Lead isotopes reveal bilateral asymmetry and vertical continuity in the Hawaiian mantle plume.

The two parallel chains of Hawaiian volcanoes ('Loa' and 'Kea') are known to have statistically different but overlapping radiogenic isotope characteristics. This has been explained by a model of a concentrically zoned mantle plume, where the Kea chain preferentially samples a more peripheral portion of the plume. Using high-precision lead isotope data for both centrally and peripherally located volcanoes, we show here that the two trends have very little compositional overlap and instead reveal bilateral, non-concentric plume zones, probably derived from the plume source in the mantle. On a smaller scale, along the Kea chain, there are isotopic differences between the youngest lavas from the Mauna Kea and Kilauea volcanoes, but the 550-thousand-year-old Mauna Kea lavas are isotopically identical to Kilauea lavas, consistent with Mauna Kea's position relative to the plume, which was then similar to that of present-day Kilauea. We therefore conclude that narrow (less than 50 kilometres wide) compositional streaks, as well as the larger-scale bilateral zonation, are vertically continuous over tens to hundreds of kilometres within the plume.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Future development of biologically relevant dosimetry.

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented.

Changing pattern of prevalence of insulin resistance in Psammomys obesus, a model of nutritionally induced type 2 diabetes.

Psammomys obesus (a desert gerbil, nicknamed the "sand rat") with innate insulin resistance was transferred to a high-energy (HE) diet at a young (8 to 20 weeks) and older (38 to 45 weeks) age. The young Psammomys progressed to in vivo insulin resistance, followed by pronounced hyperglycemia and hyperinsulinemia, as described previously. Analysis of the time dependency of these changes in response to the HE diet showed that the increase in serum glucose preceded the increase in insulin and plateaued earlier, reverting to normal together with insulin in the older Psammomys. Implants releasing insulin 2 IU/24 h did not induce appreciable hypoglycemia, a decrease in free fatty acids (FFAs), or a suppression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity in young animals after 5 hours, despite a markedly increased circulating insulin. However, in the older Psammomys, the exogenous hyperinsulinemia produced a significant decline in serum glucose and FFA and a suppression of hepatic PEPCK activity. A euglycemic-hyperinsulinemic clamp confirmed that hepatic glucose production (HGP) was lower in older Psammomys versus the young and was almost completely abolished by insulin (from 5.6 +/- 0.6 to 0.2 +/- 0.1 mg x min(-1) x kg(-1) v 10.9 +/- 0.8 to 3.9 +/- 0.5 mg x min(-1) x kg(-1)). This indicates that HGP, rather than glucose underutilization, was the main contributor to the hyperglycemia and that the hepatic insulin resistance in Psammomys is attenuated with age. In relation to the human condition, these findings point out that while the type 2 diabetes prevalence in Western populations generally increases with age, the excessive nutritional intake in high-risk populations produces a pattern of diabetes prevalence that tapers off with age. As such, the nutritionally induced diabetes in Psammomys represents a similar model for a differing pattern of the age-related prevalence of diabetes.

Pathophysiology of sleep-dependent memory consolidation processes in children.

Cognitive impairments are often associated with abnormal sleep activity in developmental disorders and pathologies of childhood. Besides, accumulated evidence indicates that post-training sleep benefits to the consolidation of recently learned information in healthy adults and children. Although sleep-dependent consolidation effects in children are clearly established for declarative memories, they remain more debated in the procedural memory domain. Nowadays, recent experimental data suggest close interactions between the development of sleep-dependent plasticity markers, cortical maturation and cognition in children. In the present review, we propose that studying sleep and memory consolidation processes in developmental disorders and acquired childhood pathologies can provide novel, enlightening clues to understand the pathophysiological mechanisms subtending the disruption of long-term cerebral plasticity processes eventually leading to cognitive and learning deficits in children.

Impact of focal interictal epileptiform discharges on behaviour and cognition in children.

It is hypothesised that focal interictal epileptiform discharges (IED) may exert a deleterious effect on behaviour and cognition in children. This hypothesis is supported by the abnormally high prevalence of IED in several developmental disorders, like specific language impairment, and of cognitive and behavioural deficits in epileptic children after excluding confounding factors such as underlying structural brain lesions, drug effects, or the occurrence of frequent or prolonged epileptic seizures. Neurophysiological and functional neuroimaging evidence suggests that IED may impact cognition through either transient effects on brain processing mechanisms, or through more long-lasting effects leading to prolonged inhibition of brain areas distant from but connected with the epileptic focus (i.e. remote inhibition effect). Sustained IED may also impair sleep-related learning consolidation processes. Nowadays, the benefits of anti-epileptic treatment aimed at reducing IED are not established except in specific situations like epileptic encephalopathies with continuous spike and waves during slow-wave sleep. Well-designed pharmacological studies are still necessary to address this issue.

Design concept for a novel SQUID-based microdosemeter.

The interest in proton and ion-beam therapy has increased substantially in recent years, leading the Bureau International des Poids et Mesures to recommend that a new quantity be defined to account for the biological effect of treatment modalities used in the radiotherapy. In response, we have begun work on the design of a new microbolometer based on the inductive superconducting transition-edge detector (ISTED) designed at the National Physical Laboratory. Our work aims to expand the use of the ISTED from its current use as an infra-red detector to the measurement of energy deposition of photons, hadrons and ions by incorporating a tissue-equivalent absorber. We present here the work carried out till date, including the detection of single visible photons, with an energy resolution of 0.2 eV and a time response of a few microseconds, using a 15-µm Superconducting QUantum Interference Device operating at 9 K. We also describe thermal computational modelling carried out for a simple ISTED absorber. Finally, we discuss the work currently in progress and that to be carried out before the detector is realised.

The binding interface database (BID): a compilation of amino acid hot spots in protein interfaces.

SUMMARY: To make information about protein interactive function easily accessible, we are mining the primary scientific literature for detailed data about protein interfaces. The Binding Interface Database (BID) organizes the vast amount of protein interaction information into tables, graphical contact maps and descriptive functional profiles. Currently data on 170 interacting protein pairs are available with over 1300 mutations described. AVAILABILITY: The BID database is freely available at http://tsailab.org/BID/ To have your protein of interest entered, contact Tiffany Fischer (tiffbrink@neo.tamu.edu) or Jerry Tsai at the email below