Tyro-3 family receptors are essential regulators of mammalian spermatogenesis

We have generated and analysed null mutations in the mouse genes encoding three structurally related receptors with tyrosine kinase activity: Tyro 3, Axl, and Mer. Mice lacking any single receptor, or any combination of two receptors, are viable and fertile, but male animals that lack all three receptors produce no mature sperm, owing to the progressive death of differentiating germ cells. This degenerative phenotype appears to result from a failure of the tropic support that is normally provided by Sertoli cells of the seminiferous tubules, whose function depends on testosterone and additional factors produced by Leydig cells. Tyro 3, Axl and Mer are all normally expressed by Sertoli cells during postnatal development, whereas their ligands, Gas6 and protein S, are produced by Leydig cells before sexual maturity, and by both Leydig and Sertoli cells thereafter. Here we show that the concerted activation of Tyro 3, Axl and Mer in Sertoli cells is critical to the role that these cells play as nurturers of developing germ cells. Additional observations indicate that these receptors may also be essential for the tropic maintenance of diverse cell types in the mature nervous, immune and reproductive systems.     

DNA overwinds when stretched

DNA is often modelled as an isotropic rod, but its chiral structure suggests the possible importance of anisotropic mechanical properties, including coupling between twisting and stretching degrees of freedom. Simple physical intuition predicts that DNA should unwind under tension, as it is pulled towards a denatured structure. We used rotor bead tracking to directly measure twist-stretch coupling in single DNA molecules. Here we show that for small distortions, contrary to intuition, DNA overwinds under tension, reaching a maximum twist at a tension of approximately 30 pN. As tension is increased above this critical value, the DNA begins to unwind. The observed twist-stretch coupling predicts that DNA should also lengthen when overwound under constant tension, an effect that we quantitatively confirm. We present a simple model that explains these unusual mechanical properties, and also suggests a possible origin for the anomalously large torsional rigidity of DNA. Our results have implications for the action of DNA-binding proteins that must stretch and twist DNA to compensate for variability in the lengths of their binding sites. The requisite coupled DNA distortions are favoured by the intrinsic mechanical properties of the double helix reported here.     

Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1

We identified 11 human pedigrees with dominantly inherited hemolytic anemias in both the hereditary stomatocytosis and spherocytosis classes. Affected individuals in these families had an increase in membrane permeability to Na and K that is particularly marked at 0 degrees C. We found that disease in these pedigrees was associated with a series of single amino-acid substitutions in the intramembrane domain of the erythrocyte band 3 anion exchanger, AE1. Anion movements were reduced in the abnormal red cells. The 'leak' cation fluxes were inhibited by SITS, dipyridamole and NS1652, chemically diverse inhibitors of band 3. Expression of the mutated genes in Xenopus laevis oocytes induced abnormal Na and K fluxes in the oocytes, and the induced Cl transport was low. These data are consistent with the suggestion that the substitutions convert the protein from an anion exchanger into an unregulated cation channel.     

Modified Dye for Water-Fast Ink-Jet Printing

A quaternary ammonium compound containing amino acid residue was synthesized by Converting 3-chloro-2-hydroxy-propyalkyldimethylammonium chlorides into its epoxide derivatives, then attaching an amino acid to the epoxide derivatives synthesized a quaternary ammonium compound containing amino acid residue. Modified dyes were prepared by the ionotropy of anionic dyes with the quaternary ammonium compound containing amino acid residue. It was discovered that the modified dyes exhibited an excellent pH controllable solubility. These modified dyes have good water solubility at pH> 8.0, but they were water insoluble at pH < 6.5. On the printing paper, modified dyes in water-based ink-jet print ink could convert to water insoluble form and give prints excellent water fastness.