From designer enzymes to monkey brains

Latest news from Nature Journals 05 February 2012

This press release contains:

---Summaries of newsworthy papers:

Genetics: Variants associated with stroke

Materials: Ultrastable polymer glasses

Chemical Biology: Protein design – now with metals!

Geoscience: Volcanic cooling not recorded by tree rings

Immunology: A cytokine’s secrets revealed

Methods: Finding mistakes in yeast gene libraries

And finally…Methods: Studying monkey and human brain similarities

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

---Geographical listing of authors

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[1] Genetics: Variants associated with stroke
DOI: 10.1038/ng.1081

Genetic variants associated with susceptibility to stroke are reported in a study this week in Nature Genetics.

Stroke represents an increasing global public health concern, as a major cause of adult chronic disability and mortality. Approximately 80% of stroke cases worldwide are ischemic – due to a restriction of blood supply – and amongst these, the three most common subtypes are large vessel, cardioembolic and small vessel stroke.

Hugh Markus and colleagues report a genome-wide association study for susceptibility to ischemic stroke in 3,548 affected individuals and 5,972 controls of European ancestry. They classified affected individuals by stroke subtype using clinical assessment, brain and vascular imaging. They identify a genomic region newly associated with large vessel stroke, including associated variants within the HDAC9 gene, encoding a histone deacetylase protein. The team also replicate three previously reported associated loci. They find that all four of these associations show heterogeneity across stroke subtypes, suggesting that there is a different mechanism predisposing to these subtypes.

Author contact:
Hugh Markus (St George’s University of London, UK)
Tel: +44 20 8725 2735; E-mail: [email protected]


[2] Materials: Ultrastable polymer glasses
DOI: 10.1038/nmat3234

Glassy polymer films that are 40% less dense and considerably more stable against ageing than standard acrylic glass are described online in Nature Materials this week. The new glasses may find use in nanotechnology and biomedical applications where polymer weight and stability are critical.

To make the glassy films, Rodney Priestley and colleagues used a pulsed laser to gently evaporate molecules out of a frozen dilute solution of standard acrylic glass — poly(methyl methacrylate) (PMMA), which is widely used in automobiles, buildings and orthopaedic surgery. The evaporated PMMA molecules were deposited on a substrate and formed a film. Using atomic force microscopy, the authors found that unlike the unstructured standard PMMA glasses made by rapidly cooling the liquid, the new glassy films consisted of stable polymer nanoglobules. They propose that the globular nanostructure confers the lower density and higher thermal and kinetic stability — in particular, a 40-degree-higher glass transition temperature and a glass-to-liquid transformation rate a hundred times slower than standard PMMA glass.

The authors also note that the fabrication of nanostructured ultrastable glasses from other polymers by pulsed-laser evaporation and deposition should be possible.

Author contact:

Rodney Priestley (Princeton University, NJ, USA)
Tel: +1 609 258 5721; E-mail: [email protected]


[3] Chemical Biology: Protein design – now with metals!
DOI: 10.1038/nchembio.777

Computationally-designed zinc-containing enzymes that can degrade molecules that are similar in structure to the nerve agent sarin are reported online this week in Nature Chemical Biology. Rational design of proteins has made important progress in recent years, identifying protein sequences with new protein folds and new enzyme activities. However, little attention has been paid to integrating metals into these systems. The incorporation of metals illustrated in this work – capable of catalyzing a wide variety of unusual reactions – should greatly broaden the reactions that are possible in protein design.

David Baker and colleagues survey a wide number of known zinc-containing enzymes to identify 12 that have shapes that could be redesigned for their new reaction. They found that one of these enzymes did show some activity in breaking apart an organophosphate molecule. Further engineering by the team, guided in part by a crystal structure of the new enzyme, led to a successful enzyme.

Author contact:

David Baker (University of Washington, Seattle, WA, USA)
Tel: +1 206 543 1295; E-mail: [email protected]


[4] Geoscience: Volcanic cooling not recorded by tree rings
DOI: 10.1038/ngeo1394

Reconstructions of past climate on the basis of tree rings may miss the short-lived cooling events caused by volcanic eruptions, reports a paper published online this week in Nature Geoscience. The work suggests that, in particular, the tree-ring-based reconstructions may be missing cooling linked to the ad 1258–1259 eruption of an unidentified volcano.

Tree-ring chronologies are often collected from regions that are at or near the minimum temperature for tree growth. Michael Mann and colleagues used numerical simulations of climate and tree growth to show that when temperatures fall abruptly for one or two growing seasons, trees in these regions undergo little or no growth. The resultant lack of a tree ring corresponding to the period of cooling thus masks the climate event in subsequent reconstructions.

These results show that a 2 °C cooling associated with the ad 1258–1259 eruption (as indicated by climate models) cannot be excluded by existing tree-ring data.

Author contact:

Michael Mann (Pennsylvania State University, University Park, PA, USA)
Tel: +1 814 863 4075; E-mail: [email protected]


[5] Immunology: A cytokine’s secrets revealed
DOI: 10.1038/ni.2227

Interleukin-35 (IL-35) – a protein secreted by certain T cells – has important immunosuppressive properties and how it achieves these effects is reported online in Nature Immunology this week.

Dario Vignali and colleagues determine the receptor for IL-35 and show it to be composed of a novel combination of known receptor components. Engagement of this receptor triggers a unique sequence of downstream signaling molecules which are responsible for suppressing target cells and – if the target is a T cell – converting it into another IL-35-expressing cell which is in its turn suppressive.

This study highlights how the immune system can use modular receptor and cytokine components in different combinations to elicit distinct functional consequences.

Author contact:

Dario A. A. Vignali (St. Jude Children's Research Hospital, Memphis, TN, USA)
Tel: +1 901 595 2332; E-mail: [email protected]


[6] Methods: Finding mistakes in yeast gene libraries
DOI 10.1038/nmeth.1890

A method for uncovering the extent that scientists incorrectly assigned gene function in libraries of mutated yeast genes is reported online in Nature Methods.

Comprehensive libraries of mutated genes in yeast are a workhorse for geneticists, and are widely used to assign gene function in genetic screens and genomics studies. But a ‘neighboring gene effect’ has been documented anecdotally, in which the neighbor of the mutated gene—not the gene itself—is actually responsible for the phenotype.

Martin Kupiec and colleagues show that the neighboring gene effect is in fact widespread, affecting on the order of one in ten genes in a prominent deletion collection. They develop and introduce freely available software that uses publicly available protein interaction data to predict the gene that truly causes a given phenotype with high accuracy.

Author contact:

Martin Kupiec (Tel Aviv University, Israel)
Tel +972 3 6409031; E-mail: [email protected])


[7] And finally…Methods: Studying monkey and human brain similarities
DOI: 10.1038/nmeth.1868

A method to find regions of the brain with similar function in both monkeys and humans is reported online this week in Nature Methods. This method could open new avenues for building more accurate evolutionary models.

Previous studies have used functional magnetic resonance imaging (fMRI) to compare how the brains of human and non-human species respond to a particular stimulus or activity. To interpret comparative fMRI studies, researchers often rely on prior knowledge of the anatomical similarity between brain regions.

Wim Vanduffel and colleagues developed a technique, interspecies activity correlation (ISAC), which can help find regions with similar functions without considering differences in the brains’ anatomy. The ISAC method is based on the premise that functionally corresponding regions should have a similar time course of activity in both species if they respond to the same features—for example, hands, faces, objects and so on—even if their anatomical location differs.

The authors validate the ISAC method by studying the similarities in fMRI responses between humans and monkeys exposed to the same clips from the movie The Good, the Bad and the Ugly. Their findings suggest that some human and monkey brain areas might have been functionally reorganized in unexpected ways.

In an accompanying News and Views article, Tor Wager and Tal Yarkoni discuss some of the limitations and challenges that the method faces and the importance of corroborating the putative homologies in future studies.

