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Article Released Wed-9th-March-2011 22:13 GMT
Contact: Ruth Institution: Nature Publishing Group
 A neural circuit for anxiety

Summaries of newsworthy papers - Comment: Vaccinate for the next H2N2 pandemic now; Palaeoclimate: El Niño variability in the Pliocene warm period; Neuroscience: Making sense of function and connection; Physics: The strongly coupled beat of a quantum drum; And finally… How the penis lost its spines


This press release is copyright Nature.

VOL.471 NO.7337 DATED 10 MARCH 2011

This press release contains:

Summaries of newsworthy papers:

Neuroscience: A neural circuit for anxiety
Comment: Vaccinate for the next H2N2 pandemic now
Neuroscience: Caspases implicated in inflammation
Palaeoclimate: El Niño variability in the Pliocene warm period
Neuroscience: Making sense of function and connection
Physics: The strongly coupled beat of a quantum drum
Developmental biology: Spotting the signals for bladder repair
Cancer: Blood cancer mutations identified
And finally… How the penis lost its spines

Mention of papers to be published at the same time with the same embargo

Geographical listing of authors

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[1] Neuroscience: A neural circuit for anxiety (AOP)
DOI: 10.1038/nature09820

***This paper will be published electronically on Nature's website on 09 March at 1800 London time / 1300 US Eastern Time as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 10 March, but at a later date. ***

A neural circuit that controls anxiety is revealed in this week’s Nature. The mouse study, which uses light-sensitive proteins to control neuronal activity, indicates that anxiety is continuously regulated by balanced opposing pathways within a brain region called the amygdala.

Stimulating the ends of neurons in the central nucleus of the amygdala has a calming effect, whereas blocking the same projection increases anxiety-related behaviours, Karl Deisseroth and colleagues demonstrate. The effects are instantaneous and reversible, but do not occur when different regions of the same cells are stimulated, suggesting that selective activation of certain connections can have different effects.

The amygdala is thought to have a role in emotional processing and generalized anxiety, but the critical subregions and connections have proved hard to pin down. This study highlights a complex network of specific cells and connections that influence anxiety, and demonstrates the potential of this technique — optogenetics — to resolve the complex neuronal circuitry underlying psychiatric disease.

Karl Deisseroth (Stanford University, CA, USA)
Tel: +1 650 736 4325; E-mail:

Comment: Vaccinate for the next H2N2 pandemic now (pp 157-158)

H2N2 influenza, which killed more than 1 million people between 1957 and 1968, could jump back into humans from the birds and swine in which it is currently circulating, warn Gary Nabel and his colleagues in a Comment piece in this week’s Nature. The 1957 pandemic is thought to have crossed to humans from birds. “Governments, regulatory agencies and industry should develop a pre-emptive vaccination programme” now, the authors argue.

Nabel and his colleagues say that if we learn anything from the 2009 H1N1 influenza, which was remarkably similar to the 1918 H1N1 Spanish flu virus, it should be that a virus that has already caused a pandemic in humans can easily jump back from animals once human immunity has waned. The “unexpected source of the 2009 H1N1 pandemic is a cautionary tale for the public-health community”, say the authors.

By testing for antibodies against H2N2 strains in the blood of 90 people in the United States, Nabel and his colleagues show preliminary evidence that people under the age of 50 have little or no immunity. This makes sense given that vaccination against H2N2 following the 1957 pandemic ended in the late 1960s.
The authors suggest three ways in which a pre-emptive vaccination strategy to prevent another H2N2 pandemic could be carried out.

Gary Nabel (National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA)
Please contact via:
The National Institute of Allergy and Infectious Diseases Office of Communications
Tel: +1 301 402 1663; E-mail:

[2] Neuroscience: Caspases implicated in inflammation (AOP)
DOI: 10.1038/nature09788

***This paper will be published electronically on Nature's website on 09 March at 1800 London time / 1300 US Eastern Time as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 10 March, but at a later date. ***

A group of enzymes best known for their involvement in cell death may contribute to inflammation in the diseased brain, suggests a rodent study published in Nature. Therapies that block the activity of these caspases could prove to be neuroprotective.

Caspase signalling regulates the activity of brain cells called microglia, Bertrand Joseph and colleagues show. In the healthy brain, microglia are scavenger cells, essential for normal brain function, but the same cells are thought to contribute to neurodegenerative disorders by secreting inflammatory neurotoxins. Blocking the caspase cascade hinders microglia activation and reduces neurotoxicity in the rat brain, the team demonstrate.

Caspase activation was also apparent in the microglia of Parkinson’s disease and Alzheimer’s disease brains, indicating that the findings in rodents may be applicable to humans. Therapies that block caspase activity could therefore help to protect vulnerable neurons in the neurodegenerative brain via an indirect mechanism — the control of microglia.

Bertrand Joseph (Karolinska Institute, Stockholm, Sweden)
Tel: +46 8 517 738 26; E-mail:

[3] Palaeoclimate: El Niño variability in the Pliocene warm period (pp 209-211)

A period in Earth history that has been widely studied as an analogue of possible future climate change seems to have had a Pacific Ocean climate more similar to today’s than has previously been suggested. This conclusion, reported in Nature this week, comes from an analysis of high-resolution oxygen isotope data preserved in fossil corals that lived in the western Pacific about 3.5 million years ago.

