Nature

Atom gravimeters and gravitational redshift

Atom gravimeters and gravitational redshift

Nature 467, E1 (2010). doi:10.1038/nature09340

Authors: Peter Wolf, Luc Blanchet, Christian J. Bordé, Serge Reynaud, Christophe Salomon & Claude Cohen-Tannoudji

Arising from: H. Müller, A. Peters & S. Chu Nature463, 926–929 (2010); Müller & Chu replyIn ref. 1 the authors present a re-interpretation of atom interferometry experiments published a decade ago. They now consider the atom interferometry experiments as a measurement of the gravitational redshift on the quantum clock operating at the Compton frequency ωC = mc2/ ≈ 2π × 3.0 × 1025 Hz, where m is the caesium (Cs) atom rest mass. They then argue that this redshift measurement compares favourably with existing as well as projected clock tests. Here we show that this interpretation is incorrect.

Categories: Literature

Müller, Peters & Chu reply

Müller, Peters & Chu reply

Nature 467, E2 (2010). doi:10.1038/nature09341

Authors: Holger Müller, Achim Peters & Steven Chu

Replying to: P. Wolf et al.Nature doi:10.1038/nature09340 (2010)We stand by our result. The Comment revisits an interesting issue that has been known for decades. Because it applies to all experiments, classical redshift tests and atom interferometry redshift tests are equivalent for all aspects in question.

Categories: Literature

Can controversies be put to REST?

Can controversies be put to REST?

Nature 467, E3 (2010). doi:10.1038/nature09305

Authors: Helle F. Jørgensen & Amanda G. Fisher

Arising from: S. K. Singh et al.Nature453, 223–227 (2008); Singh et al.replyThe contribution of REST to embryonic stem (ES) cell pluripotency has been uncertain. Two years ago, Singh et al. claimed that Rest+/− and REST knock-down ES cells expressed reduced levels of pluripotency markers, in contrast to a prior and subsequent reports. To understand the basis of this difference, we analysed the YHC334 (YHC) and RRC160 (RRC) gene-trap ES cell lines used by Singh et al., obtained directly from BayGenomics. Both REST mutant lines generated REST–βGeo fusion proteins, but expressed pluripotency genes at levels similar to appropriately matched parental wild ES cells, consistent with expression being REST–independent.

Categories: Literature

Singh et al. reply

Singh et al. reply

Nature 467, E5 (2010). doi:10.1038/nature09306

Authors: Sanjay K. Singh, Mohamedi N. Kagalwala, Jan Parker-Thornburg, Henry Adams & Sadhan Majumder

Replying to: H. F. Jørgensen & A. G. Fisher Nature 467, doi:10.1038/nature09305 (2010)Jørgensen and Fisher suggest that the discrepancy with our results could be attributable to our use of E14Tg2a (or its derivatives, such as OS25) rather than E14Tg2a.4 as the parental control line for the REST+/− cells (YHC and RRC). We have now reconfirmed our use of E14Tg2a.4 clonal cells as the control cells. Also, we have found that the YHC and RRC cells used in our experiments, originally purchased from Bay Genomics, differ from the YHC and RRC cells used by Jørgensen and Fisher with respect to pluripotency-based on alkaline phosphatase/self-renewal assays (N. Song and S.K.S., unpublished results). We are currently using other assays to confirm these observations.

Categories: Literature

The impacts of climate change on water resources and agriculture in China

The impacts of climate change on water resources and agriculture in China

Nature 467, 43 (2010). doi:10.1038/nature09364

Authors: Shilong Piao, Philippe Ciais, Yao Huang, Zehao Shen, Shushi Peng, Junsheng Li, Liping Zhou, Hongyan Liu, Yuecun Ma, Yihui Ding, Pierre Friedlingstein, Chunzhen Liu, Kun Tan, Yongqiang Yu, Tianyi Zhang & Jingyun Fang

China is the world’s most populous country and a major emitter of greenhouse gases. Consequently, much research has focused on China’s influence on climate change but somewhat less has been written about the impact of climate change on China. China experienced explosive economic growth in recent decades, but with only 7% of the world’s arable land available to feed 22% of the world’s population, China's economy may be vulnerable to climate change itself. We find, however, that notwithstanding the clear warming that has occurred in China in recent decades, current understanding does not allow a clear assessment of the impact of anthropogenic climate change on China’s water resources and agriculture and therefore China’s ability to feed its people. To reach a more definitive conclusion, future work must improve regional climate simulations—especially of precipitation—and develop a better understanding of the managed and unmanaged responses of crops to changes in climate, diseases, pests and atmospheric constituents.

