Neuroscience: Finding a source of anxiety

Summaries of newsworthy papers include Converting human skin cells into neurons more efficiently; Evolution in the oceans; Telling the good from the bad in the gut and Efficient genome-scale genetic engineering in bacteria


For papers that will be published online on 08 April 2012
This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Neuroscience: Finding a source of anxiety

Methods: Converting human skin cells into neurons more efficiently

Geoscience: Evolution in the oceans

Immunology: Telling the good from the bad in the gut

Methods: Efficient genome-scale genetic engineering in bacteria

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

· Geographical listing of authors

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[1] Neuroscience: Finding a source of anxiety
DOI: 10.1038/nn.3088

Electrical stimulation of the pregenual anterior cingulate cortex (pACC) in monkeys increases negative decision making, an effect blocked by anti-anxiety drugs, reports a study published online this week in Nature Neuroscience. This area of the brain has previously been implicated in human anxiety disorders and depression, and these results suggest how it could cause pathological behaviour.

Graybiel and colleagues offered monkeys choices between large rewards that came along with an annoying air puff, and small rewards without the air puff. They found that some of the neurons in the pACC fired before the monkey chose the large reward despite the air puff and some fired before the monkey chose the small reward to avoid the air puff. Both kinds of neurons were mostly intermingled, but in one area of the pACC, there were more neurons that fired when monkeys chose the small reward to avoid the air puff. Stimulating the neurons in this area increased the likelihood that the monkey would choose to avoid the air puff, but this effect was blocked when the animals received an anti-anxiety drug.

People with anxiety disorders and depression are known to have difficulty making decisions in which they have to trade off costs and benefits. These results suggest that the pACC could be critical for regulating negative emotional states and anxiety in decision-making.

Author Contact:
Ann Graybiel (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 253 5785; E-mail: [email protected]

[2] Methods: Converting human skin cells into neurons more efficiently
DOI: 10.1038/nmeth.1972

A strategy that greatly improves the efficiency of directly converting postnatal human fibroblasts into neurons is reported in a study this week in Nature Methods.

Mature human skin cells—fibroblasts—can be converted directly into neurons by genetically modifying the cells to express a cocktail of transcription factors. This strategy promises to be very useful for the study of neuronal development, as a means to model neurological diseases and in regenerative medicine. But the process is known to be inefficient, with only a small proportion of cells being converted. Oliver Brüstle and Philipp Koch took human fibroblasts from newborns and young children and cultured them with small molecules that are known to play a role in the production of neurons in vivo. They did this in combination with two transcription factors which subsequently increased the efficiency of neuronal conversion more than fifteen times.

The neurons that were created showed normal functional properties of neurons and expressed genes associated with neuronal cell types. Additionally, preliminary findings reported in this work suggest that this method might also increase the efficiency of direct conversion of adult human fibroblasts to neurons, which will make it possible to establish cellular models of age-related diseases as well.

Author contacts:
Oliver Brüstle (University of Bonn, Germany)
Tel: +49 228 6885 500; E-mail: [email protected]

Philipp Koch (University of Bonn, Germany)
Tel: +49 228 6885 500; E-mail: [email protected]

[3] Geoscience: Evolution in the oceans
DOI: 10.1038/ngeo1441

The world’s single most important marine calcifying organism, Emiliania huxleyi, may be able to evolve in response to ocean acidification conditions, reports a paper published online in Nature Geoscience this week.

The acidification of the world’s oceans, due to oceanic uptake of atmospheric carbon dioxide, could seriously impair marine calcifying organisms. Until now, studies looking at the effects of acidification on marine organisms have focused on physiological responses within the lifetime of individuals, and have largely ignored the potential for evolution. In a series of laboratory experiments, Thorsten Reusch and colleagues exposed populations of E. huxleyi to elevated concentrations of carbon dioxide, and around 500 asexual generations later they assessed their fitness under ocean acidification conditions. Although all populations fared worse when under ocean acidification conditions, they found that populations selected under elevated carbon dioxide conditions exhibited higher growth rates and a partial restoration of calcification, compared with populations kept under control conditions.

The researchers suggest that contemporary evolution could help to maintain marine microbial function in the face of global change.

Author contact:
Thorsten Reusch (Helmholtz-Center of Ocean Research Kiel, Germany)
Tel: +49 431 6004550; E-mail: [email protected]

[4] Immunology: Telling the good from the bad in the gut
DOI: 10.1038/ni.2263

How the immune system differentiates between pathogenic and harmless gut bacteria is reported online this week in Nature Immunology.

