Stem cells: Bypassing the middleman

Summaries of newsworthy papers: Metabolic engineering: Making the most of biomass, Cell biology: Hsp70 offers clues to lysosomal storage disorders, Climate: Quantifying the feedback; Astronomy: Gamma-ray bursts without the gamma-rays?, Chemistry: Breaking a strong bond with tungsten and Evolution: Some bare truths about running

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VOL.463 NO.7280 DATED 28 JANUARY 2010

This press release contains:

· Summaries of newsworthy papers:

Stem cells: Bypassing the middleman

Metabolic engineering: Making the most of biomass

Cell biology: Hsp70 offers clues to lysosomal storage disorders

Climate: Quantifying the feedback

Astronomy: Gamma-ray bursts without the gamma-rays?

Chemistry: Breaking a strong bond with tungsten

And finally…Evolution: Some bare truths about running

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

· Geographical listing of authors

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[1] Stem cells: Bypassing the middleman (AOP)
DOI: 10.1038/nature08797

***This paper will be published electronically on Nature's website on 27 January 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 28 January, but at a later date. ***

Mature, differentiated cells can be directed to become functional neurons without first being reverted to an embryonic state. The generation of these neurons in cell cultures could have important implications for research on neural development, neurological disease modelling and regenerative medicine.

In previous work, both mouse and human fibroblasts have been reprogrammed to pluripotency using a combination of four transcription factors. In a paper published in Nature this week, Marius Wernig and colleagues tested a pool of candidate genes in which they identified three that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. Importantly, the cells did not have to first revert to a pluripotent state, which has the potential to form tumours. The resulting cells express many neuron-specific proteins and form functional synapses. The work provides a new and powerful system for studying cellular identity and plasticity, regenerative medicine and drug discovery.

CONTACT
Marius Wernig (Stanford University School of Medicine, Palo Alto, CA, USA)
Tel: +1 650 721 2495; E-mail: [email protected]

[2] Metabolic engineering: Making the most of biomass (pp 559-562)

Researchers demonstrate that Escherichia coli can be engineered to produce two classes of potential ‘high-energy’ biofuels — fatty esters and fatty alcohols — from simple sugars in this week’s issue of Nature. The paper also describes how these bacteria can be further modified to express and secrete enzymes known as hemicellulases, enabling them to produce these molecules directly from a component of plant-derived biomass.

Increasing energy costs and environmental concerns have emphasized the need to find new sources of renewable fuels. It is believed that the microbial conversion of biomass-derived carbohydrates will be the most cost-effective and high-yielding route to obtain biofuels in the future. Jay Keasling and colleagues report an important step towards this goal, showing that it is possible to use our knowledge of fatty acid metabolism to divert key steps in metabolic pathways to generate potential ‘high-energy’ biofuels. The authors believe that this approach will significantly contribute to the ultimate goal of producing advanced biofuels and renewable chemicals on large scales in a cost-effective manner.

CONTACT
Jay Keasling (University of California, Berkeley, CA, USA)
Tel: +1 510 642 4862; E-mail: [email protected]

[3] Cell biology: Hsp70 offers clues to lysosomal storage disorders (pp 54-553; N&V)

The mechanism by which heat shock protein 70 (Hsp70) protects cells from stress and promotes cell survival is reported in this week’s Nature. The research has the potential to provide new treatments for lysosomal storage disorders and could lead to new therapies for cancer.

Hsp70 is an evolutionary conserved protein that has been implicated in cancer owing to its ability to help cells resist stress-induced death. Its activity was recently linked to lysosomes — membrane-bound organelles inside the cell that contain enzymes for breaking down and recycling unwanted cellular material. Marja Jäättelä and colleagues report that Hsp70 works by binding to a lipid called BMP, which stabilizes lysosomes and stops them from becoming ‘leaky’. The team also show that they can fix faulty lysosomes in cells from patients with the severe lysosomal disorder Niemann–Pick disease by treating with recombinant Hsp70.

CONTACT
Marja Jäättelä (Danish Cancer Society, Copenhagen, Denmark)
Tel: +45 35 25 73 18; E-mail: [email protected]

Laszlo Vigh (Hungarian Academy of Sciences, Szeged, Hungary) N&V Author
E-mail: [email protected]

[4] Climate: Quantifying the feedback (pp 527-530; N&V)

A new estimate of the feedback between temperature and atmospheric carbon dioxide (CO2) concentration has been derived from a comprehensive comparison of temperature and CO2 records spanning the past millennium. The result, which is based on more than 200,000 individual comparisons, implies that the amplification of current global warming by carbon-cycle feedback will be significantly less than recent work has suggested.

