NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 03 April 2011
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
Summaries of newsworthy papers:
Genetics: Alzheimer’s disease genetic associations
Nanotechnology: Some nanoparticles affect pregnant mice
Geoscience: Large carbon stocks in mangroves
Medicine: Distinguishing pancreatic cancer subtypes
Geoscience: Accelerating sea-level rise from Patagonian glaciers
Medicine: Keeping bone from forming in the wrong place
Photonics: Extremely stable optical lattice clocks
Chemical Biology: Cannabis without hallucinations
And finally…Neuroscience: Itching for answers
Mention of papers to be published at the same time with the same embargo
Geographical listing of authors
PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release.
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 &  Genetics: Alzheimer’s disease genetic associations
Genetic variants associated with Alzheimer’s disease are reported in two studies this week in Nature Genetics. Alzheimer’s disease, the most common form of dementia, is a neurodegenerative disorder with a high prevalence in the elderly.
Gerard Schellenberg and colleagues report a genome-wide association study for late onset Alzheimer’s disease including 8,309 cases and 7,366 cognitively normal controls. Julie Williams and colleagues conducted combined analyses of four previously reported genome-wide association studies for Alzheimer’s disease. Through replication analyses across combined and additional datasets, the two papers together report five loci newly associated with Alzheimer’s disease. This brings to 10 the number of confirmed Alzheimer’s disease susceptibility loci, and together these include candidate genes with roles in immune function, processes at the cell membrane, and lipid processing.
This work therefore highlights pathways that may be involved in neurodegeneration and Abeta clearance from the brain.
Gerald Schellenberg (University of Pennsylvania School of Medicine, Philadelphia, PA, USA)
Tel: +1 215 746 4580; E-mail: gerardsc(at)mail.med.upenn.edu Author paper 
Julie Williams (Cardiff University, UK)
Tel: +44 29 20687067; E-mail: williamsj(at)cardiff.ac.uk Author paper 
 Nanotechnology: Some nanoparticles affect pregnant mice
Silica and titanium dioxide nanoparticles injected intravenously can cause pregnancy complications in mice, suggests a paper online this week in Nature Nanotechnology. The work offers insight on the effects of nanoparticles on pregnant animals.
Nanoparticles have been shown to cross the placental barrier and induce neurotoxicity in the offspring of mice but detailed understanding of their effects on pregnant animals remains unclear. Yasuo Yoshioka and colleagues injected pregnant mice with titanium dioxide nanoparticles and various sizes of silica nanoparticles. They found that mice receiving titanium dioxide and the smallest size of silica nanoparticles had lower uterine weights and smaller foetuses than control animals that received saline solution. Other common nanomaterials such as fullerene did not induce any complications. The team showed that when the surface of the silica nanoparticles was modified with carboxyl and amine groups, the abnormalities disappeared. In addition, administering heparin with the silica nanoparticles prevented the uterine and fetus abnormalities, suggesting that the complications may involve the coagulation pathway.
Although this work shows the effects of nanoparticles on mice, the authors caution that the anatomical and structural differences between mouse and human placenta mean that the work cannot be extrapolated to humans. Nevertheless, the consequences of nanoparticles on reproductive health are important aspects to consider.
Yasuo Yoshioka (Osaka University, Japan)
Tel: +81 6 6879 8177; E-mail: yasuo(at)phs.osaka-u.ac.jp
 Geoscience: Large carbon stocks in mangroves
Mangrove forests store large amounts of carbon below ground, according to a study published online this week in Nature Geoscience. The areal extent of mangrove forests has declined by 30–50% over the past half century as a result of deforestation.
Daniel Donato and colleagues examined the carbon content of 25 mangrove forests across the Indo-Pacific region. They show that mangroves are among the most carbon-rich forests in the tropics; most of the carbon is stored below ground in sediments. They estimate that mangrove deforestation generates a loss of 0.02–0.12 petagrams of carbon per year, which is equivalent to up to 10% of carbon emissions from global deforestation.
In an accompanying News & Views article, Steven Bouillon argues that the findings “provide a strong incentive to consider mangrove ecosystems as priority areas for conservation”.
