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Systemic signals regulate ageing and rejuvenation of blood stem cell niches

Nature 463, 495 (2010). doi:10.1038/nature08749

Authors: Shane R. Mayack, Jennifer L. Shadrach, Francis S. Kim & Amy J. Wagers

Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it

Structure of a bacterial homologue of vitamin K epoxide reductase

Nature 463, 507 (2010). doi:10.1038/nature08720

Authors: Weikai Li, Sol Schulman, Rachel J. Dutton, Dana Boyd, Jon Beckwith & Tom A. Rapoport

Vitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain γ-carboxylation of many blood coagulation factors. Here, we report the 3.6 Å crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox

A relativistic type Ibc supernova without a detected γ-ray burst

Nature 463, 513 (2010). doi:10.1038/nature08714

Authors: A. M. Soderberg, S. Chakraborti, G. Pignata, R. A. Chevalier, P. Chandra, A. Ray, M. H. Wieringa, A. Copete, V. Chaplin, V. Connaughton, S. D. Barthelmy, M. F. Bietenholz, N. Chugai, M. D. Stritzinger, M. Hamuy, C. Fransson, O. Fox, E. M. Levesque, J. E. Grindlay, P. Challis, R. J. Foley, R. P. Kirshner, P. A. Milne & M. A. P. Torres

Long duration γ-ray bursts (GRBs) mark the explosive death of some massive stars and are a rare sub-class of type Ibc supernovae. They are distinguished by the production of an energetic and collimated relativistic outflow powered by a central engine (an accreting black hole or neutron star). Observationally, this outflow is manifested in the pulse of γ-rays and a long-lived radio afterglow. Until now, central-engine-driven supernovae have been discovered exclusively through their γ-ray emission, yet it is expected that a larger population goes undetected because of limited satellite sensitivity or beaming of the collimated emission away from our line of sight. In this framework, the recovery of undetected GRBs may be possible through radio searches for type Ibc supernovae with relativistic outflows. Here we report the discovery of luminous radio emission from the seemingly ordinary type Ibc SN 2009bb, which requires a substantial relativistic outflow powered by a central engine. A comparison with our radio survey of type Ibc supernovae reveals that the fraction harbouring central engines is low, about one per cent, measured independently from, but consistent with, the inferred rate of nearby GRBs. Independently, a second mildly relativistic supernova has been reported.

A mildly relativistic radio jet from the otherwise normal type Ic supernova 2007gr

Nature 463, 516 (2010). doi:10.1038/nature08713

Authors: Z. Paragi, G. B. Taylor, C. Kouveliotou, J. Granot, E. Ramirez-Ruiz, M. Bietenholz, A. J. van der Horst, Y. Pidopryhora, H. J. van Langevelde, M. A. Garrett, A. Szomoru, M. K. Argo, S. Bourke & B. Paczyński

The class of type Ic supernovae have drawn increasing attention since 1998 owing to their sparse association (only four so far) with long duration γ-ray bursts (GRBs). Although both phenomena originate from the core collapse of a massive star, supernovae emit mostly at optical wavelengths, whereas GRBs emit mostly in soft γ-rays or hard X-rays. Though the GRB central engine generates ultra-relativistic jets, which beam the early emission into a narrow cone, no relativistic outflows have hitherto been found in type Ib/c supernovae explosions, despite theoretical expectations and searches. Here we report radio (interferometric) observations that reveal a mildly relativistic expansion in a nearby type Ic supernova, SN 2007gr. Using two observational epochs 60 days apart, we detect expansion of the source and establish a conservative lower limit for the average apparent expansion velocity of 0.6c. Independently, a second mildly relativistic supernova has been reported. Contrary to the radio data, optical observations of SN 2007gr indicate a typical type Ic supernova with ejecta velocities ∼6,000 km s-1, much lower than in GRB-associated supernovae. We conclude that in SN 2007gr a small fraction of the ejecta produced a low-energy mildly relativistic bipolar radio jet, while the bulk of the ejecta were slower and, as shown by optical spectropolarimetry, mildly aspherical.