The early Pliocene warm period, between about 5 and 3 million years ago, is the most recent time when the world was warmer than it is today for extended periods of time. It has been suggested that this period was characterized by a sharply reduced east–west gradient in sea surface temperature in the equatorial Pacific Ocean — a state that in today’s climate occurs only during El Niño conditions. The possibility of a ‘permanent El Niño’ state at a time when global mean temperatures and atmospheric carbon dioxide concentrations were similar to those projected for near-term climate change is of obvious importance, but remains controversial owing to a lack of high-resolution evidence from informative sites.

To rectify this situation, Tsuyoshi Watanabe and colleagues turned to fossil corals, whose skeletons preserve geochemical information that can be used to reconstruct past sea-surface conditions with monthly resolution. In two 35-year-long oxygen isotope records from Pliocene corals in the Philippines, the authors identify the characteristic multi-year spectral signature of El Niño variability, challenging the assertion of a permanent El Niño state.

Tsuyoshi Watanabe (Hokkaido University, Sapporo, Japan)
Tel: +81 11 706 4637; E-mail:

[4] & [5] Neuroscience: Making sense of function and connection (pp 177-188; N&V)

The connectivity of single cells in the mouse visual system and how this connectivity relates to the functions of the individual cells is described in two papers published this week in Nature. The methodology and findings could be crucial in future studies of the functional relationship of neural circuits.

The key to a better understanding of neural circuits is to map out their functional connectivity. However, mapping out the wiring between neurons and relating this to individual cells’ function has been difficult due to a lack of precision in the tools used. Two studies solve this problem by using a combination of functional imaging and three-dimensional electron microscopy with micrometre precision.

Looking at the primary visual cortex of mice, Clay Reid and colleagues characterized how neurons fire in response to bars oriented at differing degrees and compared their functional property to the neurons local connectivity network. In a second study, Kevin Briggman and colleagues revealed that the dendrites of certain amacrine cells in the mouse retina make highly specific synapses with direction-selective ganglion cells depending on what direction of motion the cells preferred. These findings indicate that the directional selectivity of these retinal ganglion cells may arise from the asymmetry in the wiring of the cells that project to them.

Clay Reid (Harvard Medical School, Boston, MA, USA) Author paper [4]
Tel: +1 617 432 3621; E-mail:

Kevin Briggman (Max Planck Institute for Medical Research, Heidelberg, Germany) Author paper [5]
Tel: +49 6221 486624; E-mail:

H. Sebastian Seung (Massachusetts Institute of Technology, Cambridge, MA, USA) N&V author
Tel: +1 617 252 1693; E-mail:

[6] Physics: The strongly coupled beat of a quantum drum (pp 204-208; N&V)

A tiny aluminium membrane, acting simultaneously as a vibrating drumhead and as part of an electrical capacitor, holds the key to a new realm of quantum exploration, according to a report in this week’s Nature. John Teufel and colleagues show that a superconducting circuit incorporating the micro-scale drum displays unprecedentedly strong electromechanical coupling — a feature essential for observing and controlling long-lived quantum states of mechanical motion.

The ability to observe quantum effects in macroscopic mechanical systems should allow new ways of investigating the limitations of quantum measurements, and of exploring the quantum–classical divide. This effort requires the production of long-lived mechanical states, and ways to manipulate and probe these states at the quantum level. A promising approach to these goals comes from ‘cavity electromechanics’, in which a mechanical oscillator is coupled to an electromagnetic resonance in a tuned circuit or cavity. For this approach to work, the mechanical and electromagnetic systems need to be strongly coupled, so that the interaction between the two systems is faster than the energy dissipation in either system.

Teufel and colleagues’ dual-purpose drum lets them incorporate the mechanical oscillator directly in the electromagnetic circuit, leading to a coupling strength more than 100 times higher than has previously been achieved. The system’s performance lays the groundwork for the production and observation of quantum states that could survive for hundreds of microseconds.

John Teufel (National Institute of Standards and Technology, Boulder, CO, USA)
Tel: +1 303 497 5039; E-mail:

Miles Blencowe (Dartmouth College, Hanover, NH, USA) N&V author
Tel: +1 603 646 2969; E-mail:

[7] Developmental biology: Spotting the signals for bladder repair (AOP)
DOI: 10.1038/nature09851

***This paper will be published electronically on Nature's website on 09 March at 1800 London time / 1300 US Eastern Time as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 10 March, but at a later date. ***

Researchers have attributed the repair response of the urinary bladder to infections and injury to a signalling feedback loop between different cells in the urinary tract. This signalling may have a role in clearing bacterial infections and preventing recurrence, and may also provide insights into tumour growth in epithelial cancers, a study in mice published in Nature suggests.

