This press release contains:
· Summaries of newsworthy papers:
Neuroscience: Pain in the long run
Materials: Sugar templates for vascular tissues
Genetics: Resistance in targeted cancer therapy
Neuroscience: Restoring aging-associated memory loss
Materials: Gels for selecting tumorigenic cells
Methods: Zinc-finger nucleases cross cell membranes
Geoscience: Inner core influence on magnetic field eccentricity
Methods: Tools to study microRNA function
And finally…Climate Change: Parental help
· Geographical listing of authors
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[1] Neuroscience: Pain in the long run
DOI: 10.1038/nn.3153
Greater functional connectivity between two brain regions previously implicated in the experience of pain predicts which back-pain patients will still be in pain a year after reporting problems, according to an article published in Nature Neuroscience this week.
Vania Apkarian and colleagues studied patients with an initial episode of back pain over the course of a year. While some patients recovered during this time, the pain persisted in others. Functional and structural brain imaging showed an initial difference in functional connectivity between the nucleus accumbens and the prefrontal cortex that predicted which patients would go on to suffer from chronic pain. The authors also found gradual changes in grey matter density correlated with the experience of pain for an extended period of time.
Previous work has focused on the changes in the peripheral nerves and spinal cord that lead to chronic pain, but these results suggest that the brain may also play a role in the conversion from acute to chronic pain.
Author contact:
Vania Apkarian (Northwestern University, Chicago, IL, USA)
Tel: +1 312 503 0404; E-mail: [email protected]
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[2] Materials: Sugar templates for vascular tissues
DOI: 10.1038/nmat3357
A rapid and general moulding strategy that uses carbohydrate glass as a sacrificial template for the formation of vascular networks in engineered tissues is reported online this week in Nature Materials. The approach may enable the scaling up of engineered tissue scaffolds that maintain their function at physiological densities, and that may be used as therapeutic replacements.
Without vascular networks that can deliver nutrients and oxygen and remove metabolic byproducts, tissues quickly develop a necrotic core that suppresses their function. But constructing perfusable three-dimensional vascular tissues in the laboratory has only been possible through slow and complex procedures that are usually restricted in the types of materials and cells that can be used.
Using a mixture of glucose and sucrose, and taking advantage of three-dimensional printing, Christopher Chen and colleagues made a network of glass filaments and encased it with a suspension of living cells in their extracellular matrix. After crosslinking the matrix, the researchers dissolved the filaments in cell media. The filaments flowed out of the network leaving behind channels that could be perfused with blood within minutes.
The researchers also demonstrate that the approach is compatible with many types of cells, extracellular matrices and crosslinking strategies, and that it allows for independent control of the network geometry and cell type, both in the lining of the vascular channels and between them.
Author contact:
Christopher Chen (University of Pennsylvania, Philadelphia, PA, USA)
Tel: +1 215 746 1754; E-mail: [email protected]
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[3] Genetics: Resistance in targeted cancer therapy
DOI: 10.1038/ng.2330
A therapeutic target that may prevent or overcome the acquired resistance to treatment seen in non-small cell lung cancers (NSCLC) harboring a specific gene mutation is reported this week in Nature Genetics.
Treatment of NSCLC that have a mutation in the cell surface receptor EGFR with tyrosine kinase inhibitors, such as erlotinib, extends life by an average of about three months. However, with this treatment, tumors almost always acquire resistance.
Trever Bivona and colleagues show that the enzyme AXL kinase is upregulated in some resistant human NSCLC. They further showed that inhibiting AXL function in cell and mouse models of resistant tumors restored sensitivity to the common NSCLC drug erlotinib. The authors suggest AXL as a therapeutic target that for patients with acquired resistance in EGFR-mutant lung cancer.
Author contact:
Trever Bivona (University of California, San Francisco, CA, USA)
Tel: +1 415 476 9907; E-mail: [email protected]
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[4] Neuroscience: Restoring aging-associated memory loss
DOI: 10.1038/nn.3151
Memory impairments in older mice may be due to a decrease in DNA methylation in the brain, reports a study published online this week in Nature Neuroscience. These findings suggest a potential cause underlying the loss of memory ability that accompanies normal aging.
Methylation is a mark that is added to DNA that affects whether a gene is active or not. Hilmar Bading and colleagues found that older mice had decreased levels of a protein that methylates DNA in the hippocampus, a region of the brain known to be important in creating and storing memories. If they increased the levels of this protein in the brains of older mice, they remembered just as well as younger mice. Decreasing levels of the protein in younger mice left them just as impaired as older mice.
Author contact:
Hilmar Bading (University of Heidelberg, Germany)
Tel: +49 6221 54 8218; E-mail: [email protected]
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[5] Materials: Gels for selecting tumorigenic cells
DOI: 10.1038/nmat3361
Soft fibrin gels can promote the growth of tumorigenic cells from a pool of cancer cells, reports a study published online this week in Nature Materials. Injection of just a few of the gel-promoted cells in wild-type mice led to the formation of tumours in their lungs, suggesting that this approach to selecting tumorigenic cells could help the study of the mechanisms underlying the capacity of some cancer cells to produce tumours and to spread to distant organs.
The identification of cancer cells with tumorigenic potential has so far relied on the expression of stem-cell markers, which is often inaccurate. Ning Wang, Bo Huang and colleagues report a much more efficient and robust method for selecting tumorigenic cells. They demonstrate that a subset of cells from mouse or human cancer cell lines cultured in low-stiffness gels made of fibrin — a fibrous protein involved in blood clotting — grew more rapidly into bigger round colonies, and that a few of the cells extracted from the colonies formed tumours in both genetically identical and immunodeficient mice at the site of injection or in the lungs much more efficiently than cells cultured on top of the soft fibrin gels, on plastic dishes, or within soft collagen gels of similar stiffness.
Author contacts:
Ning Wang (University of Illinois at Urbana-Champaign and Huazhong University of Science and Technology, Wuhan, China)
Tel: +1 217 265 0913; E-mail: [email protected]
Bo Huang (Huazhong University of Science and Technology, Wuhan, China)
Tel: +86 278 360 8655; E-mail: [email protected]
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[6] Methods: Zinc-finger nucleases cross cell membranes
DOI: 10/1038/nmeth.2030
Zinc-finger nucleases (ZFNs), used for targeted genomic modification, can cross the cell membrane as proteins. The findings, published this week in Nature Methods, should enable simpler and safer delivery of these biological tools to cells.
Designer nucleases, such as ZFNs, can be used to make targeted changes in the genomes of many species and are generating excitement as tools for both research and gene therapy. The nucleases are typically delivered to the inside of cells as DNA or RNA, where the functional proteins are then generated.
Carlos Barbas and colleagues report that ZFN proteins themselves can cross the cell membrane. They do so—as observed in several mammalian cell types—at high enough levels to generate targeted genomic changes as efficiently as ZFNs delivered as DNA. Although cell membrane permeation is a property that has been reported for a small set of proteins and peptides, it was not previously known to be a feature of ZFNs.
Nucleases delivered as proteins are present in the target cells transiently and generate measurably fewer off-target genomic changes than nucleases delivered as DNA. Protein delivery of these tools avoids the risk of insertional mutagenesis associated with delivery by viral vectors as well as the toxicity associated with the cellular response to exogenous RNA.
Author contact:
Carlos Barbas (Scripps Research Institute, La Jolla, CA, USA)
Tel: +1 858 784 9098; E-mail: [email protected]
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[7] Geoscience: Inner core influence on magnetic field eccentricity
DOI: 10.1038/ngeo1506
Lopsided growth of Earth’s inner core could cause the geomagnetic field to be offset from the planet’s centre, reports a study published online this week in Nature Geoscience. Asymmetry along the boundary between the outer core and the mantle is thought to influence the structure of the magnetic field, but this study demonstrates that asymmetry of the inner core could be important too.
Peter Olson and Renaud Deguen use a numerical model to simulate the driving forces that generate Earth’s magnetic field. The inner core is thought to grow asymmetrically, with solidification occurring in one hemisphere and melting in the other. The authors show that incorporating this asymmetry into the model causes the axis of the magnetic field to be shifted away from the centre of the Earth, into the hemisphere where fastest solidification is occurring. Reconstructions of Earth’s magnetic field show that the axis of the dipole field was offset into the Western Hemisphere over the past approximately 10,000 years, and into the Eastern Hemisphere before that. The authors’ model results imply that the location of fastest inner core growth may also have shifted in the past few million years.
In an accompanying News and Views article, Christopher Finlay says: “Extrapolation of the details of simple numerical dynamo calculations to the Earth's core is controversial, but the prospect of fresh insights into the mechanism by which Earth's magnetic field operates is tantalizing.”