Broken rotational symmetry in the pseudogap phase of a high-Tc superconductor

Nature 463, 519 (2010). doi:10.1038/nature08716

Authors: R. Daou, J. Chang, David LeBoeuf, Olivier Cyr-Choinière, Francis Laliberté, Nicolas Doiron-Leyraud, B. J. Ramshaw, Ruixing Liang, D. A. Bonn, W. N. Hardy & Louis Taillefer

The nature of the pseudogap phase is a central problem in the effort to understand the high-transition-temperature (high-Tc) copper oxide superconductors. A fundamental question is what symmetries are broken when the pseudogap phase sets in, which occurs when the temperature decreases below a value T*. There is evidence from measurements of both polarized neutron diffraction and the polar Kerr effect that time-reversal symmetry is broken, but at temperatures that differ significantly from one another. Broken rotational symmetry was detected from both resistivity measurements and inelastic neutron scattering at low doping, and from scanning tunnelling spectroscopy at low temperature, but showed no clear relation to T*. Here we report the observation of a large in-plane anisotropy of the Nernst effect in YBa2Cu3Oy that sets in precisely at T* throughout the doping phase diagram. We show that the CuO chains of the orthorhombic lattice are not responsible for this anisotropy, which is therefore an intrinsic property of the CuO2 planes. We conclude that the pseudogap phase is an electronic state that strongly breaks four-fold rotational symmetry. This narrows the range of possible states considerably, pointing to stripe or nematic order.

Cleaving carbon–carbon bonds by inserting tungsten into unstrained aromatic rings

Nature 463, 523 (2010). doi:10.1038/nature08730

Authors: Aaron Sattler & Gerard Parkin

The cleavage of C–H and C–C bonds by transition metal centres is of fundamental interest and plays an important role in the synthesis of complex organic molecules from petroleum feedstocks. But while there are many examples for the oxidative addition of C–H bonds to a metal centre, transformations that feature oxidative addition of C–C bonds are rare. The paucity of transformations that involve the cleavage of C–C rather than C–H bonds is usually attributed to kinetic factors arising from the greater steric hindrance and the directional nature of the spn hybrids that form the C–C bond, and to thermodynamic factors arising from the fact that M–C bonds are weaker than M–H bonds. Not surprisingly, therefore, most examples of C–C bond cleavage either avoid the kinetic limitations by using metal compounds in which the C–C bond is held in close proximity to the metal centre, or avoid the thermodynamic limitations by using organic substrates in which the cleavage is accompanied by either a relief of strain energy or the formation of an aromatic system. Here, we show that a tungsten centre can be used to cleave a strong C–C bond that is a component of an unstrained 6-membered aromatic ring. The cleavage is enabled by the formation of an unusual chelating di(isocyanide) ligand, which suggests that other metal centres with suitable ancillary ligands could also accomplish the cleavage of strong C–C bonds of aromatic substrates and thereby provide new ways of functionalizing such molecules.

Ensemble reconstruction constraints on the global carbon cycle sensitivity to climate

Nature 463, 527 (2010). doi:10.1038/nature08769

Authors: David C. Frank, Jan Esper, Christoph C. Raible, Ulf Büntgen, Valerie Trouet, Benjamin Stocker & Fortunat Joos

