Apical protein transport

The plasma membrane of epithelial cells and hepatocytes is divided into two separate membrane compartments, the apical and the basolateral domain. This polarity is maintained by intracellular machinery that directs newly synthesized material into the correct target membrane. Apical protein sorting and trafficking require specific signals and different intracellular routes to the cell surface. Some of them depend on the integrity of sphingolipid/cholesterol-enriched membrane microdomains named ‘lipid rafts’, others use separate transport platforms. Certain characteristics of the heterogeneous population of apical sorting signals are described in this review and cellular factors associated with sorting and transport mechanisms are discussed. Received 5 May 2006; received after revision 12 June 2006; accepted 11 July 2006     

Action Research in Inter-Organisational Networks: Impartial Studies or the Trojan Horse?

This article addresses the distinct ethical challenges of action research in inter-organisational projects. Traditionally, the literature on action research has distinguished between two researcher roles: The problem-solver and the observer. Based on an action research project in a Danish inter-organisational network, a third role as legitimiser is identified as an ethical challenge. Potentially, the legitimacy that the researchers carry as academic knowledge-generating actors may be used by a particular company to involve other companies in the network. Thus, the researchers may be perceived as bringing into the other organisations a Trojan Horse containing the interests of this particular company. Lack of clarity in defining the role of the action researcher may thus jeopardise the trustworthiness of the researchers and the action research project. On the basis of the case study analysis, the article develops a number of preliminary points of ethical consideration for future research analysis.     

Recent contributions of glaciers and ice caps to sea level rise

Glaciers and ice caps (GICs) are important contributors to present-day global mean sea level rise. Most previous global mass balance estimates for GICs rely on extrapolation of sparse mass balance measurements representing only a small fraction of the GIC area, leaving their overall contribution to sea level rise unclear. Here we show that GICs, excluding the Greenland and Antarctic peripheral GICs, lost mass at a rate of 148?±?30?Gt?yr(-1) from January 2003 to December 2010, contributing 0.41?±?0.08?mm?yr(-1) to sea level rise. Our results are based on a global, simultaneous inversion of monthly GRACE-derived satellite gravity fields, from which we calculate the mass change over all ice-covered regions greater in area than 100?km(2). The GIC rate for 2003-2010 is about 30 per cent smaller than the previous mass balance estimate that most closely matches our study period. The high mountains of Asia, in particular, show a mass loss of only 4?±?20?Gt?yr(-1) for 2003-2010, compared with 47-55?Gt?yr(-1) in previously published estimates. For completeness, we also estimate that the Greenland and Antarctic ice sheets, including their peripheral GICs, contributed 1.06?±?0.19?mm?yr(-1) to sea level rise over the same time period. The total contribution to sea level rise from all ice-covered regions is thus 1.48?±?0.26?mm?(-1), which agrees well with independent estimates of sea level rise originating from land ice loss and other terrestrial sources.     

Glial versus melanocyte cell fate choice: Schwann cell precursors as a cellular origin of melanocytes

Melanocytes and Schwann cells are derived from the multipotent population of neural crest cells. Although both cell types were thought to be generated through completely distinct pathways and molecular processes, a recent study has revealed that these different cell types are intimately interconnected far beyond previously postulated limits in that they share a common post-neural crest progenitor, i.e. the Schwann cell precursor. This finding raises interesting questions about the lineage relationships of hitherto unrelated cell types such as melanocytes and Schwann cells, and may provide clinical insights into mechanisms of pigmentation disorders and for cancer involving Schwann cells and melanocytes.     

DNA、字与模型：异常字统计学

大约在15年的时间里，生物学经历了巨大的变化。而这些变化中最重要的变化是DNA序列。计算生物学中一个重要的问题是鉴别短的DNA序列（它在数学上称为字），而这些短序列都具有生物学功能。一种鉴别方法就是决定一个特定的字是否纯粹是随机的，还是由于它出现的频率或所在的位置而具有统计学意义的。     

Forecasting market impact costs and identifying expensive trades

Often, a relatively small group of trades causes the major part of the trading costs on an investment portfolio. Consequently, reducing the trading costs of comparatively few expensive trades would already result in substantial savings on total trading costs. Since trading costs depend to some extent on steering variables, investors can try to lower trading costs by carefully controlling these factors. As a first step in this direction, this paper focuses on the identification of expensive trades before actual trading takes place. However, forecasting market impact costs appears notoriously difficult and traditional methods fail. Therefore, we propose two alternative methods to form expectations about future trading costs. Applied to the equity trades of the world's second largest pension fund, both methods succeed in filtering out a considerable number of trades with high trading costs and substantially outperform no‐skill prediction methods. Copyright © 2008 John Wiley & Sons, Ltd.     

An oxygen-regulated switch in the protein synthesis machinery

Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. The initial step of protein synthesis is the binding of the eukaryotic translation initiation factor 4E (eIF4E) to the 7-methylguanosine (m(7)-GpppG) 5'?cap of messenger RNAs. Low oxygen tension (hypoxia) represses cap-mediated translation by sequestering eIF4E through mammalian target of rapamycin (mTOR)-dependent mechanisms. Although the internal ribosome entry site is an alternative translation initiation mechanism, this pathway alone cannot account for the translational capacity of hypoxic cells. This raises a fundamental question in biology as to how proteins are synthesized in periods of oxygen scarcity and eIF4E inhibition. Here we describe an oxygen-regulated translation initiation complex that mediates selective cap-dependent protein synthesis. We show that hypoxia stimulates the formation of a complex that includes the oxygen-regulated hypoxia-inducible factor 2α (HIF-2α), the RNA-binding protein RBM4 and the cap-binding eIF4E2, an eIF4E homologue. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis identified an RNA hypoxia response element (rHRE) that recruits this complex to a wide array of mRNAs, including that encoding the epidermal growth factor receptor. Once assembled at the rHRE, the HIF-2α-RBM4-eIF4E2 complex captures the 5'?cap and targets mRNAs to polysomes for active translation, thereby evading hypoxia-induced repression of protein synthesis. These findings demonstrate that cells have evolved a program by which oxygen tension switches the basic translation initiation machinery.