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10.1146/annurev.ento.010908.164537
19,542,225
Among the so-called simpler organisms, the honey bee is one of the few examples of an animal with a highly evolved social structure, a rich behavioral repertoire, an exquisite navigational system, an elaborate communication system, and an extraordinary ability to learn colors, shapes, fragrances, and navigational route...
10.1038/nrn3357
An excellent review on the visual system of the honeybee.
10.1177/1534582306289522
100,838,194
This review provides evidence for the enormous richness of insect behavior, its high flexibility, and the cross-talk between different behavioral routines. The memory structure established by multiple forms of learning represents sensory inputs and relates behaviors in such a way that representations of complex environ...
10.1038/nrn3357
This study reports the neural substrates of learning in the bee brain and other aspects of honeybee cognition.
10.1073/pnas.0408550102
20,678,576
By using harmonic radar, we report the complete flight paths of displaced bees. Test bees forage at a feeder or are recruited by a waggle dance indicating the feeder. The flights are recorded after the bees are captured when leaving the hive or the feeder and are released at an unexpected release site. A sequence of be...
10.1038/nrn3357
Using a novel device to track bees in flight, this reports the first convincing data that honeybees navigate according to Tolman's definition of a cognitive map.
10.1126/science.7638604
41,648,394
Neurophysiologists have documented the existence of multiple cortical areas responsive to different visual features. This modular organization has sparked theoretical interest in how the "binding problem" is solved. Recent data from a neurological patient (R.M.) with bilateral parietal-occipital lesions demonstrates th...
10.1038/nrn1030
This was the first study to report that feature binding resulted from bilateral parietal damage — lesions that produce a rare neuropsychological condition known as Balint's syndrome. The damage disrupts the ability to perceive the location of features and objects that are clearly seen and accurately named. The binding ...
10.1073/pnas.152694799
100,737,011
When multiple objects are simultaneously present in a scene, the visual system must properly integrate the features associated with each object. It has been proposed that this “binding problem” is solved by selective attention to the locations of the objects [Treisman, A.M. & Gelade, E. (1980) Cogn. Psychol. 12, 97...
10.1038/nrn1030
This study demonstrated that parietal activation in binding was present when stimuli were simultaneously presented in different locations but not when they were sequentially presented in the same location, consistent with findings from the Balint's syndrome patient 'RM' (reference 10) and supporting the role of space i...
10.1111/j.1460-9568.1990.tb00450.x
45,383,672
Abstract Previously we have demonstrated that neurons in the striate cortex of lightly anaesthetized cats exhibit oscillatory responses at a frequency near 50 Hz in response to their preferred stimuli. Here we have used both single and multiple unit recording techniques to determine: (i) the receptive field properties ...
10.1038/nrn1030
This evidence, for in-phase oscillations, was presented three years earlier at a Society for Neurosciences meeting. It is generally credited as the first public report of temporal correlation between neurons in unit formation and also as the beginning of the study of synchronous neural activity in perception.
10.1002/0470018860.s00295
39,362,576
Abstract Synaesthesia is experienced when stimulation of one sensory modality gives rise to a perception in a second modality, without that second modality having received any direct stimulation.
10.1038/nrn1030
In this chapter, Maurer proposes that all infants are synaesthetic owing to the massive synaptic connections that are present at birth. These connections are pruned extensively throughout early development, with modularity also developing during this period. Adult synaesthesia could be explained by residual connections...
10.1126/science.1097065
41,104,110
Inherited channelopathies are at the origin of many neurological disorders. Here we report a form of channelopathy that is acquired in experimental temporal lobe epilepsy (TLE), the most common form of epilepsy in adults. The excitability of CA1 pyramidal neuron dendrites was increased in TLE because of decreased avail...
10.1038/nrn2371
This study provided the first description of altered dendritic channels in chronic epilepsy. In this case the alteration was a downregulation of A-type K + channels.
10.1126/science.7079735
104,277,757
Interictal spikes are a simple kind of epileptic neuronal activity. Field potentials and intracellular recordings observed during interictal spikes of penicillin-treated slices of the hippocampus were reproduced by a mathematical model of a network of 100 hippocampal neurons from the region including CA2 and CA3. The m...
10.1038/nrn2371
This modelling study suggested that intrinsically bursting neurons are instrumental in synchronizing neuronal ensembles.
10.1126/science.175.4017.82
79,432,018
Male rats were exposed to prenatal or postnatal stress, or both. The prenatally stressed males showed low levels of male copulatory behavior and high rates of female lordotic responding. Postnatal stress had no effect. The modifications are attributed to stress-mediated alterations in the ratio of adrenal to gonadal an...
10.1038/nrn3818
This is one of the first studies to determine the importance of sex-specific neurodevelopmental programming that can be disrupted by maternal stress.
10.1210/en.2008-0633
80,121,339
Chronic early-life stress (ES) exerts profound acute and long-lasting effects on the hypothalamic-pituitary-adrenal system, with relevance to cognitive function and affective disorders. Our ability to determine the molecular mechanisms underlying these effects should benefit greatly from appropriate mouse models becaus...
10.1038/nrn3818
This novel and reproducible model shows how disruptions in maternal care can manifest in reprogramming of offspring stress pathways in the brain.
10.1159/000322038
60,486,645
The perinatal environment plays an important role in programming many aspects of physiology and behavior including metabolism, body weight set point, energy balance regulation and predisposition to mental health-related disorders such as anxiety, depression and attention deficit hyperactivity disorder. Maternal health ...
10.1038/nrn3818
This paper examines the sex-specific neurodevelopmental programming and resulting increased anxiety in the non-human primate that follows exposure to a maternal high-fat diet during pregnancy.
10.1159/000079744
18,048,628
Amphioxus has an assortment of cells and organs for sensing light and mechanical stimuli. Vertebrate counterparts of these structures are not always apparent, and a strong case can be made for homology in only a few instances. For example, amphioxus has anatomically simple but plausible homologs of both the pineal and ...
