The microRNA-producing enzyme Dicer1 is essential for zebrafish development

MicroRNAs (miRNAs) are produced by the Dicer1 enzyme; the role of Dicer1 in vertebrate development is unknown. Here we report target-selected inactivation of the dicer1 gene in zebrafish. We observed an initial build-up of miRNA levels, produced by maternal Dicer1, in homozygous dicer1 mutants, but miRNA accumulation stopped after a few days. This resulted in developmental arrest around day 10. These results indicate that miRNA-producing Dicer1 is essential for vertebrate development.     

Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis

The effect of high-density lipoprotein (HDL) in protecting against atherosclerosis is usually attributed to its role in 'reverse cholesterol transport'. In this process, HDL particles mediate the efflux and the transport of cholesterol from peripheral cells to the liver for further metabolism and bile excretion. Thus, cell-surface receptors for HDL on hepatocytes are chief partners in the regulation of cholesterol homeostasis. A high-affinity HDL receptor for apolipoprotein A-I (apoA-I) was previously identified on the surface of hepatocytes. Here we show that this receptor is identical to the beta-chain of ATP synthase, a principal protein complex of the mitochondrial inner membrane. Different experimental approaches confirm this ectopic localization of components of the ATP synthase complex and the presence of ATP hydrolase activity at the hepatocyte cell surface. Receptor stimulation by apoA-I triggers the endocytosis of holo-HDL particles (protein plus lipid) by a mechanism that depends strictly on the generation of ADP. We confirm this effect on endocytosis in perfused rat liver ex vivo by using a specific inhibitor of ATP synthase. Thus, membrane-bound ATP synthase has a previously unsuspected role in modulating the concentrations of extracellular ADP and is regulated by a principal plasma apolipoprotein.     

Vascular growth factors in neuropsychiatry

Recent advances in understanding the cellular and molecular basis of psychiatric illnesses have shed light on the important role played by trophic factors in modulating functional parameters associated with disease causality and drug action. Disease mechanisms are now thought to involve multiple cell types, including neurons and endothelial cells. These functionally distinct but interactively coupled cell types engage in cellular cross talk via shared and common signaling molecules. Dysregulation in their cellular signaling pathways influences brain function and alters behavioral performance. Multifunctional trophic factors such as VEGF and EPO that possess both neurotrophic and angiogenic actions are of particular interest due to their ability to rescue structural and plasticity deficits in neurons and vasculature. Obtaining insight into the behavioral, cellular and molecular actions of multi-functional trophic factors has the potential to open new and transformative therapeutic approaches.     

An information systems profession to meet the challenge of the 2000s

Technical proficiency has not enabled our profession to deliver value for money in terms of improved organisational performance. Evidence of this failure is adduced. The recommended change is to approach organisations as the information systems we develop. To achieve this we need a better understanding of information, the key resource, better ways of modelling organisations in information terms, and new tools for analysis, design, and systems development. Semiotics, the theory of sign, provides a suitable framework in which to make “information” and related concepts more precise. A semiotics of organisations leads to modelling them as systems of social norms from which information requirements can be logically deduced. This approach yields methods and tools for analyzing and designing the social, pragmatic, and semantic aspects of information systems that receive little attention in our current methodologies.     

生物医学方法指南

本书介绍了生物医学几个不同分支学科中有代表性的共同的研究方法。这些方法不仅使用最广泛，而且也是最基本的方法。书中概述了所介绍方法的目的、局限性，并提供了适用的替代方法。     

A hybrid forecasting approach for piece‐wise stationary time series

We consider the problem of forecasting a stationary time series when there is an unknown mean break close to the forecast origin. Based on the intercept‐correction methods suggested by Clements and Hendry (1998) and Bewley (2003), a hybrid approach is introduced, where the break and break point are treated in a Bayesian fashion. The hyperparameters of the priors are determined by maximizing the marginal density of the data. The distributions of the proposed forecasts are derived. Different intercept‐correction methods are compared using simulation experiments. Our hybrid approach compares favorably with both the uncorrected and the intercept‐corrected forecasts. Copyright © 2006 John Wiley & Sons, Ltd.     

Laser microbeam-induced fixation for electronmicroscopy: Visualization of transient developmental features in nematode embryos

Summary In order to study development of embryos ofCaenorhabditis elegans at an ultrastructural level, a new method of fixation has been developed. With a laser microbeam coupled to a microscope the impermeable eggshell is punctured to allow penetration of the fixative. At specific stages of embryogenesis further development can be arrested at will under visual control. As fixation occurs instantaneously, transient events (e.g. different phases of mitosis and cytokinesis) can be visualized.