Evolutionary differentiation within the northern Great Basin pocket gopher, Thomomys townsendii I. Morphological variation

Geographic and nongeographic variation in morphology was examined in Thomomys townsendii . A univariate analysis of external and cranial characters from a large population sample (66 adults; fusion of cranial sutures used as aging criteria) was used to assess variation among three adult age classes and between sexes. Only minor variation is apparent among age classes; however, sexual dimorphism is pronounced. Univariate and multivariate techniques were used to analyze external and cranial measurements and pelage characters for adults throughout the species range. These analyses show little to support the seven subspecific designations recognized by Davis (1937). The general pattern is one of homogeneity throughout the range of Thomomys townsendii . With the possible exception of T. t. nevadensis samples, current subspecies are not defined as morphological units. In fact, differentiation is found among populations within some subspecies. The most apparent pattern seen in these analyses is the divergence between the Humboldt River (including Honey Lake Valley samples) and Snake River systems. These results will be considered with those of a companion paper on the genetic variation in this species to more adequately assess the patterns of differentiation in Thomomys townsendii .     

Business Cycle Forecasts and their Implications for High Frequency Stock Market Returns

This article contributes to the literature on business cycle forecasts and their impact on asset prices by investigating how the 15‐second Xetra DAX returns reflect the monthly announcements of the two best‐known business cycle forecasts for Germany, i.e., the Ifo Business Climate Index and the ZEW Indicator of Economic Sentiment. The analysis disentangles ‘good’ macroeconomics news from ‘bad’ news and, simultaneously, considers time intervals with and without confounding announcements from other sources. Releases from both institutes lead to an immediate response of returns occurring 15 seconds after the announcements, i.e. within the first possible time interval. Announcements of both institutes are also clearly and immediately reflected in the volatility, which remains at a significantly higher level for approximately 2 minutes. Findings can be used to improve high‐frequency forecasts in stock markets. Copyright © 2011 John Wiley & Sons, Ltd.     

Biodiversity loss and its impact on humanity

The most unique feature of Earth is the existence of life, and the most extraordinary feature of life is its diversity. Approximately 9 million types of plants, animals, protists and fungi inhabit the Earth. So, too, do 7 billion people. Two decades ago, at the first Earth Summit, the vast majority of the world's nations declared that human actions were dismantling the Earth's ecosystems, eliminating genes, species and biological traits at an alarming rate. This observation led to the question of how such loss of biological diversity will alter the functioning of ecosystems and their ability to provide society with the goods and services needed to prosper.     

Structural basis for iron piracy by pathogenic Neisseria

Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.     

IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics

Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.     

Structure of the carboxy-terminal region of a KCNH channel

The KCNH family of ion channels, comprising ether-à-go-go (EAG), EAG-related gene (ERG), and EAG-like (ELK) K(+)-channel subfamilies, is crucial for repolarization of the cardiac action potential, regulation of neuronal excitability and proliferation of tumour cells. The carboxy-terminal region of KCNH channels contains a cyclic-nucleotide-binding homology domain (CNBHD) and C-linker that couples the CNBHD to the pore. The C-linker/CNBHD is essential for proper function and trafficking of ion channels in the KCNH family. However, despite the importance of the C-linker/CNBHD for the function of KCNH channels, the structural basis of ion-channel regulation by the C-linker/CNBHD is unknown. Here we report the crystal structure of the C-linker/CNBHD of zebrafish ELK channels at 2.2-? resolution. Although the overall structure of the C-linker/CNBHD of ELK channels is similar to the cyclic-nucleotide-binding domain (CNBD) structure of the related hyperpolarization-activated cyclic-nucleotide-modulated (HCN) channels, there are marked differences. Unlike the CNBD of HCN, the CNBHD of ELK displays a negatively charged electrostatic profile that explains the lack of binding and regulation of KCNH channels by cyclic nucleotides. Instead of cyclic nucleotide, the binding pocket is occupied by a short β-strand. Mutations of the β-strand shift the voltage dependence of activation to more depolarized voltages, implicating the β-strand as an intrinsic ligand for the CNBHD of ELK channels. In both ELK and HCN channels the C-linker is the site of virtually all of the intersubunit interactions in the C-terminal region. However, in the zebrafish ELK structure there is a reorientation in the C-linker so that the subunits form dimers instead of tetramers, as observed in HCN channels. These results provide a structural framework for understanding the regulation of ion channels in the KCNH family by the C-linker/CNBHD and may guide the design of specific drugs.     

The bonobo genome compared with the chimpanzee and human genomes

Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other.