The chicken B locus is a minimal essential major histocompatibility complex.

Here we report the sequence of the region that determines rapid allograft rejection in chickens, the chicken major histocompatibility complex (MHC). This 92-kilobase region of the B locus contains only 19 genes, making the chicken MHC roughly 20-fold smaller than the human MHC. Virtually all the genes have counterparts in the human MHC, defining a minimal essential set of MHC genes conserved over 200 million years of divergence between birds and mammals. They are organized differently, with the class III region genes located outside the class II and class I region genes. The absence of proteasome genes is unexpected and might explain unusual peptide-binding specificities of chicken class I molecules. The presence of putative natural killer receptor gene(s) is unprecedented and might explain the importance of the B locus in the response to the herpes virus responsible for Marek's diseases. The small size and simplicity of the chicken MHC allows co-evolution of genes as haplotypes over considerable periods of time, and makes it possible to study the striking MHC-determined pathogen-specific disease resistance at the molecular level.     

Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult

Serotonin is implicated in mood regulation, and drugs acting via the serotonergic system are effective in treating anxiety and depression. Specifically, agonists of the serotonin1A receptor have anxiolytic properties, and knockout mice lacking this receptor show increased anxiety-like behaviour. Here we use a tissue-specific, conditional rescue strategy to show that expression of the serotonin1A receptor primarily in the hippocampus and cortex, but not in the raphe nuclei, is sufficient to rescue the behavioural phenotype of the knockout mice. Furthermore, using the conditional nature of these transgenic mice, we suggest that receptor expression during the early postnatal period, but not in the adult, is necessary for this behavioural rescue. These findings show that postnatal developmental processes help to establish adult anxiety-like behaviour. In addition, the normal role of the serotonin1A receptor during development may be different from its function when this receptor is activated by therapeutic intervention in adulthood.     

Interdecadal variation in the extent of South Pacific tropical waters during the Younger Dryas event

During the Younger Dryas event, about 12,000 years ago, the Northern Hemisphere cooled by between 2 and 10 degrees C (refs 1, 2) whereas East Antarctica experienced warming. But the spatial signature of the event in the southern mid-latitudes and tropics is less well known, as records are sparse and inconclusive. Here we present high-resolution analyses of skeletal Sr/Ca and 18O/16O ratios for a giant fossil Diploastrea heliopora coral that was preserved in growth position on the raised reef terraces of Espiritu Santo Island, Vanuatu, in the southwestern tropical Pacific Ocean. Our data indicate that sea surface temperatures in Vanuatu were on average 4.5 +/- 1.3 degrees C cooler during the Younger Dryas event than today, with a significant interdecadal modulation. The amplified annual cycle of sea surface temperatures, relative to today, indicates that cooling was caused by the compression of tropical waters towards the Equator. The positive correlation in our record between the oxygen isotope ratios of sea water and sea surface temperatures suggests that the South Pacific convergence zone, which brings 18O-depleted precipitation to the area today, was not active during the Younger Dryas period.     

Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen-1

Matrix metalloproteinase 19 (MMP-19) is able to process various proteins of the basement membrane. To investigate the impact of MMP-19 activity on endothelial cells in the context of tumor extracellular matrix (ECM), we treated Matrigel matrix with an active recombinant MMP-19 and analyzed its effect on capillary-like formation. Human microvascular endothelial cells (HMEC-1) could not form capillary-like formation on Matrigel treated with recombinant MMP-19. Analyzing the Matrigel proteins, we found that MMP-19 preferentially cleaved nidogen-1. The cleavage site of nidogen-1 was mapped to Thr867-Leu868. This cleavage separates the G3 globular domain containing the binding site for the 1 chain of laminin-1 and collagen IV and thus abolishes the capacity of nidogen-1 to cross-link ECM proteins. Anti-nidogen antibodies directed against the G3 domain of nidogen-1 inhibited the capillary-like structure formation to a similar extent as MMP-19. Since nidogen-1 is thought to stabilize microvessels, MMP-19 might be one of the enzymes that interferes with stabilization or maturation of nascent vasculature.Received 10 March 2004; received after revision 30 April 2004; accepted 26 May 2004     

Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration

Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis. The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition, Vegf165 promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.     

The effect of hyperconjugation upon the boiling points of alkenes

Zusammenfassung Es wird gezeigt, dass die Hyperkonjugation einen entscheidenden Einfluss auf den Siedepunkt der einfach ungesättigten aliphatischen Kohlenwasserstoffe hat. Dieser Zusammenhang wird durch vergrösserte Elektronendelokalisierung in Molekülen, die Hyperkonjugation aufweisen, theoretisch verständlich. Ein grösseres Ausmass der Elektronendelokalisierung führt zu stärkerer Kohäsion und dadurch zu erhöhten Siedepunkten. Die neue Gesetzmässigkeit ergänzt ohne Widerspruch die bekannten Hückelschen Siedepunktsregeln und erklärt Beobachtungen, die aus keiner der bisher aufgestellten Regeln ableitbar waren. Es ist zu erwarten, dass analoge Zusammenhänge in anderen Gruppen von organischen Verbindungen aufgewiesen werden können.     

Genealogies of mouse inbred strains

The mouse is a prime organism of choice for modelling human disease. Over 450 inbred strains of mice have been described, providing a wealth of different genotypes and phenotypes for genetic and other studies. As new strains are generated and others become extinct, it is useful to review periodically what strains are available and how they are related to each other, particularly in the light of available DNA polymorphism data from microsatellite and other markers. We describe the origins and relationships of inbred mouse strains, 90 years after the generation of the first inbred strain. Given the large collection of inbred strains available, and that published information on these strains is incomplete, we propose that all genealogical and genetic data on inbred strains be submitted to a common electronic database to ensure this valuable information resource is preserved and used efficiently.     

Multiscale modelling of plastic flow localization in irradiated materials

The irradiation of metals by energetic particles causes significant degradation of the mechanical properties, most notably an increased yield stress and decreased ductility, often accompanied by plastic flow localization. Such effects limit the lifetime of pressure vessels in nuclear power plants, and constrain the choice of materials for fusion-based alternative energy sources. Although these phenomena have been known for many years, the underlying fundamental mechanisms and their relation to the irradiation field have not been clearly demonstrated. Here we use three-dimensional multiscale simulations of irradiated metals to reveal the mechanisms underlying plastic flow localization in defect-free channels. We observe dislocation pinning by irradiation-induced clusters of defects, subsequent unpinning as defects are absorbed by the dislocations, and cross-slip of the latter as the stress is increased. The width of the plastic flow channels is limited by the interaction among opposing dislocation dipole segments and the remaining defect clusters.