Development of the innervation of the urogenital complex in the fetal mouse

The developing urogenital complex of the fetal mouse was studied by means of silver impregnation and electron microscopy. These studies showed that: 1) the mesonephric field is innervated during prenatal stages (Wolffian nerve); 2) nerve penetration precedes the differentiation of the gonads and related ducts; and 3) the Wolffian nerve arises during the earliest stages from the first pair of abdominal rami communicantes. The identity between the fetal Wolffian nerve and the nerve of the suspensory ligament (higher pathway) of the adult is discussed.     

Kelvin-Helmholtz instabilities as the source of inhomogeneous mixing in nova explosions

Classical novae are thermonuclear explosions in binary stellar systems containing a white dwarf accreting material from a close companion star. They repeatedly eject 10(-4)-10(-5) solar masses of nucleosynthetically enriched gas into the interstellar medium, recurring on intervals of decades to tens of millennia. They are probably the main sources of Galactic (15)N, (17)O and (13)C. The origin of the large enhancements and inhomogeneous distribution of these species observed in high-resolution spectra of ejected nova shells has, however, remained unexplained for almost half a century. Several mechanisms, including mixing by diffusion, shear or resonant gravity waves, have been proposed in the framework of one-dimensional or two-dimensional simulations, but none has hitherto proven successful because convective mixing can only be modelled accurately in three dimensions. Here we report the results of a three-dimensional nuclear-hydrodynamic simulation of mixing at the core-envelope interface during nova outbursts. We show that buoyant fingering drives vortices from the Kelvin-Helmholtz instability, which inevitably enriches the accreted envelope with material from the outer white-dwarf core. Such mixing also naturally produces large-scale chemical inhomogeneities. Both the metallicity enhancement and the intrinsic dispersions in the abundances are consistent with the observed values.     

Development of the innervation of the urogenital complex in the fetal mouse

Summary The developing urogenital complex of the fetal mouse was studied by means of silver impregnation and electron microscopy. These studies showed that: 1) the mesonephric field is innervated during prenatal stages (Wolffian nerve); 2) nerve penetration precedes the differentiation of the gonads and related ducts; and 3) the Wolffian nerve arises during the earliest stages from the first pair of abdominal rami communicantes. The identity between the fetal Wolffian nerve and the nerve of the suspensory ligament (higher pathway) of the adult is discussed.     

Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature

We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sj?gren's syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log(10) odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity.     

Viability of rabbit bone marrow after cryopreservation (in vitro and in vivo)

Summary A technique for preservation of rabbit bone marrow is described, which preserves viability of stem cells in all 22 animals as tested by autologous bone marrow transplantation and in vitro growth. Erythroid precursors survived better than myeloid precursors as observed by in vitro and in vivo recovery.Supported by the Swiss Science Fondation 3.846.0.79.     

Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations

Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate.