Hobbit head to toe

Summaries of newsworthy papers No ticket no entry, Chromatin-modification link to memory, Unbreakable under pressure, Quirky volcano reveals its secrets and DNA origami

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This press release is copyright Nature.

VOL.459 NO.7243 DATED 07 MAY 2009

This press release contains:

· Summaries of newsworthy papers:

Cancer: No ticket no entry

Relics: Hobbit head to toe

Neuroscience: Chromatin-modification link to memory

Materials: Unbreakable under pressure

Earth science: Quirky volcano reveals its secrets

And finally… DNA origami

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

· Geographical listing of authors

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[1] Cancer: No ticket no entry (AOP)
DOI: 10.1038/nature08021

***This paper will be published electronically on Nature's website on 06 May at 1800 London time / 1300 US Eastern time (which is also when the embargo lifts) 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 07 May, but at a later date. ***

A gene ‘ticket’ that allows cancer cells admittance to the brain is reported in a paper published online this week in Nature. It’s hoped the research could help in the development of drugs to stop cancer spread.

The brain has a notoriously strict door policy, and until now little was known about how cancer cells are able to bypass this. Joan Massagué and colleagues identify three genes in mice that are involved in this process in breast cancer. Two of the genes — COX2 and HBEGF — have already been shown to help breast cancer invade the lungs, suggesting that common biological processes regulate metastasis to these two organs. A third gene, ST6GALNAC5, is found to be specifically involved in brain metastasis. It seems to work by helping the breast cancer cells ‘stick’ to blood vessels in the brain, which allows them time to slip through into the brain tissue. Without ST6GALNAC5, the cells are turned away at the door.

With further work, the authors hope that ST6GALNAC5 could become a very interesting therapeutic target.

CONTACT
Joan Massagué (Memorial Sloan-Kettering Cancer Center, Howard Hughes Medical Institute, New York, NY, USA)
Tel: +1 646 888 2044; E-mail: [email protected]

[2] & [3] Relics: Hobbit head to toe (pp 85-88; 81-84; N&V)

Since the description in 2004 of Homo floresiensis, a diminutive and tiny-brained species of human that lived on the Indonesian island of Flores until at least 12,000 years ago, debate has raged as to whether she represents a distinct species or some instance of modern humanity stricken with a form of microcephaly — a name for a collection of syndromes in which the patient has an unusually small head. Two papers in Nature this week substantiate the view that H. floresiensis was a distinct species, though even stranger than anyone had realized.

One argument for microcephaly in H. floresiensis is that her head was disproportionately small, even for a creature that might have undergone the dwarfing seen in creatures on islands. Eleanor Weston and Adrian Lister have looked at this problem by analogy, by studying fossil hippopotami dwarfed after isolation on the island of Madagascar, cut off from their African ancestors. Strikingly, Weston and Lister show that the brains of the dwarf hippos shrunk disproportionately, suggesting that the brain of H. floresiensis might have been small simply as a result of island dwarfing rather than any kind of pathology.

In a related paper, William Jungers and colleagues turn from the hobbit’s head to its feet. The researchers show that, although the feet had fully adducted big toes, just as in modern humans that walk fully upright, they were much longer relative to the rest of the lower limb than in modern humans, and instead resemble the proportions seen in some apes. Their findings raise the possibility that the ancestor of this species was not H. erectus, as many had thought, but was another more primitive and remote hominin.

CONTACT
Eleanor Weston (Natural History Museum, London, UK) Author paper [2]
Tel: +44 20 7942 5477; E-mail: [email protected]

William Jungers (Stony Brook University Medical Center, NY, USA) Author paper [3]
Tel: +1 631 444 3122; E-mail: [email protected]

Daniel Lieberman (Harvard University, Cambridge, MA, USA) N&V author
Tel: +1 617 495 5479; E-mail: [email protected]

[4] Neuroscience: Chromatin-modification link to memory (pp 55-60)

A chromatin-modifying enzyme impairs memory formation in mice, a Nature paper reveals. Histone deacetylases catalyse the removal of acetyl groups from histones, the main protein component of chromatin. Drugs that selectively block the enzyme’s activity may prove useful in human diseases in which memory is impaired.

Boosting levels of histone deacetylase 2 (HDAC2) in neurons impairs learning and memory in mice, Li-Huei Tsai and colleagues show, whereas boosting levels of a related enzyme, HDAC1, does not. In line with this, when HDAC2 is boosted, several markers of learning and memory, such as dendritic spine number, synapse density and plasticity, are reduced. In contrast, reducing expression of HDAC2 had the opposite effects on memory formation and its cellular correlates. Further work revealed that HDAC2 specifically associates with genes believed to be involved in plasticity and memory, whereas HDAC1 does not.

These studies will spur on drug-development strategies better-targeting HDAC2 instead of HDAC1, potentially enhancing the treatment of human diseases associated with memory impairment.

CONTACT
Li-Huei Tsai (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 324 1660; E-mail: [email protected]

[5] Materials: Unbreakable under pressure (pp 68-72; N&V)

A synthetic material that can change colour in response to external forces is presented this week in Nature. The material turns red as its chemical bonds undergo continuous breaking and reforming due to external mechanical stress. These changes allow researchers to readily monitor the progression of accumulated deformations.

Many biological materials do not simply fail when exposed to mechanical forces, but respond by changing or remodelling, thereby enabling processes such as hearing, muscle contraction or the growth of tissue and bone. It has been a challenge to create synthetic materials that can functionally respond to external forces while still retaining structural stability. Nancy Sottos and colleagues report new synthetic materials engineered to exhibit this trait. The team had previously shown that dissolved polymers containing mechanophores—chemical units with bonds sensitive to mechanical forces—have the ability to break and re-form their covalent bonds under directional strains.

Here, the authors incorporate mechanophores into solid polymeric materials that exhibit colour-changing properties. The same design strategy might also allow the development of synthetic materials that have self-healing properties, or of structural materials in which tracking the extent of stress damage is crucial.

CONTACT
Nancy Sottos (University of Illinois, Urbana, IL, USA)
Tel: +1 217 333 1041; E-mail: [email protected]

Christoph Weder (University of Friborg, Switzerland) N&V author
Tel: +41 26 300 9465; E-mail: [email protected]

[6] Earth science: Quirky volcano reveals its secrets (pp 77-80)

The curious, high carbonate magmas generated by an unusual Tanzanian volcano could have come from a very ‘usual’ source, a Nature paper suggests.

Oldoinyo Lengai in northern Tanzania is the only currently active volcano producing carbonatite lavas, which contain more than 50 per cent carbonate minerals and almost no silicate. Tobias Fischer and colleagues show that volcanic gases captured during an eruptive episode are very similar to those emitted along mid-ocean ridges, despite the fact that these carbonatites occur in a setting far removed from oceanic spreading centres.

This suggests that the Oldoinyo Lengai lavas can be generated from ‘typical’ mantle, like that found beneath oceans and continents, and that an unusually carbon-rich source is not necessarily required.

CONTACT
Tobias Fischer (University of New Mexico, Albuquerque, NM, USA)
Tel: +1 505 277 0284; E-mail: [email protected]

[7] And finally… DNA origami (73-76)

The unique structural motifs and self-recognition properties of DNA have been exploited in the past to generate self-assembled DNA nanostructures of several specific shapes. In Nature this week, Jørgen Kjems and co-workers use this ‘DNA origami’ method to construct a nano-sized box with lockable lid and keys.

Made of DNA, the box is 42 by 36 by 36 nanometres, which means that its internal cavity is large enough to hold a single ribosome or a poliovirus. The six faces of this hollow box are formed from parallel, interlinked DNA helices, folded into shape with the help of 220 short synthetic nucleic acid strands, known as oligonucleotides. This megadalton-sized DNA box also has a ‘lid,’ which can be opened in the presence of externally supplied ‘keys’ — two specific pieces of single-stranded DNA.

CONTACT
Jørgen Kjems (Aarhus University, Denmark)
Tel: +45 8942 2686; E-mail: [email protected]

ALSO IN THIS ISSUE…

[8] The formation of the first stars and galaxies (pp 49-54)

[9] Spatial correlation between submillimetre and Lyman-a galaxies in the SSA 22 protocluster (pp 61-63; N&V)

[10] A large iron isotope effect in SmFeAsO12xFx and Ba12xKxFe2As2 (pp 64-67)

[11] Hypusine-containing Protein eIF5A Promotes Translation Elongation (pp 118-121)

ADVANCE ONLINE PUBLICATION

***These papers will be published electronically on Nature's website on 06 May at 1800 London time / 1300 US Eastern time (which is also when the embargo lifts) 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 07 May, but at a later date. ***

[12] The structure of a cytolytic alpha-helical toxin pore reveals its assembly mechanism
DOI: 10.1038/nature08026

[13] Specificity of Sensory-Motor Connections Encoded by Sema3e-PlexinD1 Recognition
DOI: 10.1038/nature08000

[14] Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment
DOI: 10.1038/nature07952

[15] Hexameric assembly of the proteasomal ATPases is templated through their C-termini
DOI: 10.1038/nature08065

[16] Chaperone−mediated pathway of proteasome regulatory particle assembly
DOI: 10.1038/nature08063

GEOGRAPHICAL LISTING OF AUTHORS…

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.

AUSTRALIA
Wollongong: 3

CHINA
Beijing: 10
Hefei: 10

DENMARK
Aarhus: 7

FRANCE
Vandœuvre-lès-Nancy: 6

GERMANY
Goettingen: 7
Martinsried: 14

JAPAN
Kashiwa: 8
Kawaguchi: 14
Minamimaki: 9
Tokyo: 9, 14

MEXICO
Puebla: 9

NETHERLANDS
Amsterdam: 1, 4
Rotterdam: 1

SPAIN
Barcelona: 1

SWITZERLAND
Basel: 12, 13
Villigen: 12
Zurich: 12

TANZANIA
Dar Es Salaam: 6

UNITED KINGDOM
London: 2

UNITED STATES OF AMERICA

California
Berkeley: 8
La Jolla: 6
Stanford: 5

District of Columbia
Washington: 3

Illinois
Chicago: 1
Urbana: 5

Maryland
Baltimore: 11
Bethesda: 11

Massachusetts
Amherst: 9
Boston: 4, 15, 16
Cambridge: 4, 7, 8

New Jersey
Princeton: 16

New Mexico
Albuquerque: 6

New York
Bronx: 15
New York: 1, 3, 13
Stony Brook: 3

Ohio
Cincinnati: 13

Texas
Austin: 8

Virginia
Harrisonburg: 3

PRESS CONTACTS…

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

Katie McGoldrick, Nature Washington
Tel: +1 202 737 2355; E-mail: [email protected]

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

From the UK/Europe/other countries not listed above
Jen Middleton, Nature London
Tel: +44 20 7843 4502; E-mail [email protected]

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Published: 08 May 2009

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