Eight glacial cycles from an Antarctic ice core

The Antarctic Vostok ice core provided compelling evidence of the nature of climate, and of climate feedbacks, over the past 420,000 years. Marine records suggest that the amplitude of climate variability was smaller before that time, but such records are often poorly resolved. Moreover, it is not possible to infer the abundance of greenhouse gases in the atmosphere from marine records. Here we report the recovery of a deep ice core from Dome C, Antarctica, that provides a climate record for the past 740,000 years. For the four most recent glacial cycles, the data agree well with the record from Vostok. The earlier period, between 740,000 and 430,000 years ago, was characterized by less pronounced warmth in interglacial periods in Antarctica, but a higher proportion of each cycle was spent in the warm mode. The transition from glacial to interglacial conditions about 430,000 years ago (Termination V) resembles the transition into the present interglacial period in terms of the magnitude of change in temperatures and greenhouse gases, but there are significant differences in the patterns of change. The interglacial stage following Termination V was exceptionally long--28,000 years compared to, for example, the 12,000 years recorded so far in the present interglacial period. Given the similarities between this earlier warm period and today, our results may imply that without human intervention, a climate similar to the present one would extend well into the future.     

Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice

In vertebrates, skeletal muscle is a model for the acquisition of cell fate from stem cells. Two determination factors of the basic helix-loop-helix myogenic regulatory factor (MRF) family, Myf5 and Myod, are thought to direct this transition because double-mutant mice totally lack skeletal muscle fibres and myoblasts. In the absence of these factors, progenitor cells remain multipotent and can change their fate. Gene targeting studies have revealed hierarchical relationships between these and the other MRF genes, Mrf4 and myogenin, where the latter are regarded as differentiation genes. Here we show, using an allelic series of three Myf5 mutants that differentially affect the expression of the genetically linked Mrf4 gene, that skeletal muscle is present in the new Myf5:Myod double-null mice only when Mrf4 expression is not compromised. This finding contradicts the widely held view that myogenic identity is conferred solely by Myf5 and Myod, and identifies Mrf4 as a determination gene. We revise the epistatic relationship of the MRFs, in which both Myf5 and Mrf4 act upstream of Myod to direct embryonic multipotent cells into the myogenic lineage.     

Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex

Neuronal activity in the motor cortex is understood to be correlated with movements, but the impact of action potentials (APs) in single cortical neurons on the generation of movement has not been fully determined. Here we show that trains of APs in single pyramidal cells of rat motor cortex can evoke long sequences of small whisker movements. For layer-5 pyramids, we find that evoked rhythmic movements have a constant phase relative to the AP train, indicating that single layer-5 pyramids can reset the rhythm of whisker movements. Action potentials evoked in layer-6 pyramids can generate bursts of rhythmic whisking, with a variable phase of movements relative to the AP train. An increasing number of APs decreases the latency to onset of movement, whereas AP frequency determines movement direction and amplitude. We find that the efficacy of cortical APs in evoking whisker movements is not dependent on background cortical activity and is greatly enhanced in waking rats. We conclude that in vibrissae motor cortex sparse AP activity can evoke movements.     

Decoherence of matter waves by thermal emission of radiation

Emergent quantum technologies have led to increasing interest in decoherence--the processes that limit the appearance of quantum effects and turn them into classical phenomena. One important cause of decoherence is the interaction of a quantum system with its environment, which 'entangles' the two and distributes the quantum coherence over so many degrees of freedom as to render it unobservable. Decoherence theory has been complemented by experiments using matter waves coupled to external photons or molecules, and by investigations using coherent photon states, trapped ions and electron interferometers. Large molecules are particularly suitable for the investigation of the quantum-classical transition because they can store much energy in numerous internal degrees of freedom; the internal energy can be converted into thermal radiation and thus induce decoherence. Here we report matter wave interferometer experiments in which C70 molecules lose their quantum behaviour by thermal emission of radiation. We find good quantitative agreement between our experimental observations and microscopic decoherence theory. Decoherence by emission of thermal radiation is a general mechanism that should be relevant to all macroscopic bodies.     

Swarm intelligence for mixed-variable design optimization

Many engineering optimization problems frequently encounter continuous variables and discrete variables which adds considerably to the solution complexity. Very few of the existing methods can yield a globally optimal solution when the objective functions are non-convex and non-differentiable. This paper presents a hybrid swarm intelligence ap-proach (HSIA) for solving these nonlinear optimization problems which contain integer, discrete, zero-one and continuous variables. HSIA provides an improvement in global search reliability in a mixed-variable space and converges steadily to a good solution. An approach to handle various kinds of variables and constraints is discussed. Comparison testing of several examples of mixed-variable optimization problems in the literature showed that the proposed approach is superior to current methods for finding the best solution, in terms of both solution quality and algorithm robustness.     

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations.     

Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice

Here we present a strategy to determine the genetic basis of variance in complex phenotypes that arise from natural, as opposed to induced, genetic variation in mice. We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing anxiety. We also show that this locus can be subdivided into three regions, one of which contains Rgs2, which encodes a regulator of G protein signaling. We then use quantitative complementation to show that Rgs2 is a quantitative trait gene. This combined genetic and functional approach should be applicable to the analysis of any quantitative trait.     

Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome

In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task.