Literature

A table in the Outlook article 'Nanotechnology: Carrying drugs' (Nature491 (suppl. 7425), S58–S60; 201210.1038/491S58a) wrongly stated that Cerulean Pharma's drug CRLX101 is in phase I trials. In fact, it has been in phase II trials

Categories: Literature

Asymmetric synthesis: Relay catalysis at a boron centre

Nature - Wed, 02/13/2013 - 01:00

Asymmetric synthesis: Relay catalysis at a boron centre

Nature 494, 7436 (2013). doi:10.1038/494179a

Authors: Valer Jeso & Glenn C. Micalizio

A boron complex catalyses the addition of allyl groups — hydrocarbon motifs — to 'activated imines' in a relay-like process, generating synthetically useful compounds as single mirror-image isomers. See Letter p.216

Categories: Literature

50 & 100 Years Ago

Nature - Wed, 02/13/2013 - 01:00

50 & 100 Years Ago

Nature 494, 7436 (2013). doi:10.1038/494182a

50 Years AgoAnimal Dispersion in Relation to Social Behaviour. By Prof. V. C. Wynne-Edwards — The theme of this book is that over-exploitation of food resources by an animal population will lead to dissipation of the resources and deterioration of the population; that

Categories: Literature

Molecular signatures of G-protein-coupled receptors

Nature - Wed, 02/13/2013 - 01:00

Molecular signatures of G-protein-coupled receptors

Nature 494, 7436 (2013). doi:10.1038/nature11896

Authors: A. J. Venkatakrishnan, Xavier Deupi, Guillaume Lebon, Christopher G. Tate, Gebhard F. Schertler & M. Madan Babu

G-protein-coupled receptors (GPCRs) are physiologically important membrane proteins that sense signalling molecules such as hormones and neurotransmitters, and are the targets of several prescribed drugs. Recent exciting developments are providing unprecedented insights into the structure and function of several medically important GPCRs. Here, through a systematic analysis of high-resolution GPCR structures, we uncover a conserved network of non-covalent contacts that defines the GPCR fold. Furthermore, our comparative analysis reveals characteristic features of ligand binding and conformational changes during receptor activation. A holistic understanding that integrates molecular and systems biology of GPCRs holds promise for new therapeutics and personalized medicine.

Categories: Literature

The structure of the asteroid 4 Vesta as revealed by models of planet-scale collisions

Nature - Wed, 02/13/2013 - 01:00

The structure of the asteroid 4 Vesta as revealed by models of planet-scale collisions

Nature 494, 7436 (2013). doi:10.1038/nature11892

Authors: M. Jutzi, E. Asphaug, P. Gillet, J.-A. Barrat & W. Benz

Asteroid 4 Vesta seems to be a major intact protoplanet, with a surface composition similar to that of the HED (howardite–eucrite–diogenite) meteorites. The southern hemisphere is dominated by a giant impact scar, but previous impact models have failed to reproduce the observed topography. The recent discovery that Vesta’s southern hemisphere is dominated by two overlapping basins provides an opportunity to model Vesta’s topography more accurately. Here we report three-dimensional simulations of Vesta’s global evolution under two overlapping planet-scale collisions. We closely reproduce its observed shape, and provide maps of impact excavation and ejecta deposition. Spiral patterns observed in the younger basin Rheasilvia, about one billion years old, are attributed to Coriolis forces during crater collapse. Surface materials exposed in the north come from a depth of about 20 kilometres, according to our models, whereas materials exposed inside the southern double-excavation come from depths of about 60–100 kilometres. If Vesta began as a layered, completely differentiated protoplanet, then our model predicts large areas of pure diogenites and olivine-rich rocks. These are not seen, possibly implying that the outer 100 kilometres or so of Vesta is composed mainly of a basaltic crust (eucrites) with ultramafic intrusions (diogenites).