Categories: Literature

Integrating common and rare genetic variation in diverse human populations

Integrating common and rare genetic variation in diverse human populations

Nature 467, 52 (2010). doi:10.1038/nature09298

Authors:

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such

Categories: Literature

Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not

Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not

Nature 467, 59 (2010). doi:10.1038/nature09336

Authors: Vassiliki Nikoletopoulou, Heiko Lickert, José Maria Frade, Chantal Rencurel, Patrizia Giallonardo, Lixin Zhang, Miriam Bibel & Yves-Alain Barde

Neurons of the peripheral nervous system have long been known to require survival factors to prevent their death during development. But why they selectively become dependent on secretory molecules has remained a mystery, as is the observation that in the central nervous system, most neurons

Categories: Literature

Warm water vapour in the sooty outflow from a luminous carbon star

Warm water vapour in the sooty outflow from a luminous carbon star

Nature 467, 64 (2010). doi:10.1038/nature09344

Authors: L. Decin, M. Agúndez, M. J. Barlow, F. Daniel, J. Cernicharo, R. Lombaert, E. De Beck, P. Royer, B. Vandenbussche, R. Wesson, E. T. Polehampton, J. A. D. L. Blommaert, W. De Meester, K. Exter, H. Feuchtgruber, W. K. Gear, H. L. Gomez, M. A. T. Groenewegen, M. Guélin, P. C. Hargrave, R. Huygen, P. Imhof, R. J. Ivison, C. Jean, C. Kahane, F. Kerschbaum, S. J. Leeks, T. Lim, M. Matsuura, G. Olofsson, T. Posch, S. Regibo, G. Savini, B. Sibthorpe, B. M. Swinyard, J. A. Yates & C. Waelkens

The detection of circumstellar water vapour around the ageing carbon star IRC +10216 challenged the current understanding of chemistry in old stars, because water was predicted to be almost absent in carbon-rich stars. Several explanations for the water were postulated, including the vaporization of icy bodies (comets or dwarf planets) in orbit around the star, grain surface reactions, and photochemistry in the outer circumstellar envelope. With a single water line detected so far from this one carbon-rich evolved star, it is difficult to discriminate between the different mechanisms proposed. Here we report the detection of dozens of water vapour lines in the far-infrared and sub-millimetre spectrum of IRC +10216 using the Herschel satellite. This includes some high-excitation lines with energies corresponding to ∼1,000 K, which can be explained only if water is present in the warm inner sooty region of the envelope. A plausible explanation for the warm water appears to be the penetration of ultraviolet photons deep into a clumpy circumstellar envelope. This mechanism also triggers the formation of other molecules, such as ammonia, whose observed abundances are much higher than hitherto predicted.

Categories: Literature

Polar patterns of driven filaments

Polar patterns of driven filaments

Nature 467, 73 (2010). doi:10.1038/nature09312

Authors: Volker Schaller, Christoph Weber, Christine Semmrich, Erwin Frey & Andreas R. Bausch

The emergence of collective motion exhibited by systems ranging from flocks of animals to self-propelled microorganisms to the cytoskeleton is a ubiquitous and fascinating self-organization phenomenon. Similarities between these systems, such as the inherent polarity of the constituents, a density-dependent transition to ordered phases or the existence of very large density fluctuations, suggest universal principles underlying pattern formation. This idea is followed by theoretical models at all levels of description: micro- or mesoscopic models directly map local forces and interactions using only a few, preferably simple, interaction rules, and more macroscopic approaches in the hydrodynamic limit rely on the systems’ generic symmetries. All these models characteristically have a broad parameter space with a manifold of possible patterns, most of which have not yet been experimentally verified. The complexity of interactions and the limited parameter control of existing experimental systems are major obstacles to our understanding of the underlying ordering principles. Here we demonstrate the emergence of collective motion in a high-density motility assay that consists of highly concentrated actin filaments propelled by immobilized molecular motors in a planar geometry. Above a critical density, the filaments self-organize to form coherently moving structures with persistent density modulations, such as clusters, swirls and interconnected bands. These polar nematic structures are long lived and can span length scales orders of magnitudes larger than their constituents. Our experimental approach, which offers control of all relevant system parameters, complemented by agent-based simulations, allows backtracking of the assembly and disassembly pathways to the underlying local interactions. We identify weak and local alignment interactions to be essential for the observed formation of patterns and their dynamics. The presented minimal polar-pattern-forming system may thus provide new insight into emerging order in the broad class of active fluids and self-propelled particles.

Categories: Literature

Olivine water contents in the continental lithosphere and the longevity of cratons

Olivine water contents in the continental lithosphere and the longevity of cratons

Nature 467, 78 (2010). doi:10.1038/nature09317

Authors: Anne H. Peslier, Alan B. Woodland, David R. Bell & Marina Lazarov

Cratons, the ancient cores of continents, contain the oldest crust and mantle on the Earth (>2 Gyr old). They extend laterally for hundreds of kilometres, and are underlain to depths of 180–250 km by mantle roots that are chemically and physically distinct from the surrounding mantle. Forming the thickest lithosphere on our planet, they act as rigid keels isolated from the flowing asthenosphere; however, it has remained an open question how these large portions of the mantle can stay isolated for so long from mantle convection. Key physical properties thought to contribute to this longevity include chemical buoyancy due to high degrees of melt-depletion and the stiffness imparted by the low temperatures of a conductive thermal gradient. Geodynamic calculations, however, suggest that these characteristics are not sufficient to prevent the lithospheric mantle from being entrained during mantle convection over billions of years. Differences in water content are a potential source of additional viscosity contrast between cratonic roots and ambient mantle owing to the well-established hydrolytic weakening effect in olivine, the most abundant mineral of the upper mantle. However, the water contents of cratonic mantle roots have to date been poorly constrained. Here we show that olivine in peridotite xenoliths from the lithosphere–asthenosphere boundary region of the Kaapvaal craton mantle root are water-poor and provide sufficient viscosity contrast with underlying asthenosphere to satisfy the stability criteria required by geodynamic calculations. Our results provide a solution to a puzzling mystery of plate tectonics, namely why the oldest continents, in contrast to short-lived oceanic plates, have resisted recycling into the interior of our tectonically dynamic planet.

Categories: Literature

Bacterial charity work leads to population-wide resistance

Bacterial charity work leads to population-wide resistance

Nature 467, 82 (2010). doi:10.1038/nature09354

Authors: Henry H. Lee, Michael N. Molla, Charles R. Cantor & James J. Collins

Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population’s less resistant constituents, in part by producing indole, a signalling molecule generated by actively growing, unstressed cells. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.

Categories: Literature

A spindle-independent cleavage furrow positioning pathway

A spindle-independent cleavage furrow positioning pathway

Nature 467, 91 (2010). doi:10.1038/nature09334

Authors: Clemens Cabernard, Kenneth E. Prehoda & Chris Q. Doe

The mitotic spindle determines the cleavage furrow site during metazoan cell division, but whether other mechanisms exist remains unknown. Here we identify a spindle-independent mechanism for cleavage furrow positioning in Drosophila neuroblasts. We show that early and late furrow proteins (Pavarotti, Anillin, and Myosin) are localized to the neuroblast basal cortex at anaphase onset by a Pins cortical polarity pathway, and can induce a basally displaced furrow even in the complete absence of a mitotic spindle. Rotation or displacement of the spindle results in two furrows: an early polarity-induced basal furrow and a later spindle-induced furrow. This spindle-independent cleavage furrow mechanism may be relevant to other highly polarized mitotic cells, such as mammalian neural progenitors.

Categories: Literature

Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease

Gamma-secretase activating protein is a therapeutic target for Alzheimer’s disease

Nature 467, 95 (2010). doi:10.1038/nature09325

Authors: Gen He, Wenjie Luo, Peng Li, Christine Remmers, William J. Netzer, Joseph Hendrick, Karima Bettayeb, Marc Flajolet, Fred Gorelick, Lawrence P. Wennogle & Paul Greengard

Accumulation of neurotoxic amyloid-β is a major hallmark of Alzheimer’s disease. Formation of amyloid-β is catalysed by γ-secretase, a protease with numerous substrates. Little is known about the molecular mechanisms that confer substrate specificity on this potentially promiscuous enzyme. Knowledge of the mechanisms underlying its selectivity is critical for the development of clinically effective γ-secretase inhibitors that can reduce amyloid-β formation without impairing cleavage of other γ-secretase substrates, especially Notch, which is essential for normal biological functions. Here we report the discovery of a novel γ-secretase activating protein (GSAP) that drastically and selectively increases amyloid-β production through a mechanism involving its interactions with both γ-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment (APP-CTF). GSAP does not interact with Notch, nor does it affect its cleavage. Recombinant GSAP stimulates amyloid-β production in vitro. Reducing GSAP concentrations in cell lines decreases amyloid-β concentrations. Knockdown of GSAP in a mouse model of Alzheimer’s disease reduces levels of amyloid-β and plaque development. GSAP represents a type of γ-secretase regulator that directs enzyme specificity by interacting with a specific substrate. We demonstrate that imatinib, an anticancer drug previously found to inhibit amyloid-β formation without affecting Notch cleavage, achieves its amyloid-β-lowering effect by preventing GSAP interaction with the γ-secretase substrate, APP-CTF. Thus, GSAP can serve as an amyloid-β-lowering therapeutic target without affecting other key functions of γ-secretase.

Categories: Literature

Genome-wide measurement of RNA secondary structure in yeast

Genome-wide measurement of RNA secondary structure in yeast

Nature 467, 103 (2010). doi:10.1038/nature09322

Authors: Michael Kertesz, Yue Wan, Elad Mazor, John L. Rinn, Robert C. Nutter, Howard Y. Chang & Eran Segal

The structures of RNA molecules are often important for their function and regulation, yet there are no experimental techniques for genome-scale measurement of RNA structure. Here we describe a novel strategy termed parallel analysis of RNA structure (PARS), which is based on deep sequencing fragments of RNAs that were treated with structure-specific enzymes, thus providing simultaneous in vitro profiling of the secondary structure of thousands of RNA species at single nucleotide resolution. We apply PARS to profile the secondary structure of the messenger RNAs (mRNAs) of the budding yeast Saccharomyces cerevisiae and obtain structural profiles for over 3,000 distinct transcripts. Analysis of these profiles reveals several RNA structural properties of yeast transcripts, including the existence of more secondary structure over coding regions compared with untranslated regions, a three-nucleotide periodicity of secondary structure across coding regions and an anti-correlation between the efficiency with which an mRNA is translated and the structure over its translation start site. PARS is readily applicable to other organisms and to profiling RNA structure in diverse conditions, thus enabling studies of the dynamics of secondary structure at a genomic scale.

Categories: Literature

Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae

Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae

Nature 467, 108 (2010). doi:10.1038/nature09318

Authors: Hengyao Niu, Woo-Hyun Chung, Zhu Zhu, Youngho Kwon, Weixing Zhao, Peter Chi, Rohit Prakash, Changhyun Seong, Dongqing Liu, Lucy Lu, Grzegorz Ira & Patrick Sung

If not properly processed and repaired, DNA double-strand breaks (DSBs) can give rise to deleterious chromosome rearrangements, which could ultimately lead to the tumour phenotype. DSB ends are resected in a 5′ to 3′ fashion in cells, to yield single-stranded DNA (ssDNA) for the recruitment of factors critical for DNA damage checkpoint activation and repair by homologous recombination. The resection process involves redundant pathways consisting of nucleases, DNA helicases and associated proteins. Being guided by recent genetic studies, we have reconstituted the first eukaryotic ATP-dependent DNA end-resection machinery comprising the Saccharomyces cerevisiae Mre11–Rad50–Xrs2 (MRX) complex, the Sgs1–Top3–Rmi1 complex, Dna2 protein and the heterotrimeric ssDNA-binding protein RPA. Here we show that DNA strand separation during end resection is mediated by the Sgs1 helicase function, in a manner that is enhanced by Top3–Rmi1 and MRX. In congruence with genetic observations, although the Dna2 nuclease activity is critical for resection, the Mre11 nuclease activity is dispensable. By examining the top3 Y356F allele and its encoded protein, we provide evidence that the topoisomerase activity of Top3, although critical for the suppression of crossover recombination, is not needed for resection either in cells or in the reconstituted system. Our results also unveil a multifaceted role of RPA, in the sequestration of ssDNA generated by DNA unwinding, enhancement of 5′ strand incision, and protection of the 3′ strand. Our reconstituted system should serve as a useful model for delineating the mechanistic intricacy of the DNA break resection process in eukaryotes.

Categories: Literature

DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

Nature 467, 112 (2010). doi:10.1038/nature09355

Authors: Petr Cejka, Elda Cannavo, Piotr Polaczek, Taro Masuda-Sasa, Subhash Pokharel, Judith L. Campbell & Stephen C. Kowalczykowski

The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes.

Categories: Literature

Polar patterns of driven filaments

Polar patterns of driven filaments

Nature 467, 73 (2010). doi:10.1038/nature09312

Authors: Volker Schaller, Christoph Weber, Christine Semmrich, Erwin Frey & Andreas R. Bausch

The emergence of collective motion exhibited by systems ranging from flocks of animals to self-propelled microorganisms to the cytoskeleton is a ubiquitous and fascinating self-organization phenomenon. Similarities between these systems, such as the inherent polarity of the constituents, a density-dependent transition to ordered phases or the existence of very large density fluctuations, suggest universal principles underlying pattern formation. This idea is followed by theoretical models at all levels of description: micro- or mesoscopic models directly map local forces and interactions using only a few, preferably simple, interaction rules, and more macroscopic approaches in the hydrodynamic limit rely on the systems’ generic symmetries. All these models characteristically have a broad parameter space with a manifold of possible patterns, most of which have not yet been experimentally verified. The complexity of interactions and the limited parameter control of existing experimental systems are major obstacles to our understanding of the underlying ordering principles. Here we demonstrate the emergence of collective motion in a high-density motility assay that consists of highly concentrated actin filaments propelled by immobilized molecular motors in a planar geometry. Above a critical density, the filaments self-organize to form coherently moving structures with persistent density modulations, such as clusters, swirls and interconnected bands. These polar nematic structures are long lived and can span length scales orders of magnitudes larger than their constituents. Our experimental approach, which offers control of all relevant system parameters, complemented by agent-based simulations, allows backtracking of the assembly and disassembly pathways to the underlying local interactions. We identify weak and local alignment interactions to be essential for the observed formation of patterns and their dynamics. The presented minimal polar-pattern-forming system may thus provide new insight into emerging order in the broad class of active fluids and self-propelled particles.

Categories: Literature

Bacterial charity work leads to population-wide resistance

Bacterial charity work leads to population-wide resistance

Nature 467, 82 (2010). doi:10.1038/nature09354

Authors: Henry H. Lee, Michael N. Molla, Charles R. Cantor & James J. Collins

Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population’s less resistant constituents, in part by producing indole, a signalling molecule generated by actively growing, unstressed cells. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.

Categories: Literature

A law in time?

A law in time?

Nature 467, 7 (2010). doi:10.1038/467007a

Congress must act quickly to save US stem-cell research.

Categories: Literature

How continents persist

How continents persist

Nature 467, 7 (2010). doi:10.1038/467007b

Earth scientists have explained why Canada and South Africa are still here.

Categories: Literature