Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex

Neurons in the cerebral cortex are organized into anatomical columns, with ensembles of cells arranged from the surface to the white matter. Within a column, neurons often share functional properties, such as selectivity for stimulus orientation; columns with distinct properties, such as different preferred orientations, tile the cortical surface in orderly patterns. This functional architecture was discovered with the relatively sparse sampling of microelectrode recordings. Optical imaging of membrane voltage or metabolic activity elucidated the overall geometry of functional maps, but is averaged over many cells (resolution >100 microm). Consequently, the purity of functional domains and the precision of the borders between them could not be resolved. Here, we labelled thousands of neurons of the visual cortex with a calcium-sensitive indicator in vivo. We then imaged the activity of neuronal populations at single-cell resolution with two-photon microscopy up to a depth of 400 microm. In rat primary visual cortex, neurons had robust orientation selectivity but there was no discernible local structure; neighbouring neurons often responded to different orientations. In area 18 of cat visual cortex, functional maps were organized at a fine scale. Neurons with opposite preferences for stimulus direction were segregated with extraordinary spatial precision in three dimensions, with columnar borders one to two cells wide. These results indicate that cortical maps can be built with single-cell precision.     

Spatial structure of cone inputs to receptive fields in primate lateral geniculate nucleus.

Human colour vision depends on three classes of cone photoreceptors, those sensitive to short (S), medium (M) or long (L) wavelengths, and on how signals from these cones are combined by neurons in the retina and brain. Macaque monkey colour vision is similar to human, and the receptive fields of macaque visual neurons have been used as an animal model of human colour processing. P retinal ganglion cells and parvocellular neurons are colour-selective neurons in macaque retina and lateral geniculate nucleus. Interactions between cone signals feeding into these neurons are still unclear. On the basis of experimental results with chromatic adaptation, excitatory and inhibitory inputs from L and M cones onto P cells (and parvocellular neurons) were thought to be quite specific (Fig. 1a). But these experiments with spatially diffuse adaptation did not rule out the 'mixed-surround' hypothesis: that there might be one cone-specific mechanism, the receptive field centre, and a surround mechanism connected to all cone types indiscriminately (Fig. 1e). Recent work has tended to support the mixed-surround hypothesis. We report here the development of new stimuli to measure spatial maps of the linear L-, M- and S-cone inputs to test the hypothesis definitively. Our measurements contradict the mixed-surround hypothesis and imply cone specificity in both centre and surround.     

Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B

Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses. In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development.     

Plankton effect on cod recruitment in the North Sea

The Atlantic cod (Gadus morhua L.) has been overexploited in the North Sea since the late 1960s and great concern has been expressed about the decline in cod biomass and recruitment. Here we show that, in addition to the effects of overfishing, fluctuations in plankton have resulted in long-term changes in cod recruitment in the North Sea (bottom-up control). Survival of larval cod is shown to depend on three key biological parameters of their prey: the mean size of prey, seasonal timing and abundance. We suggest a mechanism, involving the match/mismatch hypothesis, by which variability in temperature affects larval cod survival and conclude that rising temperature since the mid-1980s has modified the plankton ecosystem in a way that reduces the survival of young cod.     

Mechanism of allyl alcohol-induced hepatic necrosis

Résumé Ces recherches indiquent que la répartition des lésions nécrotiques produites chimiquement peut être déterminée par la localisation intrahépatique d'enzymes métabolisant les drogues, enzymes qui synthétisent, dans les cellules où ils sont produits, les métabolites chimiquement actifs capables d'alkylation des macromolécules

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I thank Mr.John George, MissKathy Lalush and Mrs.Mary Alice Larson for their expert technical assistance.     

Biogenesis of prokaryotic pores.

The prokaryotic pore-forming proteins are synthesized in the cytoplasm, and are assembled in their functional form in the outer membrane. They begin to traverse the cytoplasmic membrane via the SecY/SecA export pathway, which is shared also by periplasmic proteins. The sorting signals that direct these proteins to the outer membrane could be present in the three-dimensional conformations of the proteins, but some results suggest that they may be present in short, contiguous sequences. Outer membrane proteins share a rather hydrophilic amino acid composition, and appear to be rich in beta-sheets (with the exception of lipoproteins). This observation as well as the demonstration of periplasmic export intermediates favor the secretion pathway through the periplasm, as opposed to export through fusion sites between the inner and the outer membrane, but such intermediates have not yet been observed with the wild type proteins under physiological conditions.     

Parallel evolution of virulence in pathogenic Escherichia coli

The mechanisms underlying the evolution and emergence of new bacterial pathogens are not well understood. To elucidate the evolution of pathogenic Escherichia coli strains, here we sequenced seven housekeeping genes to build a phylogenetic tree and trace the history of the acquisition of virulence genes. Compatibility analysis indicates that more than 70% of the informative sites agree with a single phylogeny, suggesting that recombination has not completely obscured the remnants of ancestral chromosomes. On the basis of the rate of synonymous substitution for E. coli and Salmonella enterica (4.7 x 10(-9) per site per year), the radiation of clones began about 9 million years ago and the highly virulent pathogen responsible for epidemics of food poisoning, E. coli O157:H7, separated from a common ancestor of E. coli K-12 as long as 4.5 million years ago. Phylogenetic analysis reveals that old lineages of E. coli have acquired the same virulence factors in parallel, including a pathogenicity island involved in intestinal adhesion, a plasmid-borne haemolysin, and phage-encoded Shiga toxins. Such parallel evolution indicates that natural selection has favoured an ordered acquisition of genes and the progressive build-up of molecular mechanisms that increase virulence.