Molecular phylogeny of the fern genus Elaphoglossum (Elaphoglossaceae) based on chloroplast non-coding DNA sequences: contributions of species from the Indian Ocean area

We performed a phylogenetic analysis of the fern genus Elaphoglossum using two non-coding chloroplast spacers: trnL-trnF and rps4-trnS. The sampling includes 123 species, of which 80 have not been previously sequenced, and for the first time includes species from Africa and the Indian Ocean area. The results of this expanded study largely agree with an earlier molecular study based on a smaller group of neotropical species and with the morphology-based classification of Mickel and Atehortua. We found, however, that some infrageneric groups such as section Elaphoglossum are not monophyletic. Besides section Elaphoglossum pro parte, we recognize six sections: two new monospecific, unnamed sections, and the previously established sections Lepidoglossa, Squamipedia, Amygdalifolia, and "Subulate-scaled clade." We divide the subulate-scaled clade into subsection Setosa (hydathodes present) and Polytrichia (hydathodes absent), and section Elaphoglossum is divided into subsections Platyglossa and Pachyglossa, two groups that do not appear to be supported by any single morphological character. In general, however, the main clades are supported by morphology. Finally, we discuss the species of the Indian Ocean region and their affinities with the neotropical ones. Out of the 11 species pairs postulated by Moran and Smith on the basis of morphology, two are well supported (E. eximium-E. aubertii; E. piloselloides-E. spatulatum) and three are not supported (E. ciliatum-E. humbertii; E. muscosum-E. poolii; E. paleaceum-E. deckenii), and two remain unresolved (E. erinaceum-E. hybridum; E. glabellum-E. acrostichoides) because our molecular markers were not variable enough. Four species pairs could not be tested because specimens were lacking. Unsupported species pairs are best interpreted as morphological convergences. Two additional species pairs are proposed: E. cuspidatum-E. succisaefolium; E. doanense-E. hornei. Placement of the species from the Indian Ocean suggests that at least 13 long-distance dispersal events occurred between the Neotropics and the Indian Ocean-Africa.     

Genome scan for quantitative trait loci influencing HDL levels: evidence for multilocus inheritance in familial combined hyperlipidemia

Several genome scans in search of high-density lipoprotein (HDL) quantitative trait loci (QTLs) have been performed. However, to date the actual identification of genes implicated in the regulation of common forms of HDL abnormalities remains unsuccessful. This may be due, in part, to the oligogenic and multivariate nature of HDL regulation, and potentially, pleiotropy affecting HDL and other lipid-related traits. Using a Bayesian Markov Chain Monte Carlo (MCMC) approach, we recently provided evidence of linkage of HDL level variation to the APOA1–C3–A4–A5 gene complex, in familial combined hyperlipidemia pedigrees, with an estimated number of two to three large QTLs remaining to be identified. We also presented results consistent with pleiotropy affecting HDL and triglycerides at the APOA1–C3–A4–A5 gene complex. Here we use the same MCMC analytic strategy, which allows for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. We now present results from a genome scan in search for the additional HDL QTLs in these pedigrees. We provide evidence of linkage for additional HDL QTLs on chromosomes 3p14 and 13q32, with results on chromosome 3 further supported by maximum parametric and variance component LOD scores of 3.0 and 2.6, respectively. Weaker evidence of linkage was also obtained for 7q32, 12q12, 14q31–32 and 16q23–24.     

Sensitization to UV-induced apoptosis by the histone deacetylase inhibitor trichostatin A (TSA)

UV-induced apoptosis is a protective mechanism that is primarily caused by DNA damage. Cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts are the main DNA adducts triggered by UV radiation. Because the formation of DNA lesions in the chromatin is modulated by the structure of the nucleosomes, we postulated that modification of chromatin compaction could affect the formation of the lesions and consequently apoptosis. To verify this possibility we treated human colon carcinoma RKO cells with the histone deacetylase inhibitor trichostatin A (TSA) prior to exposure to UV radiation. Our data show that pre-treatment with TSA increased UV killing efficiency by more than threefold. This effect correlated with increased formation of CPDs and consequently apoptosis. On the other hand, TSA treatment after UV exposure rather than before had no more effect than UV radiation alone. This suggests that a primed (opened) chromatin status is required to sensitize the cells. Moreover, TSA sensitization to UV-induced apoptosis is p53 dependent. p53 and acetylation of the core histones may thus contribute to UV-induced apoptosis by modulating the formation of DNA lesions on chromatin.     

