Notch1 functions as a tumor suppressor in mouse skin

Notch proteins are important in binary cell-fate decisions and inhibiting differentiation in many developmental systems, and aberrant Notch signaling is associated with tumorigenesis. The role of Notch signaling in mammalian skin is less well characterized and is mainly based on in vitro studies, which suggest that Notch signaling induces differentiation in mammalian skin. Conventional gene targeting is not applicable to establishing the role of Notch receptors or ligands in the skin because Notch1-/- embryos die during gestation. Therefore, we used a tissue-specific inducible gene-targeting approach to study the physiological role of the Notch1 receptor in the mouse epidermis and the corneal epithelium of adult mice. Unexpectedly, ablation of Notch1 results in epidermal and corneal hyperplasia followed by the development of skin tumors and facilitated chemical-induced skin carcinogenesis. Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors. Furthermore, Notch1 inactivation in the epidermis results in derepressed beta-catenin signaling in cells that should normally undergo differentiation. Enhanced beta-catenin signaling can be reversed by re-introduction of a dominant active form of the Notch1 receptor. This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin.     

High-affinity binding of beta-alanine to cerebral synaptosomes might involve glycine-receptors.

High-affinity, Na+-independent binding of beta-alanine to a synaptosomal fraction of rat brain was potently inhibited by glycine and by some other alpha-amino acids, but not by taurine or GABA. This binding mechanism, which was also sensitive to both bicuculline and strychnine, might involve synaptic receptors for both beta-alanine and glycine.     

IgG purification to measure the level of an iodinated thyroglobulin peptide, the 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine in human serum

Antibodies reacting with 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine (I2Tyr-I2Tyr) were elicited in rabbits by immunization with an oxidized yeast conjugate coupled with I2Tyr-I2Tyr. Ion-exchange chromatography was used to purify immunoglobulins, in order to improve the specificity in measurement of I2Tyr-I2Tyr level in patient serum. IgG binding capacity versus I2Tyr-I2Tyr was considerably increased after immunoglobulin purification.     

GABA stimulates the rabbit corneal endothelial fluid pump.

GABA and its analogues were shown to activate the rabbit corneal endothelial fluid pump in the micromolar range. The stimulation was abolished by bicuculline and chlorpromazine, but not by picrotoxin.     

On the regulatory properties of a halophilic malic enzyme fromHalobacterium cutirubrum

Summary The NADP-linked malic enzyme fromHalobacterium cutirubrum is strongly inhibited by acetyl-CoA and NADH, and rather weakly inhibited by oxaloacetate and glyoxylate, in the presence of very high KCl concentrations (3,M), considered physiological for the extremely halophilic bacteria.This work was supported by grants from the consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina, and the Consejo de Investigaciones de la Universidad Nacional de Rosario. JJC and MCV are members of the Carrera del Investigador Científico of the former and the latter institutions, respectively.     

Similar paracrystals of endoplasmic reticulum in the photoemitters and the photoreceptors of scale-worms

Summary Paracrystals of tubular endoplasmic reticulum are the characteristic of the luminous cells in the elytra of polynoïd worms, and they are the sources of luminescence as well as of fluorescence. Structurally similar paracrystals are now found to be the main constituent of the lens in the eyes of all the Aphroditidae.