calcium waves occur in different dendritic regions.
10.1152/jn.1994.72.1.471
10,314,137
1. We investigated the effects of metabotropic glutamate (mGlu) receptor activation on intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons. Changes in [Ca2+]i were measured using confocal imaging simultaneously with whole-cell recording techniques. Differences in [C...
10.1038/nrn3168
This is the first observation and analysis of calcium waves in neuronal dendrites. Activation by focally applying the mGluR agonist t-ACPDsuggested a role for IP 3 -mediated calcium release in generating the waves.
10.1073/pnas.0905110106
81,144,535
Synaptic plasticity is considered essential for learning and storage of new memories. Whether all synapses on a given neuron have the same ability to express long-term plasticity is not well understood. Synaptic microanatomy could affect the function of local signaling cascades and thus differentially regulate the pote...
10.1038/nrn3168
An important paper showing that uncaging glutamate over single spines evokes delayed calcium release and LTD only in those cases where the endoplasmic reticulum penetrates the spine. Blockage by mGluR antagonists and heparin suggested that the calcium release was mediated by IP 3
10.1126/science.8235594
82,772,006
Spontaneous local increases in the concentration of intracellular calcium, called "calcium sparks," were detected in quiescent rat heart cells with a laser scanning confocal microscope and the fluorescent calcium indicator fluo-3. Estimates of calcium flux associated with the sparks suggest that calcium sparks result f...
10.1038/nrn3168
The first description of stochastic, RyR-mediated, calcium sparks in myocytes. Together with reference 100, these papers initiated the field of localized calcium events in cells.
10.1126/science.2237441
81,378,418
Laser confocal microscopy was used to monitor calcium ion (Ca 2+ ) liberation from highly localized (micrometer) regions of intact Xenopus oocytes in response to photo-released inositol 1,4,5-trisphosphate (InsP 3 ). Local Ca 2+ release varied in an all-or-none manner with increasing amount of InsP 3 , in contrast to s...
10.1038/nrn3168
The first description of localized IP 3 -evoked calcium release puffs. The oocyte proved to be a favourable preparation for studying these signals as it contains few, if any, RyRs.
10.1146/annurev.genom.9.081307.164220
102,657,331
Intensive study of a few genetically tractable species with XX/XY sex chromosomes has produced generalizations about the process of sex chromosome dosage compensation that do not fare well when applied to ZZ/ZW sex chromosome systems, such as those in birds. The inherent sexual imbalance in dose of sex chromosome genes...
10.1038/nrn2754
This excellent review not only describes mechanisms of sex chromosome dosage compensation in birds but also describes and compares these mechanisms with those present in other species, including mammals.
10.1073/pnas.0505909103
58,446,851
Voltage-gated channels maintain cellular resting potentials and generate neuronal action potentials by regulating ion flux. Here, we show that Ether-à-go-go (EAG) K + channels also regulate intracellular signaling pathways by a mechanism that is independent of ion flux and depends on the position of the voltage sensor....
10.1038/nrn1988
Demonstrated that the voltage-dependent gating of the EAG channel controls the MAP kinase signalling pathway and cell proliferation by a mechanism that is independent of K + flux through the channel.
10.1126/science.1058519
62,416,831
We cloned and characterized a protein kinase and ion channel, TRP-PLIK. As part of the long transient receptor potential channel subfamily implicated in control of cell division, it is a protein that is both an ion channel and a protein kinase. TRP-PLIK phosphorylated itself, displayed a wide tissue distribution, and, ...
10.1038/nrn1988
Demonstrated that the TRPM7 non-selective cation channel has intrinsic protein kinase activity that can phosphorylate itself and exogenous substrates, and that this kinase activity is essential for channel function.
10.1523/jneurosci.1517-05.2005
123,585,373
Normal functioning of the nervous system requires precise regulation of dendritic shape and synaptic connectivity. Here, we report a severe impairment of dendritic structures in the cerebellum and motor cortex of c-Jun N-terminal kinase 1 (JNK1)-deficient mice. Using an unbiased screen for candidate mediators, we ident...
10.1038/nrn3729
This study shows that dendrite architecture is disturbed in cerebellar granule neurons isolated from Jnk1 −/− mice.
10.1111/j.1460-9568.2005.03857.x
82,733,405
Abstract We have investigated the effect of JNK1 ko, JNK2 ko, JNK3 ko, JNK2+3 ko and c‐JunAA mutation on neuronal survival in adult transgenic mice following ischemia, 6‐hydroxydopamine induced neurotoxicity, axon transection and kainic acid induced excitotoxicity. Deletion of JNK isoforms indicated the compartment‐spe...
10.1038/nrn3729
A biochemical characterization of JNK isoform expression in the rodent brain.
10.1111/j.1471-4159.2005.03037.x
19,047,319
Abstract c‐Jun N‐terminal kinases (JNKs) are thought to be involved in regulating synaptic plasticity. We therefore investigated the specific role of JNK2 in modulating long‐term potentiation (LTP) in hippocampus during development, using JNK2‐deficient mice. The morphological structure and the numbers of both NeuN, a ...
10.1038/nrn3729
A study showing that LTP is impaired in Jnk2 −/− mice.
