A note on diagrams for turning-point diagnostics

A new diagram for discriminating a forecasting technique's history with respect to the two types of turning-point errors, missed turns and false signals is presented. This diagram extends Theil's original prediction-realization (P-R) presentation so that each of the four quadrants and the axes locates a distinct type of forecasting error or correct forecast, thus reducing much of the former ambiguity. This improvement is accomplished without the loss of any information.     

Sodium-dependence of sustained force in potassium contracture of cat ventricle

Summary Following exposure to low-Na solution, the initial phase of K-contracture in cat ventricle is prominent while the second (sustained) phase is markedly attenuated. Monensin, a Na-specific ionophore, enhances the second phase of K-contracture following exposure to low-Na solution.This study is supported by NIH grant HL-19044 and a Grantin-Aid from the American Heart Association-Greater Miami Affiliate.The authors wish to thank Ms Diane Rodman for invaluable technical assistance.     

Cytonuclear genomic dissociation in African elephant species

African forest and savanna elephants are distinct species separated by a hybrid zone. Because hybridization can affect the systematic and conservation status of populations, we examined gene flow between forest and savanna elephants at 21 African locations. We detected cytonuclear dissociation, indicative of different evolutionary histories for nuclear and mitochondrial genomes. Both paternally (n = 205 males) and biparentally (n = 2,123 X-chromosome segments) inherited gene sequences indicated that there was deep genetic separation between forest and savanna elephants. Yet in some savanna locales distant from present-day forest habitats, many individuals with savanna-specific nuclear genotypes carried maternally transmitted forest elephant mitochondrial DNA. This extreme cytonuclear dissociation implies that there were ancient episodes of hybridization between forest females and savanna males, which are larger and reproductively dominant to forest or hybrid males. Recurrent backcrossing of female hybrids to savanna bulls replaced the forest nuclear genome. The persistence of residual forest elephant mitochondria in savanna elephant herds renders evolutionary interpretations based on mitochondrial DNA alone misleading and preserves a genomic record of ancient habitat changes.     

The melanocyte differentiation program predisposes to metastasis after neoplastic transformation

The aggressive clinical behavior of melanoma suggests that the developmental origins of melanocytes in the neural crest might be relevant to their metastatic propensity. Here we show that primary human melanocytes, transformed using a specific set of introduced genes, form melanomas that frequently metastasize to multiple secondary sites, whereas human fibroblasts and epithelial cells transformed using an identical set of genes generate primary tumors that rarely do so. Notably, these melanomas have a metastasis spectrum similar to that observed in humans with melanoma. These observations indicate that part of the metastatic proclivity of melanoma is attributable to lineage-specific factors expressed in melanocytes and not in other cell types analyzed. Analysis of microarray data from human nevi shows that the expression pattern of Slug, a master regulator of neural crest cell specification and migration, correlates with those of other genes that are important for neural crest cell migrations during development. Moreover, Slug is required for the metastasis of the transformed melanoma cells. These findings indicate that melanocyte-specific factors present before neoplastic transformation can have a pivotal role in governing melanoma progression.     

Lipid-protein interactions in double-layered two-dimensional AQP0 crystals

Lens-specific aquaporin-0 (AQP0) functions as a specific water pore and forms the thin junctions between fibre cells. Here we describe a 1.9 A resolution structure of junctional AQP0, determined by electron crystallography of double-layered two-dimensional crystals. Comparison of junctional and non-junctional AQP0 structures shows that junction formation depends on a conformational switch in an extracellular loop, which may result from cleavage of the cytoplasmic amino and carboxy termini. In the centre of the water pathway, the closed pore in junctional AQP0 retains only three water molecules, which are too widely spaced to form hydrogen bonds with each other. Packing interactions between AQP0 tetramers in the crystalline array are mediated by lipid molecules, which assume preferred conformations. We were therefore able to build an atomic model for the lipid bilayer surrounding the AQP0 tetramers, and we describe lipid-protein interactions.     

Changes in carbon dioxide during an oceanic anoxic event linked to intrusion into Gondwana coals

The marine sedimentary record exhibits evidence for episodes of enhanced organic carbon burial known as 'oceanic anoxic events' (OAEs). They are characterized by carbon-isotope excursions in marine and terrestrial reservoirs and mass extinction of marine faunas. Causal mechanisms for the enhancement of organic carbon burial during OAEs are still debated, but it is thought that such events should draw down significant quantities of atmospheric carbon dioxide. In the case of the Toarcian OAE (approximately 183 million years ago), a short-lived negative carbon-isotope excursion in oceanic and terrestrial reservoirs has been interpreted to indicate raised atmospheric carbon dioxide caused by oxidation of methane catastrophically released from either marine gas hydrates or magma-intruded organic-rich rocks. Here we test these two leading hypotheses for a negative carbon isotopic excursion marking the initiation of the Toarcian OAE using a high-resolution atmospheric carbon dioxide record obtained from fossil leaf stomatal frequency. We find that coincident with the negative carbon-isotope excursion carbon dioxide is first drawn down by 350 +/- 100 p.p.m.v. and then abruptly elevated by 1,200 +/- 400 p.p.m.v, and infer a global cooling and greenhouse warming of 2.5 +/- 0.1 degrees C and 6.5 +/- 1 degrees C, respectively. The pattern and magnitude of carbon dioxide change are difficult to reconcile with catastrophic input of isotopically light methane from hydrates as the cause of the negative isotopic signal. Our carbon dioxide record better supports a magma-intrusion hypothesis, and suggests that injection of isotopically light carbon from the release of thermogenic methane occurred owing to the intrusion of Gondwana coals by Toarcian-aged Karoo-Ferrar dolerites.