The metabolism of hexamethylphosphoramide and hexamethylthiophosphoramide

Résumé L'hexaméthylphosphoramide (I), un agent antispermatogénique efficient pour rongeurs, est dégradé par une succession de déméthylations (I II III IV) pour inactifs metabolites. Le thio-analogue (V), à moins qu'il soit metabolisé (I), est inactif au cours d'un cheminement alternatif (V VI II).

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This work was supported by grants from the Ford Foundation and the Wellcome Trust.     

A physical map of the mouse genome

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.     

Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls

A genetic association between NOTCH4 and schizophrenia has previously been proposed. Unsing all markers previously shown to be associated, we found no evidence for such in three independent family-based samples (n=519 parent-offspring trios), and a case-control sample derived from the same ethnic background as the original observation. These data strongly suggest that NOTCH4 is not a significant susceptibility allele for schizophrenia.     

Plant pathogens and integrated defence responses to infection.

Plants cannot move to escape environmental challenges. Biotic stresses result from a battery of potential pathogens: fungi, bacteria, nematodes and insects intercept the photosynthate produced by plants, and viruses use replication machinery at the host's expense. Plants, in turn, have evolved sophisticated mechanisms to perceive such attacks, and to translate that perception into an adaptive response. Here, we review the current knowledge of recognition-dependent disease resistance in plants. We include a few crucial concepts to compare and contrast plant innate immunity with that more commonly associated with animals. There are appreciable differences, but also surprising parallels.     

Effects of melezitose and stachyose on adult longevity and virus persistence in Culicoides sonorensis (Diptera: Ceratopogonidae)

A wide variety of blood-feeding Diptera feed on extrafloral sugar sources such as homopteran honeydew. The significance of these sugar sources to insect survival and disease transmission is poorly known. Culicoides sonorensis, a biting midge, can survive on plant sugars but might also feed on homopteran honeydew. The survival of C. sonorensis fed 10% melezitose or 10% stachyose was compared to that of C. sonorensis fed 10% sucrose. A significantly greater number of C. sonorensis survived longer when fed melezitose than when fed either stachyose or sucrose. The effect of sugar meals on vector competence was measured using bluetongue and epizootic hemorrhagic disease viruses. There was no significant difference in viral persistence. However, if C. sonorensis feeds on homopteran honeydew in the wild, a larger number of midges could survive to transmit orbiviruses.     

Collective synthesis of natural products by means of organocascade catalysis

Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine.     

The auroral footprint of Enceladus on Saturn

Although there are substantial differences between the magnetospheres of Jupiter and Saturn, it has been suggested that cryovolcanic activity at Enceladus could lead to electrodynamic coupling between Enceladus and Saturn like that which links Jupiter with Io, Europa and Ganymede. Powerful field-aligned electron beams associated with the Io-Jupiter coupling, for example, create an auroral footprint in Jupiter's ionosphere. Auroral ultraviolet emission associated with Enceladus-Saturn coupling is anticipated to be just a few tenths of a kilorayleigh (ref. 12), about an order of magnitude dimmer than Io's footprint and below the observable threshold, consistent with its non-detection. Here we report the detection of magnetic-field-aligned ion and electron beams (offset several moon radii downstream from Enceladus) with sufficient power to stimulate detectable aurora, and the subsequent discovery of Enceladus-associated aurora in a few per cent of the scans of the moon's footprint. The footprint varies in emission magnitude more than can plausibly be explained by changes in magnetospheric parameters--and as such is probably indicative of variable plume activity.