Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Rab-GTPases, together with their cofactors, mediate the attachment step in the membrane fusion of vesicles. But how bilayer mixing--the subsequent core process of fusion--is catalysed remains unclear. Ca2+/calmodulin controls this terminal process in many intracellular fusion events. Here we identify V0, the membrane-integral sector of the vacuolar H+-ATPase, as a target of calmodulin on yeast vacuoles. Between docking and bilayer fusion, V0 sectors from opposing membranes form complexes. V0 trans-complex formation occurs downstream from trans-SNARE pairing, and depends on both the Rab-GTPase Ypt7 and calmodulin. The maintenance of existing complexes and completion of fusion are independent of trans-SNARE pairs. Reconstituted proteolipids form sealed channels, which can expand to form aqueous pores in a Ca2+/calmodulin-dependent fashion. V0 trans-complexes may therefore form a continuous, proteolipid-lined channel at the fusion site. We propose that radial expansion of such a protein pore may be a mechanism for intracellular membrane fusion.     

Setting up a Discipline: Conflicting Agendas of the Cambridge History of Science Committee, 1936–1950

Traditionally the domain of scientists, the history of science became an independent field of inquiry only in the twentieth century and mostly after the Second World War. This process of emancipation was accompanied by a historiographical departure from previous, ‘scientistic’ practices, a transformation often attributed to influences from sociology, philosophy and history. Similarly, the liberal humanists who controlled the Cambridge History of Science Committee after 1945 emphasized that their contribution lay in the special expertise they, as trained historians, brought to the venture. However, the scientists who had founded the Committee in the 1930s had already advocated a sophisticated contextual approach: innovation in the history of science thus clearly came also from within the ranks of scientists who practised in the field. Moreover, unlike their scientist predecessors on the Cambridge Committee, the liberal humanists supported a positivistic protocol that has since been criticized for its failure to properly contextualize early modern science. Lastly, while celebrating the rise of modern science as an international achievement, the liberal humanists also emphasized the peculiar Englishness of the phenomenon. In this respect, too, their outlook had much in common with the practices from which they attempted to distance their project.     

Retinoids, a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology.

A review of recent investigations in the retinoid field is presented. Retinoic acid exerts a prophylactic and a therapeutic effect on chemically induced benign and malignant epithelial tumors in mice. In clinical studies positive therapeutic results have been obtained in patients with preneoplastic and neoplastic epithelial lesions. However, treatment with retinoic acid is limited by serious side effects (hypervitaminosis A syndrome). Therefore, the synthesis of analogs of retinoic acid (retinoids) possessing a more favorable therapeutic ratio has been initiated. Among a large series of synthesized compounds, certain aromatic analogs proved to have a particularly favorable therapeutic ratio. The structure-activity relationship of the most active retinoids is discussed including some biological data concerning prophylaxis and therapy of epithelial tumors. The total synthesis of retinoids according to various building schemes is discussed in detail. Methods for the synthesis of the cyclic end group, of the polyene chain component, and of the full retinoid skeleton are described. Metabolic studies of retinoic acid and of the most active retinoid, as well as the synthesis of some isolated metabolites are outlined. Suggestions concerning the mechanism of action of retinoids are made. Some clinical results on the treatment of acne, psoriasis and precancerous conditions are reported.     

A newTrichoplusia ni antennal receptor neuron that responds to attomolar concentrations of a minor pheromone component

Summary A newly discovered third class of sensillum trichodea on the antenna ofTrichoplusia ni contains an olfactory receptor neuron that responds to (Z)-9-tetradecen-1-ol acetate at 1×10^–18 M. The threshold of this neuron is 100–1000 times lower than the thresholds of two previously described pheromone-sensitive neurons that detect (Z)-7-dodecen-1-ol acetate and (Z)-7-tetradecen-1-ol acetate. The sensitivity and selectivity of this receptor neuron is evidence that (Z)-9-tetradecen-1-ol acetate may be important for sexual behavior.     

Setting up a discipline, II: British history of science and “the end of ideology”, 1931-1948

For the history of science the 1940s were a transformative decade, when salient scholars like Herbert Butterfield or Alexandre Koyré set out to shape postwar culture by promoting new standards for understanding science. Some years ago I placed these developments in a tradition of enduring arts-science tensions and the contemporary notion that previous, “scientistic”, historical practices needed to be confronted with disinterested codes of historical craft (Mayer, 2000). Here, I want to further explore the ideological dimensions of the processes through which the academic study of science became institutionalized. Butterfield’s generation of science historians moulded perception of science in highly specific ways. Whereas the scientist-historians of the 1930s put scientific innovation into its socio-economic contexts, postwar accounts portrayed the birth of modern science as an intellectual revolution. Anti-Marxism formed a defining feature of the process by which the image of scientific work as a disinterested journey of the mind came to be institutionalized. Rather than spelling the end of ideology, appointments processes in the early Cold War years reveal disagreement about what science was to be invariably coextensive with dissent about social and political order. Rather than testifying to irreconcilable conflicts between interestedness and historical craft, the work of both the 1930s and 40s speaks of surprisingly productive relations between the two.