Categories: Literature

Hybrid circuit cavity quantum electrodynamics with a micromechanical resonator

Nature - Wed, 02/13/2013 - 01:00

Hybrid circuit cavity quantum electrodynamics with a micromechanical resonator

Nature 494, 7436 (2013). doi:10.1038/nature11821

Authors: J.-M. Pirkkalainen, S. U. Cho, Jian Li, G. S. Paraoanu, P. J. Hakonen & M. A. Sillanpää

Hybrid quantum systems with inherently distinct degrees of freedom have a key role in many physical phenomena. Well-known examples include cavity quantum electrodynamics, trapped ions, and electrons and phonons in the solid state. In those systems, strong coupling makes the constituents lose their individual character and form dressed states, which represent a collective form of dynamics. As well as having fundamental importance, hybrid systems also have practical applications, notably in the emerging field of quantum information control. A promising approach is to combine long-lived atomic states with the accessible electrical degrees of freedom in superconducting cavities and quantum bits (qubits). Here we integrate circuit cavity quantum electrodynamics with phonons. Apart from coupling to a microwave cavity, our superconducting transmon qubit, consisting of tunnel junctions and a capacitor, interacts with a phonon mode in a micromechanical resonator, and thus acts like an atom coupled to two different cavities. We measure the phonon Stark shift, as well as the splitting of the qubit spectral line into motional sidebands, which feature transitions between the dressed electromechanical states. In the time domain, we observe coherent conversion of qubit excitation to phonons as sideband Rabi oscillations. This is a model system with potential for a quantum interface, which may allow for storage of quantum information in long-lived phonon states, coupling to optical photons or for investigations of strongly coupled quantum systems near the classical limit.

Categories: Literature

Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols

Nature - Wed, 02/13/2013 - 01:00

Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols

Nature 494, 7436 (2013). doi:10.1038/nature11844

Authors: Daniel L. Silverio, Sebastian Torker, Tatiana Pilyugina, Erika M. Vieira, Marc L. Snapper, Fredrik Haeffner & Amir H. Hoveyda

The discovery of catalysts that can be used to synthesize complex organic compounds by enantioselective transformations is central to advances in the life sciences; for this reason, many chemists aim to discover catalysts that allow for preparation of chiral molecules as predominantly one mirror-image isomer. The ideal catalyst should not contain precious elements and should bring reactions to completion in a few hours through operationally simple procedures. Here we introduce a set of small organic molecules that can catalyse reactions of unsaturated organoboron reagents with imines and carbonyls; the products of the reactions are enantiomerically pure amines and alcohols, which might serve as intermediates in the preparation of biologically active molecules. A distinguishing feature of this catalyst class is the presence of a ‘key’ proton embedded within their structure. Catalysts are derived from the abundant amino acid valine and are prepared in large quantities in four steps with inexpensive reagents. Reactions are scalable, do not demand stringent conditions, and can be performed with as little as 0.25 mole per cent catalyst in less than six hours at room temperature to generate products in more than 85 per cent yield and ≥97:3 enantiomeric ratio. The efficiency, selectivity and operational simplicity of the transformations and the range of boron-based reagents are expected to render this advance important for future progress in syntheses of amines and alcohols, which are useful in chemistry, biology and medicine.

Categories: Literature

Insolation-induced mid-Brunhes transition in Southern Ocean ventilation and deep-ocean temperature

Nature - Wed, 02/13/2013 - 01:00

Insolation-induced mid-Brunhes transition in Southern Ocean ventilation and deep-ocean temperature

Nature 494, 7436 (2013). doi:10.1038/nature11790

Authors: Qiuzhen Yin

Glacial–interglacial cycles characterized by long cold periods interrupted by short periods of warmth are the dominant feature of Pleistocene climate, with the relative intensity and duration of past and future interglacials being of particular interest for civilization. The interglacials after 430,000 years ago were characterized by warmer climates and higher atmospheric concentrations of carbon dioxide than the interglacials before, but the cause of this climatic transition (the so-called mid-Brunhes event (MBE)) is unknown. Here I show, on the basis of model simulations, that in response to insolation changes only, feedbacks between sea ice, temperature, evaporation and salinity caused vigorous pre-MBE Antarctic bottom water formation and Southern Ocean ventilation. My results also show that strong westerlies increased the pre-MBE overturning in the Southern Ocean via an increased latitudinal insolation gradient created by changes in eccentricity during austral winter and by changes in obliquity during austral summer. The stronger bottom water formation led to a cooler deep ocean during the older interglacials. These insolation-induced differences in the deep-sea temperature and in the Southern Ocean ventilation between the more recent interglacials and the older ones were not expected, because there is no straightforward systematic difference in the astronomical parameters between the interglacials before and after 430,000 years ago. Rather than being a real ‘event’, the apparent MBE seems to have resulted from a series of individual interglacial responses—including notable exceptions to the general pattern—to various combinations of insolation conditions. Consequently, assuming no anthropogenic interference, future interglacials may have pre- or post-MBE characteristics without there being a systematic change in forcings. These findings are a first step towards understanding the magnitude change of the interglacial carbon dioxide concentration around 430,000 years ago.

