Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis

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Spironolactone-related inhibitors of type II 17beta-hydroxysteroid dehydrogenase: chemical synthesis, receptor binding affinities, and proliferative/antiproliferative activities.

The family of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyzes the formation and inactivation of testosterone (T), dihydrotestosterone (DHT), and estradiol (E2), thus playing a crucial role in the regulation of active steroid hormones in target tissues. Among the five known 17beta-HSD enzymes, type II catalyzes the oxidation of E2 into estrone (E1), T into androstenedione, DHT into androstanedione, and 20alpha-dihydroprogesterone into progesterone. Specific inhibitors are thus an interesting means to study the regulation and to probe the structure of type II 17beta-HSD. In this context, we have efficiently synthesized a series of 7alpha-thioalkyl and 7alpha-thioaryl derivatives of spironolactone that inhibit type II 17beta-HSD. These new C19-steroidal inhibitors possess two important pharmacophores, namely 17-spiro-gamma-lactone and a bulky side-chain at the 7alpha-position. It was found that a para-substituted benzylthio group at the 7alpha-position enhances the inhibitory potency of spironolactone derivatives on type II 17beta-HSD. In fact, the compound with a para-hydroxy-benzylthio group showed an IC50 value of 0.5 microM against type II 17beta-HSD, whereas the compound with a para-[2-(1-piperidinyl)-ethoxy]-benzylthio group inhibited this enzyme with an IC50 value of 0.7 microM. The latter inhibitor is more selective than the former because it did not show any inhibitory potency against P450 aromatase as well as any affinity towards four steroid receptors (AR, PR, GR, ER). As a result, this inhibitor did not show any proliferative effect on androgen-sensitive Shionogi cells and estrogen-sensitive ZR-75-1 cells. These findings contribute to a better knowledge of the structure of type II 17beta-HSD and offer an interesting tool to study the regulation of this enzyme in several biological systems.     

A single genetic locus in the phytopathogen Pantoea stewartii enables gut colonization and pathogenicity in an insect host

Aphids are typically exposed to a variety of epiphytic and phytopathogenic bacteria, many of which have entomopathogenic potential. Here we describe the interaction between Pantoea stewartii ssp. stewartii DC283 (DC283), an enteric phytopathogen and causal agent of Stewart's wilt, and the pea aphid, Acyrthosiphon pisum . When ingested by aphids, DC283 establishes and aggregates in the crop and gut, preventing honeydew flow and excretion, resulting in aphid death in 72 h. A mutagenesis screen identified a single locus, termed ucp1 (yo u c annot p ass), whose disruption abolishes aphid pathogenicity. Moreover, the expression of ucp1 in Escherichia coli is sufficient to mediate the hindgut aggregation phenotype by this normally avirulent species. Ucp1 is related to six other proteins in the DC283 genome, each having a common N-terminal region and a divergent C-terminus, but only ucp1 has a role in pathogenicity. Based on predicted motifs and secondary structure, Ucp1 is a membrane-bound protein that functions in bacterial adhesion and promotes the formation of aggregates that are lethal to the insect host. These results illustrate that the enteric plant pathogenic bacteria have the capacity to exploit alternative non-plant hosts, and retain genetic determinants for colonizing the gut.     

Immunological study of a hemophiliac treated according to the Bonn protocol for 2 1/2 years

A major haemophiliac A, 27 years old, has been treated during 30 months, with high dosage of imported Factor VIII, in order to reduce the titer of a F VIII antibody. A good clinical result has been obtained. No sign of immunodeficiency has been observed. Normal values were obtained for T4/T8, ratio B2 microglobulin and no antibody was detected against the LAV virus isolated from cases of AIDS.     

Expression of laminin by human fibroblasts, HT1080 fibrosarcoma cells and MCF-7 breast adenocarcinoma cells. Lack of regulation by the cell density and extracellular matrix.

We have cultured normal fibroblasts, fibrosarcoma HT1080 cells and breast adenocarcinoma MCF-7 cells on various substrates (plastic, collagen type I, laminin). All cell types used adhered on the three substrates with, however, a delayed attachment on laminin. On all substrates, cell grew as monolayer with the exception of MCF-7 cells that formed clusters on laminin. The epithelial MCF-7 cells as well as mesenchymal cells (fibroblasts and tumoral HT1080 cells) synthesized laminin and expressed mRNA coding for laminin B1 chain and for the 67 kD laminin binding protein. The levels of these mRNAs were not modulated by culture conditions which affect cell morphology nor by cell density.     

Which adult male savanna baboons form coalitions?

We investigated the mechanism of alliance formation among adult male savanna baboons by comparing the characteristics of males that formed coalitions frequently with males that never or seldom took part in coalitions. We observed three groups: two of Papio cynocephalus cynocephalusin Amboseli National Park, Kenya, and one of P. c. anubisin the vicinity of Gilgil, Kenya. We considered four hypotheses: (1) Males must be familiar with each other, (2) males must have an affinitive bond, (3) males must have more than average experience, and (4) the combined fighting ability of the coalition partners relative to the fighting ability of their opponent determines the likelihood that a coalition is formed. We conclude that relative fighting ability forms the key factor in coalition formation. High- ranking males do not form coalitions often, since they hardly need them. Low- ranking males rarefy form coalitions, since they cannot form effective coalitions among themselves. Affinity (“friendship”) may play a role as an additional factor. The relation of coalition formation with age and period of residence, which was found in several studies, can be explained largely by the correlation between these parameters and fighting ability.