Stylet jaws of Chrysopetalidae (Annelida)

Micro-CT imaging elucidates jaw and pharynx structure in 14 nominal taxa belonging to Chrysopetalinae, Dysponetinae and Calamyzinae (Chrysopetalidae: Annelida). Systematic evaluation of chrysopetalid jaw form in each taxon is used to compare inter-generic relationships within and between each subfamily and with other polychaete families possessing lateral pairs of jaws. Jaw morphology proves diagnostic at all levels including agreement with current molecular phylogenetic analyses of the Chrysopetalidae. The greatest diversity of pharynx and jaw form, associated with sensory body characters, is found amongst taxa of the epibenthic Chrysopetalinae. It is hypothesized that the paired stylet jaws interlock to pierce prey tissue, and, in concert with a highly muscular pharynx, suck out prey fluids that pass down the internal groove of the stylets. Three generic groups are identified based on congruence of jaw form, and novel buccal structures are revealed in some taxa: a pharyngeal calcareous ‘ring’ and extensive pharyngeal glands. A continuum across free-living and facultative symbiont lifestyles is represented across all Chrysopetalinae. Dysponetinae comprises free-living, very small individuals that exhibit a meiofaunal lifestyle. All species possess one type of simple, tanned rod-like stylet jaws and certain simplified body structures. Calamyzinae species possess polyphyletic jaw forms and grades of radically simplified sensory morphologies. Free-living, bacteriovore calamyzins inhabit extreme chemosynthetic habitats and lack jaws, or possess modified jaws composed of an anterior platelet and posterior grooved jaw, present in the larvae and lost in the adult. New observations of an ectoparasitic Calamyzinae include details of a specialized mouth opening and stylet jaw present in a species that exhibits cryptic coloration, while grooved jaws are revealed for the first time in an obligate symbiont calamyzin. The grooved jaw form is considered a non-homoplasious synapomorphy that supports the monophyly of the family Chrysopetalidae.     

The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia

Anonychia and hyponychia congenita (OMIM 206800) are rare autosomal recessive conditions in which the only presenting phenotype is the absence or severe hypoplasia of all fingernails and toenails. After determining linkage to chromosome 20p13, we identified homozygous or compound heterozygous mutations in the gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, in eight affected families. Rspo4 expression was specifically localized to developing mouse nail mesenchyme at embryonic day 15.5, suggesting a crucial role in nail morphogenesis.     

The oxidation state of Hadean magmas and implications for early Earth's atmosphere

Magmatic outgassing of volatiles from Earth's interior probably played a critical part in determining the composition of the earliest atmosphere, more than 4,000 million years (Myr) ago. Given an elemental inventory of hydrogen, carbon, nitrogen, oxygen and sulphur, the identity of molecular species in gaseous volcanic emanations depends critically on the pressure (fugacity) of oxygen. Reduced melts having oxygen fugacities close to that defined by the iron-wüstite buffer would yield volatile species such as CH(4), H(2), H(2)S, NH(3) and CO, whereas melts close to the fayalite-magnetite-quartz buffer would be similar to present-day conditions and would be dominated by H(2)O, CO(2), SO(2) and N(2) (refs 1-4). Direct constraints on the oxidation state of terrestrial magmas before 3,850?Myr before present (that is, the Hadean eon) are tenuous because the rock record is sparse or absent. Samples from this earliest period of Earth's history are limited to igneous detrital zircons that pre-date the known rock record, with ages approaching ～4,400?Myr (refs 5-8). Here we report a redox-sensitive calibration to determine the oxidation state of Hadean magmatic melts that is based on the incorporation of cerium into zircon crystals. We find that the melts have average oxygen fugacities that are consistent with an oxidation state defined by the fayalite-magnetite-quartz buffer, similar to present-day conditions. Moreover, selected Hadean zircons (having chemical characteristics consistent with crystallization specifically from mantle-derived melts) suggest oxygen fugacities similar to those of Archaean and present-day mantle-derived lavas as early as ～4,350?Myr before present. These results suggest that outgassing of Earth's interior later than ～200?Myr into the history of Solar System formation would not have resulted in a reducing atmosphere.     

Combination forecasts of output growth in a seven‐country data set

This paper uses forecast combination methods to forecast output growth in a seven‐country quarterly economic data set covering 1959–1999, with up to 73 predictors per country. Although the forecasts based on individual predictors are unstable over time and across countries, and on average perform worse than an autoregressive benchmark, the combination forecasts often improve upon autoregressive forecasts. Despite the unstable performance of the constituent forecasts, the most successful combination forecasts, like the mean, are the least sensitive to the recent performance of the individual forecasts. While consistent with other evidence on the success of simple combination forecasts, this finding is difficult to explain using the theory of combination forecasting in a stationary environment. Copyright © 2004 John Wiley & Sons, Ltd.     

DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.     

On the history of the isomorphism problem of dynamical systems with special regard to von Neumann’s contribution

This article reviews some major episodes in the history of the spatial isomorphism problem of dynamical systems theory (ergodic theory). In particular, by analysing, both systematically and in historical context, a hitherto unpublished letter written in 1941 by John von Neumann to Stanislaw Ulam, this article clarifies von Neumann’s contribution to discovering the relationship between spatial isomorphism and spectral isomorphism. The main message of the article is that von Neumann’s argument described in his letter to Ulam is the very first proof that spatial isomorphism and spectral isomorphism are not equivalent because spectral isomorphism is weaker than spatial isomorphism: von Neumann shows that spectrally isomorphic ergodic dynamical systems with mixed spectra need not be spatially isomorphic.     

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.