Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile

Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ～2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.     

Implications of changes in the UK social and occupational classifications in 2001 for vital statistics

In 2001, three simultaneous changes were introduced which influence the reporting of vital statistics by socio-economic status. Registrar General's Social Class was replaced by the new National Statistics Socio-Economic Status (NS SEC); the Standard Occupational Classification (SOC) was updated from SOC90 to SOC2000; and the coding of employment status on vital statistics changed to stay in line with census coding and SOC2000. This article reports on these changes and describes a method for coding data prior to 2001 to NS SEC (named NS SEC90) in order to facilitate the analysis of health inequalities over time. NS SEC90 allocates 90 per cent of deaths to the same analytical category as NS SEC. This figure varies according to sub group.     

A lower limit for atmospheric carbon dioxide levels 3.2 billion years ago

The quantification of greenhouse gases present in the Archaean atmosphere is critical for understanding the evolution of atmospheric oxygen, surface temperatures and the conditions for life on early Earth. For instance, it has been argued that small changes in the balance between two potential greenhouse gases, carbon dioxide and methane, may have dictated the feedback cycle involving organic haze production and global cooling. Climate models have focused on carbon dioxide as the greenhouse gas responsible for maintaining above-freezing surface temperatures during a time of low solar luminosity. However, the analysis of 2.75-billion-year (Gyr)-old palaeosols--soil samples preserved in the geologic record--have recently provided an upper constraint on atmospheric carbon dioxide levels well below that required in most climate models to prevent the Earth's surface from freezing. This finding prompted many to look towards methane as an additional greenhouse gas to satisfy climate models. Here we use model equilibrium reactions for weathering rinds on 3.2-Gyr-old river gravels to show that the presence of iron-rich carbonate relative to common clay minerals requires a minimum partial pressure of carbon dioxide several times higher than present-day values. Unless actual carbon dioxide levels were considerably greater than this, climate models predict that additional greenhouse gases would still need to have a role in maintaining above-freezing surface temperatures.     

Mangroves enhance the biomass of coral reef fish communities in the Caribbean

Mangrove forests are one of the world's most threatened tropical ecosystems with global loss exceeding 35% (ref. 1). Juvenile coral reef fish often inhabit mangroves, but the importance of these nurseries to reef fish population dynamics has not been quantified. Indeed, mangroves might be expected to have negligible influence on reef fish communities: juvenile fish can inhabit alternative habitats and fish populations may be regulated by other limiting factors such as larval supply or fishing. Here we show that mangroves are unexpectedly important, serving as an intermediate nursery habitat that may increase the survivorship of young fish. Mangroves in the Caribbean strongly influence the community structure of fish on neighbouring coral reefs. In addition, the biomass of several commercially important species is more than doubled when adult habitat is connected to mangroves. The largest herbivorous fish in the Atlantic, Scarus guacamaia, has a functional dependency on mangroves and has suffered local extinction after mangrove removal. Current rates of mangrove deforestation are likely to have severe deleterious consequences for the ecosystem function, fisheries productivity and resilience of reefs. Conservation efforts should protect connected corridors of mangroves, seagrass beds and coral reefs.     

Methane oxidation by an extremely acidophilic bacterium of the phylum Verrucomicrobia

Aerobic methanotrophic bacteria consume methane as it diffuses away from methanogenic zones of soil and sediment. They act as a biofilter to reduce methane emissions to the atmosphere, and they are therefore targets in strategies to combat global climate change. No cultured methanotroph grows optimally below pH 5, but some environments with active methane cycles are very acidic. Here we describe an extremely acidophilic methanotroph that grows optimally at pH 2.0-2.5. Unlike the known methanotrophs, it does not belong to the phylum Proteobacteria but rather to the Verrucomicrobia, a widespread and diverse bacterial phylum that primarily comprises uncultivated species with unknown genotypes. Analysis of its draft genome detected genes encoding particulate methane monooxygenase that were homologous to genes found in methanotrophic proteobacteria. However, known genetic modules for methanol and formaldehyde oxidation were incomplete or missing, suggesting that the bacterium uses some novel methylotrophic pathways. Phylogenetic analysis of its three pmoA genes (encoding a subunit of particulate methane monooxygenase) placed them into a distinct cluster from proteobacterial homologues. This indicates an ancient divergence of Verrucomicrobia and Proteobacteria methanotrophs rather than a recent horizontal gene transfer of methanotrophic ability. The findings show that methanotrophy in the Bacteria is more taxonomically, ecologically and genetically diverse than previously thought, and that previous studies have failed to assess the full diversity of methanotrophs in acidic environments.     