Categories: Literature

Biodiversity decreases disease through predictable changes in host community competence

Nature - Wed, 02/13/2013 - 01:00

Biodiversity decreases disease through predictable changes in host community competence

Nature 494, 7436 (2013). doi:10.1038/nature11883

Authors: Pieter T. J. Johnson, Daniel L. Preston, Jason T. Hoverman & Katherine L. D. Richgels

Accelerating rates of species extinctions and disease emergence underscore the importance of understanding how changes in biodiversity affect disease outcomes. Over the past decade, a growing number of studies have reported negative correlations between host biodiversity and disease risk, prompting suggestions that biodiversity conservation could promote human and wildlife health. Yet the generality of the diversity–disease linkage remains conjectural, in part because empirical evidence of a relationship between host competence (the ability to maintain and transmit infections) and the order in which communities assemble has proven elusive. Here we integrate high-resolution field data with multi-scale experiments to show that host diversity inhibits transmission of the virulent pathogen Ribeiroia ondatrae and reduces amphibian disease as a result of consistent linkages among species richness, host composition and community competence. Surveys of 345 wetlands indicated that community composition changed nonrandomly with species richness, such that highly competent hosts dominated in species-poor assemblages whereas more resistant species became progressively more common in diverse assemblages. As a result, amphibian species richness strongly moderated pathogen transmission and disease pathology among 24,215 examined hosts, with a 78.4% decline in realized transmission in richer assemblages. Laboratory and mesocosm manipulations revealed an approximately 50% decrease in pathogen transmission and host pathology across a realistic diversity gradient while controlling for host density, helping to establish mechanisms underlying the diversity–disease relationship and their consequences for host fitness. By revealing a consistent link between species richness and community competence, these findings highlight the influence of biodiversity on infection risk and emphasize the benefit of a community-based approach to understanding infectious diseases.

Categories: Literature

A deal on the horizon

Nature - Tue, 02/12/2013 - 01:00

A deal on the horizon

Nature 494, 7436 (2013). doi:10.1038/494147a

Leaders have finally thrashed out the European Union budget for the next seven years. But how much money will go to research is yet to be confirmed.

Categories: Literature

Science agencies prepare for cuts

Nature - Tue, 02/12/2013 - 01:00

Science agencies prepare for cuts

Nature 494, 7436 (2013). http://www.nature.com/doifinder/10.1038/494158a

Author: Meredith Wadman

Scientists already feeling the bite of US budget sequester.

Categories: Literature

Europe scales back research plans

Nature - Tue, 02/12/2013 - 01:00

Europe scales back research plans

Nature 494, 7436 (2013). http://www.nature.com/doifinder/10.1038/494159a

Author: Alison Abbott

Leaders propose 13% cut to commission’s proposals.

Categories: Literature

Company offers portable peer review

Nature - Tue, 02/12/2013 - 01:00

Company offers portable peer review

Nature 494, 7436 (2013). http://www.nature.com/doifinder/10.1038/494161a

Author: Richard Van Noorden

Author-pays service cuts down on redundant reviews.

Categories: Literature

NANOG-dependent function of TET1 and TET2 in establishment of pluripotency

Nature - Sun, 02/10/2013 - 01:00

NANOG-dependent function of TET1 and TET2 in establishment of pluripotency

Nature 495, 7441 (2013). doi:10.1038/nature11925

Authors: Yael Costa, Junjun Ding, Thorold W. Theunissen, Francesco Faiola, Timothy A. Hore, Pavel V. Shliaha, Miguel Fidalgo, Arven Saunders, Moyra Lawrence, Sabine Dietmann, Satyabrata Das, Dana N. Levasseur, Zhe Li, Mingjiang Xu, Wolf Reik, José C. R. Silva & Jianlong Wang