Author contact:
Peter Olson (Johns Hopkins University, Baltimore, MD, USA)
Tel: +1 410 516 7707; E-mail: [email protected]
Christopher Finlay (Technical University of Denmark, Copenhagen, Denmark) N&V author
Tel: +45 35325740; E-mail: [email protected]
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[8] Methods: Tools to study microRNA function
DOI: 10.1038/nmeth.2078
Two sets of tools that explore the function of microRNAs in human cells are reported this week in Nature Methods. The new resources will help to unravel how microRNAs, which play an important role in regulating gene expression, function on a much larger scale than was previously possible.
One of the tools offered by Brian Brown and colleagues is a library of virus vectors that can be introduced into cells to ‘sense’ the presence and activity of the vast majority of human microRNAs. Their assay, called Sensor-seq, uses the sensory library to provide a snapshot of microRNA activity in a given cell type in a single rapid experiment. The other tool is a series of ‘decoys’, each of which can bind a specific microRNA and inhibit its activity so that researchers can learn its function—a technique analogous to gene knockout.
Unlike what is generally assumed, the researchers found that the majority of microRNAs detected in cells have no effect on the expression of their target genes because they exist below a threshold required for activity. Sensor-seq also reveals which microRNAs have activity that is specific to certain tissues. Including target sites for these in engineered viruses or plasmids can selectively remove the engineered vectors from those tissues.
Author contact:
Brian Brown (Mount Sinai School of Medicine, New York, NY, USA)
Tel +1 212 659 9202; E-mail: [email protected]
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[9] And finally…Climate Change: Parental help
DOI: 10.1038/nclimate1599
Reef fish display the capacity to acclimatize to warmer, acidified ocean conditions — like those predicted in modelling studies for later this century — when multiple generations are considered. These findings, published online this week in Nature Climate Change, indicate that some marine organisms might be more resilient to climate change impacts than previously thought.
The negative impacts of warmer and/or more acidic waters have been demonstrated for a wide variety of marine organisms, but the way that species might adjust over multiple generations is rarely considered. In an experimental set-up, Gabrielle Miller and co-workers demonstrate that plausible future ocean temperature and pH conditions do indeed reduce the condition and survival rate of juvenile anemone fish, but that these negative effects are absent when parents are subjected to the same altered conditions.
These findings demonstrate the potential importance of non-genetic parental effects in moderating ocean acidification impacts.
Author contact:
Gabrielle Miller (James Cook University, Townsville, Australia)
Tel: +61 7 4781 5574; E-mail: [email protected]
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NATURE (http://www.nature.com/nature)
[10] Structural insights into electron transfer in caa3-type cytochrome oxidase
DOI: 10.1038/nature11182
[11] RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis
DOI: 10.1038/nature11217
[12] Live imaging of stem cell and progeny behaviour in physiological hair-follicle regeneration
DOI: 10.1038/nature11218
[13] A map of the cis-regulatory sequences in the mouse genome
DOI: 10.1038/nature11243
[14] ‘Slings’ enable neutrophil rolling at high shear
DOI: 10.1038/nature11248
[15] NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens
DOI: 10.1038/nature11250
[16] Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice
DOI: 10.1038/nature11310
NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)
[17] Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors
DOI: 10.1038/nbt.2249
[18] Hybrid error correction and de novo assembly of single-molecule sequencing reads
DOI: 10.1038/nbt.2280
[19] A hybrid approach for the automated finishing of bacterial genomes
DOI: 10.1038/nbt.2288
NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)
[20] Direct inhibition of the cold-activated TRPM8 ion channel by Gαq
DOI: 10.1038/ncb2529
[21] Metabolic differentiation in the embryonic retina
DOI: 10.1038/ncb2531
[22] Centralspindlin and a-catenin regulate Rho signalling at the epithelial zonula adherens
DOI: 10.1038/ncb2532
[23] External push and internal pull forces recruit curvature-sensing N-BAR domain proteins to the plasma membrane
DOI: 10.1038/ncb2533
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
[24] Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration
DOI: 10.1038/nchembio.1018
[25] Quality control of disulfide bond formation in pilus subunits by the chaperone FimC
DOI: 10.1038/nchembio.1019
NATURE CHEMISTRY (http://www.nature.com/nchem)
[26] Total synthesis of marinomycin A using salicylate as a molecular switch to mediate dimerization
DOI: 10.1038/nchem.1330
[27] Utilizing redox-chemistry to elucidate the nature of exciton transitions in supramolecular dye nanotubes
DOI: 10.1038/nchem.1380
[28] Revealing the stereospecific chemistry of the reaction of Cl with aligned CHD3(v1=1)
DOI: 10.1038/nchem.1383
NATURE CLIMATE CHANGE (http://www.nature.com/nclimate)
[29] Relative outcomes of climate change mitigation related to global temperature versus sea-level rise
DOI: 10.1038/nclimate1529
[30] Inhibition of the positive snow-albedo feedback by precipitation in interior Antarctica
DOI: 10.1038/nclimate1590
[31] Projected response of an endangered marine turtle population to climate change
DOI: 10.1038/nclimate1582
[32] Impact of climate change on the Baltic Sea ecosystem over the past 1,000 years
DOI: 10.1038/nclimate1595
[33] Changes to dryland rainfall result in rapid moss mortality and altered soil fertility
DOI: 10.1038/nclimate1596
NATURE GENETICS (http://www.nature.com/naturegenetics)
[34] Structural haplotypes and recent evolution of the human 17q21.31 region
DOI: 10.1038/ng.2334
[35] Structural diversity and African origin of the 17q21.31 inversion polymorphism
DOI: 10.1038/ng.2335
[36] The yak genome and adaptation to life at high altitude
DOI: 10.1038/ng.2343
[37] Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease
DOI: 10.1038/ng.2337
NATURE GEOSCIENCE (http://www.nature.com/ngeo)
[38] Seismic imaging of a large horizontal vortex at abyssal depths beneath the Sub-Antarctic Front
DOI: 10.1038/ngeo1502
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
[39] The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-b and suppresses TH2 differentiation
DOI: 10.1038/ni.2362
[40] Aiolos promotes TH17 differentiation by directly silencing Il2 expression
DOI: 10.1038/ni.2363
[41] Integration of the movement of signaling microclusters with cellular motility in immunological synapses
DOI: 10.1038/ni.2364
NATURE MATERIALS (http://www.nature.com/naturematerials)
[42] The predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite
DOI: 10.1038/nmat3362
[43] The nature of strength enhancement and weakening by pentagon–heptagon defects in graphene
DOI: 10.1038/nmat3370
NATURE MEDICINE (http://www.nature.com/naturemedicine)
[44] IL-23 promotes spondyloarthropathy by acting on ROR-gt+ CD3+CD4–CD8– double negative entheseal resident cells
DOI: 10.1038/nm.2817
NATURE METHODS (http://www.nature.com/nmeth)
[45] Scanning angle interference microscopy reveals cell dynamics at the nanoscale
DOI: 10.1038/nmeth.2077
[46] forestSV: structural variant discovery through statistical learning
DOI: 10.1038/nmeth.2085
NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)
[47] Metal–oxide–semiconductor field-effect transistor with a vacuum channel
DOI: 10.1038/nnano.2012.107
[48] Vanadium pentoxide nanoparticles mimic vanadium haloperoxidases and thwart biofilm formation
DOI: 10.1038/nnano.2012.91
[49] Anderson–Mott transition in arrays of a few dopant atoms in a silicon transistor
DOI: 10.1038/nnano.2012.94
NATURE NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[50] Memory signals are temporally dissociated in and across human hippocampus and perirhinal cortex
DOI: 10.1038/nn.3154
NATURE PHOTONICS (http://www.nature.com/nphoton)
[51] Solution-processed inorganic bulk nanoheterojunctions and their application to solar cells
DOI: 10.1038/nphoton.2012.139
NATURE PHYSICS (http://www.nature.com/naturephysics)
[52] The origin and non-quasiparticle nature of Fermi arcs in Bi2Sr2CaCu2O8+d
DOI: 10.1038/nphys2352
[53] Ultrafast entangling gates between nuclear spins using photo-excited triplet states
DOI: 10.1038/nphys2353
NATURE STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[54] Stochastic expression dynamics of a transcription factor revealed by single-molecule noise analysis
DOI: 10.1038/nsmb.2336
[55] Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase
DOI: 10.1038/nsmb.2329
[56] Architecture of the RNA polymerase II preinitiation complex and mechanism of ATP-dependent promoter opening
DOI: 10.1038/nsmb.2334
[57] Unraveling cell type–specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs
DOI: 10.1038/nsmb.2339
[58] Proof reading of pre-40S ribosome maturation by a translation initiation factor and 60S subunits
DOI: 10.1038/nsmb.2308
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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.
