Distinct representations of olfactory information in different cortical centres

Sensory information is transmitted to the brain where it must be processed to translate stimulus features into appropriate behavioural output. In the olfactory system, distributed neural activity in the nose is converted into a segregated map in the olfactory bulb. Here we investigate how this ordered representation is transformed in higher olfactory centres in mice. We have developed a tracing strategy to define the neural circuits that convey information from individual glomeruli in the olfactory bulb to the piriform cortex and the cortical amygdala. The spatial order in the bulb is discarded in the piriform cortex; axons from individual glomeruli project diffusely to the piriform without apparent spatial preference. In the cortical amygdala, we observe broad patches of projections that are spatially stereotyped for individual glomeruli. These projections to the amygdala are overlapping and afford the opportunity for spatially localized integration of information from multiple glomeruli. The identification of a distributive pattern of projections to the piriform and stereotyped projections to the amygdala provides an anatomical context for the generation of learned and innate behaviours.     

Late Holocene methane rise caused by orbitally controlled increase in tropical sources

Considerable debate surrounds the source of the apparently 'anomalous' increase of atmospheric methane concentrations since the mid-Holocene (5,000?years ago) compared to previous interglacial periods as recorded in polar ice core records. Proposed mechanisms for the rise in methane concentrations relate either to methane emissions from anthropogenic early rice cultivation or an increase in natural wetland emissions from tropical or boreal sources. Here we show that our climate and wetland simulations of the global methane cycle over the last glacial cycle (the past 130,000?years) recreate the ice core record and capture the late Holocene increase in methane concentrations. Our analyses indicate that the late Holocene increase results from natural changes in the Earth's orbital configuration, with enhanced emissions in the Southern Hemisphere tropics linked to precession-induced modification of seasonal precipitation. Critically, our simulations capture the declining trend in methane concentrations at the end of the last interglacial period (115,000-130,000?years ago) that was used to diagnose the Holocene methane rise as unique. The difference between the two time periods results from differences in the size and rate of regional insolation changes and the lack of glacial inception in the Holocene. Our findings also suggest that no early agricultural sources are required to account for the increase in methane concentrations in the 5,000?years before the industrial era.     

Overcoming lability of extremely long alkane carbon-carbon bonds through dispersion forces

Steric effects in chemistry are a consequence of the space required to accommodate the atoms and groups within a molecule, and are often thought to be dominated by repulsive forces arising from overlapping electron densities (Pauli repulsion). An appreciation of attractive interactions such as van der Waals forces (which include London dispersion forces) is necessary to understand chemical bonding and reactivity fully. This is evident from, for example, the strongly debated origin of the higher stability of branched alkanes relative to linear alkanes and the possibility of constructing hydrocarbons with extraordinarily long C-C single bonds through steric crowding. Although empirical bond distance/bond strength relationships have been established for C-C bonds (longer C-C bonds have smaller bond dissociation energies), these have no present theoretical basis. Nevertheless, these empirical considerations are fundamental to structural and energetic evaluations in chemistry, as summarized by Pauling as early as 1960 and confirmed more recently. Here we report the preparation of hydrocarbons with extremely long C-C bonds (up to 1.704??), the longest such bonds observed so far in alkanes. The prepared compounds are unexpectedly stable--noticeable decomposition occurs only above 200?°C. We prepared the alkanes by coupling nanometre-sized, diamond-like, highly rigid structures known as diamondoids. The extraordinary stability of the coupling products is due to overall attractive dispersion interactions between the intramolecular H???H contact surfaces, as is evident from density functional theory computations with and without inclusion of dispersion corrections.     

A closely packed system of low-mass, low-density planets transiting Kepler-11

When an extrasolar planet passes in front of (transits) its star, its radius can be measured from the decrease in starlight and its orbital period from the time between transits. Multiple planets transiting the same star reveal much more: period ratios determine stability and dynamics, mutual gravitational interactions reflect planet masses and orbital shapes, and the fraction of transiting planets observed as multiples has implications for the planarity of planetary systems. But few stars have more than one known transiting planet, and none has more than three. Here we report Kepler spacecraft observations of a single Sun-like star, which we call Kepler-11, that reveal six transiting planets, five with orbital periods between 10 and 47?days and a sixth planet with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases. The degree of coplanarity and proximity of the planetary orbits imply energy dissipation near the end of planet formation.     

Human metabolic individuality in biomedical and pharmaceutical research

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.     

Programming the magnitude and persistence of antibody responses with innate immunity

Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques.