Amnionless,essential for mouse gastrulation,is mutated in recessive hereditary megaloblastic anemia

The amnionless gene, Amn, on mouse chromosome 12 encodes a type I transmembrane protein that is expressed in the extraembryonic visceral layer during gastrulation. Mice homozygous with respect to the amn mutation generated by a transgene insertion have no amnion. The embryos are severely compromised, surviving to the tenth day of gestation but seem to lack the mesodermal layers that normally produce the trunk. The Amn protein has one transmembrane domain separating a larger, N-terminal extracellular region and a smaller, C-terminal cytoplasmic region. The extracellular region harbors a cysteine-rich domain resembling those occurring in Chordin, found in Xenopus laevis embryos, and Sog, found in Drosophila melanogaster. As these cysteine-rich domains bind bone morphogenetic proteins (Bmps), it has been speculated that the cysteine-rich domain in Amn also binds Bmps. We show that homozygous mutations affecting exons 1-4 of human AMN lead to selective malabsorption of vitamin B12 (a phenotype associated with megaloblastic anemia 1, MGA1; OMIM 261100; refs. 5,6) in otherwise normal individuals, suggesting that the 5' end of AMN is dispensable for embryonic development but necessary for absorption of vitamin B12. When the 5' end of AMN is truncated by mutations, translation is initiated from alternative downstream start codons.     

Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome

We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. Moreover, we suggest that the KAL1 gene product, the extracellular matrix protein anosmin-1, is involved in FGF signaling and propose that the gender difference in anosmin-1 dosage (because KAL1 partially escapes X inactivation) explains the higher prevalence of the disease in males.     

The interaction of free radicals in protein and melanin

Résumé L'addition de mélanine au blanc d'uf frais diminue la concentration des radicaux libres due à la lumière de 366 mµ. Cela permet de supposer que la mélanine agit comme un capteur d'électrons.     

Reciprocal biological activities of the cyclic tetrapeptides chlamydocin and HC-toxin

Chlamydocin, a potent cytostatic agent against cultured mammalian cells, and HC-toxin, a host-specific phytotoxin, are cyclic tetrapeptides containing the same epoxide alpha-amino acid. We show here that these compounds have reciprocal biological activity; HC-toxin is cytostatic against cultured mastocytoma cells, and chlamydocin has host-specific toxin activity against maize. Chlamydocin and another related cyclic peptide, Cyl-2, are less host-specific than HC-toxin because maize tolerant to HC-toxin is more sensitive to chlamydocin and Cyl-2.     

Pathogenesis and therapy of psoriasis

Psoriasis is one of the most common human skin diseases and is considered to have key genetic underpinnings. It is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells, dendritic cells and various immune-related cytokines and chemokines implicated in pathogenesis. The newest therapies for psoriasis target its immune components and may predict potential treatments for other inflammatory human diseases.