High resolution magic angle spinning NMR spectroscopy used to investigate the ability of drugs to bind to synthetic melanin

Iodobenzamides are known to possess an affinity for melanoma tissue dependent on tumor pigmentation. In order to investigate the molecular interactions of drugs with melanin in vitro, a synthetic pigment swelled in deuterium buffer at physiological pH was used. The spectra of various mixtures of each Iodobenzamide (BZ) with melanin were studied at 25 degrees C by NMR under MAS conditions. The drug which interacts with the pigment exhibits linewidths greater than those observed for the free drug in solution. Line-broadening of the resonance occurred for the N-methyl group of acetylcholine or N-ethyl and aromatic groups of BZ. However, linewidths associated with methanol or hippuric acid were less altered by the presence of melanin. These observations indicate the specificity of the interaction between some drug moieties and the sites of melanin. From the concentration dependence of line-broadening, the apparent equilibrium dissociation constant (K(d)) of drug interaction with melanin was approached. It seems that the residual concentration-dependent line-broadening is caused by perturbations of ligand exchange between free and bound states and by differences in magnetic susceptibility present in the sample at the pigment-interacting drug moiety interface. Taken together, these results demonstrate the utility of this technique for investigating binding drugs.     

Mechanisms of placebo effect and of conditioning: neurobiological data in human and animals

A placebo is a sham treatment such as pill, liquid, injection, devoid of biological activity and used in pharmacology as a control for the activity of a drug. In many cases, this placebo induces biological or psychological effects in the human. Two theories have been proposed to explain the placebo effect: the conditioning theory which states that the placebo effect is a conditioned response, and the mentalistic theory for which the patient expectation is the primary basis of the placebo effect. The mechanisms involved in these processes are beginning to be understood through new techniques of investigation in neuroscience. Dopamine and endorphins have been clearly involved as mediators of the placebo effect. Brain imaging has demonstrated that the placebo effect activates the brain similarly as the active drug and in the same brain area. This is the case for a dopamine placebo in the Parkinson'disease, for analgesic-caffeine- or antidepressor-placebo in the healthy subject. It remains to be understood how conditioning and expectancy are able to activate, in the brain, memory loops that reproduce the expected biological response.     

Effects of phosphorus intake on phosphorus flow in growing pigs: application and comparison of two models

A comparison of the models of Vitti et al. (2000, J. Anim. Sci. 78, 2706-2712) and Fernández (1995c, Livest. Prod. Sci. 41, 255-261) was carried out using two data sets on growing pigs as input. The two models compared were based on similar basic principles, although their aims and calculations differed. The Vitti model employs the rate:state formalism and describes phosphorus (P) flow between four pools representing P content in gut, blood, bone and soft tissue in growing goats. The Fernández model describes flow and fractional recirculation between P pools in gut, blood and bone in growing pigs. The results from both models showed similar trends for P absorption from gut to blood and net retention in bone with increasing P intake, with the exception of the 65 kg results from Date Set 2 calculated using the Fernández model. Endogenous loss from blood back to gut increased faster with increasing P intake in the Fernández than in the Vitti model for Data Set 1. However, for Data Set 2, endogenous loss increased with increasing P intake using the Vitti model, but decreased when calculated using the Fernández model. Incorporation of P into bone was not influenced by intake in the Fernández model, while in the Vitti model there was an increasing trend. The Fernández model produced a pattern of decreasing resorption in bone with increasing P intake, with one of the data sets, which was not observed when using the Vitti model. The pigs maintained their P homeostasis in blood by regulation of P excretion in urine.     

Differential range and activity of various forms of the Hedgehog protein

Background  

The Hedgehog (Hh) family of secreted proteins act as extra cellular messengers to control and coordinate growth and differentiation. The mechanism by which Hh protein travels across a field of cells, and results in a range of specific effects relating to the distance from the source, has been the subject of much debate. It has been suggested that the range and activity of the pathway can be linked to modifications of the Hh protein, specifically the addition of lipid groups at N- and C-terminal sites.