Pharmacodynamic profile of CQP 201-403, a novel 8α-amino-ergoline

Summary The profile of action in animals of CQP 201-403, a novel 8-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and to be more potent than bromocriptine (Parlodel^®).In memory of Dr Annemarie Closse, who died 14 June 1987.     

Cryptic genetic variation promotes rapid evolutionary adaptation in an RNA enzyme

Cryptic variation is caused by the robustness of phenotypes to mutations. Cryptic variation has no effect on phenotypes in a given genetic or environmental background, but it can have effects after mutations or environmental change. Because evolutionary adaptation by natural selection requires phenotypic variation, phenotypically revealed cryptic genetic variation may facilitate evolutionary adaptation. This is possible if the cryptic variation happens to be pre-adapted, or "exapted", to a new environment, and is thus advantageous once revealed. However, this facilitating role for cryptic variation has not been proven, partly because most pertinent work focuses on complex phenotypes of whole organisms whose genetic basis is incompletely understood. Here we show that populations of RNA enzymes with accumulated cryptic variation adapt more rapidly to a new substrate than a population without cryptic variation. A detailed analysis of our evolving RNA populations in genotype space shows that cryptic variation allows a population to explore new genotypes that become adaptive only in a new environment. Our observations show that cryptic variation contains new genotypes pre-adapted to a changed environment. Our results highlight the positive role that robustness and epistasis can have in adaptive evolution.     

Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs.     

Optimal temperatures for growth and upper thermal tolerance of juvenile northern leatherside chub

We examined optimal temperatures for growth and the upper thermal tolerance of juvenile northern leatherside chub ( Lepidomeda copei ). We conducted 2 experiments using the acclimated chronic-exposure method to estimate optimal temperature for growth of age-0 northern leatherside chub (range 12.8–28.3 °C). Upper thermal tolerance was estimated using the critical thermal maximum (CTM) and upper incipient lethal temperature (UILT) methods for fish acclimated at 15, 18, 23, and 28 °C. We also measured stream temperatures in Yellow Creek, Summit County, Utah, during July–August 2006 to compare our results to actual summer stream temperatures. Survival in growth tests was not significantly different between treatment temperatures in either experiment (P > 0.098). The optimal temperature for growth in the 1st trial estimated from the 2nd-order polynomial regression was 23.0 °C, falling outside the range of experimental temperatures (12.8–22.2 °C). The estimated optimal temperature for growth in the 2nd trial was 23.2 °C. In the upper thermal tolerance tests, juvenile northern leatherside chub had CTM values between 29.6 and 35.0 °C; CTM values increased as acclimation temperature increased. Upper incipient lethal temperatures (LT50) ranged from 26.5 to 30.2 °C, increasing with acclimation temperature. Summer stream temperatures in Yellow Creek had a lower mean (14.0–18.1 °C) than did the optimal temperature for growth determined in these studies, but these temperatures exhibited diel fluctuations as large as 15.7 °C.     

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.     

Pigeons homing: Some experiments for testing the olfactory hypothesis

Summary Homing experiments on Swiss pigeons show that the birds use olfactory cues for navigational purposes and that outward journey detours influence their initial orientation.This work was supported by the Consiglio Nazionale delle Ricerche and by the Swiss National Foundation for Scientific Research.