10.1038/nrn2283
This paper provides a summary of the rhabdomeric and ciliary photoreceptor organs in the primitive chordate amphioxus.
10.1126/science.1099955
19,079,482
For vision, insect and vertebrate eyes use rhabdomeric and ciliary photoreceptor cells, respectively. These cells show distinct architecture and transduce the light signal by different phototransductory cascades. In the marine rag-worm Platynereis , we find both cell types: rhabdomeric photoreceptor cells in the eyes a...
10.1038/nrn2283
This study presents the discovery that an invertebrate (protostome) species possessed ciliary photoreceptors expressing a ciliary opsin, in addition to rhabdomeric photoreceptors expressing a rhabdomeric opsin.
10.1242/dev.02678
107,385,964
Mechanisms for shaping and folding sheets of cells during development are poorly understood. An example is the complex reorganisation of the forebrain neural plate during neurulation, which must fold a sheet into a tube while evaginating two eyes from a single contiguous domain within the neural plate. We, for the firs...
10.1038/nrn2283
By following the trajectories of individual identified cells, the authors of this study were able to track the morphological development of the zebrafish eye. This paper contains some excellent animations.
10.1073/pnas.0909181107
36,819,130
Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery ...
10.1038/nrmicro2737
A study in which metabolic networks are used to search for antimicrobials.
10.1113/jphysiol.2009.181917
107,134,533
Mammalian cochlear inner hair cells (IHCs) are specialized to process developmental signals during immature stages and sound stimuli in adult animals. These signals are conveyed onto auditory afferent nerve fibres. Neurotransmitter release at IHC ribbon synapses is controlled by L‐type Ca V 1.3 Ca 2+ channels, the biop...
10.1038/nrn2924
In this paper, single-channel recording from inner hair cells of the mouse cochlea provided additional estimates of the numbers of channels associated with each active zone ( ∼ 180 per ribbon) and the maximum open probability ( ∼ 0.15).
10.1073/pnas.0813213106
103,415,027
Sound coding at hair cell ribbon synapses is tightly regulated by Ca 2+ . Here, we used patch-clamp, fast confocal Ca 2+ imaging and modeling to characterize synaptic Ca 2+ signaling in cochlear inner hair cells (IHCs) of hearing mice. Submicrometer fluorescence hotspots built up and collapsed at the base of IHCs withi...
10.1038/nrn2924
Fluorescent calcium indicators and calcium channel immunolabeling were used in this study to chart 'active zones' in cochlear inner hair cells. The covariation in the number of calcium channels and ribbon size found in this study may provide a mechanism for diversifying the activity of postsynaptic afferent neurons.
10.1073/pnas.0709067105
78,060,674
Synaptic vesicles release neurotransmitter by following a process of vesicle docking and exocytosis. Although these steps are well established, it has been difficult to observe and measure these rates directly in living synapses. Here, by combining the direct imaging of single synaptic vesicles and synaptic ribbons, I ...
10.1038/nrn2924
Together with reference 18, this paper provided evidence for turnover of ribbon-associated synaptic vesicles during depolarization of retinal bipolar neurons.
10.1073/pnas.0705756104
45,490,598
At the first synapse in the auditory pathway, the receptor potential of mechanosensory hair cells is converted into a firing pattern in auditory nerve fibers. For the accurate coding of timing and intensity of sound signals, transmitter release at this synapse must occur with the highest precision. To measure directly ...
10.1038/nrn2924
This study showed that paired recordings from inner hair cells and type I afferent dendrites describe a 'linear' synaptic transfer function. This is explained by an increase in release probability, with no change in the average amplitude of postsynaptic currents.
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/nrn1297
The first demonstration of Ca 2+ entry into presynaptic terminals through an ionotropic presynaptic receptor.
10.1073/pnas.96.17.9932
40,067,626
Exogenous application of agonists at the kainate subtype of glutamate receptors has been shown to depress evoked monosynaptic inhibition by γ-aminobutyric acid (GABA)ergic interneurons in the hippocampus. This observation has led to the hypothesis that synaptic release of endogenous glutamate might have a disinhibitory...
10.1038/nrn1297
These authors showed that endogenously released glutamate could act on presynaptic kainate receptors.
10.1038/ncomms11934
62,156,012
Abstract Multifactorial mechanisms underlying late-onset Alzheimer’s disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral protei...
10.1038/nrn.2017.48
This was one of the largest and most comprehensive biomarker studies to show the early role of vascular dysregulation in memory dysfunction in AD prior to cerebral amyloidosis and tau-mediated neurodegeneration.
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/nrn.2017.48
This paper was the first to demonstrate altered neurovascular coupling by Aβ.
10.1002/ana.20493
82,451,837
Abstract Cerebral blood flow (CBF) velocity is decreased in patients with Alzheimer's disease. It is being debated whether this reflects diminished demand because of advanced neurodegeneration or that cerebral hypoperfusion contributes to dementia. We examined the relation of CBF velocity as measured with transcranial ...
10.1038/nrn.2017.48
This large population-based study showed that diminished CBF precedes cognitive decline and hippocampal atrophy.
10.1126/science.1067903
104,018,399
Neurons receive thousands of synaptic inputs throughout elaborate dendritic trees. Here we determine the somatic impact of excitatory postsynaptic potentials (EPSPs) generated at known dendritic sites in neocortical pyramidal neurons. As inputs became more distal, somatic EPSP amplitude decreased, whereas use-dependent...
10.1038/nrn1327
This study indicates that, in neocortical neurons, synaptic strength does not increase as a function of distance from the soma. This is in contrast to experiments in hippocampal neurons (see reference 106).
10.1126/science.2402638
83,056,391
Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been impli...
