Mechanosensitivity of mammalian auditory hair cells in vitro

Intracellular responses recorded in vitro from the cochleas of anaesthetized mammals have shown that the mechanoreceptive inner and outer hair cells are sharply tuned, accounting for many of the properties of the afferent fibres in the auditory nerve. However, in vivo it has not been possible to measure directly the excitatory mechanical input to these cells (the displacement of their mechanosensitive stereocilia) and thus to determine the relationship between the receptor potentials and displacement of their stereocilia. As a means of circumventing this technical difficulty, we have developed an organ culture of the mouse cochlea and here we describe the receptor potentials generated by the hair cells in response to direct displacement of their stereocilia.     

On the continuity of reference of the elements: a response to Hendry

Robin Hendry has recently argued that although the term ‘element’ has traditionally been used in two different senses (basic substance and simple substance), there has nonetheless been a continuity of reference. The present article examines this author’s historical and philosophical claims and suggests that he has misdiagnosed the situation in several respects. In particular it is claimed that Hendry’s arguments for the nature of one particular element, oxygen, do not generalize to all elements as he implies. The second main objection is to Hendry’s view that the qua problem can be illuminated by appeal to the intention of scientists.     

Resurrecting ancestral alcohol dehydrogenases from yeast

Modern yeast living in fleshy fruits rapidly convert sugars into bulk ethanol through pyruvate. Pyruvate loses carbon dioxide to produce acetaldehyde, which is reduced by alcohol dehydrogenase 1 (Adh1) to ethanol, which accumulates. Yeast later consumes the accumulated ethanol, exploiting Adh2, an Adh1 homolog differing by 24 (of 348) amino acids. As many microorganisms cannot grow in ethanol, accumulated ethanol may help yeast defend resources in the fruit. We report here the resurrection of the last common ancestor of Adh1 and Adh2, called Adh(A). The kinetic behavior of Adh(A) suggests that the ancestor was optimized to make (not consume) ethanol. This is consistent with the hypothesis that before the Adh1-Adh2 duplication, yeast did not accumulate ethanol for later consumption but rather used Adh(A) to recycle NADH generated in the glycolytic pathway. Silent nucleotide dating suggests that the Adh1-Adh2 duplication occurred near the time of duplication of several other proteins involved in the accumulation of ethanol, possibly in the Cretaceous age when fleshy fruits arose. These results help to connect the chemical behavior of these enzymes through systems analysis to a time of global ecosystem change, a small but useful step towards a planetary systems biology.     

Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.     

Synthetic biology: engineering Escherichia coli to see light

We have designed a bacterial system that is switched between different states by red light. The system consists of a synthetic sensor kinase that allows a lawn of bacteria to function as a biological film, such that the projection of a pattern of light on to the bacteria produces a high-definition (about 100 megapixels per square inch), two-dimensional chemical image. This spatial control of bacterial gene expression could be used to 'print' complex biological materials, for example, and to investigate signalling pathways through precise spatial and temporal control of their phosphorylation steps.     

Global azimuthal seismic anisotropy and the unique plate-motion deformation of Australia

Differences in the thickness of the high-velocity lid underlying continents as imaged by seismic tomography, have fuelled a long debate on the origin of the 'roots' of continents. Some of these differences may be reconciled by observations of radial anisotropy between 250 and 300 km depth, with horizontally polarized shear waves travelling faster than vertically polarized ones. This azimuthally averaged anisotropy could arise from present-day deformation at the base of the plate, as has been found for shallower depths beneath ocean basins. Such deformation would also produce significant azimuthal variation, owing to the preferred alignment of highly anisotropic minerals. Here we report global observations of surface-wave azimuthal anisotropy, which indicate that only the continental portion of the Australian plate displays significant azimuthal anisotropy and strong correlation with present-day plate motion in the depth range 175-300 km. Beneath other continents, azimuthal anisotropy is only weakly correlated with plate motion and its depth location is similar to that found beneath oceans. We infer that the fast-moving Australian plate contains the only continental region with a sufficiently large deformation at its base to be transformed into azimuthal anisotropy. Simple shear leading to anisotropy with a plunging axis of symmetry may explain the smaller azimuthal anisotropy beneath other continents.