SERRATE coordinates shoot meristem function and leaf axial patterning in Arabidopsis

Leaves of flowering plants are determinate organs produced by pluripotent structures termed shoot apical meristems. Once specified, leaves differentiate an adaxial (upper) side specialized for light capture, and an abaxial (lower) side specialized for gas exchange. A functional relationship between meristem activity and the differentiation of adaxial leaf fate has been recognized for over fifty years, but the molecular basis of this interaction is unclear. In Arabidopsis thaliana, activity of the class I KNOX (KNOTTED1-like homeobox) genes SHOOTMERISTEMLESS (STM) and BREVIPEDICELLUS (BP) is required for meristem function but excluded from leaves, whereas members of the HD-Zip III (class III homeodomain leucine zipper) protein family function to promote both meristem activity and adaxial leaf fate. Here we show that the zinc-finger protein SERRATE acts in a microRNA (miRNA) gene-silencing pathway to regulate expression of the HD-Zip III gene PHABULOSA (PHB) while also limiting the competence of shoot tissue to respond to KNOX expression. Thus, SERRATE acts to coordinately regulate meristem activity and leaf axial patterning.     

An anaerobic mitochondrion that produces hydrogen

Hydrogenosomes are organelles that produce ATP and hydrogen, and are found in various unrelated eukaryotes, such as anaerobic flagellates, chytridiomycete fungi and ciliates. Although all of these organelles generate hydrogen, the hydrogenosomes from these organisms are structurally and metabolically quite different, just like mitochondria where large differences also exist. These differences have led to a continuing debate about the evolutionary origin of hydrogenosomes. Here we show that the hydrogenosomes of the anaerobic ciliate Nyctotherus ovalis, which thrives in the hindgut of cockroaches, have retained a rudimentary genome encoding components of a mitochondrial electron transport chain. Phylogenetic analyses reveal that those proteins cluster with their homologues from aerobic ciliates. In addition, several nucleus-encoded components of the mitochondrial proteome, such as pyruvate dehydrogenase and complex II, were identified. The N. ovalis hydrogenosome is sensitive to inhibitors of mitochondrial complex I and produces succinate as a major metabolic end product--biochemical traits typical of anaerobic mitochondria. The production of hydrogen, together with the presence of a genome encoding respiratory chain components, and biochemical features characteristic of anaerobic mitochondria, identify the N. ovalis organelle as a missing link between mitochondria and hydrogenosomes.     

Animal behaviour: elephants are capable of vocal learning

There are a few mammalian species that can modify their vocalizations in response to auditory experience--for example, some marine mammals use vocal imitation for reproductive advertisement, as birds sometimes do. Here we describe two examples of vocal imitation by African savannah elephants, Loxodonta africana, a terrestrial mammal that lives in a complex fission-fusion society. Our findings favour a role for vocal imitation that has already been proposed for primates, birds, bats and marine mammals: it is a useful form of acoustic communication that helps to maintain individual-specific bonds within changing social groupings.     

Astronomical pacing of methane release in the Early Jurassic period

A pronounced negative carbon-isotope (delta13C) excursion of approximately 5-7 per thousand (refs 1-7) indicates the occurrence of a significant perturbation to the global carbon cycle during the Early Jurassic period (early Toarcian age, approximately 183 million years ago). The rapid release of 12C-enriched biogenic methane as a result of continental-shelf methane hydrate dissociation has been put forward as a possible explanation for this observation. Here we report high-resolution organic carbon-isotope data from well-preserved mudrocks in Yorkshire, UK, which demonstrate that the carbon-isotope excursion occurred in three abrupt stages, each showing a shift of -2 per thousand to -3 per thousand. Spectral analysis of these carbon-isotope measurements and of high-resolution carbonate abundance data reveals a regular cyclicity. We interpret these results as providing strong evidence that methane release proceeded in three rapid pulses and that these pulses were controlled by astronomically forced changes in climate, superimposed upon longer-term global warming. We also find that the first two pulses of methane release each coincided with the extinction of a large proportion of marine species.     

Cyclosporins: Immunosuppressive agents with antitumor activity

Summary Initial screening of the 2 recently developed immunosuppressive agents, cyclosporin A and cyclosporin C, in 11 murine transplantable neoplasms revealed significant increase of lifespan with long-term survivors after i.p. injection to the ascites tumors, Taper liver, Sarcoma 180J and Ehrlich.This work was supported in part by grant CA-08748 from the National Cancer Institute, National Institutes of HealthDepartment of Health, Education and Welfare. The authors are indebted to Drs Dorris J. Hutchison, M.N. Teller and H. Stähelin for helpful discussions, and to Dr A. von Wartburg of Sandoz AG, Basel, for the supply of the cyclosporins.