Giant granules in adrenaline-secreting chromaffin cells of lizard adrenal glands after metyrapone administration

Summary Secretory granules of extraordinary size, some of them bigger than the cell nucleus, abound in the adrenaline cells of lizard adrenals after metyrapone injections during 7 days. In these granules, the bounding membrane is studded with ribosomes, and the core is formed by rounded small subunits. Some granules of this type are also found in noradrenaline cells. They may represent an exceptionally increased elaboration and storage of adrenaline, induced by metyrapone probably through its action on steroidogenic tissue.This research forms part of project No. 31.26.S1-1154 supported by the Consejo Nacional de Investigaciones Científícas y Tecnológicas.     

Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium

The autosomal dominant, giant-platelet disorders, May-Hegglin anomaly (MHA; MIM 155100), Fechtner syndrome (FTNS; MIM 153640) and Sebastian syndrome (SBS), share the triad of thrombocytopenia, large platelets and characteristic leukocyte inclusions ('D?hle-like' bodies). MHA and SBS can be differentiated by subtle ultrastructural leukocyte inclusion features, whereas FTNS is distinguished by the additional Alport-like clinical features of sensorineural deafness, cataracts and nephritis. The similarities between these platelet disorders and our recent refinement of the MHA (ref. 6) and FTNS (ref. 7) disease loci to an overlapping region of 480 kb on chromosome 22 suggested that all three disorders are allelic. Among the identified candidate genes is the gene encoding nonmuscle myosin heavy chain 9 (MYH9; refs 8-10), which is expressed in platelets and upregulated during granulocyte differentiation. We identified six MYH9 mutations (one nonsense and five missense) in seven unrelated probands from MHA, SBS and FTNS families. On the basis of molecular modelling, the two mutations affecting the myosin head were predicted to impose electrostatic and conformational changes, whereas the truncating mutation deleted the unique carboxy-terminal tailpiece. The remaining missense mutations, all affecting highly conserved coiled-coil domain positions, imparted destabilizing electrostatic and polar changes. Thus, our results suggest that mutations in MYH9 result in three megakaryocyte/platelet/leukocyte syndromes and are important in the pathogenesis of sensorineural deafness, cataracts and nephritis.     

Specific isomerization of rhodopsin-bound 11-cis-retinal to all-trans-retinal under thermal denaturation

The natural ligand of the retinal photoreceptor rhodopsin, 11-cis-retinal, is isomerized to its all-trans configuration as a consequence of light absorption in the first step of the visual phototransduction process. Here we show, by means of difference spectroscopy and high-performance liquid chromatography analysis, that thermal denaturation of rhodopsin induces the same type of isomerization. This effect is likely due to thermally induced conformational rearrangements of amino acid residues in the retinal-binding pocket – possibly implying helical movements – and highlights the tight coupling between 11-cis-retinal and opsin. This effect could have implications in the instability and functional changes seen for certain mutations in rhodopsin associated with retinal disease, and in the stability of the different conformers induced by mutations in other G protein-coupled receptors.Received 25 March 2003; received after revision 6 August 2003; accepted 9 September 2003     

Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis

Widespread demyelination and axonal loss are the pathological hallmarks of multiple sclerosis. The multifocal nature of this chronic inflammatory disease of the central nervous system complicates cellular therapy and puts emphasis on both the donor cell origin and the route of cell transplantation. We established syngenic adult neural stem cell cultures and injected them into an animal model of multiple sclerosis--experimental autoimmune encephalomyelitis (EAE) in the mouse--either intravenously or intracerebroventricularly. In both cases, significant numbers of donor cells entered into demyelinating areas of the central nervous system and differentiated into mature brain cells. Within these areas, oligodendrocyte progenitors markedly increased, with many of them being of donor origin and actively remyelinating axons. Furthermore, a significant reduction of astrogliosis and a marked decrease in the extent of demyelination and axonal loss were observed in transplanted animals. The functional impairment caused by EAE was almost abolished in transplanted mice, both clinically and neurophysiologically. Thus, adult neural precursor cells promote multifocal remyelination and functional recovery after intravenous or intrathecal injection in a chronic model of multiple sclerosis.     

Dinemorphan N-demethylation by mouse liver microsomes

Dinemorphan, an antitussive drug, is N-demethylated in vitro by mouse liver microsomes with biphasic kinetics showing two apparent Km and Vmax. Moreover, dinemorphan N-demethylation is inhibited by CO, SKF-525A, metyrapone and it is specifically catalyzed by a phenobarbital-inducible form of cytochrome P-450.     

Analysis and prediction of the population in Spain: 1910-2000

"The starting hypothesis of this paper was the actual occurrence of important interactions between demographic and socio-economic factors when trying to reach population forecasts that may be more efficient than those obtained by mere extrapolative methods. In order to be able to implement this approach to the Spanish case it has been necessary to reconstruct first the Spanish population series by age and sex groups from 1910 to 1980. Later, we proceed to obtain population forecasts using alternative modeling strategies and comment on the potential problems that the new demographic situation may have for future public policy."     

The grapevine genome sequence suggests ancestral hexaploidization in major angiosperm phyla

The analysis of the first plant genomes provided unexpected evidence for genome duplication events in species that had previously been considered as true diploids on the basis of their genetics. These polyploidization events may have had important consequences in plant evolution, in particular for species radiation and adaptation and for the modulation of functional capacities. Here we report a high-quality draft of the genome sequence of grapevine (Vitis vinifera) obtained from a highly homozygous genotype. The draft sequence of the grapevine genome is the fourth one produced so far for flowering plants, the second for a woody species and the first for a fruit crop (cultivated for both fruit and beverage). Grapevine was selected because of its important place in the cultural heritage of humanity beginning during the Neolithic period. Several large expansions of gene families with roles in aromatic features are observed. The grapevine genome has not undergone recent genome duplication, thus enabling the discovery of ancestral traits and features of the genetic organization of flowering plants. This analysis reveals the contribution of three ancestral genomes to the grapevine haploid content. This ancestral arrangement is common to many dicotyledonous plants but is absent from the genome of rice, which is a monocotyledon. Furthermore, we explain the chronology of previously described whole-genome duplication events in the evolution of flowering plants.