The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis:results of a phase II study

This study was designed to assess the potential of the continuous erythropoietin receptor activator (C.E.R.A.) to correct anemia at extended administration intervals in erythropoiesis-stimulating agent-naīve patients with chronic kidney disease (CKD) not on dialysis and to determine its optimal starting dose.

Climate variability drives anchovies and sardines into the North and Baltic Seas

European anchovy (Engraulis encrasicolus) and sardine (Sardina pilchardus) are southern, warm water species that prefer temperatures warmer than those found in boreal waters. After about 40 years of absence, they were again observed in the 1990s in increasing quantities in the North Sea and the Baltic Sea. Whereas global warming probably played a role in these northward migrations, the North Atlantic Oscillation (NAO), the Atlantic Multidecadal Oscillation (AMO) and the contraction of the subpolar gyre were important influences. Sardine re-invaded the North Sea around 1990, probably mainly as a response to warmer temperatures associated with the strengthening of the NAO in the late 1980s. However, increasing numbers of anchovy eggs, larvae, juveniles and adults have been recorded only since the mid-1990s, when, particularly, summer temperatures started to increase. This is probably a result of the complex dynamics of ocean–atmosphere coupling involving changes in North Atlantic current structures, such as the contraction of the subpolar gyre, and dynamics of AMO. Apparently, climate variability drives anchovies and sardines into the North and Baltic Seas. Here, we elucidate the climatic background of the return of anchovies and sardines to the northern European shelf seas and the changes in the North Sea fish community in the mid-1990s in response to climate variability.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Heme oxygenase-1: a metabolic nike

SIGNIFICANCE: Heme degradation, which was described more than 30 years ago, is still very actively explored with many novel discoveries on its role in various disease models every year.

RECENT ADVANCES: The heme oxygenases (HO) are metabolic enzymes that utilize NADPH and oxygen to break apart the heme moiety liberating biliverdin (BV), carbon monoxide (CO), and iron. Heme that is derived from hemoproteins can be toxic to the cells and if not removed immediately, it causes cell apoptosis and local inflammation. Elimination of heme from the milieu enables generation of three products that influences numerous metabolic changes in the cell.

CRITICAL ISSUES: CO has profound effects on mitochondria and cellular respiration and other hemoproteins to which it can bind and affect their function, while BV and bilirubin (BR), the substrate and product of BV, reductase, respectively, are potent antioxidants. Sequestration of iron into ferritin and its recycling in the tissues is a part of the homeodynamic processes that control oxidation-reduction in cellular metabolism. Further, heme is an important component of a number of metabolic enzymes, and, therefore, HO-1 plays an important role in the modulation of cellular bioenergetics.

FUTURE DIRECTIONS: In this review, we describe the cross-talk between heme oxygenase-1 (HO-1) and its products with other metabolic pathways. HO-1, which we have labeled Nike, the goddess who personified victory, dictates triumph over pathophysiologic conditions, including diabetes, ischemia, and cancer.

Cement As a Waste Form for Nuclear Fission Products: The Case of 90Sr and Its Daughters

One of the main challenges faced by the nuclear industry is the long-term confinement of nuclear waste. Because it is inexpensive and easy to manufacture, cement is the material of choice to store large volumes of radioactive materials, in particular the low-level medium-lived fission products. It is therefore of utmost importance to assess the chemical and structural stability of cement containing radioactive species. Here, we use ab initio calculations based on density functional theory (DFT) to study the effects of ⁹⁰Sr insertion and decay in C-S-H (calcium-silicate-hydrate) in order to test the ability of cement to trap and hold this radioactive fission product and to investigate the consequences of its β-decay on the cement paste structure. We show that ⁹⁰Sr is stable when it substitutes the Ca²⁺ ions in C-S-H, and so is its daughter nucleus ⁹⁰Y after β-decay. Interestingly, ⁹⁰Zr, daughter of ⁹⁰Y and final product in the decay sequence, is found to be unstable compared to the bulk phase of the element at zero K but stable when compared to the solvated ion in water. Therefore, cement appears as a suitable waste form for ⁹⁰Sr storage.

Electron-phonon thermalization in a scalable method for real-time quantum dynamics

We present a quantum simulation method that follows the dynamics of out-of-equilibrium many-body systems of electrons and oscillators in real time. Its cost is linear in the number of oscillators and it can probe time scales from attoseconds to hundreds of picoseconds. Contrary to Ehrenfest dynamics, it can thermalize starting from a variety of initial conditions, including electronic population inversion. While an electronic temperature can be defined in terms of a nonequilibrium entropy, a Fermi-Dirac distribution in general emerges only after thermalization. These results can be used to construct a kinetic model of electron-phonon equilibration based on the explicit quantum dynamics.

Introducing the CTA concept

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. © 2013 Elsevier B.V. All rights reserved.