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NeurosciencePromiscuous vesicles p.178

The unexpected finding that neurons can co-release two neurotransmitter molecules, dopamine and GABA, through a common mechanism provides a further advance in our understanding of the nervous system. See Letter p.262

John T. Williams

doi: 10.1038/490178a

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Organic chemistrySingle molecules put a ring on it p.179

A variant of a classical reaction has been used to generate short-lived chemical species called arynes, allowing the one-step synthesis of structurally complex benzene derivatives from simple precursors. See Article p.208

John T. S. Yeoman & Sarah E. Reisman

doi: 10.1038/490179a

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PalaeontologyCambrian nervous wrecks p.180

Fossilized remains of an arthropod from the Cambrian period provide an unusual example of preservation of the brain and nervous system, and shed new light on when and how these tissues evolved. See Letter p.258

Graham E. Budd

doi: 10.1038/490180a

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Animal migrationCatching the wave p.182

Observations of the migration patterns of Norwegian red deer show that some animals ride waves of greener vegetation as spring spreads across the landscape, whereas others jump ahead in anticipation of this higher-quality food.

John M. Fryxell & Tal Avgar

doi: 10.1038/490182a

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Earth scienceWhen an oceanic tectonic plate cracks p.183

Analyses of two recent earthquakes of great magnitude show how complex the breaking of the oceanic lithosphere can be, how it is linked to earlier great events and how it triggers seismicity worldwide. See Letters p.240, p.245 & p.250

Jean-Yves Royer

doi: 10.1038/490183a

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Brain developmentThe neuron family tree remodelled p.185

The discovery of different classes of neuronal progenitor cell, destined to give rise to neurons in specific layers of the cerebral cortex, could presage the revision of a 50-year-old model of brain development.

Oscar Marín

doi: 10.1038/490185a

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Reviews

Perspective

A call for transparent reporting to optimize the predictive value of preclinical research p.187

Story C. Landis, Susan G. Amara, Khusru Asadullah, Chris P. Austin, Robi Blumenstein, Eileen W. Bradley, Ronald G. Crystal, Robert B. Darnell, Robert J. Ferrante, Howard Fillit + et al.

doi: 10.1038/nature11556

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Articles

The hexadehydro-Diels–Alder reaction p.208

Arynes (aromatic systems containing, formally, a carbon–carbon triple bond) are among the most versatile of all reactive intermediates in organic chemistry. They can be ‘trapped’ to give products that are used as pharmaceuticals, agrochemicals, dyes, polymers and other fine chemicals. Here we explore a strategy that unites the de novo generation of benzynes—through a hexadehydro-Diels–Alder reaction—with their in situ elaboration into structurally complex benzenoid products. In the hexadehydro-Diels–Alder reaction, a 1,3-diyne is engaged in a [4+2] cycloisomerization with a ‘diynophile’ to produce the highly reactive benzyne intermediate. The reaction conditions for this simple, thermal transformation are notable for being free of metals and reagents. The subsequent and highly efficient trapping reactions increase the power of the overall process. Finally, we provide examples of how this de novo benzyne generation approach allows new modes of intrinsic reactivity to be revealed.

Thomas R. Hoye, Beeraiah Baire, Dawen Niu, Patrick H. Willoughby & Brian P. Woods

doi: 10.1038/nature11518

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Small heat-shock proteins protect from heat-stroke-associated neurodegeneration p.213

Heat stroke is a life-threatening condition, characterized by catastrophic collapse of thermoregulation and extreme hyperthermia. In recent years, intensification of heat waves has caused a surge of heat-stroke fatalities. The mechanisms underlying heat-related pathology are poorly understood. Here we show that heat stroke triggers pervasive necrotic cell death and neurodegeneration in Caenorhabditis elegans. Preconditioning of animals at a mildly elevated temperature strongly protects from heat-induced necrosis. The heat-shock transcription factor HSF-1 and the small heat-shock protein HSP-16.1 mediate cytoprotection by preconditioning. HSP-16.1 localizes to the Golgi, where it functions with the Ca2+- and Mn2+-transporting ATPase PMR-1 to maintain Ca2+ homeostasis under heat stroke. Preconditioning also suppresses cell death inflicted by diverse insults, and protects mammalian neurons from heat cytotoxicity. These findings reveal an evolutionarily conserved mechanism that defends against diverse necrotic stimuli, and may be relevant to heat stroke and other pathological conditions involving necrosis in humans.

Nikos Kourtis, Vassiliki Nikoletopoulou & Nektarios Tavernarakis

doi: 10.1038/nature11417

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Retinal waves coordinate patterned activity throughout the developing visual system p.219

The morphological and functional development of the vertebrate nervous system is initially governed by genetic factors and subsequently refined by neuronal activity. However, fundamental features of the nervous system emerge before sensory experience is possible. Thus, activity-dependent development occurring before the onset of experience must be driven by spontaneous activity, but the origin and nature of activity in vivo remains largely untested. Here we use optical methods to show in live neonatal mice that waves of spontaneous retinal activity are present and propagate throughout the entire visual system before eye opening. This patterned activity encompassed the visual field, relied on cholinergic neurotransmission, preferentially initiated in the binocular retina and exhibited spatiotemporal correlations between the two hemispheres. Retinal waves were the primary source of activity in the midbrain and primary visual cortex, but only modulated ongoing activity in secondary visual areas. Thus, spontaneous retinal activity is transmitted through the entire visual system and carries patterned information capable of guiding the activity-dependent development of complex intra- and inter-hemispheric circuits before the onset of vision.

James B. Ackman, Timothy J. Burbridge & Michael C. Crair

doi: 10.1038/nature11529

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A neural circuit for spatial summation in visual cortex p.226

The response of cortical neurons to a sensory stimulus is modulated by the context. In the visual cortex, for example, stimulation of a pyramidal cell's receptive-field surround can attenuate the cell’s response to a stimulus in the centre of its receptive field, a phenomenon called surround suppression. Whether cortical circuits contribute to surround suppression or whether the phenomenon is entirely relayed from earlier stages of visual processing is debated. Here we show that, in contrast to pyramidal cells, the response of somatostatin-expressing inhibitory neurons (SOMs) in the superficial layers of the mouse visual cortex increases with stimulation of the receptive-field surround. This difference results from the preferential excitation of SOMs by horizontal cortical axons. By perturbing the activity of SOMs, we show that these neurons contribute to pyramidal cells' surround suppression. These results establish a cortical circuit for surround suppression and attribute a particular function to a genetically defined type of inhibitory neuron.

Hillel Adesnik, William Bruns, Hiroki Taniguchi, Z. Josh Huang & Massimo Scanziani

doi: 10.1038/nature11526

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Letters

FTO genotype is associated with phenotypic variability of body mass index p.267

Jian Yang, Ruth J. F. Loos, Joseph E. Powell, Sarah E. Medland, Elizabeth K. Speliotes, Daniel I. Chasman, Lynda M. Rose, Gudmar Thorleifsson, Valgerdur Steinthorsdottir, Reedik Mägi + et al.

doi: 10.1038/nature11401

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