Daniel Donato (USDA Forest Service, Hilo, HI, USA)
Tel: +1 808 933 8121; E-mail: donato.danc(at)gmail.com
Steven Bouillon (Katholieke Universiteit Leuven, Belgium) N&V author
Tel: +32 498513608; E-mail: steven.bouillon(at)ees.kuleuven.be
 Medicine: Distinguishing pancreatic cancer subtypes
Gene signatures can help define different types of pancreatic tumours reports research published online this week in Nature Medicine. The gene signatures that characterize these subtypes of tumours may be useful in treating specific patients with specific drugs to maximize their responses.
Pancreatic ductal adenocarcinoma (PDA) is a deadly form of cancer; overall survival is typically 6 months from diagnosis. Numerous clinical trials of agents effective in other cancers have failed to benefit unselected PDA patient populations, although some patients do occasionally respond. Studies in other tumours have shown that variability in response is determined in part by molecular differences between tumours and that treatment outcomes improve by targeting drugs to tumour subtypes in which they are selectively effective—breast and lung cancers provide some of the best examples.
Identification of PDA molecular subtypes has previously been limited by a lack of tumor specimens available for study. Joe Gray and his colleagues overcame this problem by combining analysis of gene-expression profiles of primary PDA samples from several studies, along with human and mouse PDA cell lines. On the basis of this analysis, the authors defined three PDA subtypes and showed evidence for differences in clinical outcome and therapeutic response among them.
The gene signatures that characterize these subtypes may be useful for the design of clinical trials of new drugs targeted to individual tumor subtypes.
Joe Gray (Oregon Health Sciences University, Portland, OR, USA)
Tel: +1 503 494 6500; E-mail: grayjo(at)ohsu.edu
 Geoscience: Accelerating sea-level rise from Patagonian glaciers
The rate of melting in the Patagonian Icefields was markedly higher in the late twentieth century than the preceding few centuries reports a paper published online in Nature Geoscience.
Neil Glasser, Stephan Harrison and colleagues estimated the amount of ice loss in the northern and southern Patagonian Icefields, and hence the amount of meltwater entering the oceans, since the Little Ice Age. Maximum glacier extent occurred in 1870 in the north and 1650 in the south. They found that following this maximum, the northern and southern icefields were responsible for a sea-level rise of just a few thousandths of a millimetre per year, respectively.
This estimate of long-term sea-level rise is one order of magnitude lower than estimates for the past 50 years, suggesting that the rate of melting has increased substantially over the twentieth century.
Neil Glasser (Aberystwyth University, UK)
Tel: +44 197 0622785; E-mail: nfg(at)aber.ac.uk
Stephan Harrison (University of Exeter, UK)
Tel: +44 132 6377046; E-mail: stephan.harrison(at)exeter.ac.uk
 Medicine: Keeping bone from forming in the wrong place
Activators of a certain nuclear receptor prevent heterotopic ossification – the formation of bone within soft tissues, such as the skin, after surgery or trauma – in mice reports a paper published online in Nature Medicine this week.
Diseases such as fibrodysplasia ossificans progressiva (FOP) are characterized by heterotopic ossification. Patients with FOP often carry a mutation in a gene known as ALK2, and mice genetically modified to carry a related mutation show heterotopic ossification. Using this mouse model, Masahiro Iwamoto and colleagues found that retinoic acid receptor-gamma agonists prevent the abnormal bone formation, raising the possibility that this strategy may also be effective against heterotopic ossification in humans.
Masahiro Iwamoto (The Children's Hospital of Philadelphia, PA, USA)
Tel: +1 267 425 2072; E-mail: IwamotoM(at)email.chop.edu
 Photonics: Extremely stable optical lattice clocks
An extremely stable and accurate optical lattice clock whose 17th digit can be determined in an averaging time of 15 minutes is reported online this week in Nature Photonics. The work will enable global positioning systems to detect height differences of around 10 cm in tens of minutes.
Current optical lattice clocks are limited by the Dick effect – a source of unwanted noise associated with the laser probing scheme used to read out the frequency of the clock.
The optical lattice clock of Hidetoshi Katori and co-workers avoids this boundary, allowing it to achieve stabilities approaching the quantum projection noise limit. This work therefore represents a major step towards the practical realization of optical lattice clocks.