10.1038/nrn1585
A seminal study that indicated that the STN should be a key target in stereotactic neurosurgery for PD.
10.1159/000100803
80,726,168
Stereotactic thalamotomy of the thalamic nucleus ventralis intermedius (VIM) is routinely used for movement disorders. During this procedure, it has been observed that high-frequency (100 Hz) stimulation of VIM was able to stop the extrapyramidal tremor. In patients with bilateral tremor of extrapyramidal origin, who w...
10.1038/nrn1585
The first study to apply the technique of DBS in humans.
10.1126/science.8456317
59,868,806
Neurons maintain their electrical activity patterns despite channel turnover, cell growth, and variable extracellular conditions. A model is presented in which maximal conductances of ionic currents depend on the intracellular concentration of calcium ions and so, indirectly, on activity. Model neurons with activity-de...
10.1038/nrn1949
This theoretical paper was the first attempt to suggest that neuronal excitability might be controlled by a negative feedback, homeostatic mechanism in which the neuron's target activity is maintained despite channel turnover.
10.1146/annurev.neuro.28.061604.135751
105,322,886
Homeostasis is a specialized form of regulation that precisely maintains the function of a system at a set point level of activity. Recently, homeostatic signaling has been suggested to control neural activity through the modulation of synaptic efficacy and membrane excitability ( Davis & Goodman 1998a , Turrigiano...
10.1038/nrn1949
This review article provides a discussion of the outstanding questions relevant to homeostatic regulation. In particular, it addresses what is known about how targets for homeostatic regulation might be set.
10.1073/pnas.0308188100
107,062,282
At central synapses, P/Q-type Ca 2+ channels normally provide a critical Ca 2+ entry pathway for neurotransmission. Nevertheless, we found that nerve terminals lacking α 1A (Ca V 2.1), the pore-forming subunit of P/Q-type channels, displayed a remarkable preservation of synaptic function. Two consistent physiological c...
10.1038/nrn1949
Remarkably, genetic knockouts of the P/Q type Ca 2+ channel have relatively little effect on synaptic transmission, because of compensation by other mechanisms.
10.1126/science.281.5382.1515
81,658,668
Nerve growth is regulated by attractive and repulsive factors in the nervous system. Microscopic gradients of Collapsin-1/Semaphorin III/D (Sema III) and myelin-associated glycoprotein trigger repulsive turning responses by growth cones of cultured Xenopus spinal neurons; the repulsion can be converted to attraction by...
10.1038/nrn1254
References 20 and 226 showed that changes in the levels of cyclic nucleotides could qualitatively regulate axonal responses, which revealed not only a striking phenomenon, but also raises an interesting mechanistic question. Later work by the same and other groups also indicates that this is helpful for designing thera...
10.1126/science.281.5377.706
81,444,520
The unc-129 gene, like the unc-6 netrin gene, is required to guide pioneer motoraxons along the dorsoventral axis of Caenorhabditis elegans . unc-129 encodes a member of the transforming growth factor–β (TGF-β) superfamily of secreted signaling molecules and is expressed in dorsal, but not ventral, rows of body wall mu...
10.1038/nrn1254
The first report of genetic evidence indicating that a morphogen of the TGFβ family functions in axon guidance, possibly using a non-canonical TGFβ signalling pathway.
10.1126/science.50621
109,170,647
In Rana pipiens embryos, eye anlagen were moved to the evacuated ear position, where they continued to differentiate and sent their optic nerve fibers into the hindbrain. Upon entering the medulla, the optic fibers turned caudally, penetrated the spinal cord, and traversed the dorsolateral white matter to the caudal en...
10.1038/nrn1254
References 29 and 31 are the classic papers on the chemoaffinity hypothesis of axon guidance. A must-read for anyone entering the field.
10.1126/science.279.5347.105
58,564,343
Developing axons reach their final targets as a result of a series of axonal projections to successive intermediate targets. Long-range chemoattraction by intermediate targets plays a key role in this process. Growing axons, however, do not stall at the intermediate targets, where the chemoattractant concentration is e...
10.1038/nrn1254
An interesting paper showing that commissural axons are attracted by the floor plate (and netrin) before crossing the floor plate, but are not attracted by the floor plate or netrin after crossing.
10.1523/jneurosci.23-16-06651.2003
19,247,467
Interneurons in the olfactory bulb (OB) are generated not only in the developing embryo but also throughout the postnatal life of mammals from neuronal precursor cells migrating from the anterior subventricular zone (SVZa) of the mammalian forebrain. We discovered that the OB secretes a diffusible activity that attract...
10.1038/nrn1254
Evidence that there are more guidance cues to be defined molecularly, and that molecular cues might be used even in adult stages for directional guidance.
10.1242/dev.127.4.801
104,444,424
Neural receptor-linked protein tyrosine phosphatases (RPTPs) are required for guidance of motoneuron and photoreceptor growth cones in Drosophila. These phosphatases have not been implicated in growth cone responses to specific guidance cues, however, so it is unknown which aspects of axonal pathfinding are controlled ...
10.1038/nrn1254
In this study, RPTPs were found to interact with Slit/Robo signalling.
10.1126/science.1058445
59,543,960
Axonal growth cones that cross the nervous system midline change their responsiveness to midline guidance cues: They become repelled by the repellent Slit and simultaneously lose responsiveness to the attractant netrin. These mutually reinforcing changes help to expel growth cones from the midline by making a once-attr...
10.1038/nrn1254
This article provides a molecular basis for crosstalk between different guidance pathways (Slit/Robo and netrin/DCC) at the receptor level.
10.1038/ismej.2010.118
62,587,127
Abstract The populations of dominant species within the human colonic microbiota can potentially be modified by dietary intake with consequences for health. Here we examined the influence of precisely controlled diets in 14 overweight men. Volunteers were provided successively with a control diet, diets high in resista...