Gabriel Núñez and colleagues looked at infection by pathogenic bacteria and compared them to non-pathogenic gut bacteria. Intestinal phagocytes—immune cells that ingest harmful bacteria or dying cells—were completely unresponsive to all bacteria tested, with one exception: only pathogenic bacteria could stimulate high amounts of the inflammatory cytokine IL-1. The authors found that intestinal phagocytes used an intracellular protein complex to distinguish between pathogenic and harmless bacteria.

Author contact:
Gabriel Núñez (University of Michigan, Ann Arbor, MI, USA)
Tel: +1 734 764 8514; E-mail: [email protected]

[5] Methods: Efficient genome-scale genetic engineering in bacteria
DOI: 10.1038/nmeth.1971

A highly efficient method for genetically engineering bacteria is reported online this week in Nature Methods. The efficiency gains make it possible to rapidly produce custom bacteria in which entire metabolic pathways have been redesigned for genetic studies or biotechnological applications.

One of the most effective ways to introduce many genetic changes is multiplex automated genome engineering (MAGE), in which short stretches of DNA are inserted one at a time into a bacterial chromosome over many iterations. The process is automated but is limited to very short changes—typically up to three bases of DNA sequence at any given location—and requires a lot of instrumentation.

Harris Wang, Duhee Bang and colleagues greatly improve on the efficiency of MAGE by selecting for changes at the site of interest and for an antibiotic resistance marker nearby. This co-selection enables them to insert 20 DNA bases at each site and increases the chances of producing multiple changes in each iteration.

Using co-selection MAGE (Cos-MAGE), the authors alter the promoters of 12 genes in the same metabolic pathway in only 4 days, enhancing production of the industrially relevant dye indigo and the anti-leukemia factor indirubin. The improved efficiency also makes it feasible for smaller laboratories lacking robotics to carry out genome-scale engineering.

Author contacts:
Harris Wang (Harvard University, Cambridge, MA, USA)
Tel: +1 617 955 9575; E-mail: [email protected]

Duhee Bang (Yonsei University, Seoul, Korea)
Tel: +82 10 3357 0611; E-mail: [email protected]

Items from other Nature journals to be published online at the same time and with the same embargo:

Nature (

[6] An inverse relationship to germline transcription defines centromeric chromatin in C. elegans
DOI: 10.1038/nature10973

[7] Inositol-1,4,5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes
DOI: 10.1038/nature10988

[8] Systematic discovery of structural elements governing stability of mammalian messenger RNAs
DOI: 10.1038/nature11013


[9] FLASH assembly of TALENs for high-throughput genome editing
DOI: 10.1038/nbt.2170


[10] Increased mobility of double-strand breaks requires Mec1, Rad9 and the homologous recombination machinery
DOI: 10.1038/ncb2465

[11] Increased chromosome mobility facilitates homology search during recombination
DOI: 10.1038/ncb2472

[12] Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning
DOI: 10.1038/ncb2473


[13] Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells
DOI: 10.1038/nchembio.935


[14] Plot-scale evidence of tundra vegetation change and links to recent summer warming
DOI: 10.1038/nclimate1465

[15] Biogeochemical and ecological feedbacks in grassland responses to warming
DOI: 10.1038/nclimate1486


[16] Abrupt change in the dip of the subducting plate beneath north Chile
DOI: 10.1038/ngeo1447


[17] A genome-wide association meta-analysis identifies new childhood obesity loci
DOI: 10.1038/ng.2247

[18] Bayesian method to predict individual SNP genotypes from gene expression data
DOI: 10.1038/ng.2248

[19] Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes
DOI: 10.1038/ng.2246


[20] Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells
DOI: 10.1038/ni.2267


[21] Ultrafast transient generation of spin-density-wave order in the normal state of BaFe2As2 driven by coherent lattice vibrations
DOI: 10.1038/nmat3294


[22] NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components
DOI: 10.1038/nm.2717

[23] Unbiased identification of target antigens of CD8+ T cells with combinatorial libraries coding for short peptides
DOI: 10.1038/nm.2720


[24] Segregation of molecules at cell division reveals native protein localization
DOI: 10.1038/nmeth.1955

[25] Derivation of iPSCs in stirred suspension bioreactors
DOI: 10.1038/nmeth.1973

[26] FLEXIQinase, a mass spectrometry-based assay, to unveil multikinase mechanisms
DOI: 10.1038/nmeth.1970


[27] Normalization of tumour blood vessels improves the delivery of nanomedicines in a size dependent manner
DOI: 10.1038/nnano.2012.45

[28] Remote Joule heating by a carbon nanotube
DOI: 10.1038/nnano.2012.39


[29] microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons
DOI: 10.1038/nn.3082


[30] Phase-locked coherent modes in a patterned metal–organic microcavity
DOI: 10.1038/nphoton.2012.49