Nature Photonics’ April issue features additional content relating to this subject. You can access this content from March 31st onwards at http://www.nature.com/nphoton/journal/v5/n4/index.html
Hidetoshi Katori (University of Tokyo, Japan)
Tel: +81 3 5841 6845; E-mail: katori(at)amo.t.u-tokyo.ac.jp
 Chemical Biology: Cannabis without hallucinations
The analgesic effects seen after marijuana use are mediated by the drug’s active component THC binding to the ion channel GlyR, therefore enabling the development of a THC variant that has only analgesic properties, reports a study online in Nature Chemical Biology. The high and psychomotor impairment associated with cannabinoid-based medications limit their further development as pain-relievers, but the modified compounds described in this study may lead to new drugs that minimize those side effects.
Marijuana is both analgesic and psychoactive and both of these effects can be attributed to its active component, THC. The psychoactive effects are known to be mediated by THC binding to the cannabinoid receptor CB1R however the mechanisms involved in the analgesic effects are less well known. Li Zhang and colleagues found that THC binds to transmembrane segments of GlyR and specific hydrogen-bonding interactions occur between THC chemical constituents and the receptor. The team found that removal of the hydroxyl groups of THC led to a compound that no longer activated GlyR. These data allowed them to design THC analogs that activate GlyRs but lack CB1R activity.
Li Zhang (National Institute of Health, Bethesda, MD, USA)
Tel: +1 301 443 3755; E-mail: lzhang(at)mail.nih.gov
 And finally…Neuroscience: Itching for answers
An ion channel critical for some forms of itch is identified in a paper published online this week in Nature Neuroscience.
Itch, like pain, serves a protective function under normal conditions; however, chronic, pathological itch is a debilitating condition that accompanies numerous skin and systemic disorders. In many cases, pathological itch is resistant to antihistamine treatments.
Diana Bautista and colleagues used a host of pharmacological and genetic techniques to probe the pathways of histamine-independent itch in mice. They report that two chemicals that elicit histamine-independent itch – including the antimalarial drug chloroquine, which can produce itching as an adverse side effect – control neuronal excitability via an ion channel called TRPA1. Sensory neurons of mice deficient in TRPA1 have a substantially diminished response to chloroquine and the team found that the mice show little to no scratching in response to the drug.
These findings in mice may provide insight into pathological histamine-independent itch in humans.
Diana Bautista (University of California, Berkeley, CA, USA)
Tel: +1 510 642 1794; E-mail: dbautista(at)berkeley.edu
Items from other Nature journals to be published online at the same time and with the same embargo:
 Ephrin Bs are essential components of the Reelin pathway to regulate neuronal migration
 Neuronal activity is required for the development of specific cortical interneuron subtypes
 Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation
 Genome-wide analysis reveals novel molecular features of mouse recombination hotspots
 Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
 Cholesterol modulates glycolipid conformation and receptor activity
NATURE CHEMISTRY (http://www.nature.com/nchem)
 Stereoselective C–C bond formation catalysed by engineered carboxymethylproline synthases
 Biodegradable nanostructures with selective lysis of microbial membranes
NATURE GENETICS (http://www.nature.com/naturegenetics)
 A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids
NATURE GEOSCIENCE (http://www.nature.com/ngeo)
 Aseismic zone and earthquake segmentation associated with a deep subducted seamount in Sumatra
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
 The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells
NATURE MATERIALS (http://www.nature.com/naturematerials)
 Rotation-reversal symmetries in crystals and handed structures
 Bottom-gated epitaxial graphene
 Polymer nanosieve membranes for CO2-capture applications
NATURE METHODS (http://www.nature.com/nmeth)
 A more efficient method to generate integration-free human iPS cells
 A genome-scale shRNA resource for transgenic RNAi in Drosophila
NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)
 Nanoparticles reduce nickel allergy by capturing metal ions
 Nanoscale Joule heating, Peltier cooling and current crowding at graphene–metal contacts
 Scalable nanostructured membranes for solid-oxide fuel cells
NATURE NEUROSCIENCE (http://www.nature.com/natureneuroscience)
 D-Serine regulates cerebellar LTD and motor coordination through the d2 glutamate receptor in the developing mouse
 Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy
 Perceptual learning as improved probabilistic inference in early sensory areas
NATURE PHOTONICS (http://www.nature.com/nphoton)
 Nanofocusing of mid-infrared energy with tapered transmission lines
NATURE PHYSICS (http://www.nature.com/naturephysics)
 Hydrodynamic nucleation of quantized vortex pairs in a polariton quantum fluid
 Single spontaneous photon as a coherent beamsplitter for an atomic matter-wave
 Tunable Kondo effect in graphene with defects
 Direct measurement of the energy dissipated by quantum turbulence
NATURE STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
 Structural basis for CRISPR RNA-guided DNA recognition by Cascade
 Single-molecule paleoenzymology probes the chemistry of resurrected enzymes
 The client protein p53 adopts a molten globule-like state in the presence of Hsp90
 Structure of catalytically competent intein caught in a redox trap with functional and evolutionary implications
GEOGRAPHICAL LISTING OF AUTHORS
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.
