Effect of spermine on the kinetics of estradiol hydroxylation by rat liver microsomes

Résumé L'addition de spermine au microsomes du foie de rats femelles modifie leK _m du système enzymatique qui transforme 1'estradiol en 2-hydroxyestradiol et aussi en des produits aqueux. La nouvelle valeur resemble à celle qu'ont trouve avec des rats mâles, mais leV _max de la réaction reste inchangé. L'action de la spermine dans ce système est discutée.     

Altered arterial connective tissue in racing greyhound dogs.

Vascular collagen and elastin contents and the ratio of collagen/elastin (C/E) were studied in racing greyhound dogs, a breed which exhibits increased cardiac output. As compared to mongrel dogs, vascular C/E was lower, suggesting a greater distensibility of vessels as an adaptive response to hemodynamic stress.     

Comparative chromosome mapping of a conserved homoeo box region in mouse and human

Specific genes are assumed to regulate pattern formation in the mammalian embryo, but as yet none has been identified unequivocally. It is possible that such genes in mammals may be identified by virtue of a conserved coding sequence, because many of the Drosophila melanogaster homoeotic and segmentation genes, which have crucial roles in the regulation of segmental pattern formation during embryonic development, contain a 180-base pair (bp) DNA sequence, the homoeo box, and that sequences homologous to the Drosophila homoeo box are also present in 6-10 copies in higher animals, including mammals. Although the assumption that the homoeo box identifies genes responsible for pattern formation in mammals remains to be validated, it is a particularly attractive hypothesis given the strong conservation of homoeo boxes over vast evolutionary distances. Here we report the localization of a human homoeo box region, previously cloned and shown to contain two homoeo boxes within a sequence of 5-kilobases (kb), to the long arm of chromosome 17. We show that two single-copy homoeo box-flanking probes derived from this region strongly hybridize to single-copy restriction fragments in mouse genomic DNA and that these conserved homoeo box-flanking sequences map to mouse chromosome 11. This may be significant as several genes that map to chromosome 17 in human also map to chromosome 11 in the mouse, implying that a segment of mouse chromosome 11 is homologous to a region of human chromosome 17. Taken together, these data suggest that the homoeo box region detected with our probes is highly conserved in human and mouse.     

Localisation of phencyclidine-induced changes in brain energy metabolism

The abuse of phencyclidine [1(1-phencylohexyl)piperidine, PCP], commonly referred to as angel dust or hog, is rapidly reaching epidemic proportions. PCP users often appear violent and increases in PCP-implicated homicides and suicides have been reported. In animal studies PCP has been demonstrated in brain up to 48 h after administration, long after blood levels become undetectable. However, there is little further information on the distribution of PCP within the central nervous system with regard to the possible sites of action. Recently, Sokoloff and associates described a new technique which can be used to visualise possible sites of drug action. The technique is based on the premise that neuronal activity is closely related to energy metabolism. Therefore, by directly monitoring 2-deoxy-D-glucose consumption before and after a pharmacological stimulus, we can obtain autoradiographic evidence of changes in neuronal activity in discrete areas brain as a response to that stimulus. Using this procedure, we now report that PCP causes dramatic changes in glucose metabolism in very specific regions of the rat brain.     

The mouse fidgetin gene defines a new role for AAA family proteins in mammalian development

The mouse mutation fidget arose spontaneously in a heterogeneous albino stock. This mutant mouse is characterized by a side-to-side head-shaking and circling behaviour, due to reduced or absent semicircular canals. Fidget mice also have small eyes, associated with cell-cycle delay and insufficient growth of the retinal neural epithelium, and lower penetrance skeletal abnormalities, including pelvic girdle dysgenesis, skull bone fusions and polydactyly. By positional cloning, we found the gene mutated in fidget mice, fidgetin (Fign), which encodes a new member of the 'meiotic' or subfamily-7 (SF7; ref. 7) group of ATPases associated with diverse cellular activities (AAA proteins). We also discovered two closely related mammalian genes. AAA proteins are molecular chaperones that facilitate a variety of functions, including membrane fusion, proteolysis, peroxisome biogenesis, endosome sorting and meiotic spindle formation, but functions for the SF7 AAA proteins are largely unknown. Fidgetin is the first mutant AAA protein found in a mammalian developmental mutant, thus defining a new role for these proteins in embryonic development.     

Fluorescent pigments in corals are photoprotective

All reef-forming corals depend on the photosynthesis performed by their algal symbiont, and such corals are therefore restricted to the photic zone. The intensity of light in this zone declines over several orders of magnitude--from high and damaging levels at the surface to extreme shade conditions at the lower limit. The ability of corals to tolerate this range implies effective mechanisms for light acclimation and adaptation. Here we show that the fluorescent pigments (FPs) of corals provide a photobiological system for regulating the light environment of coral host tissue. Previous studies have suggested that under low light, FPs may enhance light availability. We now report that in excessive sunlight FPs are photoprotective; they achieve this by dissipating excess energy at wavelengths of low photosynthetic activity, as well as by reflecting of visible and infrared light by FP-containing chromatophores. We also show that FPs enhance the resistance to mass bleaching of corals during periods of heat stress, which has implications for the effect of environmental stress on the diversity of reef-building corals, such as enhanced survival of a broad range of corals allowing maintenance of habitat diversity.     

Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice

Tuberculosis is the leading cause of death in the world resulting from a single bacterial infection. Despite its enormous burden on world health, little is known about the molecular mechanisms of pathogenesis of Mycobacterium tuberculosis. Bacterial multiplication and concomitant tissue damage within an infected host, including experimentally infected mice, occurs primarily in the lungs-the favoured niche of M. tuberculosis. Although it has been proposed that the distinctive cell wall of M. tuberculosis is important for virulence, rigorous genetic proof has been lacking. Here, using signature-tagged mutagenesis, we isolated three attenuated M. tuberculosis mutants that cannot synthesize or transport a complex, cell wall-associated lipid called phthiocerol dimycocerosate (PDIM) which is found only in pathogenic mycobacteria. Two mutants have transposon insertions affecting genes implicated in PDIM synthesis; the third has a disruption in a gene encoding a large transmembrane protein required for proper subcellular localization of PDIM. Synthesis and transport of this complex lipid is only required for growth in the lung; all three mutants are unaffected for growth in the liver and spleen. This clearly shows that a lipid is required for M. tuberculosis virulence.     

Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism

Morphogens act in developing tissues to control the spatial arrangement of cellular differentiation. The activity of a morphogen has generally been viewed as a concentration-dependent response to a diffusible signal, but the duration of morphogen signalling can also affect cellular responses. One such example is the morphogen sonic hedgehog (SHH). In the vertebrate central nervous system and limbs, the pattern of cellular differentiation is controlled by both the amount and the time of SHH exposure. How these two parameters are interpreted at a cellular level has been unclear. Here we provide evidence that changing the concentration or duration of SHH has an equivalent effect on intracellular signalling. Chick neural cells convert different concentrations of SHH into time-limited periods of signal transduction, such that signal duration is proportional to SHH concentration. This depends on the gradual desensitization of cells to ongoing SHH exposure, mediated by the SHH-dependent upregulation of patched 1 (PTC1), a ligand-binding inhibitor of SHH signalling. Thus, in addition to its role in shaping the SHH gradient, PTC1 participates cell autonomously in gradient sensing. Together, the data reveal a novel strategy for morphogen interpretation, in which the temporal adaptation of cells to a morphogen integrates the concentration and duration of a signal to control differential gene expression.