10.1038/nrmicro3344
This study is a carefully controlled human dietary trial that demonstrates rapid and reversible changes in the relative abundance of specific bacterial groups in response to carbohydrate intake.
10.1073/pnas.1322269111
41,673,717
Significance The mammalian intestines contain an enormous number of microorganisms within the lumen. Given the constant exposure to these microbes, the intestinal immune system has the difficult task of maintaining tolerance to commensal bacteria while remaining responsive to potential pathogens. The mechanisms by whic...
10.1038/nrmicro3344
This study provides evidence that the inhibition of HDACs by butyrate is responsible for anti-inflammatory effects in colonic macrophages.
10.1126/science.1241165
62,606,488
Protecting the Guts Regulatory T cells (T regs ) in the gut are important sentinels in maintaining the peace between our gut and its trillions of resident bacteria and have been shown to be regulated by specific strains of bacteria in mouse models. Smith et al. (p. 569 , published online 4 July; see the Perspective by ...
10.1038/nrmicro3344
This study shows that propionate has an anti-inflammatory effect via the modulation of cT Reg cells.
10.1126/science.1191175
41,714,003
Blocking Interfering Microbes Irinotecan is a widely used anticancer pro-drug that is converted in the liver into the active form, but when it gets into the gut, the normally benign microbial flora can convert it into the toxic form, which kills the rapidly multiplying gut epithelium as it would kill rapidly dividing t...
10.1038/nrmicro3344
This paper describes the design of an inhibitor that specifically targets bacterial β-glucuronidases, which protects against chemotherapy-associated toxicity in a mouse model.
10.1186/2049-2618-1-16
84,365,278
Abstract Background Numerous cancers have been linked to microorganisms. Given that colorectal cancer is a leading cause of cancer deaths and the colon is continuously exposed to a high diversity of microbes, the relationship between gut mucosal microbiome and colorectal cancer needs to be explored. Metagenomic studies...
10.1038/nrmicro3344
This study identifies a potential polymicrobial signature of Gram-negative anaerobic bacteria that is associated with CRC tissue.
10.1038/ismej.2011.109
41,669,885
Abstract Despite a long-suspected role in the development of human colorectal cancer (CRC), the composition of gut microbiota in CRC patients has not been adequately described. In this study, fecal bacterial diversity in CRC patients (n=46) and healthy volunteers (n=56) were profiled by 454 pyrosequencing of the V3 reg...
10.1038/nrmicro3344
This study finds that the faecal microbiota of patients with CRC and healthy controls differs.
10.1128/mbio.00692-13
41,594,890
ABSTRACT Recent studies have shown that individuals with colorectal cancer have an altered gut microbiome compared to healthy controls. It remains unclear whether these differences are a response to tumorigenesis or actively drive tumorigenesis. To determine the role of the gut microbiome in the development of colorect...
10.1038/nrmicro3344
This study provides evidence that the composition of the gut microbiota influences the development of carcinogen-induced tumours in the intestines of mice.
10.1073/pnas.92.5.1664
82,224,309
Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli O157:H7 are intestinal pathogens that profoundly damage the microvilli and subapical cytoskeleton of epithelial cells. Here we report finding in EPEC a 35-kbp locus containing several regions implicated in formation of these lesions. DNA probes thro...
10.1038/nrmicro818
The first description of a pathogenicity island in enteric E. coli pathotypes.
10.1073/pnas.89.3.947
101,172,031
Intestinal guanylate cyclase mediates the action of the heat-stable enterotoxin to cause a decrease in intestinal fluid absorption and to increase chloride secretion, ultimately causing diarrhea. An endogenous ligand that acts on this guanylate cyclase has not previously been found. To search for a potential endogenous...
10.1038/nrmicro818
This paper suggests that STa evolved as a molecular mimic of an endogenous ligand. This model is necessary, not only to understand ETEC pathogenesis and evolution, but also to provide a context for future studies of microbial evolution.
10.1128/jb.176.15.4691-4699.1994
41,122,112
Enteroaggregative Escherichia coli (EAggEC) has been associated with persistent pediatric diarrhea in the developing world, yet the pathogenetic mechanisms of EAggEC infection are unknown. Our previous data have suggested that aggregative adherence of some EAggEC strains to HEp-2 cells is mediated by flexible, bundle-f...
10.1038/nrmicro818
Describes the emergence of AggR as a global regulator of virulence genes in EAEC
10.1073/pnas.180094797
125,159,840
The evolutionary relationships of 46 Shigella strains representing each of the serotypes belonging to the four traditional Shigella species (subgroups), Dysenteriae, Flexneri, Boydii, and Sonnei, were determined by sequencing of eight housekeeping genes in four regions of the chromosome. Analysis revealed a very simila...
10.1038/nrmicro818
This paper suggests that Shigella should be considered within the species Escherichia coli , and that their evolution represents adaptation to a specific pathogenetic niche, a phenomenon that has occurred on several occasions over many years.
10.1128/iai.66.9.4036-4042.1998
60,338,948
ABSTRACT Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanis...
10.1038/nrmicro818
DAEC exhibits a unique pathogenetic scheme that includes cytoskeletal sabotage.
10.1073/pnas.252529799
104,369,460
We present the complete genome sequence of uropathogenic Escherichia coli , strain CFT073. A three-way genome comparison of the CFT073, enterohemorrhagic E. coli EDL933, and laboratory strain MG1655 reveals that, amazingly, only 39.2% of their combined (nonredundant) set of proteins actually are common to all three str...
10.1038/nrmicro818
The first complete nucleotide sequence of a representative uropathogenic strain of E. coli and shows that EHEC, UPEC and E. coli K-12 share only 39.2% of the combined set of predicted proteins.
10.1046/j.1365-2958.2000.02110.x
101,042,822
Urinary tract infection (UTI) is a very common extraintestinal infection, and Escherichia coli is by far the most common causative organism. Uropathogenic E. coli possess traits that distinguish them from commensal strains of E. coli , such as secretion systems that allow virulence factors to be targeted to extracytopl...
10.1038/nrmicro818
Describes the identification of a new toxin of uropathogenic E. coli
10.1073/pnas.96.26.15196
18,501,865
Enterohemorrhagic Escherichia coli O157:H7 and enteropathogenic E. coli cause a characteristic histopathology in intestinal cells known as attaching and effacing. The attaching and effacing lesion is encoded by the Locus of Enterocyte Effacement (LEE) pathogenicity island, which encodes a type III secretion system, the...
10.1038/nrmicro818
First report that enteric bacterial virulence factors are regulated by quorum sensing.
10.1126/science.1221428
19,415,690
Promoting the Male X Chromosome In mammals and fruit flies, females have a double dose of the X chromosome compared to males, and to compensate for this imbalance, in fruit flies, transcription from across most of the male X chromosome is boosted by twofold. Conrad et al. (p. 742 , published online 19 July) measured th...
10.1038/nsmb.2763
Provides evidence in favor of improved RNA-polymerase promoter recruitment as the molecular mechanism underlying dosage compensation in male D. melanogaster with references 44–46 as follow-up commentaries (alternative model presented in ref. 64)
10.1101/gad.1751109
20,112,255
In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis -acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discret...
10.1038/nsmb.2763
Provides evidence that C. elegans dosage compensation occurs through global rather than local control of gene expression
10.1098/rstb.2002.1108
65,274,703
Human colour vision originates in the cone photoreceptors, whose spatial density peaks in the fovea and declines rapidly into the periphery. For this reason, one expects to find a large representation of the cone–rich fovea in those cortical locations that support colour perception. Human occipital cortex contains seve...
10.1038/nrn1138
An extensive neuroimaging investigation into the representation of visual stimuli in different cortical areas.
10.1146/annurev.neuro.23.1.315
38,258,993
A typical scene contains many different objects that, because of the limited processing capacity of the visual system, compete for neural representation. The competition among multiple objects in visual cortex can be biased by both bottom-up sensory-driven mechanisms and top-down influences, such as selective attention...
10.1038/nrn755
References 8 and 9 review the effects of attention on neural mechanisms in the human visual cortex, and discuss the interaction between the frontoparietal network and the visual cortex.
10.1152/jn.1996.76.5.2841
84,559,635
1. Posterior parietal cortex contains neurons that are visually responsive and active in relation to saccadic eye movements. We recorded from single neurons in a subregion of parietal cortex, the lateral intraparietal area (LIP), in alert rhesus monkeys. To characterize more completely the circumstances under which LIP...
10.1038/nrn755
Shows how preparatory signals for visual attention and eye movements are combined in LIP neurons.
10.1146/annurev.neuro.24.1.167
83,551,177
▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of pat...
10.1038/nrn755
References 40 and 41 review the role of the prefrontal cortex in attention and executive control.
10.1083/jcb.200307069
38,556,262
Neuronal polarity is, at least in part, mediated by the differential sorting of membrane proteins to distinct domains, such as axons and somata/dendrites. We investigated the pathways underlying the subcellular targeting of NgCAM, a cell adhesion molecule residing on the axonal plasma membrane. Following transport of N...
10.1038/nrn1938
Proposes mechanisms of directed targeting or transcytosis for the axonal cell adhesion molecule, NgCAM.
10.1126/science.1085167
83,326,586
The sorting of sodium channels to axons and the formation of clusters are of primary importance for neuronal electrogenesis. Here, we showed that the cytoplasmic loop connecting domains II and III of the Na v 1 subunit contains a determinant conferring compartmentalization in the axonal initial segment of rat hippocamp...
10.1038/nrn1938
Reports the identification of a motif in the II–III loop of Nav1.2 channels that is necessary and sufficient to target these channels to the AIS.
10.1126/science.1086998
41,602,820
Axonal voltage-gated potassium (Kv1) channels regulate action-potential invasion and hence transmitter release. Although evolutionarily conserved, what mediates their axonal targeting is not known. We found that Kv1 axonal targeting required its T1 tetramerization domain. When fused to unpolarized CD4 or dendritic tran...
10.1038/nrn1938
Reports that the T1 domain of Kv1 channels is necessary and sufficient to target to the axons that depend on proper association with Kvβ.
10.1083/jcb.200506005
104,222,460
The traffic of Kv4 K+ channels is regulated by the potassium channel interacting proteins (KChIPs). Kv4.2 expressed alone was not retained within the ER, but reached the Golgi complex. Coexpression of KChIP1 resulted in traffic of the channel to the plasma membrane, and traffic was abolished when mutations were introdu...
10.1038/nrn1938
Describes that KChIP1 can increase surface expression of Kv4.2 by a pathway that is COPII independent.
10.1126/science.278.5337.474
60,985,659
Although previous analyses indicate that neocortical neurons originate from the cortical proliferative zone, evidence suggests that a subpopulation of neocortical interneurons originates within the subcortical telencephalon. For example, γ-aminobutyric acid (GABA)–expressing cells migrate in vitro from the subcortical ...
10.1038/nrn1954
A combination of slice migration studies and the analysis of Dlx1 Dlx2 mutant mice was used to demonstrate that many cortical interneurons originate in the subcortical telencephalon.
10.1113/jphysiol.2004.073353
29,309,504
Whole‐cell patch‐clamp recordings followed by histochemical staining and single‐cell RT‐PCR were obtained from 180 Martinotti interneurones located in layers II to VI of the somatosensory cortex of Wistar rats (P13–P16) in order to examine their anatomical, electrophysiological and molecular properties. Martinotti cell...
10.1038/nrn1954
Combined intracellular recording and single-cell RT-PCR to correlate a neuron's transcriptosome with its physiological properties. This technique is becoming increasingly important to understanding the molecular basis for interneuron subtype function.
