Dissociation of glucocorticoid effects of C-21 steroids at high concentrations in thymocytes

A dissociation between inhibition of RNA synthesis and cell lysis was observed when thymocytes of adrenalectomized rats were incubated with high concentrations of pregn-4-ene-11 beta-ol-3,20-dione and pregna-1,4-diene-11 beta-ol-3,20-dione. In contrast, no dissociation of these effects was found with the typical glucocorticoids cortisol and corticosterone, nor with their 1,4-diene analogs under the same conditions.     

Intranuclear crystalloids in arcuate nucleus neurons after clomiphene citrate administration

The action of high doses of clomiphene citrate on the nuclei of hypothalamic arcuate neurons of male cats has been studied. Clomiphene produces an accumulation of typical crystalloid material in the nuclei. After administration of a protein-synthesis inhibitor, no such material was observed in clomiphene-treated animals. These ultrastructural features could possibly be due to a more intense protein synthesis in the hypothalamic arcuate neurons.     

Chemical communication: butterfly anti-aphrodisiac lures parasitic wasps

To locate their hosts, parasitic wasps can 'eavesdrop' on the intraspecific chemical communications of their insect hosts. Here we describe an example in which the information exploited by the parasitic wasp Trichogramma brassicae is a butterfly anti-aphrodisiac that is passed from male to female Pieris brassicae butterflies during mating, to render them less attractive to conspecific males. When the tiny wasp detects the odour of a mated female butterfly, it rides on her (Fig. 1) to her egg-laying sites and then parasitizes the freshly laid eggs. If this fascinating strategy is widespread in nature, it could severely constrain the evolution of sexual communication between hosts.     

Acid-base equilibrium in the heart-lung preparation

Résumé Etude de l'équilibre acide-basique de la préparation cur-poumon de l'étourneau, réalisée avec la technique habituelle et les moyens de corriger les altérations constatées. La recherche des causes de ces altérations a permis de conclure que l'alcalose respiratoire est due à la ventilation dont on se sert habituellement, tandis que l'acidose métabolique est due à une production de métabolites acides déclanchés surtout par la saignée des animaux donneurs et par la glucolyse qui se produit à partir de l'extraction du sang et jusqu'au moment de son emploi dans la préparation.

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This work has been supported by a grant from the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.     

ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner

R-spondin proteins strongly potentiate Wnt signalling and function as stem-cell growth factors. Despite the biological and therapeutic significance, the molecular mechanism of R-spondin action remains unclear. Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. Inhibition of ZNRF3 enhances Wnt/β-catenin signalling and disrupts Wnt/planar cell polarity signalling in vivo. Notably, R-spondin mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors. Mechanistically, R-spondin interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3. These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration.     

Fungal genus Hypocrea/Trichoderma: from barcodes to biodiversity

Hypocrea/Trichoderma is a genus of soil-borne or wood-decaying fungi containing members important to mankind as producers of industrial enzymes and biocontrol agents against plant pathogens, but also as opportunistic pathogens of immunocompromised humans and animals, while others can cause damage to cultivated mushroom. With the recent advent of a reliable, BarCode-aided identification system for all known taxa of Trichoderma and Hypocrea, it became now possible to study some of the biological fundamentals of the diversity in this fungal genus in more detail. In this article, we will therefore review recent progress in （1） the understanding of the geographic distribution of individual taxa; （2） mechanisms of speciation leading to development of mushroom diseases and facultative human mycoses; and （3） the possible correlation of specific traits of secondary metabolism and molecular phylogeny.     

Clones identification of Sequoia sempervirens (D. Don) Endl. in Chile by using PCR-RAPDs technique

A protocol of polymerase chain reaction-random amplified polymorphic DNAs (PCR-RAPDs) was established to analyse the gene diversity and genotype identification for clones of Sequoia sempervirens (D. Don) Endl. in Chile. Ten (out of 34) clones from introduction trial located in Voipir-Villarrica, Chile, were studied. The PCR-RAPDs technique and a modified hexadecyltrimethylammonium bromide (CTAB) protocol were used for genomic DNA extraction. The PCR tests were carried out employing 10-mer random primers. The amplification products were detected by electrophoresis in agarose gels. Forty nine polymorphic bands were obtained with the selected primers (BG04, BF07, BF12, BF13, and BF14) and were ordered according to their molecular size. The genetic similarity between samples was calculated by the Jaccard index and a dendrogram was constructed using a cluster analysis of unweighted pair group method using arithmetic averages (UPGMA). Of the primers tested, 5 (out of 60) RAPD primers were selected for their reproducibility and high polymorphism. A total of 49 polymorphic RAPD bands were detected out of 252 bands. The genetic similarity analysis demonstrates an extensive genetic variability between the tested clones and the dendrogram depicts the genetic relationships among the clones, suggesting a geographic relationship. The results indicate that the RAPD markers permitted the identification of the assayed clones, although they are derived from the same geographic origin.     

Cellular and molecular action of the putative GABA-mimetic,gabapentin

Gabapentin was originally designed as an anti-convulsant gamma-aminobutyric acid (GABA) mimetic capable of crossing the blood-brain barrier. In the present review we show that although gabapentin is not a GABA mimetic, it has great utility as an add-on therapy for epilepsy and as a first-line treatment for neuropathic pain. We summarise the studies that have been performed which demonstrate that gabapentin appears to interact with a novel binding site expressed at high density within the central nervous system (CNS), namely the alpha2delta voltage-dependent calcium channel subunit. The review continues by examining the effects of gabapentin on calcium channel function and neurotransmitter release before, in the latter part of the review, summarising the more recently discovered actions of gabapentin in relation to intracellular signalling.     

Characterization of the common genetic defect in humans deficient in debrisoquine metabolism

In population studies of individuals given the antihypertensive drug debrisoquine, two distinct phenotypes have been described: extensive metabolizers excrete 10-200 times more of the urinary metabolite 4-hydroxydebrisoquine than poor metabolizers. In family studies the poor-metabolizer phenotype behaves as an autosomal recessive trait with an incidence between 5% and 10% in the white population of Europe and North America, and extends to the deficient metabolism of more than 20 commonly prescribed drugs. Clinical studies have shown that such individuals are at high risk for the development of adverse side effects from these and probably many other drugs. Here we show that poor metabolizers have negligible amounts of the cytochrome P450 enzyme P450db1. We have cloned the human P450db1 complementary DNA and expressed it in mammalian cell culture. Furthermore, by directly cloning and sequencing cDNAs from several poor-metabolizer livers, we have identified three variant messenger RNAs that are products of mutant genes producing incorrectly spliced db1 pre-mRNA, providing a molecular explanation for one of man's most commonly defective genes (frequency of mutant alleles 35-43%).