Author contact:

Wim Vanduffel (Massachusetts General Hospital, Boston, MA, USA and Leuven Medical School, Belgium)
Tel: +1 617 726 0318; E-mail: [email protected]

Tor D. Wager (University of Colorado, Boulder, CO, USA) N&V author
Tel: +1 303 492 7487; E-mail: [email protected]


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

Nature (

[8] DNase I sensitivity QTLs are a major determinant of human expression variation
DOI: 10.1038/nature10808

[9] Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway
DOI: 10.1038/nature10794

[10] Structural basis for recognition of H3K56-acetylated histone H3–H4 by the chaperone Rtt106
DOI: 10.1038/nature10861


[11] CLASPs prevent irreversible multipolarity by ensuring spindle-pole resistance to traction forces during chromosome alignment
DOI: 10.1038/ncb2423


[12] Small molecule-induced DNA damage identifies alternative DNA structures in human genes
DOI: 10.1038/nchembio.780


[13] Genetically encoded norbornene directs site-specific cellular protein labelling via a rapid bioorthogonal reaction
DOI: 10.1038/nchem.1250

[14] A two-dimensional polymer prepared by organic synthesis
DOI: 10.1038/nchem.1265


[15] Multi-centennial tree-ring record of ENSO-related activity in New Zealand
DOI: 10.1038/nclimate1374

[16] Impacts of incentives to reduce emissions from deforestation on global species extinctions
DOI: 10.1038/nclimate1375

[17] Global warming under old and new scenarios using IPCC climate sensitivity range estimates
DOI: 10.1038/nclimate1385

[18] Limited forcing of glacier loss through land-cover change on Kilimanjaro
DOI: 10.1038/nclimate1390


[19] Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis
DOI: 10.1038/ng.1067

[20] Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility
DOI: 10.1038/ng.1071

[21] Common variants at 11p13 are associated with susceptibility to tuberculosis
DOI: 10.1038/ng.1080

[22] Differential confounding of rare and common variants in spatially structured populations
DOI: 10.1038/ng.1074


[23] Soil production limits and the transition to bedrock-dominated landscapes
DOI: 10.1038/ngeo1380

[24] Internal boundary layer model for the evolution of desert dune fields
DOI: 10.1038/ngeo1381


[25] A CD74-dependent MHC class I endolysosomal cross-presentation pathway
DOI: 10.1038/ni.2225

[26] Elevated and sustained expression of the transcription factors Egr1 and Egr2 controls NKT lineage differentiation in response to TCR signaling
DOI: 10.1038/ni.2230


[27] Self-limited plasmonic welding of silver nanowire junctions
DOI: 10.1038/nmat3238

[28] The shear mode of multilayer graphene
DOI: 10.1038/nmat3245


[29] Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis
DOI: 10.1038/nm.2629

[30] Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass
DOI: 10.1038/nm.2665


[31] Library-free methylation sequencing with bisulfite padlock probes
DOI: 10.1038/nmeth.1871

[32] Polyubiquitin-sensor proteins reveal localization and linkage-type dependence of cellular ubiquitin signaling
DOI: 10.1038/nmeth.1888


[33] Tunable doping of a metal with molecular spins
DOI: 10.1038/nnano.2012.1

[34] Direct observation of the spin-dependent Peltier effect
DOI: 10.1038/nnano.2012.2


[35] Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling
DOI: 10.1038/nn.3037

[36] A role for primary cilia in glutamatergic synaptic integration of adult-born neurons
DOI: 10.1038/nn.3042

[37] Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses
DOI: 10.1038/nn.3041


[38] Integration of gigahertz-bandwidth semiconductor devices inside microstructured optical fibres
DOI: 10.1038/nphoton.2011.352

[39] Comb-based radiofrequency photonic filters with rapid tunability and high selectivity
DOI: 10.1038/nphoton.2011.350

[40] Understanding intermediate-band solar cells
DOI: 10.1038/nphoton.2012.1

Nature PHYSICS (

[41] Femtosecond torsional relaxation
DOI: 10.1038/nphys2210

[42] Local probing of propagating acoustic waves in a gigahertz echo chamber
DOI: 10.1038/nphys2217

[43] Shallow pockets and very strong coupling superconductivity in FeSexTe1-x
DOI: 10.1038/nphys2216

[44] A molecular conveyor belt by controlled delivery of single molecules into ultrashort laser pulses
DOI: 10.1038/nphys2214


[45] ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4
DOI: 10.1038/nsmb.2217

[46] Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins
DOI: 10.1038/nsmb.2219

[47] Structural characterization of full-length NSF and 20S particles
DOI: 10.1038/nsmb.2237

[48] Structure and mechanism of the UvrA–UvrB DNA damage sensor
DOI: 10.1038/nsmb.2240



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.