10.1242/dev.02090
62,306,324
Fate determination in the mammalian forebrain, where mature phenotypes are often not achieved until postnatal stages of development, has been an elusive topic of study despite its relevance to neuropsychiatric disease. In the ventral telencephalon, major subgroups of cerebral cortical interneurons originate in the medi...
10.1038/nrn1954
Showed that after patterning has been established, and independent of proliferation, the levels of the interneuron-specifying transcription factor Nkx2.1 are plastic within MGE progenitors depending on their activation by the signaling molecule sonic hedgehog.
10.1128/jvi.72.8.6581-6591.1998
101,722,635
ABSTRACT The small nuclear structures known as ND10 or PML nuclear bodies have been implicated in a variety of cellular processes including response to stress and interferons, oncogenesis, and viral infection, but little is known about their biochemical properties. Recently, a ubiquitin-specific protease enzyme (named ...
10.1038/nrmicro3015
The first demonstration of viral engagement with the SUMO pathway.
10.1073/pnas.171616898
79,469,704
A common complaint among pain patients is that they lose their appetite. These accounts are anecdotal, however, and the neural mechanism underlying pain-induced loss of appetite remains unknown. In this study, we documented the occurrence of appetite loss in patients under migraine attack and investigated the neuronal ...
10.1038/nrn3057
This study shows that sensitization of trigeminovascular neurons disrupts feeding in rodents, possibly through activation of hypothalamic neurons. It demonstrates a mechanism by which migraine in patients may alter food intake.
10.1111/j.1526-4610.2007.00776.x
60,829,916
Background.— Migraine sufferers experience premonitory symptoms which suggest that primary hypothalamic dysfunction is a likely trigger of the attacks. Neuroendocrine and laboratory data also support this hypothesis. To date, positron emission tomography (PET) scans of migraine sufferers have demonstrated activation of...
10.1038/nrn3057
Together with reference 55, this was the first demonstration of hypothalamic activation during cluster headache and migraine, respectively. The studies put forward the argument that central changes may be responsible for the pain, vascular and autonomic symptoms that occur in cluster headache and migraine, and emphasiz...
10.1002/ana.20193
38,270,940
Abstract It is considered that the site of action of the abortive antimigraine compounds acting at serotonin, 5‐HT 1B/1D, receptors (triptans) is the trigeminovascular system. We tested whether there is a non‐trigeminal site of action. The 5‐HT 1B/1D agonist, naratriptan, was microinjected into the ventrolateral periaq...
10.1038/nrn3057
The authors showed that triptans that are targeted to the vlPAG can attenuate dural-evoked nociceptive trigeminovascular neurons — the first clear indication that triptans can act in areas other than the TNC to exert their therapeutic affects.
10.1111/j.1526-4610.2009.01501.x
4,672,645
Objective.— To understand the mechanism of action of oxygen treatment in cluster headache. Background.— Trigeminal autonomic cephalalgias, including cluster headache, are characterized by unilateral head pain in association with ipsilateral cranial autonomic features. They are believed to involve activation of the trig...
10.1038/nrn3057
This is the first study to show a mechanism of action for the therapeutic effects of oxygen in cluster headache, and a lack of therapeutic effect in migraine. There is also a clear demonstration that SuS stimulation can cause activation in the medullary and cervical dorsal horn.
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/nrn3057
The clearest demonstration so far of cortical signal changes that are consistent with CSD during migraine aura.
10.1126/science.1115360
124,023,113
Ciliary neurotrophic factor (CNTF) induces weight loss in obese rodents and humans, and for reasons that are not understood, its effects persist after the cessation of treatment. Here we demonstrate that centrally administered CNTF induces cell proliferation in feeding centers of the murine hypothalamus. Many of the ne...
10.1038/nrn2054
Provides evidence that CNTF influences body weight through effects on neurogenesis in the hypothalamus, raising interesting questions about the relationship between behaviour and neurogenesis in novel brain areas.
10.1073/pnas.91.15.7109
16,765,139
The neuropoietic cytokine cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) acts as a trophic factor, enhancing neuronal survival, and as a differentiation factor, altering neuronal gene expression. There is also evidence that its plays a role in the response of adult neural tissue to injury. We h...
10.1038/nrn2054
The first demonstration that LIF is an important mediator of neural injury responses. This paper identifies the timecourse and cellular source of Lif expression after peripheral nerve injury in the adult.
10.1002/glia.20177
103,885,518
Abstract Injury to the mammalian spinal cord is accompanied by a delayed, secondary wave of oligodendrocyte apoptosis that arises several days after the initial injury. A strong candidate to support oligodendrocyte survival after spinal cord injury is the pleiotropic cytokine, leukemia inhibitory factor (LIF). In vitro...
10.1038/nrn2054
Along with reference 120, this paper extends the observation that LIF can promote oligodendrocyte survival in models of spinal cord injury.
10.1002/cne.21980
124,127,523
Abstract Area V6A, a functionally defined region in the anterior bank of the parietooccipital sulcus, has been subdivided into dorsal and ventral cytoarchitectonic fields (V6Ad and V6Av). The aim of this study was to define the cortical connections of the cytoarchitectonic field V6Ad. Retrograde and bidirectional neuro...
10.1038/nrn3008
A detailed recent neuroanatomical tracing study showing the involvement of V6Ad within the parieto–premotor pathway.
10.1073/pnas.0905314106
20,402,501
Evidence from macaque monkey tracing studies suggests connectivity-based subdivisions within the precuneus, offering predictions for similar subdivisions in the human. Here we present functional connectivity analyses of this region using resting-state functional MRI data collected from both humans and macaque monkeys. ...
10.1038/nrn3008
A broad survey of the functional connectivity of the precuneus. Provides critical converging evidence for the existence of the parieto–medial temporal pathway in humans.