10.1523/jneurosci.2625-06.2006
81,795,263
A critical transition in neuron development is formation of the axon, which establishes the polarized structure of the neuron that underlies its entire input and output capabilities. The morphological events that occur during axonogenesis have long been known, yet the molecular determinants underlying axonogenesis rema...
10.1038/nrn3729
A study demonstrating that JNK activity is important for axonal growth.
10.1111/j.1471-4159.2005.03580.x
103,164,565
Abstract Large numbers of neurons are eliminated by apoptosis during nervous system development. For instance, in the mouse dorsal root ganglion (DRG), the highest incidence of cell death occurs between embryonic days 12 and 14 (E12–E14). While the cause of cell death and its biological significance in the nervous syst...
10.1038/nrn3729
This report shows that JNK is activated by the guidance molecule semaphorin 3A.
10.1523/jneurosci.4491-11.2011
42,506,382
Phosphorylation plays a central role in the dynamic regulation of the processing of the amyloid precursor protein (APP) and the production of amyloid-β (Aβ), one of the clinically most important factors that determine the onset of Alzheimer's disease (AD). This has led to the hypothesis that aberrant Aβ production asso...
10.1038/nrn3729
The study validates that JNK activity contributes to the formation of amyloid plaques in vivo using mice with targeted deletion of Mkk4 and Mkk7 in the nervous system.
10.1111/j.0022-3646.1991.00395.x
62,444,690
ABSTRACT Scytonemin, the yellow‐brown pigment of cyanobacterial (blue‐green algal) extracellular sheaths, was found in species thriving in habitats exposed to intense solar radiation. Scytonemin occurred predominantly in sheaths of the outermost parts or top layers of cyanobacterial mats, crusts, or colonies. Scytonemi...
10.1038/nrmicro2649
The first study of scytonemin in the modern era; it provided a foundation for our understanding of the ecology and physiology of scytonemin, and ignited interest in microbial sunscreens.
10.1139/w98-119
62,385,590
The relationship of polyketide melanogenesis molecular biology to that of nonmelanin-producing pathways in a wide range of fungi and other organisms is discussed. Analytical methods and fundamental properties of melanins are discussed and fungal melanin properties are compared with those of animal and bacterial melanin...
10.1038/nrmicro2649
A comprehensive, critical review on fungal melanins. A 'must read'.
10.1111/j.1751-1097.1992.tb09596.x
124,878,010
Abstract— The proposed photoprotective role of the UV‐A absorbing, extracellular pigment scytonemin was studied in the terrestrial cyanobacterium Chlorogloeopsis sp. strain O‐89‐Cgs(1). UV‐A (315–400 nm) caused growth delay, cell growth restarting only when scytonemin had accumulated in the extracellular envelopes. Cul...
10.1038/nrmicro2649
This paper was the first to provide strong evidence for the proposed protective role of scytonemin as a passive UVA sunscreen.
10.1146/annurev.physiol.64.081501.155802
103,171,447
▪ Abstract Organisms living in clear, shallow water are exposed to the damaging wavelengths of solar ultraviolet radiation (UVR) coincident with the longer wavelengths of photosynthetically available radiation (PAR) also necessary for vision. With the general exception of bacteria, taxonomically diverse marine and fres...
10.1038/nrmicro2649
A comprehensive review on the discovery, occurrence, physiology and ecology of mycosporines with an emphasis on the marine environment.
10.1111/j.1751-1097.1996.tb02435.x
103,851,401
Abstract A photoprotective role of ultraviolet radiation‐absorbing mycosporine‐like amino acids (MAAs) in eggs of the green sea urchin Strongylocentrotus droebachiensis was demonstrated by comparing UV‐induced delays in the first division of embryos having either high or low concentrations of MAAs. Embryos from adult u...
10.1038/nrmicro2649
A model demonstration of the role of dietary MAAs in metazoans.
10.1046/j.1529-8817.1998.340928.x
65,261,672
Marine phytoplankton are sensitive to inhibition of photosynthesis by solar ultraviolet (UV) radiation, although sensitivity varies, depending on the growth environment. A mechanism suggested to increase resistance to UV inhibition is the accumulation of UV‐absorbing compounds, such as the mycosporine‐like amino acids ...
10.1038/nrmicro2649
A model demonstration of the role of primary MAAs in phytoplankters.
10.1126/science.1193637
107,344,844
Enzymes for Sunscreen Synthesis Many fungi, cyanobacteria, algae, and other marine organisms can biosynthesize small molecules termed mycosporine and mycosporine-like amino acids (MAAs) that, among other functions, protect them from harmful UV exposure. A formulation containing MAAs is used as a sunscreen in skin care ...
10.1038/nrmicro2649
This 'must-read' contribution resolved much of the MAA biosynthetic pathway and its genetic basis in cyanobacteria.
10.1128/aem.60.10.3864-3866.1994
83,114,192
Melanized Cryptococcus neoformans cells were less susceptible than nonmelanized cells to the fungicidal effects of UV light. Phenoloxidase-catalyzed production of melanin-like pigments may serve to protect the fungus against ionizing radiation.
10.1038/nrmicro2649
This study demonstrates the photoprotective role of eumelanins in fungi.