Brisbane: 1
Hobart: 16
Melbourne: 15, 17
Newcastle: 1
Perth: 1
Innsbruck: 18
Laxenburg: 16
Leuven: 1, 7
Rio de Janeiro: 16
Montreal: 29
Vancouver: 25
Beijing: 28, 47
Tianjin: 28
Copenhagen: 19
Lyngby: 3
Lyon: 8
Montpellier: 15, 16
Banjul: 21
Bayreuth: 18
Berlin: 18, 42, 44
Dortmund: 11
Freiburg: 44
Garching: 44
Goettingen: 29
Hamburg: 21
Lubeck: 21, 25
Mainz: 2
Munich: 1, 44
Munster: 1
Neuherberg: 1
Potsdam: 17
Kumasi: 21
Legon: 21
Crete: 2
Reykjavik: 1
Bandung: 21
Dublin: 1
Haifa: 43
Ramat Aviv: 6
Rehovot: 3
Chieti: 7
Milan: 1, 41
Parma: 7
Rome: 20, 21
Turin: 28
Suita: 36
Enschede: 33
Groningen: 20, 34
Leiden: 21
Nijmegen: 20, 21
Utrecht: 11
Zwolle: 20
Auckland: 15
Canterbury: 15
Laguna: 16
Krakow: 1
Porto: 11
Samara: 21
Thuwal: 27
Bucheon-si: 45
Daegu: 45
Seoul: 9
Madrid: 40
Gothenburg: 42
Lund: 1
Bellinzona: 11
Dubendorf: 14
Lausanne: 28, 39
Zurich: 11, 14, 15, 17
Lviv: 16
Aberdeen: 1
Birmingham: 20
Brighton: 21
Cambridge: 1, 12, 13, 16, 21, 28, 37, 41
Dundee: 1
Edinburgh: 1
Glasgow: 40
London: 1, 21, 28
Norwich: 16
Oxford: 1, 21, 22, 28
Southampton: 38
Wolverhampton: 20
Tuscaloosa: 24
Tempe: 23
Berkeley: 30
La Jolla: 31
Los Angeles: 47
Menlo Park: 27
Pasadena: 23
Sacramento: 30
San Francisco: 26, 35
Stanford: 5, 9, 27
Fort Collins: 32
Chicago: 8, 26
West Lafayette: 39
Iowa City: 19
Baltimore: 1, 5, 32
Bethesda: 1, 32
Boston: 1, 6, 7, 29, 39
Cambridge: 1, 6, 41, 48
Charlestown: 7
Worcester: 29
Austin: 45
Rochester: 10
St Louis: 7
Reno: 14
New Jersey
Princeton: 2, 7
Somerset: 39
New Mexico
Los Alamos: 41
New York
New York: 35, 46
Oneonta: 32
Stony Brook: 36
North Carolina
Durham: 8
Raleigh: 13
Cincinnati: 1
Columbus: 5
Philadelphia: 5, 24
University Park: 4, 38
Rhode Island
Bristol: 4
Memphis: 5
Austin: 12
Salt Lake City: 20
Arlington: 16
Charlottesville: 1
Seattle: 3



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Rachel Twinn (Nature London)
Tel: +44 20 7843 4658; E-mail: [email protected]

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Elissa Bolt
Tel: +1 617 475 9241, E-mail: [email protected]

Nature Chemistry (London)
Stuart Cantrill
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Rory Howlett
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Myles Axton
Tel: +1 212 726 9324; E-mail: [email protected]

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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)
Hugh Ash
Tel: +1 212 726 9627; E-mail: [email protected]

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

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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]

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Tel: +44 20 7843 4555; E-mail: [email protected]

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Published: 06 Feb 2012

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