Phenyl-substituted aminomethylene-bisphosphonates inhibit human P5C reductase and show antiproliferative activity against proline-hyperproducing tumour cells

In certain cancers, such as breast, prostate and some lung and skin cancers, the gene for the enzyme catalysing the second and last step in proline synthesis, δ¹-pyrroline-5-carboxylate (P5C) reductase, has been found upregulated. This leads to a higher proline content that exacerbates the effects of the so-called proline-P5C cycle, with tumour cells effectively using this method to increase cell survival. If a method of reducing or inhibiting P5C reductase could be discovered, it would provide new means of treating cancer. To address this point, the effect of some phenyl-substituted derivatives of aminomethylene-bisphosphonic acid, previously found to interfere with the catalytic activity of plant and bacterial P5C reductases, was evaluated in vitro on the human isoform 1 (PYCR1), expressed in E. coli and affinity purified. The 3.5-dibromophenyl- and 3.5-dichlorophenyl-derivatives showed a remarkable effectiveness, with IC₅₀ values lower than 1 µM and a mechanism of competitive type against both P5C and NADPH. The actual occurrence in vivo of enzyme inhibition was assessed on myelogenous erythroleukemic K562 and epithelial breast cancer MDA-MB-231 cell lines, whose growth was progressively impaired by concentrations of the dibromo derivative ranging from 10⁻⁶ to 10⁻⁴M. Interestingly, growth inhibition was not relieved by the exogenous supply of proline, suggesting that the effect relies on the interference with the proline-P5C cycle, and not on proline starvation.     

Validity of the reduced version of the Morningness-Eveningness Questionnaire

Sleep and Biological Rhythms - The aim of the present work was to validate the reduced version of the Morningness-Eveningness Questionnaire (MEQr) using circadian motor activity as external...     

Functional Anatomy of the Ovule in Broad Bean (Vicia faba L.): Ultrastructural Seed Development and Nutrient Pathways

Ovules of broad bean (Vicia faba L.) were studied to discloseultrastructural features, which can facilitate nutrient transportto the embryo sac from 10 d after pollination (DAP) to the matureseed. Fertilization occurs during the first 24 h after pollination.The endosperm is a coenocyte, which is eventually consumed bythe embryo. By 10 DAP the inner integument is degraded and theouter integument adjoins the embryo sac boundary. The heart-shapedembryo approaches the embryo sac boundary at two sites, whichhere are named contact zones. Small integument cells in theneighbourhood of the first formed contact zones become separatedby prominent intercellular spaces. A heterogenous scatteringmaterial, probably representing secretion products accumulatesin these spaces. By 14-16 DAP the integument exudate disappears,and the suspensor degenerates. As the contact zones increasein size, wall ingrowths form a bridging network in the narrowspace between the embryo sac boundary and the extra-embryonicpart of the endosperm wall. The epidermal cells of the embryoseparate adjacent to these zones, and develop conspicuous wallingrowths. At 20 DAP vacuoles showing various stages in formationof protein bodies appear in the cells of the embryo.Copyright1994, 1999 Academic Press Vicia faba, broad beans, ovule, seed, nutrient transport     

Palaeodistribution modelling does not support disjunct Pleistocene refugia in several Central American plant taxa

Aim We combine evidence from palaeoniche modelling studies of several tree species to estimate the extent of Central American forest during the Last Glacial Maximum (LGM). In particular, we ask whether the distributions of these species are likely to have changed since the LGM, and whether LGM distributions coincide with previously proposed Pleistocene refugia in this area. Location Central American wet and seasonally dry forests. Methods We developed ecological niche models using two simulations of Pleistocene climate and occurrence data for 15 Neotropical plant species. We focused on palaeodistribution models of three ‘focal’ tree species that occur in wet and seasonally dry Central American forests, where recent phylogeographic data suggest Pleistocene differentiation coincident with previously proposed refugia. We added predictions from six wet‐forest and six seasonally dry‐forest obligate plant species to gauge whether Pleistocene range shifts were specific to habitat type. Correlation analyses were performed between projected LGM and present distributions, LGM distributions and previously proposed refugia. We also asked whether modelled palaeodistributions were smaller than their current extents. Results According to our models, the ranges of the study species were not reduced during the LGM, and did not correlate with refugial models, regardless of habitat type. Relative range sizes between present and LGM distributions did not indicate significant range changes since the LGM. However, relative range sizes differed overall between the two palaeoclimate models. Main conclusions Many of the modelled palaeodistributions of study species were not restricted to refugia during the LGM, regardless of forest type. While constrained from higher elevations, most species found suitable habitat at coastal margins and on newly exposed land due to lowered sea levels during the LGM. These results offer no corroboration for Pleistocene climate change as a driver of genetic differentiation in the ‘focal’ species. We offer alternative explanations for genetic differentiation found in plant species in this area.     

Further surveys of Pseliodinium vaubanii Sournia (Pirrophyta) in the Adriatic sea

Abstract

The presence, in the North Adriatic sea and in the Chioggia and Marano lagoons, of Pseliodinium vaubanii a rare dinoflagellate species, is reported. Our results showed that Pseliodinium vaubanii is a very frequent and abundant species in these environments.     

Cyclic lipopeptide-producing Pseudomonas koreensis group strains dominate the cocoyam rhizosphere of a Pythium root rot suppressive soil contrasting with P. putida prominence in conducive soils

Pseudomonas isolates from tropical environments have been underexplored and may form an untapped reservoir of interesting secondary metabolites. In this study, we compared Pseudomonas and cyclic lipopeptide (CLP) diversity in the rhizosphere of a cocoyam root rot disease (CRRD) suppressive soil in Boteva, Cameroon with those from four conducive soils in Cameroon and Nigeria. Compared with other soils, Boteva andosols were characterized by high silt, organic matter, nitrogen and calcium. Besides, the cocoyam rhizosphere at Boteva was characterized by strains belonging mainly to the P. koreensis and P. putida (sub)groups, with representations in the P. fluorescens, P. chlororaphis, P. jessenii and P. asplenii (sub)groups. In contrast, P. putida isolates were prominent in conducive soils. Regarding CLP diversity, Boteva was characterized by strains producing 11 different CLP types with cocoyamide A producers, belonging to the P. koreensis group, being the most abundant. However, putisolvin III-V producers were the most dominant in the rhizosphere of conducive soils in both Cameroon and Nigeria. Furthermore, we elucidated the chemical structure of putisolvin derivatives—putisolvin III-V, and described its biosynthetic gene cluster. We show that high Pseudomonas and metabolic diversity may be driven by microbial competition, which likely contributes to soil suppressiveness to CRRD.