Following injury, heightened activity of the Sonic hedgehog (Shh) and Wnt signalling feedback loop between basal cells and stromal cells leads to regenerative proliferation of bladder epithelial cells, Philip Beachy and colleagues report. The researchers postulate that the therapeutic activation of this pathway could be used to treat urinary tract infections, which occur in around 10% of women per year and have a six-month recurrence rate of around 26%.

Philip Beachy (Stanford University, CA, USA)
Tel: +1 650 723 4521; E-mail:

[8] & [9] Cancer: Blood cancer mutations identified (pp 189-195 and pp 235-239)

Newly identified mutations that may underlie lymphoma development are presented in two Nature papers. The studies suggest a potential benefit for therapies that modify protein acetylation.

Teams lead by Riccardo Dalla-Favera and Charles Mullighan identified frequent somatic mutations in CREBBP and EP300, genes that encode related acetyltransferases which influence gene expression by adding acetyl groups to histones and other transcriptional regulators.

The mutations are present in three different sub-types of B cell lymphoma, and can be found in primary tumours or acquired at relapse. These studies may provide a rationale for the use of histone deacetylase inhibitors in certain B-cell lymphomas.

Riccardo Dalla-Favera (Columbia University, New York, NY, USA) Author paper [8]
Tel: +1 212 851 5273; E-mail:

Charles Mullighan (St Jude Children's Research Hospital, Memphis, TN, USA) Author paper [9]
Tel: +1 901 595 3387; E-mail:

[10] And finally… How the penis lost its spines (pp 216-219)

The human penis is, thankfully, spineless thanks to the evolutionary loss of a non-coding chunk of DNA, suggests a Nature paper, which describes how regulatory DNA deletions have helped sculpt the evolution of human-specific traits.

Gill Bejerano and colleagues used comparative genomics to identify 510 human-specific deletions — sequences that are highly conserved between chimpanzees and other species, but absent in the human genome. The deletions represent regulatory chunks of DNA — sequences that can influence the expression of nearby genes — and they lie almost exclusively in non-coding DNA stretches, close to genes involved in hormone signalling and neural function.

One deletion removes a neural regulatory sequence near a tumour suppressor gene, a loss that correlates with the expansion of specific brain regions in humans. Another eliminates a regulatory sequence near the human androgen receptor gene, a molecular change linked to the human anatomical loss of sensory whiskers and keratinized penile spines. Penile spines are commonly found in other animals, including chimpanzees, macaques and mice, but a more simplified morphology tends to be associated with the monogamous behaviour of certain primates.

Many studies have tried to address the question of what makes us human by searching for extra features that we have in comparison with our close relatives, but Bejerano and colleagues have found interesting, human-specific characteristics by looking for what we have lost over the course of evolution.

Gill Bejerano (Stanford University, CA, USA)
Tel: +1 650 723 7666; E-mail:

David Kingsley (Stanford University, CA, USA) Co-author
Tel: +1 650 387 4183; E-mail:


[11] DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair (pp 240-244)

[12] Crucial role forDNAligase III inmitochondria but not in Xrcc1-dependent repair (pp 245-248)


***These papers will be published electronically on Nature's website on 09 March at 1800 London time / 1300 US Eastern Time as part of our AOP (ahead of print) programme. Although we have included them on this release to avoid multiple mailings they will not appear in print on 10 March, but at a later date. ***

[13] Collapse of long-range charge order tracked by time-resolved photoemission at high momenta
DOI: 10.1038/nature09829

[14] Crystal structure of metarhodopsin II
DOI: 10.1038/nature09789

[15] The structural basis of agonist-induced activation in constitutively active rhodopsin
DOI: 10.1038/nature09795


The following list of places refers to the whereabouts of authors on the papers numbered in this release. For example, London: 4 - this means that on paper number four, there will be at least one author affiliated to an institute or company in London. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

Toronto: 14

Paris: 12

Berlin: 14
Heidelberg: 5
Kaiserlslautern: 13
Kiel: 13

Novara: 8

Chiba: 3
Kashiwa: 3
Sapporo: 3
Tokyo: 3
Tsukuba: 3
Yokohama: 3

Quezon City: 3

Chonju: 14

Seville: 2

Lund: 2
Stockholm: 2

Villigen: 15

Cambridge: 15
London: 2, 14


Berkeley: 13
Stanford: 1, 7, 10

Boulder: 6, 13

Athens: 10

Baltimore: 7
Bethesda: 9
Rockville: 9

Boston: 4
Cambridge: 4
Waltham: 15

Chicago: 8

St Louis: 7

New York
New York: 8, 12

Pittsburgh: 4, 12
University Park: 10

Memphis: 8, 9, 11, 12

Austin: 13

From North America and Canada
Neda Afsarmanesh, Nature New York
Tel: +1 212 726 9231; E-mail:

From Japan, Korea, China, Singapore and Taiwan
Mika Nakano, Nature Tokyo
Tel: +81 3 3267 8751; E-mail:

From the UK
Rebecca Walton, Nature, London
Tel: +44 20 7843 4502; E-mail:

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Keywords associated to this article: Nature, NPG, anxiety, amygdala, flu, H2N2, caspase, neuroscience, neurodegenerative disease, el nino, climate change, neural connectivity, quantum, bladder, cancer, penis,
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