Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1

Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.     

CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Altered growth and function of synoviocytes, the intimal cells which line joint cavities and tendon sheaths, occur in a number of skeletal diseases. Hyperplasia of synoviocytes is found in both rheumatoid arthritis and osteoarthritis, despite differences in the underlying aetiologies of the two disorders. We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome. Using a positional-candidate approach, we identified mutations in a gene (CACP) encoding a secreted proteoglycan as the cause of CACP. The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins. In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium. The similarity of CACP sequence to that of other protein families and the expression of CACP in non-skeletal tissues suggest it may have diverse biological activities.     

Evolution and ecological correlates of uniparental reproduction in freshwater snails

We review the spatial and temporal correlates of uniparental reproduction in freshwater snails as they pertain to the ecological hypotheses for the maintenance of biparental sex. The biogeographic evidence from two species (Potamopyrgus antipodarum andBulinus truncatus) presently supports the Red Queen hypothesis that biparental reproduction is selected as a way to reduce the risk to progeny of parasite attack. Uniparental reproduction in these species is associated with low levels of infection by parasites (castrating digenetic trematodes), suggesting that parthenogenesis or self-fertilization can replace cross-fertilization when the risk of infection is low. In addition, inB. truncatus, the opportunity for cross-fertilization coincides with the season in which parasite attack is highest. In a third species (Campeloma decisum), parthenogenetic reproduction is correlated with latitude and the presence of a non-castrating trematode that may prevent cross-fertilization; these patterns suggest that parthenogenesis has been selected as a mechanism to assure reproduction. Finally, we discuss the spotty taxonomic distribution of parthenogenetic species.     

Threo-3,4-Dihydroxyphenylserine,a poor source of noradrenaline in the rat

Résumé Chez le rat, les injections dedl-thréo-3,4-dihydroxyphénylsérine, un précurseur pharmacologique synthétique de la noradrénaline, provoquent une conversion de moins de 1% au 4-hydroxy-3-méthoxyphényl-glycol, le métabolite urinaire majeur de la noradrénaline dans cette espèce. Un nouveau cheminement qui entraîne une coupure latérale de la chaîne prit environ 10% de la dose et un autre 10% fût excrété comme un amino-acideO-méthylé; le sort de quelque 80% est inconnu.     

Human sweat components — Attractancy and repellency to mosquitoes

Zusammenfassung Es wird gezeigt, dass menschliche Schweissabsonderungen verschiedener Versuchspersonen auf weibliche Moskitos (Aedes aegypti) verschieden attraktiv sind. Mit Diethyläther (pH 1) lassen sich im Schweiss sowohl «anlockende» wie auch «abschreckende» Bestandteile extrahieren. Für den «repellent effect» sind teilweise gleiche Mischungen von Milchsäure und Milchsäureanhydrid verantwortlich. Zwei weitere, noch nicht identifizierte Substanzen zeigten im Zwei-Kammer-Olfaktometer identische «repellent» Wirkungen.

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This study was supported by U.S. Army Medical Research and Development Command, Dept. of the Army, Contracts No. DA 49-193-MD-2465 (W. Skinner) and No. DA 49-193-MD-2466 (H. Maibach). We thank Dr.L. Pope, Superintendent, and the inmates of the California Medical Faculty, Vacaville, California, USA, for their cooperation in this study.     

The properties of neuraminidase-treated crystalline ceruloplasmin

Résumé On sait que la plasmine céruléenne crystalline rétroplacentaire humaine ainsi qua la plasmine apocérulécnne empêchent l'hémaglutination virale. Cet effet pourrait être attribué aux résidus d'acide sialique, car l'action préventive disparaît après traitement de la plasmine céruléenne par la neuraminidase.