Role for mouse macrophage IgG Fc receptor as ligand-dependent ion channel

The interaction of ligands with the mouse macrophage Fc receptor which binds IgG2b and IgG1 immune complexes (FcR gamma 2b/gamma 1) triggers phagocytosis and secretion of various mediators of inflammation. FcR gamma 2b/gamma 1 has been purified using a monoclonal anti-FcR antibody, 2.4G2, and seems to be an integral membrane glycoprotein of molecular weight (Mr) 47,000-60,000 (ref. 6). Monoclonal antibody 2.4G2 is suitable as a tool for functional studies of FcR because it binds to a functional site of the receptor and induces cellular responses that are normally associated with the occupied receptor. We reported previously that binding of ligands to the macrophage FcR resulted in Na+/K+ ion fluxes through the plasma membrane, and that similar ion fluxes were observed in proteoliposomes containing reconstituted FcR. We have now incorporated FcR into planar lipid bilayers and report here that FcR gamma 2b/gamma 1 forms ligand-dependent cation-selective ion channels, with a conductance of 60 pS in 1 M KCl and an average open channel lifetime of 250 ms. The conductance decays to baseline levels within a few minutes. These results suggest a receptor-ionophore model for the signalling of phagocytosis and inflammatory responses.     

A diacylglycerol analogue reduces neuronal calcium currents independently of protein kinase C activation

Diacylglycerol analogues (for example 1,2-oleoylacetylglycerol, OAG) and phorbol esters are activators of protein kinase C, and have been widely used to study the function of this enzyme in both intact cells and cell-free preparations. Electrophysiological studies have shown that these activators can either depress or increase Ca2+ currents, or decrease K+ currents when applied outside the cell. It has been assumed that these effects are mediated by protein kinase C activation. Here we report that micromolar levels of OAG and phorbol esters depress Ca2+ currents in chick sensory neurons independently of their effect as activators of protein kinase C. The depression of the Ca2+ current is rapid and is unaffected by intracellular application of the protein kinase C inhibitors staurosporin, sphingosine and H-7. Furthermore, the activators were ineffective when applied intracellularly, indicating that their site of action is on the outside of the membrane.     

Forecasting Errors,Directional Accuracy and Profitability of Currency Trading: The Case of EUR/USD Exchange Rate

We provide a comprehensive study of out‐of‐sample forecasts for the EUR/USD exchange rate based on multivariate macroeconomic models and forecast combinations. We use profit maximization measures based on directional accuracy and trading strategies in addition to standard loss minimization measures. When comparing predictive accuracy and profit measures, data snooping bias free tests are used. The results indicate that forecast combinations, in particular those based on principal components of forecasts, help to improve over benchmark trading strategies, although the excess return per unit of deviation is limited. Copyright © 2016 John Wiley & Sons, Ltd.     

The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond

The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF's ability to swiftly distribute signals across vast distances in the central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury.     

Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system Junior

The breast cancer resistance protein, also known as ABCG2, is one of the most highly studied ATP-binding cassette (ABC) transporters because of its ability to confer multidrug resistance. The lack of information on the physiological role of ABCG2 in humans severely limits cancer chemotherapeutic approaches targeting this transporter. We report here that ABCG2 comprises the molecular basis of a new blood group system (Junior, Jr) and that individuals of the Jr(a-) blood type have inherited two null alleles of ABCG2. We identified five frameshift and three nonsense mutations in ABCG2. We also show that the prevalence of the Jr(a-) blood type in the Japanese and European Gypsy populations is related to the p.Gln126* and p.Arg236* protein alterations, respectively. The identification of ABCG2(-/-) (Jr(a-)) individuals who appear phenotypically normal is an essential step toward targeting ABCG2 in cancer and also in understanding the physiological and pharmacological roles of this promiscuous transporter in humans.     

Combining forecasts based on multiple encompassing tests in a macroeconomic core system

This paper investigates whether and to what extent multiple encompassing tests may help determine weights for forecast averaging in a standard vector autoregressive setting. To this end we consider a new test‐based procedure, which assigns non‐zero weights to candidate models that add information not covered by other models. The potential benefits of this procedure are explored in extensive Monte Carlo simulations using realistic designs that are adapted to UK and to French macroeconomic data, to which trivariate vector autoregressions (VAR) are fitted. Thus simulations rely on potential data‐generating mechanisms for macroeconomic data rather than on simple but artificial designs. We run two types of forecast ‘competitions’. In the first one, one of the model classes is the trivariate VAR, such that it contains the generating mechanism. In the second specification, none of the competing models contains the true structure. The simulation results show that the performance of test‐based averaging is comparable to uniform weighting of individual models. In one of our role model economies, test‐based averaging achieves advantages in small samples. In larger samples, pure prediction models outperform forecast averages. Copyright © 2010 John Wiley & Sons, Ltd.