Molecular control of the pluripotent state is thought to reside in a core circuitry of master transcription factors including the homeodomain-containing protein NANOG, which has an essential role in establishing ground state pluripotency during somatic cell reprogramming. Whereas the genomic occupancy of NANOG has been extensively investigated, comparatively little is known about NANOG-associated proteins and their contribution to the NANOG-mediated reprogramming process. Using enhanced purification techniques and a stringent computational algorithm, we identify 27 high-confidence protein interaction partners of NANOG in mouse embryonic stem cells. These consist of 19 previously unknown partners of NANOG that have not been reported before, including the ten-eleven translocation (TET) family methylcytosine hydroxylase TET1. We confirm physical association of NANOG with TET1, and demonstrate that TET1, in synergy with NANOG, enhances the efficiency of reprogramming. We also find physical association and reprogramming synergy of TET2 with NANOG, and demonstrate that knockdown of TET2 abolishes the reprogramming synergy of NANOG with a catalytically deficient mutant of TET1. These results indicate that the physical interaction between NANOG and TET1/TET2 proteins facilitates reprogramming in a manner that is dependent on the catalytic activity of TET1/TET2. TET1 and NANOG co-occupy genomic loci of genes associated with both maintenance of pluripotency and lineage commitment in embryonic stem cells, and TET1 binding is reduced upon NANOG depletion. Co-expression of NANOG and TET1 increases 5-hydroxymethylcytosine levels at the top-ranked common target loci Esrrb and Oct4 (also called Pou5f1), resulting in priming of their expression before reprogramming to naive pluripotency. We propose that TET1 is recruited by NANOG to enhance the expression of a subset of key reprogramming target genes. These results provide an insight into the reprogramming mechanism of NANOG and uncover a new role for 5-methylcytosine hydroxylases in the establishment of naive pluripotency.

Categories: Literature

Membrane potential dynamics of grid cells

Nature - Sun, 02/10/2013 - 01:00

Membrane potential dynamics of grid cells

Nature 495, 7440 (2013). doi:10.1038/nature11973

Authors: Cristina Domnisoru, Amina A. Kinkhabwala & David W. Tank

During navigation, grid cells increase their spike rates in firing fields arranged on a markedly regular triangular lattice, whereas their spike timing is often modulated by theta oscillations. Oscillatory interference models of grid cells predict theta amplitude modulations of membrane potential during firing field traversals,

Categories: Literature

‘See-saw’ expression of microRNA-198 and FSTL1 from a single transcript in wound healing

Nature - Sun, 02/10/2013 - 01:00

‘See-saw’ expression of microRNA-198 and FSTL1 from a single transcript in wound healing

Nature 495, 7439 (2013). doi:10.1038/nature11890

Authors: Gopinath M. Sundaram, John E. A. Common, Felicia E. Gopal, Satyanarayana Srikanta, Krishnaswamy Lakshman, Declan P. Lunny, Thiam C. Lim, Vivek Tanavde, E. Birgitte Lane & Prabha Sampath

Post-transcriptional switches are flexible effectors of dynamic changes in gene expression. Here we report a new post-transcriptional switch that dictates the spatiotemporal and mutually exclusive expression of two alternative gene products from a single transcript. Expression of primate-specific exonic microRNA-198 (miR-198), located in the 3′-untranslated region of follistatin-like 1 (FSTL1) messenger RNA, switches to expression of the linked open reading frame of FSTL1 upon wounding in a human ex vivo organ culture system. We show that binding of a KH-type splicing regulatory protein (KSRP, also known as KHSRP) to the primary transcript determines the fate of the transcript and is essential for the processing of miR-198: transforming growth factor-β signalling switches off miR-198 expression by downregulating KSRP, and promotes FSTL1 protein expression. We also show that FSTL1 expression promotes keratinocyte migration, whereas miR-198 expression has the opposite effect by targeting and inhibiting DIAPH1, PLAU and LAMC2. A clear inverse correlation between the expression pattern of FSTL1 (pro-migratory) and miR-198 (anti-migratory) highlights the importance of this regulatory switch in controlling context-specific gene expression to orchestrate wound re-epithelialization. The deleterious effect of failure of this switch is apparent in non-healing chronic diabetic ulcers, in which expression of miR-198 persists, FSTL1 is absent, and keratinocyte migration, re-epithelialization and wound healing all fail to occur.

Categories: Literature

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