Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia

Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (MIM 123000) was linked to chromosome 5p15.2-p14.1 (ref. 3) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and pathologic calcification, bone mineralization and bone resorption. Here we carry out mutation analysis of ANKH, revealing six different mutations in eight of nine families. The mutations predict single amino acid substitutions, deletions or insertions. Using a helix prediction program, we propose for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of PPi. The mutations occur at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. Our results link the PPi channel ANK with bone formation and remodeling.     

Genetic evidence for Near-Eastern origins of European cattle

The limited ranges of the wild progenitors of many of the primary European domestic species point to their origins further east in Anatolia or the fertile crescent. The wild ox (Bos primigenius), however, ranged widely and it is unknown whether it was domesticated within Europe as one feature of a local contribution to the farming economy. Here we examine mitochondrial DNA control-region sequence variation from 392 extant animals sampled from Europe, Africa and the Near East, and compare this with data from four extinct British wild oxen. The ancient sequences cluster tightly in a phylogenetic analysis and are clearly distinct from modern cattle. Network analysis of modern Bos taurus identifies four star-like clusters of haplotypes, with intra-cluster diversities that approximate to that expected from the time depth of domestic history. Notably, one of these clusters predominates in Europe and is one of three encountered at substantial frequency in the Near East. In contrast, African diversity is almost exclusively composed of a separate haplogroup, which is encountered only rarely elsewhere. These data provide strong support for a derived Near-Eastern origin for European cattle.     

Geographic structure and dynamics of coevolutionary selection

Coevolution of species is one of the major processes organizing the Earth's biodiversity. Recent coevolutionary theory has indicated that the geographic structure of species has the potential to impose powerful and continuing effects on coevolutionary dynamics, if that structure creates selection mosaics and coevolutionary hotspots across landscapes. Here we confirm that current coevolutionary selection in interspecific interactions can be highly divergent across both narrow and broad geographic scales, thereby fueling continuing coevolution of taxa. Study of a widespread plant insect interaction across a broad range of habitats for several years showed that an insect functioning both as a pollinator and a floral parasite can be strongly mutualistic in some habitats but commensal or antagonistic in neighbouring habitats. The results for one of the habitats span seven years, demonstrating that the local structure of coevolutionary selection can remain stable across multiple generations. Conservation of the evolutionary processes maintaining long-term biological diversity may require preservation of the conditions that allow a long-term shifting geographic mosaic of coevolutionary hotspots and coldspots.     

Attack and brood production by the Douglas-fir beetle (Coleoptera: Scolytidae) in Douglas-fir, Pseudotsuga menziesii var. glauca (Pinaceae), following a wildfire

In 1994 ground fire ignited in forests of Douglas-fir, Pseudotsuga menziesii var. glauca (Mirb.) Franco, on Beaver Mountain, Utah. The Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins, attacked a range of moderately fire-injured host conifers in 1995. Logistic regression models run for 1995 data illustrated that 1 year after the fire event the Douglas-fir beetle selected and attacked large-diameter Douglas-fir with 60%-80% bole char, 60%-80% crown volume scorch, and 50%-70% probability of mortality due to fire. In 1996 beetle preference shifted to smallerdiameter trees with lighter fire injury, because most large, fire-damaged conifers were colonized by beetles in 1995. Although beetle populations did not reach outbreak proportions outside the fire boundary, host selection shifted to green trees in 1997 along the burn perimeter. Log linear analysis indicated that increased brood production was conditioned by increased diameter and moderate fire damage to the trees.     

Synchrotron X-ray tomographic microscopy of fossil embryos

Fossilized embryos from the late Neoproterozoic and earliest Phanerozoic have caused much excitement because they preserve the earliest stages of embryology of animals that represent the initial diversification of metazoans. However, the potential of this material has not been fully realized because of reliance on traditional, non-destructive methods that allow analysis of exposed surfaces only, and destructive methods that preserve only a single two-dimensional view of the interior of the specimen. Here, we have applied synchrotron-radiation X-ray tomographic microscopy (SRXTM), obtaining complete three-dimensional recordings at submicrometre resolution. The embryos are preserved by early diagenetic impregnation and encrustation with calcium phosphate, and differences in X-ray attenuation provide information about the distribution of these two diagenetic phases. Three-dimensional visualization of blastomere arrangement and diagenetic cement in cleavage embryos resolves outstanding questions about their nature, including the identity of the columnar blastomeres. The anterior and posterior anatomy of embryos of the bilaterian worm-like Markuelia confirms its position as a scalidophoran, providing new insights into body-plan assembly among constituent phyla. The structure of the developing germ band in another bilaterian, Pseudooides, indicates a unique mode of germ-band development. SRXTM provides a method of non-invasive analysis that rivals the resolution achieved even by destructive methods, probing the very limits of fossilization and providing insight into embryology during the emergence of metazoan phyla.     

Neural population dynamics during reaching

Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from what is known about primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well the analogy between motor and visual cortex holds. Single-neuron responses in motor cortex are complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. Here we find that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behaviour. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate an unexpected yet surprisingly simple structure in the population response. This underlying structure explains many of the confusing features of individual neural responses.     

Initiation of check cell division by trypsin action at the cell surface

Trypsin immobilised on polystyrene beads causes initiation of cell division which cannot be accounted for by trypsin released into the medium or into the cells. Also, initiation by soluble trypsin is inhibited by immobilised soybean trypsin inhibitor. These results demonstrate that trypsin can initiate proliferation at the cell surface.