Mate choice, frequency dependence, and the maintenance of resistance to parasitism in a simultaneous hermaphrodite

Biomphalaria glabrata are simultaneous hermaphroditic freshwatersnails that act as intermediate hosts for the macroparasitictrematode Schistosoma mansoni, a causative agent of schistosomiasis.Heritability and strain-specificity of both snail resistanceand susceptibility to schistosome infection have been demonstrated,genetic variability for which is maintained, in part, throughtrade-offs between high fitness costs associated with infectionand those associated with resistance. However, despite sucha high cost of resistance and a low prevalence of infectionin natural snail populations, genes for resistance are maintainedwithin snail populations over successive generations, includingin the complete absence of parasite pressure in laboratory populations.This may be indicative of alternative benefits of resistancegenes, in addition to parasite defense, such as differentialmating success between genotypes. Here we examined the mateand gender choice of snails across a multi-factorial range ofpotential partner combinations. These included host-resistanceor susceptibility genotype, host genotype frequency within thepopulation, current parasite infection status, and parasitegenotype. We demonstrate recognition and discrimination by hostsnails depending on host and/or parasite genotype for each ofthese factors. In particular, our results suggest that a raremating advantage to resistant genotypes may be a potential explanationfor the maintenance of highly costly resistance genes withinintermediate host populations under conditions of low or zeroparasite pressure.     

In utero-initiated cancer: the role of reactive oxygen species

It is becoming more evident that not only can drugs and environmental chemicals interfere with normal fetal development by causing structural malformations, such as limb defects, but that xenobiotic exposure during development can also cause biochemical and functional abnormalities that may ultimately lead to cancer later on in life. Fetal toxicity may be partly mediated by the embryonic bioactivation of xenobiotics to free radical intermediates that can lead to oxidative stress and potentially lead, in some cases, to carcinogenesis. Using a number of examples, this review will focus on the role of reactive oxygen species (ROS) in the mechanisms pertaining to in utero initiated cancers.     

Minor pollinator–prey conflict in the carnivorous plant, Drosera anglica

We studied the physical and temporal isolation of two arthropod guilds interacting with Drosera anglica Huds., a terrestrial carnivorous plant. Flowers are separated from basal trap leaves by a leafless stalk. Since arthropods are potentially employed both as prey and pollinators, we asked whether separation of traps from flowers reduces the frequency with which flower visitors are captured by the leaves. Plants captured prey throughout the season, with peak trapping activity occurring before flowering began. The diverse prey spectrum included at least 109 species in 94 genera in 26 of 37 identified families representing 11 arthropod orders. The most common prey were adult flies of Nematocera, particularly Ceratopogonidae (50%) and Chironomidae (42%). The following taxa were periodically abundant: Acarina, Diptera–Cecidomyiidae, Chloropidae, Sciaridae, Hemiptera nymphs and Thysanoptera–Thripidae. Flies (Diptera) were chief flower visitors (95%), dominated by Syrphidae (66%), Bombyliidae and Muscidae (10% each), Calliphoridae (7%), Tachinidae and Dolichopodidae (3% each). Additionally, visitors were a bee (Hymenoptera–Halictidae) and thrips (Thysanoptera–Thripidae). Four families were common to both guilds: Diptera–Dolichopodidae, Muscidae, Tachinidae; and Thysanoptera–Thripidae. However, direct comparisons of identified taxa within these families showed that overlap between flower visitors and prey occurred for Thrips sp. larvae alone, which comprised only 3% of all flower visitors and 0.5% of prey. Drosera anglica exploits distinct guilds of insects for pollinators and prey.     

Role of alveolar macrophage and migrating neutrophils in hemorrhage-induced priming for ALI subsequent to septic challenge

Acute lung injury (ALI) is identified with the targeting/sequestration of polymorphonuclear leukocytes (PMN) to the lung. Instrumental to PMN targeting are chemokines [e.g., macrophage inflammatory protein-2 (MIP-2), keratinocyte-derived chemokine (KC), etc.] produced by macrophage, PMN, and other resident pulmonary cells. However, the relative contribution of resident pulmonary macrophages as opposed to PMN in inducing ALI is poorly understood. We therefore hypothesize that depletion of peripheral blood PMN and/or the oblation of a macrophage-mediated PMN chemokine signal (via macrophage deficiency) will reduce the inflammation and ALI observed in mice following hemorrhage (Hem) and subsequent sepsis (CLP) in our murine model of ALI. To examine this we pretreated mice with either 500 microg anti-mouse Gr1 antibody/animal (to deplete PMN) or subjected mice deficient in mature macrophage (B6C3Fe-a/a-CsF1op) to Hem (90 min at 35 +/- 5 mmHg) followed by resuscitation. Twenty-four hours post-Hem, mice were subjected to CLP and killed 24 h later, and lung tissue samples were collected. Our data showed that in the absence of either peripheral blood PMN or mature tissue macrophages there was a suppression of IL-6, KC, and MIP-2 levels in lung tissue from Hem/CLP mice as well as a reduction in PMN influx to the lung and lung injury (bronchoalveolar lavage fluid protein). In contrast, lung tissue IL-10 and TNF-alpha levels were suppressed in the macrophage-deficient Hem/CLP mice compared with PMN-depleted Hem/CLP mice. Together, these data suggest that both the PMN and the macrophage are required to induce inflammation seen here, however, macrophage not PMN regulate the release of IL-10, independent of local changes in TNF.     