The processes controlling the carbon flux and carbon storage of the atmosphere, ocean and terrestrial biosphere are temperature sensitive and are likely to provide a positive feedback leading to amplified anthropogenic warming. Owing to this feedback, at timescales ranging from interannual to the 20–100-kyr cycles of Earth's orbital variations, warming of the climate system causes a net release of CO2 into the atmosphere; this in turn amplifies warming. But the magnitude of the climate sensitivity of the global carbon cycle (termed γ), and thus of its positive feedback strength, is under debate, giving rise to large uncertainties in global warming projections. Here we quantify the median γ as 7.7 p.p.m.v. CO2 per °C warming, with a likely range of 1.7–21.4 p.p.m.v. CO2 per °C. Sensitivity experiments exclude significant influence of pre-industrial land-use change on these estimates. Our results, based on the coupling of a probabilistic approach with an ensemble of proxy-based temperature reconstructions and pre-industrial CO2 data from three ice cores, provide robust constraints for γ on the policy-relevant multi-decadal to centennial timescales. By using an ensemble of >200,000 members, quantification of γ is not only improved, but also likelihoods can be assigned, thereby providing a benchmark for future model simulations. Although uncertainties do not at present allow exclusion of γ calculated from any of ten coupled carbon–climate models, we find that γ is about twice as likely to fall in the lowermost than in the uppermost quartile of their range. Our results are incompatibly lower (P < 0.05) than recent pre-industrial empirical estimates of ∼40 p.p.m.v. CO2 per °C (refs 6, 7), and correspondingly suggest ∼80% less potential amplification of ongoing global warming.

Foot strike patterns and collision forces in habitually barefoot versus shod runners

Nature 463, 531 (2010). doi:10.1038/nature08723

Authors: Daniel E. Lieberman, Madhusudhan Venkadesan, William A. Werbel, Adam I. Daoud, Susan D’Andrea, Irene S. Davis, Robert Ojiambo Mang’Eni & Yannis Pitsiladis

Humans have engaged in endurance running for millions of years, but the modern running shoe was not invented until the 1970s. For most of human evolutionary history, runners were either barefoot or wore minimal footwear such as sandals or moccasins with smaller heels and little cushioning relative to modern running shoes. We wondered how runners coped with the impact caused by the foot colliding with the ground before the invention of the modern shoe. Here we show that habitually barefoot endurance runners often land on the fore-foot (fore-foot strike) before bringing down the heel, but they sometimes land with a flat foot (mid-foot strike) or, less often, on the heel (rear-foot strike). In contrast, habitually shod runners mostly rear-foot strike, facilitated by the elevated and cushioned heel of the modern running shoe. Kinematic and kinetic analyses show that even on hard surfaces, barefoot runners who fore-foot strike generate smaller collision forces than shod rear-foot strikers. This difference results primarily from a more plantarflexed foot at landing and more ankle compliance during impact, decreasing the effective mass of the body that collides with the ground. Fore-foot- and mid-foot-strike gaits were probably more common when humans ran barefoot or in minimal shoes, and may protect the feet and lower limbs from some of the impact-related injuries now experienced by a high percentage of runners.

Hsp70 stabilizes lysosomes and reverts Niemann–Pick disease-associated lysosomal pathology

Nature 463, 549 (2010). doi:10.1038/nature08710

Authors: Thomas Kirkegaard, Anke G. Roth, Nikolaj H. T. Petersen, Ajay K. Mahalka, Ole Dines Olsen, Irina Moilanen, Alicja Zylicz, Jens Knudsen, Konrad Sandhoff, Christoph Arenz, Paavo K. J. Kinnunen, Jesper Nylandsted & Marja Jäättelä

Heat shock protein 70 (Hsp70) is an evolutionarily highly conserved molecular chaperone that promotes the survival of stressed cells by inhibiting lysosomal membrane permeabilization, a hallmark of stress-induced cell death. Clues to its molecular mechanism of action may lay in the recently reported stress- and cancer-associated translocation of a small portion of Hsp70 to the lysosomal compartment. Here we show that Hsp70 stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential co-factor for lysosomal sphingomyelin metabolism. In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70–BMP interaction by BMP antibodies or a point mutation in Hsp70 (Trp90Phe), as well as the pharmacological and genetic inhibition of ASM, effectively revert the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann–Pick disease (NPD) A and B—severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1) encoding for ASM—is also associated with a marked decrease in lysosomal stability, and this phenotype can be effectively corrected by treatment with recombinant Hsp70. Taken together, these data open exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway.