Climate warming causes many changes in the global carbon cycle, with the net effect generally considered to be an increase in atmospheric CO2 with increasing temperature — in other words, a positive feedback between temperature and CO2. Uncertainty in the magnitude of this feedback has led to a wide range in projections of current global warming: about 40% of the uncertainty in these projections comes from this source.

Recent attempts to quantify the feedback by examining the co-variation of pre-industrial climate and CO2 records yielded estimates of about 40 parts per million by volume (p.p.m.v.) CO2 per degree Celsius, which would imply significant amplification of current warming trends.

In this week’s Nature, David Frank and colleagues extend this empirical approach by comparing nine global-scale temperature reconstructions with CO2 data from three Antarctic ice cores over the period ad 1050–1800. The authors derive a likely range for the feedback strength of 1.7–21.4 p.p.m.v. CO2 per degree Celsius, with a median value of 7.7. They conclude that the recent estimates of 40 p.p.m.v. CO2 per degree Celsius can be excluded with 95% confidence, suggesting significantly less amplification of current warming.

CONTACT
David Frank (Swiss Federal Research Institute WSL, Birmensdorf, Switzerland)
Tel: +41 44 739 2282; E-mail: [email protected]

Hugues Goosse (Universite Catholique de Louvain, Louvain-la-Neuve, Belgium) N&V Author
Tel: +32 10 47 32 98; E-mail: [email protected]

[5] & [6] Astronomy: Gamma-ray bursts without the gamma-rays? (pp 513-515; 516-518)

Two recent supernovae appear to have ejected material at more than half the speed of light, implying the presence of powerful ‘central engines’ driving the outflows. The observations shed new light on the relationship between type Ib/c supernovae and the extremely energetic explosions known as gamma-ray bursts.

Type Ib/c supernovae and long-duration gamma-ray bursts are both thought to originate from core collapses of massive stars, but supernovae emit light at mostly visible wavelengths, whereas -ray bursts emit mostly gamma-rays or X-rays. These latter, high-energy emissions come from tightly focused outflows of material travelling at near-light (relativistic) speeds, driven by a ‘central engine’, thought to be the accretion of matter onto a black hole or neutron star. Although a few type Ib/c supernovae have been associated with gamma-ray bursts, their optical and radio emissions have yielded no evidence of relativistic expansion

In this week’s Nature, two teams of astronomers report evidence for mildly relativistic expansion in two type Ib/c supernovae. Alicia Soderberg and colleagues detected radio emission from supernova 2009bb implying a mean expansion velocity of 0.85 times the speed of light (0.85c), and a minimum energy comparable to those of the radio afterglows of nearby gamma-ray bursts. Similarly, from radio observations of supernova 2007gr, Chryssa Kouveliotou and colleagues inferred an expansion velocity for a small fraction of the ejecta of at least 0.6c.

As SN 2009bb was the only relativistic supernova found in a radio survey of 143 nearby supernovae, Soderberg and colleagues conclude that the fraction of type Ib/c supernovae that harbour central engines is only about 1% — a figure consistent with the inferred rate of nearby gamma-ray bursts. Kouveliotou and colleagues suggest that most or all type Ic supernovae may produce mildly relativistic jets, but that these jets may account for only a small fraction of the total energy, making them hard to detect.

CONTACT

Alicia Soderberg (Harvard-Smithsonian Center for Astrophysics, Cambridge, MA, USA)
Tel: +1 617 496 7919; E-mail: [email protected] Author paper [5]

Chryssa Kouveliotou (NASA/Marshall Space Flight Center, Huntsville, AL, USA)
Tel: +1 256 961 7604; E-mail: [email protected] Author paper [6]

[7] Chemistry: Breaking a strong bond with tungsten (pp 523-526; N&V)

An organic compound containing tungsten has been used to break a particularly strong bond between two carbon atoms. The unusual mechanism of this reaction may inspire other new ways of breaking carbon–carbon bonds, and may ultimately lead to new methods for turning petroleum-derived feedstocks into valuable chemicals.

Transition-metal complexes, containing a central metal atom bound to other atoms or molecules, can be used to break carbon–hydrogen bonds by insertion of the metal atom between the carbon and hydrogen. This process, which is of both fundamental and practical interest, has also been applied to carbon–carbon bonds, but with limited success. The rare successful cases have typically involved carbon–carbon bonds that are anomalously weak, or have required complexes in which the bond to be broken is held very close to the metal atom.