Mutation analysis of the natriuretic peptide precursor B (NPPB) gene in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetically heterogenous disease caused by mutations in genes that primarily encode sarcomeric proteins. No mutation is identified in up to 40% of HCM patients, suggesting other causative genes exist. Natriuretic peptide precursor B (NPPB; also known as "BNP") is a cardiac hormone involved in body fluid homeostasis and cardiac myocyte growth. NPPB concentrations are markedly increased in patients with ventricular hypertrophy, and it is therefore possible mutations in the NPPB gene could cause HCM. METHODS: Genomic DNA was extracted from peripheral blood in 238 consecutive probands with HCM. The coding regions and intron/exon boundaries in the NPPB gene were amplified by PCR, and products were screened for sequence variants using high-performance liquid chromatography, followed by direct DNA sequencing. RESULTS: Four sequence variants in the NPPB gene were identified in 9 of the 238 probands screened. Two of the variants were intronic, one was a synonymous variant at codon 79, and the final variant resulted in an amino acid substitution from arginine to histidine at codon 47 (Arg47His). The Arg47His variant was identified in a control population consisting of 204 chromosomes at an allelic frequency of 0.5%, and is therefore unlikely to cause disease. CONCLUSION: No disease causing mutations were identified in the NPPB gene in this cohort, indicating that mutations in this gene are unlikely to be responsible for HCM.     

A simple vector system to improve performance and utilisation of recombinant antibodies

Background  

Isolation of recombinant antibody fragments from antibody libraries is well established using technologies such as phage display. Phage display vectors are ideal for efficient display of antibody fragments on the surface of bacteriophage particles. However, they are often inefficient for expression of soluble antibody fragments, and sub-cloning of selected antibody populations into dedicated soluble antibody fragment expression vectors can enhance expression.     

The unfolded protein response transducer Ire1p contains a nuclear localization sequence recognized by multiple beta importins

The Ire1p transmembrane receptor kinase/endonuclease transduces the unfolded protein response (UPR) from the endoplasmic reticulum (ER) to the nucleus in Saccharomyces cerevisiae. In this study, we analyzed the capacity of a highly basic sequence in the linker region of Ire1p to function as a nuclear localization sequence (NLS) both in vivo and in vitro. This 18-residue sequence is capable of targeting green fluorescent protein to the nucleus of yeast cells in a process requiring proteins involved in the Ran GTPase cycle that facilitates nuclear import. Mutagenic analysis and importin binding studies demonstrate that the Ire1p linker region contains overlapping potential NLSs: at least one classical NLS (within sequences 642KKKRKR647 and/or 653KKGR656) that is recognized by yeast importin alpha (Kap60p) and a novel betaNLS (646KRGSRGGKKGRK657) that is recognized by several yeast importin beta homologues. Kinetic binding data suggest that binding to importin beta proteins would predominate in vivo. The UPR, and in particular ER stress-induced HAC1 mRNA splicing, is inhibited by point mutations in the Ire1p NLS that inhibit nuclear localization and also requires functional RanGAP and Ran GEF proteins. The NLS-dependent nuclear localization of Ire1p would thus seem to be central to its role in UPR signaling.     

Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry

Immune responses arise from a wide variety of cells expressing unique combinations of multiple cell-surface proteins. Detailed characterization is hampered, however, by limitations in available probes and instrumentation. Here, we use the unique spectral properties of semiconductor nanocrystals (quantum dots) to extend the capabilities of polychromatic flow cytometry to resolve 17 fluorescence emissions. We show the need for this power by analyzing, in detail, the phenotype of multiple antigen-specific T-cell populations, revealing variations within complex phenotypic patterns that would otherwise remain obscure. For example, T cells specific for distinct epitopes from one pathogen, and even those specific for the same epitope, can have markedly different phenotypes. The technology we describe, encompassing the detection of eight quantum dots in conjunction with conventional fluorophores, should expand the horizons of flow cytometry, as well as our ability to characterize the intricacies of both adaptive and innate cellular immune responses.     

The effect of the captive environment on activity of captive cotton-top tamarins (Saguinus oedipus)

This study examined captive cotton-top tamarin (Saguinus oedipus) behavior across 3 different exhibits: (a) a rainforest (30.5 m in diameter), where tamarins free-ranged with other species; (b) a caged outdoor exhibit (5 m in diameter); and (c) a caged enclosure, with access indoors (6 × 9m) and outdoors (2.5 × 2.5 m). The study observed tamarins using focal animal scan sampling in 10 min blocks. Scoring was on the percentage of intervals in which they engaged in 12 behaviors. The findings show significant differences in activity, inactivity, and visibility across exhibits and have important implications for reintroduction efforts.     

CellML2SBML: conversion of CellML into SBML

CellML and SBML are XML-based languages for storage and exchange of molecular biological and physiological reaction models. They use very similar subsets of MathML to specify the mathematical aspects of the models. CellML2SBML is implemented as a suite of XSLT stylesheets that, when applied consecutively, convert models expressed in CellML into SBML without significant loss of information. The converter is based on the most recent stable versions of the languages (CellML version 1.1; SBML Level 2 Version 1), and the XSLT used in the stylesheets adheres to the XSLT version 1.0 specification. Of all 306 models in the CellML repository in April 2005, CellML2SBML converted 91% automatically into SBML. Minor manual changes to the unit definitions in the originals raised the percentage of successful conversions to 96%. Availability: http://sbml.org/software/cellml2sbml/. Supplementary information: Instructions for use and further documentation available on http://sbml.org/software/cellml2sbml/