Trans-Golgi network sorting

The trans-Golgi network (TGN) is a major secretory pathway sorting station that directs newly synthesized proteins to different subcellular destinations. The TGN also receives extracellular materials and recycled molecules from endocytic compartments. In this review, we summarize recent progress on understanding TGN structure and the dynamics of trafficking to and from this compartment. Protein sorting into different transport vesicles requires specific interactions between sorting motifs on the cargo molecules and vesicle coat components that recognize these motifs. Current understanding of the various targeting signals and vesicle coat components that are involved in TGN sorting are discussed, as well as the molecules that participate in retrieval to this compartment in both yeast and mammalian cells. Besides proteins, lipids and lipid-modifying enzymes also participate actively in the formation of secretory vesicles. The possible mechanisms of action of these lipid hydrolases and lipid kinases are discussed. Finally, we summarize the fundamentally different apical and basolateral cell surface delivery mechanisms and the current facts and hypotheses on protein sorting from the TGN into the regulated secretory pathway in neuroendocrine cells. Received 2 November 2000; received after revision 19 February 2001; accepted 19 February 2001     

The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros

The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution.     

Host origin of marrow stromal cells following allogeneic bone marrow transplantation

Although it is generally agreed that stromal cells are important in the regulation of haematopoietic cell development, the origin of these phenotypically diverse cells has been a subject for debate for more than 50 years. Data which support the concept of a separate origin for the haematopoietic stem cell and the marrow stroma are derived from cytogenetic or enzyme marker studies of explanted and expanded stromal cells grown under conditions that do not allow haematopoiesis in vitro. Recent evidence in man and in mouse suggesting that the stromal cells capable of transferring the haematopoietic microenvironment in vitro are transplantable seemingly questions this dichotomy, one interpretation being the existence of a common haematopoietic/stromal 'stem cell'. We used in situ hybridization to discriminate donor cells from host in blood and bone marrow samples obtained from patients with functioning sex-mismatched but HLA-identical allografts. Without exception, marrow-derived stromal cells that proliferate in long-term cultures were found to be of host genotype, whereas the macrophage component of the adherent layer in these cultures originated from the donor.     

Evoked responses and neuronal activity in the lateral geniculate

Résumé Il a paru intéressant de préciser les relations de temps et de phase entre la réponse évoquée massive et la réponse des neurones du corps genouillé latéral. Des microéléctrodes ont été implantées dans le corps genouillé latéral du chat et des réponses ont été évoquées par stimulation visuelle. On a pu démontrer que la probabilité aussi bien que la fréquence de la décharge neuronique varient en raison de la première dérivée de la réponse massive à ondes lentes.

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Aided by grants Nos. NB 07145 and FO5 TW 1017 from the National Institutes of Health.     

Newtonianism in early Enlightenment Germany, c. 1720 to 1750: metaphysics and the critique of dogmatic philosophy

The acceptance of Newton’s ideas and Newtonianism in the early German Enlightenment is usually described as hesitant and slow. Two reasons help to explain this phenomenon. One is that those who might have adopted Newtonian arguments were critics of Wolffianism. These critics, however, drew on indigenous currents of thought, pre-dating the reception of Newton in Germany and independent of Newtonian science. The other reason is that the controversies between Wolffians and their critics focused on metaphysics. Newton’s reputation, however, was that of a mathematician, and one point, on which Wolffians and their opponents agreed, was that mathematics was of no use in the solution of metaphysical questions. The appeal to Newton as an authority in metaphysics, it was argued, was the fault of Newton’s over-zealous disciples in Britain, who tried to transform him from a mathematician into the author of a general philosophical system. It is often argued that the Berlin Academy after 1743 included a Newtonian group, but even there the reception of Newtonianism was selective. Philosophers such as Leonhard Euler were also reluctant to be labelled ‘Newtonians’, because this implied a dogmatic belief in Newton’s ideas. Only after the mid-eighteenth century is ‘Newtonianism’ increasingly accepted in the sense of a philosophical system.     

An examination of factors contributing to delphi accuracy

Three experiments examined the accuracy in the Delphi method. The first experiment assessed the accuracy of group predictions over 1-, 2- and 3- month time spans. Results indicated that predictions derived from the group were more accurate than those of 95 per cent of the individual panelists, but did not exceed in accuracy the best panelists. Experiment 2 evaluated the gross contributions of polling and feedback to Delphi accuracy. The manipulations did not improve the group's ability to forecast the probabilities of the occurrence of events, but did decrease the error in predicting when the events would occur. Experiment 3 separated the effects of polling and feedback as determinants of accuracy. Neither manipulation improved the accuracy of the group's predictions of whether an event would occur. The effect of iterated polling was to reduce the group's error in predicting the time course for those scenarios that did occur.     

Systems and reengineering: Relating the reengineering paradigm to systems methodologies

Recently the topic of business process reengineering (BPR) has emerged to prominence in a number of guises, e.g. Hammer and Champy (1993). BPR is accepted here as containing a core paradigm with the potential to mobilize and channel change to secure radical improvements in organizational performance. This is contrasted with Continuous Improvement methods which deliver gradual improvements. In this paper BPR is conceputalised as an approach comprised of an emerging group of systems methodologies. These are related to other approaches and methodologies using the Total Systems Intervention framework of Flood and Jackson (1991). In keeping with the framework the main assumptions and metaphors that underlie the BPR literature are examined. BPR methodologies are characterised as rooted mainly in the hard systems approach with the machine metaphor dominating. The possibility is discussed of BPR methodologies based around other than hard system approaches.