AUSTRALIA
Brisbane: 22
Clayton: 10
Melbourne: 29
Townsville: 9
BELGIUM
Ghent: 15
CAMEROON
Yaoundé: 35
CANADA:
Quebec: 30
CHINA
Beijing: 36, 37, 43
Changchun: 54
Chengdu: 36, 37
Fuzhou: 36
Hanzhong: 36
Jilin: 36
Jinan: 36
Kunming: 37
Lanzhou: 37
Nanjing: 36
Nantong: 36
Renqiu: 36
Shanghai: 36, 37
Shenzhen: 36, 37
Shijiazhuang: 36
Tangshan: 36
Urumchi: 36
Wuhan: 5, 36
Xi’an: 36
Xinle: 36
Yuxian: 36
Zhangqiu: 36
Zhengzhou: 36
COSTA RICA
Playa Grande: 31
DENMARK
Copenhagen: 32, 37
FRANCE
Grenoble: 30
Montpellier: 57
Paris: 35, 42, 44
GERMANY
Berlin: 27
Bonn: 50
Heidelberg: 4
Lubeck: 36
Mainz: 48
Rostock: 32
GREECE
Crete: 28
IRELAND
Dublin: 10
Limerick: 10
ITALY
Agrate Brianza: 49
Milan: 49
JAPAN
Chiba: 39
Fukuoka: 24
Hiroshima: 52
Ibaraki: 49, 52
Kumamoto: 24
Nagoya: 24
Osaka: 24
Saitama: 10, 24
Sendai: 24
Tokyo: 14, 24, 49
Tsukuba: 6, 24
KENYA
Nairobi: 35
NETHERLANDS
Amsterdam: 48
Den Burg: 32
Groningen: 27
Utrecht: 22, 37
NORWAY
Bergen: 32
SOUTH KOREA
Seoul: 3, 37
SPAIN
Barcelona: 3, 51
San Juan de Alicante: 20
SUDAN
Khartoum: 35
SWEDEN
Lund: 32
SWITZERLAND
Villigen: 25
Zurich: 25
TAIWAN
Hsinchu: 28
Taipei: 28
TANZANIA
Dar es Salaam: 35
UNITED KINGDOM
Aberystwyth: 37
Birmingham: 44
Cambridge: 17, 21, 22, 38
Cardiff: 37
Durham: 38
Leicester: 36
Liverpool: 26
London: 21
Oxford: 44, 53, 55
Southampton: 38
UNITED STATES OF AMERICA
California
Berkeley: 45
Davis: 37
Emeryville: 1
Fort Irwin: 33
La Jolla: 6, 13, 14, 46
Menlo Park: 19
Palo Alto: 44
San Francisco: 3, 22, 25, 41, 45, 57
Stanford: 23
Walnut Creek: 18
Colorado
Boulder: 29, 43, 52
Denver: 41
Connecticut
Farmington: 23
New Haven: 3, 12, 35
Florida
Tallahassee: 45
Georgia
Atlanta: 19
Illinois
Chicago: 35, 1
Urbana: 5, 37
Indiana
Bloomington: 26
Fort Wayne: 31
Maryland
Baltimore: 7, 18, 54
Bethesda: 16
Chevy Chase: 11
College Park: 18
Frederick: 18
Rockville: 13
Massachusetts
Boston: 11, 16, 19, 34, 36, 40
Cambridge: 2, 11, 21, 27, 34, 36, 43, 55
Charlestown: 40
Michigan
Ann Arbor: 35
Missouri
St Louis: 36
New Jersey
Princeton: 29, 31
New York
Cold Spring Harbor: 18
Ithaca: 33
New York: 3, 8, 17, 19
Stony Brook: 54
Upton: 52
North Carolina
Chapel Hill: 23
Durham: 18
Ohio
Cleveland: 3, 39
Pennsylvania
Collegeville: 15
Philadelphia: 2, 31, 35, 36
Pittsburgh: 24, 47
Tennessee
Memphis: 15
Texas
Austin: 27
Dallas: 21
Utah
Moab: 33
Vermont
Burlington: 24
Washington
Seattle: 35, 56
PRESS CONTACTS…
For media inquiries relating to embargo policy for all the Nature Research Journals:
Rachel Twinn (Nature London)
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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Tel: +81 3 3267 8751; E-mail: [email protected]
For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:
Nature Biotechnology (New York)
Michael Francisco
Tel: +1 212 726 9288; E-mail: [email protected]
Nature Cell Biology (London)
Sowmya Swaminathan
Tel: +44 20 7843 4656; E-mail: [email protected]
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
Tel: +1 212 726 9319; E-mail: [email protected]
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)
Michelle Montoya
Tel: +1 212 726 9331; E-mail: [email protected]
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