Vienna: 26, 35
Toronto: 1, 11, 16
Paris: 2, 20, 31
Erlangen: 2, 23
Frankfurt am Main: 11
Goettingen: 2, 17
Munich: 2, 35
San Giovanni Rotondo: 2
Fukuoka: 21, 30
Tokyo: 3, 8, 19, 21, 30
Yokohama: 19, 21
Warsaw: 2, 34
Madrid: 2, 31
San Sebastian: 33
Stockholm: 6, 39
Lausanne: 5, 34
Cambridge: 2, 15
London: 1, 2, 32, 38
Oxford: 2, 17, 20
UNITED STATES OF AMERICA
Berkeley: 5, 10, 36, 38
Irvine: 1, 7
La Jolla: 1, 26, 40
Los Angeles: 1, 32
Redwood City: 5
San Francisco: 1, 5, 25
San Jose: 18
District of Columbia
Washington: 2, 4
Jacksonville: 1, 2
Atlanta: 1, 39
West Lafayette: 39
Baltimore: 1, 10
Bethesda: 2, 9, 14, 21
College Park: 36
Boston: 1, 2, 26, 27, 29
Cambridge: 1, 27, 29
Ann Arbor: 1, 7
Rochester: 1, 2
St Louis: 1, 2
Cold Spring Harbor: 26
New York: 1, 12, 13, 39
Portland: 1, 5
Philadelphia: 1, 7
Pittsburgh: 1, 2, 9
University Park: 22
Fort Worth: 1
Provo: 1, 2
For media inquiries relating to embargo policy for all the Nature Research Journals:
Rachel Twinn (Nature London)
Tel: +44 20 7843 4658; E-mail: r.twinn(at)nature.com
Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: n.afsarmanesh(at)us.nature.com
Ruth Francis (Head of Press, Nature, London)
Tel: +44 20 7843 4562; E-mail: r.francis(at)nature.com
For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:
Nature Biotechnology (New York)
Tel: +1 212 726 9288; E-mail: biotech(at)us.nature.com
Nature Cell Biology (London)
Tel: +44 20 7843 4656; E-mail: cellbio(at)nature.com
Nature Chemical Biology (Boston)
Tel: +1 617 475 9241, E-mail: chembio(at)us.nature.com
Nature Chemistry (London)
Tel: +44 20 7014 4018; E-mail: s.cantrill(at)nature.com
Nature Climate Change (London)
Tel: +44 20 7014 4009; E-mail: nclimate(at)nature.com
Nature Genetics (New York)
Tel: +1 212 726 9324; E-mail: [email protected]
Nature Geoscience (London)
Tel: +44 20 7843 4042; E-mail: h.langenberg(at)nature.com
Nature Immunology (New York)
Tel: +1 212 726 9372; E-mail: immunology(at)us.nature.com
Nature Materials (London)
Tel: +44 20 7843 4531; E-mail: materials(at)nature.com
Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: medicine(at)us.nature.com
Nature Methods (New York)
Tel: +1 212 726 9627; E-mail: methods(at)us.nature.com
Nature Nanotechnology (London)
Tel: +44 20 7014 4019; Email: p.rodgers(at)nature.com
Nature Neuroscience (New York)
Tel: +1 212 726 9319; E-mail: neurosci(at)us.nature.com
Nature Photonics (Tokyo)
Tel: +81 3 3267 8776; E-mail: o.graydon(at)natureasia.com
Nature Physics (London)
Tel: +44 20 7843 4555; E-mail: a.wright(at)nature.com
Nature Structural & Molecular Biology (New York)
Tel: +1 212 726 9326; E-mail: nsmb(at)us.nature.com
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