Microbial production of fatty-acid-derived fuels and chemicals from plant biomass

Nature 463, 559 (2010). doi:10.1038/nature08721

Authors: Eric J. Steen, Yisheng Kang, Gregory Bokinsky, Zhihao Hu, Andreas Schirmer, Amy McClure, Stephen B. del Cardayre & Jay D. Keasling

Increasing energy costs and environmental concerns have emphasized the need to produce sustainable renewable fuels and chemicals. Major efforts to this end are focused on the microbial production of high-energy fuels by cost-effective ‘consolidated bioprocesses’. Fatty acids are composed of long alkyl chains and represent nature’s ‘petroleum’, being a primary metabolite used by cells for both chemical and energy storage functions. These energy-rich molecules are today isolated from plant and animal oils for a diverse set of products ranging from fuels to oleochemicals. A more scalable, controllable and economic route to this important class of chemicals would be through the microbial conversion of renewable feedstocks, such as biomass-derived carbohydrates. Here we demonstrate the engineering of Escherichia coli to produce structurally tailored fatty esters (biodiesel), fatty alcohols, and waxes directly from simple sugars. Furthermore, we show engineering of the biodiesel-producing cells to express hemicellulases, a step towards producing these compounds directly from hemicellulose, a major component of plant-derived biomass.

Making the paper: David Frank

Nature 463, 400 (2010). doi:10.1038/7280400a

Wealth of data cuts uncertainty in climate-warming predictions.

Abstractions

Nature 463, 400 (2010). doi:10.1038/7280400b

First authorWarfarin has long been a household name thanks to its uses as a drug and in controlling rodent pests. Its protein target is less well known — the enzyme VKOR, which, in mammals, catalyses the generation of vitamin K hydroquinone. This is an

From the blogosphere

Nature 463, 400 (2010). doi:10.1038/7280400c

A recent literature search had Jennifer Rohn, a posdoc at University College London, seeing double. On her Nature Network blog, Mind the Gap, she describes how she turned up what seemed to be the exact same paper, with the same author list, published in two

Learning to share

Nature 463, 401 (2010). doi:10.1038/463401a

By opening up its database of potential malaria drugs, GlaxoSmithKline has blazed a path that other pharmaceutical companies should follow.

Valid concerns

Nature 463, 401 (2010). doi:10.1038/463401b

The reporting of candidate biomarkers for disease must be rigorous to drive translational research.

False alarms

Nature 463, 402 (2010). doi:10.1038/463402a

British scientists must adopt a positive tone if they hope to protect their gains in funding.

Genetics: Protein's billion-year history

Nature 463, 404 (2010). doi:10.1038/463404a

Cell Cycle Epub ahead of print (2010)Despite having a small genome and only four cell types, the simple creature Trichoplax adhaerens holds clues about the evolutionary origin of p53, the most commonly mutated human tumour-suppressor gene.David Lane and his colleagues at

Material science: Speedy silk imprinting

Nature 463, 404 (2010). doi:10.1038/463404b

Biomaterials: Super snail shells

Nature 463, 404 (2010). doi:10.1038/463404c

Proc. Natl Acad. Sci. USA107, 987–992 (2010) 10.1073/pnas.0912988107The mechanical properties of an unusual, trilayered armour from a deep-sea snail have been revealed by Christine Ortiz of the Massachusetts Institute of Technology in Cambridge and her colleagues.Using

Regenerative biology: New nerve cells connect

Nature 463, 404 (2010). doi:10.1038/463404d

J. Neurosci.30, 894–904 (2010) 10.1523/JNEUROSCI.4318-09.2010Transplanting nerve-cell precursors derived from embryonic stem cells into the brain may be a promising repair strategy, but getting the cells to connect with the right parts of the brain has proved challenging.