Corneal avascularity is due to soluble VEGF receptor-1

Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.     

Genome sequencing in microfabricated high-density picolitre reactors

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.     

Foliage age as a factor in food utilization by the western spruce budworm, Choristoneura occidentalis

The influence of current year foliage age on food consumption and utilization by the western spruce budworm, Choristoneura occidentalis (Lepidoptera:Tortricidae), was examined. Larvae were fed immature foliage of Douglas-fir ( Pseudotsuga menziesii var. glauca ), Engelmann spruce ( Picea engelmannii ), and corkbark fir ( Abies lasiocarpa var. arizonica ) in June and August of 1981 and Douglas fir in June and July of 1982. All larvae feeding on early season (June) foliage reached maturity. Larvae feeding on middle (July) and late (August) season foliage died before reaching pupation. Relative growth rate and efficiency of conversion of ingested food decreased with foliage age in both the 1981 and 1982 experiments. Relative consumption rate increased with foliage age in the 1981 and decreased in the 1982 experiment.     

Size, structure, and habitat characteristics of populations of Braya humilis var. humilis (Brassicaceae): an alpine disjunct from Colorado

Size, structure, and habitat characteristics were studied in three populations of Braya humilis var. humilis (C. A. Meyer) Robins, in Gray & Wats. (Brassicaceae), a small, herbaceous perennial of the alpine tundra in central Colorado. There was a significant association between numbers of reproductive, juvenile, and seedling individuals and population location. Plant size within reproductive, juvenile, and seedling size classes varied significantly among three populations. Plots containing Braya had significantly lower total plant cover, a different set of dominant plant species, more rock, bare ground, and less litter than plots without Braya . Braya appears to be restricted to calcareous substrates that experience a moderate level of disturbance, such as solifluction lobes and abandoned roads. Populations are small despite the existence of much potential habitat. Population studies are necessary for active conservation management of Braya .     

Estimates of site potential for Douglas-fir based on site index for several southwestern habitat types

Estimates of site potential for Douglas-fir based on measured site indexes in 450 stands are compared between 10 southwestern habitat types. Significant differences in site potential are found between the habitat types studied.     

High levels of gene flow in the California vole ( Microtus californicus ) are consistent across spatial scales

Gene flow links the genetic and demographic structures of species. Despite the fact that similar genetic and demographic patterns shape both local population structure and regional phylogeography, the 2 levels of population connectivity are rarely studied simultaneously. Here, we studied gene flow in the California vole ( Microtus californicus ), a small-bodied rodent with limited vagility but high local abundance. Within a 4.86-km 2 preserve in central California, genetic diversity in 6 microsatellites was high, and Bayesian methods indicated a single genetic cluster. However, individual-based genetic analysis detected a clear signal for isolation-by-distance (IBD) and fine-scale population structure. Mitochondrial cytochrome b sequencing revealed 11 unique haplotypes from the one local area where we sequenced 62 individuals. Phylogeographic analysis of these individuals combined with those sampled from the northern geographic range of the species (the range of the species spans western North America from southern Oregon to northern Mexico and is centered geographically within the state of California) again indicated a lack of structure but a signal for IBD. Patterns of gene flow thus are consistent across spatial scales: while dispersal of the California vole is limited across geographic distance, there is nonetheless considerable movement across the landscape. We conclude that in this species, high local population abundances overcome the potential genetic and demographic effects of limited dispersal.     

Insect behavior at the leaf surface and learning as aspects of host plant selection

Summary Direct observations on the feeding behavior of insect herbivores are uncommon, but important. The important aspects of host-plant selection by phytophagous insects that have been revealed by such observations are the role of chemicals in the leaf surface, and learning. There are few detailed reports of behavior at the leaf surface, but these indicate that many, if not all, insects exhibit behavior pattenrs that can be interpreted as an examination of the quality of the surface and acceptance or rejection may follow without further testing. A number of experiments show that chemicals from the leaf surface commonly contribute to the acceptability or otherwise of a plant and in most cases so far the active chemicals are of widespread occurrence, not having a specific association with the host plant. Some experiments show that the association between surface chemicals and plant palatability is learned, but in other cases there is evidence of an innate response. Habituation to deterrent chemicals has been demonstrated in the laboratory, but not in the field. Food aversion learning also occurs and may be important in dietary switching by polyphagous insects.     

Absence of naturally occurring coronary atherosclerosis in squirrel monkeys (Saimiri sciurea) treated with chondroitin sulfate A

Zusammenfassung Die überraschende Atheromatosehemmende Wirkung von Chondroitin-Sulfat konnte nun auch beiSaimiri scurea, einem Primaten mit hoher Inzidenz von Atheromatose, nachgewiesen werden.

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Supported in part by grants from the Heart Institute of the National Institutes of Health, U. S. Public Health Service, John A. Hartford Foundation, Inc., and other donors.     

Conversion of psoralen DNA monoadducts in E. coli to interstrand DNA cross links by near UV light (320–360 nm): Inability of angelicin to form cross links,in vivo

Summary Both angelicin and psoralen monoadducts formed in vivo in E. coli by near UV light produce lethal and mutagenic effects. However psoralen monoadducts are converted to cross links by higher doses of UV; angelicin monoadducts are not. The relevance of these results to psoralen photosensitization is discussed.Supported by the National Research Council of Canada.     

Differences in cerebral morphology in 2 stocks of mutant mice heterozygous for the loop-tail (Lp)-gene

Summary Adult loop-tail heterozygotes (Lp/+) from a stock ofLp-mice which consistently fail to show head wobbling exhibit normal brain morphology with respect to size and shape of lateral ventricles and nearby nuclei. Loop-tail heterozygotes from a head wobbling stock ofLp-mice show enlargement and deformity of the lateral ventricles.Supported by research grant HD09562 from the National Institutes of Health.