In this week’s Nature, Aaron Sattler and Gerard Parkin report using a tungsten-bearing complex to break a carbon–carbon bond that is stronger than average, and not kept especially close to the tungsten metal. The reaction seems to be driven instead by the formation of a particularly stable (and therefore energetically favourable) intermediate molecule — a mechanism that may suggest more general routes to the breaking of strong carbon–carbon bonds, with eventual applications ranging from pharmaceutical synthesis to the conversion of fossil fuels into high-value chemicals.

CONTACT

Gerard Parkin (Columbia University, New York, NY, USA)
Tel: +1 212 854 824; E-mail: [email protected]

Alan Goldman (Rutgers University, Piscataway, New Jersey, USA) N&V Author
Tel: +1 732 445 5232; E-mail: [email protected]

[8] And finally…Evolution: Some bare truths about running (pp 531-535; N&V)

Runners in sports shoes tend to run differently from those who run barefoot, and who have never worn shoes. Research published online by Nature this week shows that habitually unshod runners usually land on the ball of the foot (fore-foot strike) or sometimes with a flat foot (mid-foot strike), whereas shod runners tend to land on their heels (rear-foot strike). The barefoot style of running reduces how much of the body’s mass comes to a sudden stop, eliminating the impact shock. This makes barefoot running comfortable and may minimize some impact-related injuries.

Modern humans show many adaptations for long-distance running, acquired during humanity’s long evolutionary history. Cushioned sports shoes, in contrast, date back only to the 1970s.
Using kinematic and kinetic analyses Daniel Lieberman and colleagues show that barefoot runners who fore-foot strike generate smaller collision forces than shod rear-foot strikers. Although there are anecdotal reports of reduced injuries in barefoot populations, more work is needed to test the hypothesis that either barefoot individuals or those with minimal footwear have reduced injury rates.

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

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

ALSO IN THIS ISSUE…

[9] Systemic signals regulate ageing and rejuvenation of blood stem cell niches (pp 495-500)
DOI: 10.1038/nature08749

[10] Structure of a bacterial homologue of vitamin K epoxide reductase (pp 507-512)
DOI: 10.1038/nature08720

[11] Broken rotational symmetry in the pseudogap phase of a high-Tc superconductor (pp 519-522)
DOI: 10.1038/nature08716

ADVANCE ONLINE PUBLICATION

***This paper will be published electronically on Nature's website on 27 January 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 28 January, but at a later date. ***

[12] The cells and peripheral representation of sodium taste in mice
DOI: 10.1038/nature08783

**************************************************************

***The following paper will be published electronically on Nature’s website on 22 January at 1800 London time / 1300 US Eastern time. The paper is under embargo until this time. The rest of the above articles on this release remain under embargo until 27 January at 1800 London time / 1300 US Eastern time ***

[13] Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency
DOI: 10.1038/nature08829

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
Epping: 5
Hawthorn: 6
Perth: 6

CANADA
Kingston: 5
Sherbrooke: 11
Toronto: 5, 6, 11
Vancouver: 11

CHILE
La Serena: 5
Santiago: 5

DENMARK
Copenhagen: 3, 5
Odense: 3

FINLAND
Helsinki: 3

GERMANY
Berlin: 3
Bonn: 3
Dresden: 11
Mainz: 4

HUNGARY
Budapest: 6

INDIA
Mumbai: 5

KENYA
Eldoret: 8

NETHERLANDS
Dwingeloo: 6
Leiden: 6

POLAND
Warsaw: 3

RUSSIA
Moscow: 5

SOUTH AFRICA
Krugersdorp: 5, 6

SWEDEN
Stockholm: 5

SWITZERLAND
Bern: 4
Birmensdorf: 4
Lausanne: 12

UNITED KINGDOM
Cambridge: 13
Glasgow: 8
Hatfield: 6

UNITED STATES OF AMERICA

Alabama
Huntsville: 5, 6

Arizona
Tucson: 5

California
Berkeley: 2
Emeryville: 2
La Jolla: 12
Los Angeles: 13
Palo Alto: 1
Santa Cruz: 6
San Francisco: 2

Hawaii
Honolulu: 5

Maryland
Bethesda: 12

Massachusetts
Boston: 9, 10
Cambridge: 5, 8

Michigan
Ann Arbor: 8

Delaware
Newark: 8

New Mexico
Albuquerque: 6

New York
New York: 7, 12

Rhode Island
Providence: 8

Virginia
Ashburn: 12
Charlottesville: 5

PRESS CONTACTS…

From North America and Canada
Neda Afsarmanesh, Nature New York
Tel: +1 212 726 9231; 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
Rachel Twinn, Nature, London
Tel: +44 20 7843 4658; E-mail: [email protected]

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Published: 27 Jan 2010

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