Nature PHYSICS (

[31] Observation of the kinetic condensation of classical waves
DOI: 10.1038/nphys2278

[32] Interferometric measurement of local spin fluctuations in a quantum gas
DOI: 10.1038/nphys2280


[33] Crystal structure of a group II intron in the pre-catalytic state
DOI: 10.1038/nsmb.2270

[34] Human prion protein binds Argonaute and promotes accumulation of microRNA effector complexes
DOI: 10.1038/nsmb.2273

[35] Synergistic substrate binding determines the stoichiometry of transport of a prokaryotic H+/Cl− exchanger
DOI: 10.1038/nsmb.2277

[36] ATP binding controls distinct structural transitions of Escherichia coli DNA gyrase in complex with DNA
DOI: 10.1038/nsmb.2278


The following list of places refers to the whereabouts of authors on the papers numbered in this release. 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.

Melbourne: 14
Perth: 17

Calgary: 25
Edmonton: 14
Hamilton: 17
London: 19
Montreal: 6, 8
Ottawa: 7
Saskatoon: 14
Toronto: 8, 17
Trois-Rivieres: 14
Vancouver: 14
Yukon: 14

Santiago: 16, 31

Shanghai: 13
Yunnan: 13

Nicosia: 27

Copenhagen: 14, 17
Gentofte: 17
Roskilde: 14

Tartu: 17

Helsinki: 17
Muhos: 14
Oulu: 17
Tampere: 17
Turku: 17

Dijon: 31
Illkirch: 34
Lyon: 34
Perpignan: 34
Strasbourg: 34
Valbonne: 31

Bonn: 2, 26
Cologne: 20
Dresden: 30
Dusseldorf: 2
Essen: 17
Hamburg: 32
Karlsruhe: 21
Kiel: 2, 3, 16
Konstanz: 21
Marburg: 17
Martinsried: 23
Munich: 23
Neuherberg: 17
Regensburg: 21

Hong Kong: 6

Garoabaer: 14
Reykjavik: 14

Dublin: 17, 22

Hokkaido: 14
Osaka: 20

Amsterdam: 14, 17
Groningen: 17
Rotterdam: 17

As: 14
Tromso: 14
Trondheim: 14

Rio Piedras: 14

Doha: 17

Moscow: 14

Singapore: 19

Ljubljana: 21

Cheongju: 21
Seoul: 5, 19

Barcelona: 17
Zaragoza: 17

Abisko: 14
Gothenburg: 14
Umea: 14

Basel: 10, 35
Davos: 14
Fribourg: 21
Zurich: 32, 34

Belfast: 17, 19
Bristol: 17
Cambridge: 17
London: 17, 29
Manchester: 29
Oxford: 17


Anchorage: 14
Fairbanks: 14

Flagstaff: 15
Tempe: 14

Berkeley: 14, 36
Davis: 14
La Jolla: 6, 7, 20
Los Angeles: 17
San Diego: 6, 33
Santa Cruz: 6
Stanford: 36

Aurora: 6
Fort Collins: 14

New Haven: 33

Gainesville: 20
Miami: 14

Argonne: 33
Chicago: 19

Ames: 9

Baltimore: 12
Chevy Chase: 33
College Park: 28

Amherst: 24
Boston: 5, 9, 17, 24, 26, 27
Cambridge: 1, 17, 24, 27, 31
Charlestown: 9
Woods Hole: 14

Allendale: 14
Ann Arbor: 4
Grand Rapids: 19

New Jersey
Princeton: 8, 31

New Mexico
Ranchos de Taos: 14

New York
Ithaca: 6
New York: 7, 8, 11, 18, 35

North Carolina
Chapel Hill: 6

Cleveland: 22

Philadelphia: 17
Pittsburgh: 12

El Paso: 14
Houston: 20

Seattle: 18


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Tel: +44 20 7843 4658; E-mail: [email protected]

Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: [email protected]

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Nature Cell Biology (London)
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Nature Chemical Biology (Boston)
Elissa Bolt
Tel: +1 617 475 9241, E-mail: [email protected]

Nature Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: [email protected]

Nature Climate Change (London)
Rory Howlett
Tel: +44 20 7014 4009; E-mail: [email protected]

Nature Genetics (New York)
Myles Axton
Tel: +1 212 726 9324; E-mail: [email protected]

Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)
Vincent Dusastre
Tel: +44 20 7843 4531; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)
Ray Parker
Tel: +1 212 726 9627; E-mail: [email protected]

Nature Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)
Kalyani Narasimhan
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Nature Photonics (Tokyo)
Oliver Graydon
Tel: +81 3 3267 8776; E-mail: [email protected]

Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)
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Tel: +1 212 726 9331; E-mail: [email protected]

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Published: 08 Apr 2012

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