We analyzed the whole genome sequences of a family of four, consisting of two siblings and their parents. Family-based sequencing allowed us to delineate recombination sites precisely, identify 70% of the sequencing errors (resulting in 99.999% accuracy), and identify very rare single nucleotide polymorphisms. We also directly estimated a human intergeneration mutation rate of ~1.1 x 10(-8) per position per haploid genome. Both offspring in this family have two recessive disorders-Miller syndrome, for which the gene was concurrently identified, and primary ciliary dyskinesia, for which causative genes have been previously identified. Family-based genome analysis enabled us to narrow the candidate genes for both of these Mendelian disorders to only four. Our results demonstrate the unique value of complete genome sequencing in families.

Cyanobacterial carbon fixation is a major component of the global carbon cycle. This process requires the carboxysome, an organelle-like proteinaceous microcompartment that sequesters the enzymes of carbon fixation from the cytoplasm. Here, fluorescently tagged carboxysomes were found to be spatially ordered in a linear fashion. As a consequence, cells undergoing division evenly segregated carboxysomes in a nonrandom process. Mutation of the cytoskeletal protein ParA specifically disrupted carboxysome order, promoted random carboxysome segregation during cell division, and impaired carbon fixation after disparate partitioning. Thus, cyanobacteria use the cytoskeleton to control the spatial arrangement of carboxysomes and to optimize the metabolic process of carbon fixation.

Meiotic crossovers (COs) are tightly regulated to ensure that COs on the same chromosome are distributed far apart (crossover interference, COI) and that at least one CO is formed per homolog pair (CO homeostasis). CO formation is controlled in part during meiotic double-strand break (DSB) creation in Caenorhabditis elegans, but a second level of control must also exist because meiotic DSBs outnumber COs. We show that the antirecombinase RTEL-1 is required to prevent excess meiotic COs, probably by promoting meiotic synthesis-dependent strand annealing. Two distinct classes of meiotic COs are increased in rtel-1 mutants, and COI and homeostasis are compromised. We propose that RTEL-1 implements the second level of CO control by promoting noncrossovers.

The concept that astrocytes release neuroactive molecules (gliotransmitters) to affect synaptic transmission has been a paradigm shift in neuroscience research over the past decade. This concept suggests that astrocytes, together with pre- and postsynaptic neuronal elements, make up a functional synapse. Astrocyte release of gliotransmitters (for example, glutamate and adenosine triphosphate) is generally accepted to be a Ca(2+)-dependent process. We used two mouse lines to either selectively increase or obliterate astrocytic G(q) G protein-coupled receptor Ca(2+) signaling to further test the hypothesis that astrocytes release gliotransmitters in a Ca(2+)-dependent manner to affect synaptic transmission. Neither increasing nor obliterating astrocytic Ca(2+) fluxes affects spontaneous and evoked excitatory synaptic transmission or synaptic plasticity. Our findings suggest that, at least in the hippocampus, the mechanisms of gliotransmission need to be reconsidered.

Remobilization to the atmosphere of only a small fraction of the methane held in East Siberian Arctic Shelf (ESAS) sediments could trigger abrupt climate warming, yet it is believed that sub-sea permafrost acts as a lid to keep this shallow methane reservoir in place. Here, we show that more than 5000 at-sea observations of dissolved methane demonstrates that greater than 80% of ESAS bottom waters and greater than 50% of surface waters are supersaturated with methane regarding to the atmosphere. The current atmospheric venting flux, which is composed of a diffusive component and a gradual ebullition component, is on par with previous estimates of methane venting from the entire World Ocean. Leakage of methane through shallow ESAS waters needs to be considered in interactions between the biogeosphere and a warming Arctic climate.

Nucleation is a fundamental step in atmospheric new-particle formation. However, laboratory experiments on nucleation have systematically failed to demonstrate sulfuric acid particle formation rates as high as those necessary to account for ambient atmospheric concentrations, and the role of sulfuric acid in atmospheric nucleation has remained a mystery. Here, we report measurements of new particles (with diameters of approximately 1.5 nanometers) observed immediately after their formation at atmospherically relevant sulfuric acid concentrations. Furthermore, we show that correlations between measured nucleation rates and sulfuric acid concentrations suggest that freshly formed particles contain one to two sulfuric acid molecules, a number consistent with assumptions that are based on atmospheric observations. Incorporation of these findings into global models should improve the understanding of the impact of secondary particle formation on climate.

The Neoproterozoic was an era of great environmental and biological change, but a paucity of direct and precise age constraints on strata from this time has prevented the complete integration of these records. We present four high-precision U-Pb ages for Neoproterozoic rocks in northwestern Canada that constrain large perturbations in the carbon cycle, a major diversification and depletion in the microfossil record, and the onset of the Sturtian glaciation. A volcanic tuff interbedded with Sturtian glacial deposits, dated at 716.5 million years ago, is synchronous with the age of the Franklin large igneous province and paleomagnetic poles that pin Laurentia to an equatorial position. Ice was therefore grounded below sea level at very low paleolatitudes, which implies that the Sturtian glaciation was global in extent.

Stellar wind standoff by a planetary magnetic field prevents atmospheric erosion and water loss. Although the early Earth retained its water and atmosphere, and thus evolved as a habitable planet, little is known about Earth's magnetic field strength during that time. We report paleointensity results from single silicate crystals bearing magnetic inclusions that record a geodynamo 3.4 to 3.45 billion years ago. The measured field strength is approximately 50 to 70% that of the present-day field. When combined with a greater Paleoarchean solar wind pressure, the paleofield strength data suggest steady-state magnetopause standoff distances of < or = 5 Earth radii, similar to values observed during recent coronal mass ejection events. The data also suggest lower-latitude aurora and increases in polar cap area, as well as heating, expansion, and volatile loss from the exosphere that would have affected long-term atmospheric composition.

Sestrins are conserved proteins that accumulate in cells exposed to stress, potentiate adenosine monophosphate-activated protein kinase (AMPK), and inhibit activation of target of rapamycin (TOR). We show that the abundance of Drosophila sestrin (dSesn) is increased upon chronic TOR activation through accumulation of reactive oxygen species that cause activation of c-Jun amino-terminal kinase and transcription factor Forkhead box O (FoxO). Loss of dSesn resulted in age-associated pathologies including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction, which were prevented by pharmacological activation of AMPK or inhibition of TOR. Hence, dSesn appears to be a negative feedback regulator of TOR that integrates metabolic and stress inputs and prevents pathologies caused by chronic TOR activation that may result from diminished autophagic clearance of damaged mitochondria, protein aggregates, or lipids.

The Cretaceous-Paleogene boundary approximately 65.5 million years ago marks one of the three largest mass extinctions in the past 500 million years. The extinction event coincided with a large asteroid impact at Chicxulub, Mexico, and occurred within the time of Deccan flood basalt volcanism in India. Here, we synthesize records of the global stratigraphy across this boundary to assess the proposed causes of the mass extinction. Notably, a single ejecta-rich deposit compositionally linked to the Chicxulub impact is globally distributed at the Cretaceous-Paleogene boundary. The temporal match between the ejecta layer and the onset of the extinctions and the agreement of ecological patterns in the fossil record with modeled environmental perturbations (for example, darkness and cooling) lead us to conclude that the Chicxulub impact triggered the mass extinction.

Desmurget et al. (Reports, 8 May 2009, p. 811) applied direct electrical stimulation (DES) to the human cortex to study the origin of movement intention. Their interpretation assumed that DES causes cortical activation, whereas it is possible that it actually evokes deactivation. The lack of certain knowledge about the true effects of DES limits its use for validation of cognitive models.