10.1152/jn.2000.83.3.1550
39,008,957
Dorsolateral prefrontal and posterior parietal cortex share reciprocal projections. They also share nearly identical patterns of neuronal activation during performance of memory-guided saccades. To test the hypothesis that the reciprocal projections between parietal and prefrontal neurons may entrain their parallel act...
10.1038/nrn3008
This reinforces the functional relevance of the parieto–prefrontal pathway by showing the reciprocal effect of inactivation in the posterior parietal and prefrontal cortices.
10.1111/j.1460-9568.2008.06395.x
19,150,519
Abstract The general view on the functional role of the monkey inferior parietal lobule (IPL) convexity mainly derives from studies carried out more than two decades ago and does not account for the functional complexity suggested by more recent neuroanatomical findings. We investigated this issue by recording multi‐ a...
10.1038/nrn3008
A broad survey of the response properties of neurons across the IPL, elucidating the distribution of various visual and somatosensory response properties. These distributions provide evidence for the shift in function between rIPL and cIPL and in doing so highlight the importance of these large-scale surveys of the res...
10.1159/000276398
39,151,977
<i>Background/Aims:</i> Heading disorientation (HD) is a type of pure topographical disorientation. Reported cases showing HD have been very few so far, and its underlying mechanism remains unclear. The aim of this study is to find the anatomic substrates of HD and to demonstrate a possible underlying mecha...
10.1038/nrn3008
This study is notable for both the specificity of the lesion (case 1), and the simplicity of the task used to demonstrate that RSC is crucial for updating representations after changes in heading.
10.1002/cne.21141
82,232,318
Abstract Although the perirhinal and parahippocampal cortices have been shown to be critically involved in memory processing, the boundaries and extent of these areas have been controversial. To produce a more objective and reproducible description, the architectonic boundaries and structure of the perirhinal (areas 35...
10.1038/nrn3008
This provides the crucial neuroanatomical evidence necessary to effectively subdivide and characterize the parahippocampal and perirhinal cortices in different macaque species.
10.1210/en.2013-1934
125,090,385
Glucagon-like peptide 1 (GLP-1) analogs are increasingly being used in the treatment of type 2 diabetes. It is clear that these drugs lower blood glucose through an increase in insulin secretion and a lowering of glucagon secretion; in addition, they lower body weight and systolic blood pressure and increase heart rate...
10.1038/nrneph.2017.123
Study that gives important insight into the molecular mode of action of GLP-1 by identifying the cellular localization of GLP-1R in monkey and human tissue using the most extensively validated monoclonal antibody to date.
10.2337/dc17-0061
125,278,393
OBJECTIVE Antihyperglycemic agents, such as empagliflozin, stimulate proximal tubular natriuresis and improve cardiovascular and renal outcomes in patients with type 2 diabetes. Because dipeptidyl peptidase 4 (DPP-4) inhibitors are used in combination with sodium–glucose cotransporter 2 (SGLT2) inhibitors, we examined ...
10.1038/nrneph.2017.123
Clinical study suggesting that DPP-4 inhibition blocks distal, rather than proximal, sodium reabsorption after prolonged therapy in patients with T2DM, potentially as a result of decreased inactivation of SDF1 α rather than a mechanism involving GLP-1.
10.1111/dom.12808
18,288,425
Aims Among patients with type 2 diabetes and albuminuria, cardiorenal morbidity and mortality are high despite multifactorial treatment. Short‐term reduction in albuminuria is considered suggestive of long‐term renoprotective effects. We evaluated the renal effects of the glucagon‐like peptide‐1 ( GLP ‐1) receptor agon...
10.1038/nrneph.2017.123
Placebo-controlled cross-over trial in patients with T2DM and albuminuria that shows that liraglutide therapy reduces 24-h urinary albumin excretion by lowering blood pressure, rather than by improving HbA 1c levels and body weight.
10.1111/dom.12816
103,047,328
Dulaglutide is a once‐weekly glucagon‐like peptide‐1 receptor agonist approved for the treatment of type 2 diabetes (T2D). Integrated data from 9 phase II and III trials in people with T2D (N = 6005) were used to evaluate the effects of dulaglutide on estimated glomerular filtration rate ( eGFR [Chronic Kidney Disease ...
10.1038/nrneph.2017.123
Analysis of pooled phase II and phase III RCTs that describes the albuminuria-lowering effect of dulaglutide compared to insulin glargine and other active comparators beyond glycaemic control.
10.2337/db13-1029
83,034,034
Kidney fibrosis is the final common pathway of all progressive chronic kidney diseases, of which diabetic nephropathy is the leading cause. Endothelial-to-mesenchymal transition (EndMT) has emerged as one of the most important origins of matrix-producing fibroblasts. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been ...
10.1038/nrneph.2017.123
Preclinical study in mice with streptozotocin-induced diabetes that showed glucose-independent amelioration of kidney fibrosis with the DPP-4 inhibitor linagliptin.
10.1111/dom.13041
62,637,003
Aims The MARLINA ‐ T2D study ( ClinicalTrials.gov , NCT 01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard‐of‐care in individuals with type 2 diabetes and albuminuria. Methods A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48–86 mmol/mol), estim...
10.1038/nrneph.2017.123
This sufficiently powered clinical study did not find a beneficial effect of linagliptin versus placebo on albuminuria in patients with T2DM, although exploratory analyses indicated more responders and fewer non-responders in terms of UACR in the linagliptin group.
10.2337/dc16-0621
125,284,998
OBJECTIVE Dipeptidyl peptidase 4 inhibitors may have a protective effect in diabetic nephropathy. RESEARCH DESIGN AND METHODS We studied renal outcomes of 16,492 patients with type 2 diabetes, randomized to saxagliptin versus placebo and followed for a median of 2.1 years in the Saxagliptin Assessment of Vascular Outco...
10.1038/nrneph.2017.123
Secondary analysis of renal end points in a cardiovascular safety trial of a DPP-4 inhibitor in patients with T2DM at high cardiovascular risk, showing that saxagliptin reduces albuminuria in a glucose-independent manner.
10.1073/pnas.1421785112
62,612,241
The large class of adhesion G protein-coupled receptors (aGPCRs) bind extracellular matrix or neighboring cell-surface ligands to regulate organ and tissue development through an unknown activation mechanism. We examined aGPCR activation using two prototypical aGPCRs, GPR56 and GPR110. Active dissociation of the noncov...
10.1038/nrn.2016.86
Using pharmacological approaches, this study identified the Stachel sequence tethered agonist for the aGPCRs GPR56 and GPR110. Together with reference 6, this study described a new activation mechanism for the aGPCR class.
10.1126/science.1092780
18,284,251
The mammalian cerebral cortex is characterized by complex patterns of anatomical and functional areas that differ markedly between species, but the molecular basis for this functional subdivision is largely unknown. Here, we show that mutations in GPR56 , which encodes an orphan G protein–coupled receptor (GPCR) with a...
10.1038/nrn.2016.86
In this paper mutations of GPR56 are identified as the underlying cause for cortical development defects in patients with BFPP. Together with reference 72, this study links the dysfunction of aGPCRs with a neurological ailment for the first time.
10.1126/science.1244392
41,171,346
Development of surface folds of the human brain is controlled in sections. [Also see Perspective by Rash and Rakic ]
10.1038/nrn.2016.86
This investigation uses GWAS data, mRNA–Seq and mouse genetics to directly implicate the regional expression of GPR56 in the forebrain as a phylogenetic driving force of neural stem cell proliferation, gyral patterning and neocortex evolution in higher mammals.
10.1126/science.1173474
102,324,117
Making Myelin The myelin sheath insulates neurons and facilitates rapid axonal conduction, and its disruption is characteristic of some neurological disorders, such as multiple sclerosis. Axonal signals stimulate Schwann cells to form myelin in peripheral nerves, but the mechanism is not completely known. By characteri...
10.1038/nrn.2016.86
This study defined the essential function of GPR126 in Schwann cell myelination. This study was also one of the first to provide in vivo evidence that aGPCRs probably couple to heterotrimeric G proteins.
10.1126/science.271.5249.662
59,636,434
Targeted integration of exogenous DNA into the genome of malaria parasites will allow their phenotype to be modulated by means of gene disruption or the stable expression of foreign and mutated genes. Described here is the site-specific integration through reciprocal exchange, and subsequent expression, of a selectable...
10.1038/nrmicro3111
The first genetic transformation by homologous recombination in P. berghei erythrocytic stages.
10.1111/j.1550-7408.1990.tb01260.x
103,943,530
ABSTRACT. Studies of in vitro interactions between Plasmodium berghei sporozoites and peritoneal macrophages from mice and rats were performed. A videomicroscopic analysis was made of interactions observed by phase‐contrast microscopy. Our results showed a diversity of dynamic interactions between sporozoites and macro...
10.1038/nrmicro3111
The first observation of Plasmodium sp.sporozoites traversing host cells in vitro
10.1126/science.291.5501.141
62,227,704
Intracellular bacteria and parasites typically invade host cells through the formation of an internalization vacuole around the invading pathogen. Plasmodium sporozoites, the infective stage of the malaria parasite transmitted by mosquitoes, have an alternative mechanism to enter cells. We observed breaching of the pla...
10.1038/nrmicro3111
A study that shows the membrane-wounding activity of Plasmodium spp. sporozoites.
10.1073/pnas.1009346107
40,854,121
The first step of Plasmodium development in vertebrates is the transformation of the sporozoite, the parasite stage injected by the mosquito in the skin, into merozoites, the stage that invades erythrocytes and initiates the disease. The current view is that, in mammals, this stage conversion occurs only inside hepatoc...
10.1038/nrmicro3111
The first observation of merozoite formation in the skin of mice.
10.1073/pnas.1303858110
2,668,677
CD8 + T cells are specialized cells of the adaptive immune system capable of finding and eliminating pathogen-infected cells. To date it has not been possible to observe the destruction of any pathogen by CD8 + T cells in vivo. Here we demonstrate a technique for imaging the killing of liver-stage malaria parasites by ...
10.1038/nrmicro3111
The first In vivo imaging of pathogen killing by CD8 + T cells.
10.1146/annurev.physchem.58.032806.104637
104,161,199
Stochastic chemical kinetics describes the time evolution of a well-stirred chemically reacting system in a way that takes into account the fact that molecules come in whole numbers and exhibit some degree of randomness in their dynamical behavior. Researchers are increasingly using this approach to chemical kinetics i...
10.1038/nrn3025
A review of stochastic descriptions of chemical kinetics: theory and simulations.
10.1126/science.1152089
19,200,203
AMPA glutamate receptors (AMPARs) mediate fast excitatory synaptic transmission. Upon fast consecutive synaptic stimulation, transmission can be depressed. Recuperation from fast synaptic depression has been attributed solely to recovery of transmitter release and/or AMPAR desensitization. We show that AMPAR lateral di...
10.1038/nrn3025
This work shows how the exchange between desensitized neurotransmitter receptors and naive functional receptors by lateral diffusion contributes to the recovery from synaptic depression.
10.1111/jsm.12365
62,299,828
Abstract Introduction Sex steroids and genital surgery are known to affect sexual desire, but little research has focused on the effects of cross-sex hormone therapy and sex reassignment surgery on sexual desire in trans persons. Aim This study aims to explore associations between sex reassignment therapy (SRT) and sex...
10.1038/nrurol.2017.64
Evaluation of the sexual desires experienced by transgender patients after gender-confirming surgery.