Mouse models for multistep tumorigenesis.

The mouse is an ideal model system for studying the molecular mechanisms underlying the pathogenesis of human cancer. The generation of transgenic and gene-knockout mice has been instrumental in determining the role of major determinants in this process, such as oncogenes and tumor-suppressor genes. In the past few years, modeling cancer in the mouse has increased in its complexity, allowing in vivo dissection of the fundamental concepts underlying cooperative oncogenesis in various tumor types. In this review, we discuss how this transition has been facilitated, providing relevant examples. We also review how, in the post-genome era, novel methodologies will further accelerate the study of multi-step tumorigenesis in the mouse.     

Rediscovery of Nebela ansata (Amoebozoa: Arcellinida) in eastern North America: biogeographical implications

Aim The question whether free‐living protists are generally cosmopolitan is currently a matter of debate. In this study we investigate the geographical distribution of a distinctive testate amoeba species, Nebela ansata, and use our data to assess the potential for highly restricted distribution patterns in some protist species. Location Global. Methods We analysed (1) 3400 testate amoeba publications from North America and other continents, (2) unpublished slides of the Penard Collection of the Natural History Museum, London, UK, and (3) 104 Sphagnum samples from eastern North America. Non‐metric multidimensional scaling (NMDS) was used to visualize the similarities in testate amoeba community composition among 1012 North American samples, including two communities that contained N. ansata. Results We rediscovered N. ansata at a site in New Jersey located close to its type locality, and in Nova Scotia. We also report the existence of an apparently unpublished museum specimen originally collected from New Jersey. Our extensive literature survey confirmed the presence of this species only in the temperate part of eastern North America. The NMDS revealed that communities with N. ansata were less similar to each other than to communities from other parts of North America, suggesting that favourable habitats for N. ansata occur in other Sphagnum‐dominated peatlands, a habitat type that has been extensively sampled in North America and elsewhere. Main conclusions These data provide an unusually convincing case of a free‐living microorganism with a very limited distribution range in the temperate part of eastern North America. The remarkably restricted distribution of N. ansata highlights the extent of our ignorance about the natural history of free‐living microorganisms, and raises questions about the lack of attention to microbial diversity in conservation biology.     

Differential response to abiotic stress controls species distributions at biogeographic transition zones

Understanding range limits is critical to predicting species responses to climate change. Subtropical environments, where many species overlap at their range margins, are cooler, more light‐limited and variable than tropical environments. It is thus likely that species respond variably to these multi‐stressor regimes and that factors other than mean climatic conditions drive biodiversity patterns. Here, we tested these hypotheses for scleractinian corals at their high‐latitude range limits in eastern Australia and investigated the role of mean climatic conditions and of parameters linked to abiotic stress in explaining the distribution and abundance of different groups of species. We found that environmental drivers varied among taxa and were predominantly linked to abiotic stress. The distribution and abundance of tropical species and gradients in species richness (alpha diversity) and turnover (beta diversity) were best explained by light limitation, whereas minimum temperatures and temperature fluctuations best explained gradients in subtropical species, species nestedness and functional diversity. Variation in community structure (considering species composition and abundance) was most closely linked to the combined thermal and light regime. Our study demonstrates the role of abiotic stress in controlling the distribution of species towards their high‐latitude range limits and suggests that, at biogeographic transition zones, robust predictions of the impacts of climate change require approaches that account for various aspects of physiological stress and for species abundances and characteristics. These findings support the hypothesis that abiotic stress controls high‐latitude range limits and caution that projections solely based on mean temperature could underestimate species’ vulnerabilities to climate change.     

Capsicum spp in vitro liquid cell suspensions: A useful system for the production of capsaicinoids and polyphenols

Capsicum are among the most extensively cultivated and consumed plant species in the world, because of their unique pungency, aroma and colour. The typical burning sensation caused by chili peppers is due to the occurrence of a group of alkaloids named capsaicinoids. In the present study, the production of solid callus and cell suspensions from hypocotyl explants of three different chili pepper cultivars (Capsicum annuum L. cv. Mazzolino, Capsicum chinense Jacq. cv. Naga Morich and Pimenta de Neyde), was optimised. In addition, C. chinense cv. Naga Morich cell suspensions were supplemented with biotic elicitors (methyl-jasmonate and chitosan) and with precursors and intermediates of capsaicin biosynthesis (vanillin, phenylalanine and valine), and both cells and media were analysed for capsaicinoid, polyphenol, flavonoid contents and for antioxidant activity. This is the first report regarding capsaicinoid elicitation with pure chitosan and with a combination of precursors of both phenylpropanoid and valine pathways. Overall, the highest capsaicinoid levels were detected in cell extracts from cultures treated with 10 μM methyl-jasmonate and with a combination of phenylalanine and valine amino acids (100 μM each). The present results confirm the possibility of using hypocotyl chili pepper cell suspensions to produce high amounts of health beneficial metabolites.     

A review of the palm genus <Emphasis Type="Italic">Acrocomia</Emphasis>: Neotropical green gold

The genus Acrocomia, popularly known as macaw palm or macaúba, occurs in savanna areas and open forests of tropical America, with distribution from Central to southern South America. They are important oleaginous palm trees, due to their role in ecosystems and local economies and their potential for biofuel production and vegetable oil. Although the taxonomy of the genus is not resolved because of observed phenotypic diversity in A. aculeata (Jacq.) Lodd. ex Mart., there are several conflicting treatments. Some authors recognize three caulescent spp. occurring in South America: A. aculeata, A. intumescens Drude, and A. totai Mart, although a new one was described recently—Acrocomia corumbaensis. Because some Latin American governments want to expand production of macaw palm in their territory as raw material for agro-energy, several groups have been encouraged to study this genus, focusing on the production of biodiesel, seed germination, phenotypic aspects, and genetic diversity. The goal of this review is to compile key information available in the literature and herbarium data, focusing on South American populations of the genus.     

Fluorescent, internally quenched, peptides for exploring the pH-dependent substrate specificity of cathepsin B.

Cathepsin B is a cysteine protease that in tumor tissues is localized in both acidic lysosomes and extracellular spaces. It can catalyze the cleavage of peptide bonds by two mechanisms: endoproteolytic attack with a pH optimum around 7.4, and attack from the C-terminus with a pH optimum at 4.5-5.5. In this work, seven fluorescent, internally quenched, decapeptides have been synthesized using the prototypical cathepsin B selective substrate Z-Phe-Arg-AMC as a lead, and used to identify the structural factors determining the susceptibility of peptides to hydrolysis at acidic and neutral pH values. Each peptide differs from the others in one amino acid (residue 6) and contains a highly fluorescent Nma group linked to the alpha-amino function of the N-terminal Orn residue and a Dnp group linked to the side chain of the Lys(8) residue acting as a quencher. Proteolytic cleavage was monitored by measuring the increase of fluorescence at 440 nm upon excitation at 340 nm, and the cleavage sites were determined by HPLC followed by ESI-MS analysis. Peptides containing Ala or Phe at position 6 are good substrates for the enzyme at both pH 5.0 and 7.4. By contrast, those containing Glu, Asp, Lys or Val are not cleaved at all by cathepsin B at pH 7.4, and are poorly hydrolyzed at pH 5.0. These findings provide new information for the rational design of cathepsin B-activated peptide-containing anticancer drugs.