Rehabilitating theory: refusal of the ‘bottom-up’ construction of scientific phenomena

In this paper I inquire into Bogen and Woodward’s (1988) data/phenomena distinction, which in a similar way to Cartwright’s construal of the model of superconductivity (1995)—although in a different domain—argues for a ‘bottom-up’ construction of phenomena from data without the involvement of theory. I criticise Bogen and Woodward’s account by analysing their melting point of lead example in depth, which is usually cited in the literature to illustrate the data/phenomenon distinction. Yet, the main focus of this paper lies on Matthias Kaiser’s (1995) case study of the plate tectonic revolution, the most extensive case study that has been put forth to support the bottom-up construction of phenomena. On the basis of new historical evidence, which has been overlooked not only by Kaiser but also by the entire historical literature on the plate tectonic revolution, I demonstrate that phenomena are not constructed from the bottom-up but rather, admittedly counter-intuitively, from the top-down.     

The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia

Seven Fanconi anemia-associated proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCL) form a nuclear Fanconi anemia core complex that activates the monoubiquitination of FANCD2, targeting FANCD2 to BRCA1-containing nuclear foci. Cells from individuals with Fanconi anemia of complementation groups D1 and J (FA-D1 and FA-J) have normal FANCD2 ubiquitination. Using genetic mapping, mutation identification and western-blot data, we identify the defective protein in FA-J cells as BRIP1 (also called BACH1), a DNA helicase that is a binding partner of the breast cancer tumor suppressor BRCA1.     

Lifespan and mitochondrial control of neurodegeneration

We examine the allometric (comparative scaling) relationships between rates of neurodegeneration resulting from equivalent mutations in a diverse group of genes from five mammalian species with different maximum lifespan potentials. In both retina and brain, rates of neurodegeneration vary by as much as two orders of magnitude and are strongly correlated with maximum lifespan potential and rates of formation of mitochondrial reactive oxygen and nitrogen species (RONS). Cell death in these disorders is directly or indirectly regulated by the intrinsic mitochondrial cell death pathway. Mitochondria are the main source of RONS production and integrate cellular stress signals to coordinate the intrinsic pathway. We propose that these two functions are intimately related and that steady-state RONS-mediated signaling or damage to the mitochondrial stress-integration machinery is the principal factor setting the probability of cell death in response to a diverse range of cellular stressors. This provides a new and unifying framework for investigating neurodegenerative disorders.     

Proteorhodopsin in the ubiquitous marine bacterium SAR11

Proteorhodopsins are light-dependent proton pumps that are predicted to have an important role in the ecology of the oceans by supplying energy for microbial metabolism. Proteorhodopsin genes were first discovered through the cloning and sequencing of large genomic DNA fragments from seawater. They were later shown to be widely distributed, phylogenetically diverse, and active in the oceans. Proteorhodopsin genes have not been found in cultured bacteria, and on the basis of environmental sequence data, it has not yet been possible to reconstruct the genomes of uncultured bacterial strains that have proteorhodopsin genes. Although the metabolic effect of proteorhodopsins is uncertain, they are thought to function in cells for which the primary mode of metabolism is the heterotrophic assimilation of dissolved organic carbon. Here we report that SAR11 strain HTCC1062 ('Pelagibacter ubique'), the first cultivated member of the extraordinarily abundant SAR11 clade, expresses a proteorhodopsin gene when cultured in autoclaved seawater and in its natural environment, the ocean. The Pelagibacter proteorhodopsin functions as a light-dependent proton pump. The gene is expressed by cells grown in either diurnal light or in darkness, and there is no difference between the growth rates or cell yields of cultures grown in light or darkness.     

Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension

Lipid bilayer membranes--ubiquitous in biological systems and closely associated with cell function--exhibit rich shape-transition behaviour, including bud formation and vesicle fission. Membranes formed from multiple lipid components can laterally separate into coexisting liquid phases, or domains, with distinct compositions. This process, which may resemble raft formation in cell membranes, has been directly observed in giant unilamellar vesicles. Detailed theoretical frameworks link the elasticity of domains and their boundary properties to the shape adopted by membranes and the formation of particular domain patterns, but it has been difficult to experimentally probe and validate these theories. Here we show that high-resolution fluorescence imaging using two dyes preferentially labelling different fluid phases directly provides a correlation between domain composition and local membrane curvature. Using freely suspended membranes of giant unilamellar vesicles, we are able to optically resolve curvature and line tension interactions of circular, stripe and ring domains. We observe long-range domain ordering in the form of locally parallel stripes and hexagonal arrays of circular domains, curvature-dependent domain sorting, and membrane fission into separate vesicles at domain boundaries. By analysing our observations using available membrane theory, we are able to provide experimental estimates of boundary tension between fluid bilayer domains.     

Glutamate and GABA levels and glutamate decarboxylase activity in brain regions of rats after prolonged treatment with alkali cations

Resume L'administration chronique des cations des métaux alcalins (Na⁺, Rb⁺, Cs⁺) à les rats a provoqué la croissance des niveaux de glutamate et GABA dans certaines régions du cerveau. On n'a remarqué aucun changement en activité GAD de ces régions.     

Fortschritte und Ergebnisse der Zellkulturmethodik

Summary In this brief review, the development of modern quantitative methods for the cultivation of mammalien cellsin vitro is described, and present knowledge of their nutritional requirements is presented. In addition, some applications of these techniques in biochemistry, pharmacology, virology, genetics, and radiobiology are discussed.