Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality risk estimates

The Radiation Effects Research Foundation has recently implemented a new dosimetry system, DS02, to replace the previous system, DS86. This paper assesses the effect of the change on risk estimates for radiation-related solid cancer and leukemia mortality. The changes in dose estimates were smaller than many had anticipated, with the primary systematic change being an increase of about 10% in gamma-ray estimates for both cities. In particular, an anticipated large increase of the neutron component in Hiroshima for low-dose survivors did not materialize. However, DS02 improves on DS86 in many details, including the specifics of the radiation released by the bombs and the effects of shielding by structures and terrain. The data used here extend the last reported follow-up for solid cancers by 3 years, with a total of 10,085 deaths, and extends the follow-up for leukemia by 10 years, with a total of 296 deaths. For both solid cancer and leukemia, estimated age-time patterns and sex difference are virtually unchanged by the dosimetry revision. The estimates of solid-cancer radiation risk per sievert and the curvilinear dose response for leukemia are both decreased by about 8% by the dosimetry revision, due to the increase in the gamma-ray dose estimates. The apparent shape of the dose response is virtually unchanged by the dosimetry revision, but for solid cancers, the additional 3 years of follow-up has some effect. In particular, there is for the first time a statistically significant upward curvature for solid cancer on the restricted dose range 0-2 Sv. However, the low-dose slope of a linear-quadratic fit to that dose range should probably not be relied on for risk estimation, since that is substantially smaller than the linear slopes on ranges 0-1 Sv, 0-0.5 Sv, and 0- 0.25 Sv. Although it was anticipated that the new dosimetry system might reduce some apparent dose overestimates for Nagasaki factory workers, this did not materialize, and factory workers have significantly lower risk estimates. Whether or not one makes allowance for this, there is no statistically significant city difference in the estimated cancer risk.     

Topological constraints in nucleic acid hybridization kinetics

A theoretical examination of kinetic mechanisms for forming knots and links in nucleic acid structures suggests that molecules involving base pairs between loops are likely to become topologically trapped in persistent frustrated states through the mechanism of ‘helix-driven wrapping’. Augmentation of the state space to include both secondary structure and topology in describing the free energy landscape illustrates the potential for topological effects to influence the kinetics and function of nucleic acid strands. An experimental study of metastable complementary ‘kissing hairpins’ demonstrates that the topological constraint of zero linking number between the loops effectively prevents conversion to the minimum free energy helical state. Introduction of short catalyst strands that break the topological constraint causes rapid conversion to full duplex.     

ZRANK: reranking protein docking predictions with an optimized energy function

Protein-protein docking requires fast and effective methods to quickly discriminate correct from incorrect predictions generated by initial-stage docking. We have developed and tested a scoring function that utilizes detailed electrostatics, van der Waals, and desolvation to rescore initial-stage docking predictions. Weights for the scoring terms were optimized for a set of test cases, and this optimized function was then tested on an independent set of nonredundant cases. This program, named ZRANK, is shown to significantly improve the success rate over the initial ZDOCK rankings across a large benchmark. The amount of test cases with No. 1 ranked hits increased from 2 to 11 and from 6 to 12 when predictions from two ZDOCK versions were considered. ZRANK can be applied either as a refinement protocol in itself or as a preprocessing stage to enrich the well-ranked hits prior to further refinement.     

Individual flowering phenology shapes plant–pollinator interactions across ecological scales affecting plant reproduction

The balance of pollination competition and facilitation among co‐flowering plants and abiotic resource availability can modify plant species and individual reproduction. Floral resource succession and spatial heterogeneity modulate plant–pollinator interactions across ecological scales (individual plant, local assemblage, and interaction network of agroecological infrastructure across the farm). Intraspecific variation in flowering phenology can modulate the precise level of spatio‐temporal heterogeneity in floral resources, pollen donor density, and pollinator interactions that a plant individual is exposed to, thereby affecting reproduction. We tested how abiotic resources and multi‐scale plant–pollinator interactions affected individual plant seed set modulated by intraspecific variation in flowering phenology and spatio‐temporal floral heterogeneity arising from agroecological infrastructure. We transplanted two focal insect‐pollinated plant species (Cyanus segetum and Centaurea jacea, n = 288) into agroecological infrastructure (10 sown wildflower and six legume–grass strips) across a farm‐scale experiment (125 ha). We applied an individual‐based phenologically explicit approach to match precisely the flowering period of plant individuals to the concomitant level of spatio‐temporal heterogeneity in plant–pollinator interactions, potential pollen donors, floral resources, and abiotic conditions (temperature, water, and nitrogen). Individual plant attractiveness, assemblage floral density, and conspecific pollen donor density (C. jacea) improved seed set. Network linkage density increased focal species seed set and modified the effect of local assemblage richness and abundance on C. segetum. Mutual dependence on pollinators in networks increased C. segetum seed set, while C. jacea seed set was greatest where both specialization on pollinators and mutual dependence was high. Abiotic conditions were of little or no importance to seed set. Intra‐ and interspecific plant–pollinator interactions respond to spatio‐temporal heterogeneity arising from agroecological management affecting wild plant species reproduction. The interplay of pollinator interactions within and between ecological scales affecting seed set implies a co‐occurrence of pollinator‐mediated facilitative and competitive interactions among plant species and individuals.     

Purification and receptor binding properties of complexes between lutropin and monovalent antibodies against its alpha subunit.

A complex between bovine lutropin (LH) and monovalent antibodies (Fab fragments) directed against its alpha subunit, which is common to the glycoprotein hormones, has been purified by gel filtration and chromatography on concanavalin A-Sepharose. The complex is heterogenous with respect to molecular size; 70--80% of the hormone is complexed with either two or three Fab fragments. The LH-Fab alpha complexes retain only about 13% receptor binding activity as compared to LH when measured in a radioligand receptor assay in which the radiolabeled ligand is human choriogonadotropin. (Use of the human hormone as labeled ligand permits direct measurement of competition between receptor and the bovine complex because the alpha portion of the human hormone does not cross react significantly with antibodies directed against bovine alpha subunits.) Complex formation does not lead to dissociation of the lutropin into its subunits, as shown with a homologous LH-beta immunoassay which distinguishes free beta subunit from intact LH. Complexing of LH with Fab-alpha fragments also causes little or no change in the affinity of the hormone's beta subunit for anti-LH-beta antibodies indicating that significant changes in beta subunit conformation did not occur. The data show that at least two well-separated antigenic regions on the alpha subunit are exposed to the surface in the intact hormone. They are also in agreement with the proposal that the loss of binding activity to receptor is due to steric effects rather than to changes in conformation or dissociation, and that there may be sites on the alpha subunit which interact directly with the receptor.     

Stimulation of sodium-calcium exchange by cholesterol incorporation into isolated cardiac sarcolemmal vesicles

Modification of the cholesterol content of highly purified cardiac sarcolemma from dog ventricles was accomplished by incubation with phosphatidylcholine liposomes containing various amounts of cholesterol. The degree of cholesterol enrichment could be varied by changing the liposomal cholesterol/phospholipid ratio or varying the liposome-membrane incubation time. Na+-Ca2+ exchange measured in cholesterol-enriched sarcolemmal vesicles was increased up to 48% over control values. The stimulation of Na+-Ca2+ exchange was associated with an increased affinity of the exchanger for Ca2+ (Km = 17 microM compared with Km = 22 microM for control preparations). Na+-Ca2+ exchange measured in cholesterol-depleted membrane preparations was decreased by 15%. This depressed activity was associated with a decreased affinity of the exchanger for Ca2+ (Km = 27 microM). These changes were not due to either a change in membrane permeability to Ca2+ or an increase in the amount of Ca2+ bound to sarcolemmal vesicles. The stimulating effect of cholesterol enrichment was specific to the Na+-Ca2+ exchange process since sarcolemmal Ca2+-Mg2+ ATPase activity was depressed 40% by cholesterol enrichment. Further, K+-p-nitrophenylphosphatase and Na+-K+ ATPase activities were depressed in both cholesterol-depleted and cholesterol-enriched sarcolemmal vesicles. In situ oxidation of membrane cholesterol completely eliminated Na+-Ca2+ exchange. These results suggest that cholesterol is intimately associated with Na+-Ca2+ exchange and may interact with the exchange protein and modulate its activity.     

Metapopulation dynamics and foraging plasticity in a highly vagile seabird,the southern rockhopper penguin

Population connectivity is driven by individual dispersal potential and modulated by natal philopatry. In seabirds, high vagility facilitates dispersal yet philopatry is also common, with foraging area overlap often correlated with population connectivity. We assess the interplay between these processes by studying past and current connectivity and foraging niche overlap among southern rockhopper penguin colonies of the coast of southern South America using genomic and stable isotope analyses. We found two distinct genetic clusters and detected low admixture between northern and southern colonies. Stable isotope analysis indicated niche variability between colonies, with Malvinas/Falklands colonies encompassing the species entire isotopic foraging niche, while the remaining colonies had smaller, nonoverlapping niches. A recently founded colony in continental Patagonia differed in isotopic niche width and position with Malvinas/Falklands colonies, its genetically identified founder population, suggesting the exploitation of novel foraging areas and/or prey items. Additionally, dispersing individuals found dead across the Patagonian shore in an unusual mortality event were also assigned to the northern cluster, suggesting northern individuals reach southern localities, but do not breed in these colonies. Facilitated by variability in foraging strategies, and especially during unfavorable conditions, the number of dispersing individuals may increase and enhance the probability of founding new colonies. Metapopulation demographic dynamics in seabirds should account for interannual variability in dispersal behavior and pay special attention to extreme climatic events, classically related to negative effects on population trends.