Ten Years of the Relative Risk Model and Regional Scale Ecological Risk Assessment

It has been 10 years since the publication of the relative risk model (RRM) for regional scale ecological risk assessment. The approach has since been used successfully for a variety of freshwater, marine, and terrestrial environments in North America, South America, and Australia. During this period the types of stressors have been expanded to include more than contaminants. Invasive species, habitat loss, stream alteration and blockage, temperature, change in land use, and climate have been incorporated into the assessments. Major developments in the RRM have included the extensive use of geographical information systems, uncertainty analysis using Monte Carlo techniques, and its application to retrospective assessments to determine causation. The future uses of the RRM include assessments for forestry and conservation management, an increasing use in invasive species evaluation, and in sustainability. Developments in risk communication, the use of Bayesian approaches, and in uncertainty analyses are on the horizon.     

Innate and learned components of human visual preference.

BACKGROUND: Recent claims in neuroscience and evolutionary biology suggest that the aesthetic sense reflects preferences for image signals whose characteristics best fit innate brain mechanisms of visual recognition. RESULTS: This hypothesis was tested by behaviourally measuring, for a set of initially unfamiliar images, the effects of category learning on preference judgements by humans, and by relating the observed data to computationally reconstructed internal representations of categorical concepts. Category learning induced complex shifts in preference behaviour. Two distinct factors - complexity and bilateral symmetry - could be identified from the data as determinants of preference judgements. The effect of the complexity factor varied with object knowledge acquired through category learning. In contrast, the impact of the symmetry factor proved to be unaffected by learning experience. Computer simulations suggested that the preference for pattern complexity relies on active (top-down) mechanisms of visual recognition, whereas the preference for pattern symmetry depends on automatic (bottom-up) mechanisms. CONCLUSIONS: Human visual preferences are not fully determined by (objective) structural regularities of image stimuli but also depend on their learned (subjective) interpretation. These two aspects are reflected in distinct complementary factors underlying preference judgements, and may be related to complementary modes of visual processing in the brain.     

Human MxA Protein Protects Mice Lacking a Functional Alpha/Beta Interferon System against La Crosse Virus and Other Lethal Viral Infections

The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-alpha/beta). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the beta subunit of the IFN-alpha/beta receptor (IFNAR-1(-/-) mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA-transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1(-/-) mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens.     

Potential for biotic interference of a classical biological control agent of the soybean aphid

The degree to which resident biota can inhibit the ability of an introduced biological control agent to establish and be effective is termed biotic interference. Studying biotic interference prior to a release using the actual agent is logistically difficult, however, due to quarantine restrictions. An alternative solution is to study biotic interference against a surrogate species in the intended range of introduction, with the expectation that biotic interference against the actual agent will be similar. This study assessed how biotic interference, mostly by generalist predators, may affect establishment of classical biological control agents of the soybean aphid, Aphis glycines Matsumura, in North America. The parasitoid Aphidius colemani Viereck was used as a surrogate for Asian aphidiine braconids such as Binodoxys communis (Gahan). We conducted a factorial field experiment that measured the effect of releasing A. colemani and of excluding resident natural enemies using field cages on soybean aphid populations. We also conducted molecular gut-contents analyses on predators collected in release plots to determine which species fed upon A. colemani. Releasing A. colemani in open field plots increased soybean aphid control beyond that observed in open field plots alone, despite indications that intraguild predation of A. colemani occurred. Thus, biotic interference was not sufficient to eliminate the contribution of A. colemani on soybean aphid suppression during the course of our experiment. Molecular gut-contents analysis revealed that at least two predators, Harmonia axyridis (Pallas) and Chrysoperla carnea Stephens, engaged in intraguild predation against A. colemani. The prolonged effect of intraguild predation on parasitoid establishment remains to be determined.     

Subcellular Distribution of Cadmium and Nickel in Chronically Exposed Wild Fish: Inferences Regarding Metal Detoxification Strategies and Implications for Setting Water Quality Guidelines for Dissolved Metals

The objective of this study was to investigate metal detoxification in chronically exposed juvenile yellow perch (YP: Perca flavescens) and to field test the commonly assumed threshold toxicity model. Fish were collected from lakes located along a cadmium (Cd) and nickel (Ni) concentration gradient. Ambient dissolved metal concentrations were measured to evaluate exposure and total hepatic metal concentrations were determined as a measure of metal bioaccumulation. Hepatic metal partitioning among potentially metal-sensitive fractions (heat-denatured proteins, organelles) and detoxified metal fractions (metallothionein) was determined after differential centrifugation of YP liver homogenates. Major proportions of hepatic Cd were found in the heat-stable cytosolic peptides and proteins fraction (HSP; including metallothioneins), whereas Ni was mainly found in the potentially metal-sensitive heat-denaturable proteins fraction (HDP). For these chronically exposed fish there was no threshold exposure concentration below which binding of Cd or Ni to the heat-denaturable protein fraction or the organelle fraction did not occur. Metal detoxification was clearly incomplete and P. flavescens was subject to some metal-related stress, as evidenced notably by endocrine perturbations. Similar subcellular partitioning results were obtained when juvenile yellow perch were transferred from a reference lake to a Cd-contaminated lake and Cd accumulation was followed over time; there was no accumulation threshold below which Cd binding to the putative metal-sensitive fractions (HDP and organelles) did not occur. The presence of Cd and Ni in these fractions, even for low exposure concentrations and low hepatic accumulation, contradicts the threshold toxicity model that underpins metal toxicology theory and that is implicitly used in setting water quality guidelines for metals. Chronically exposed YP appear to have settled for a tradeoff between the cost of turning on their detoxification apparatus at full capacity, to completely suppress metal binding to metal-sensitive sites, and the alternative cost of allowing some binding of inappropriate metals to metal-sensitive sites.     

Use of enzyme penicillin acylase in selective amidation/amide hydrolysis to resolve ethyl 3-amino-4-pentynoate isomers

The beta-amino acid, (S)-ethyl-3-amino-4-pentynoate, is a chiral synthon used in the synthesis of xemilofiban hydrochloride, an anti-platelet agent. A biocatalytic approach was developed to resolve (R)- and (S)-enantiomers of ethyl 3-amino-4-pentynoate in enantiomerically pure form employing the enzyme Penicillin acylase. In the acylation, phenylacetic acid was used as an acylating agent. We have shown that both the acylation and deacylation can be employed and that the activity of the enzyme Penicillin acylase can be controlled by maintaining an appropriate pH of the reaction medium.     

Migration through a Major Andean Ecogeographic Disruption as a Driver of Genetic and Phenotypic Diversity in a Wild Tomato Species

Evolutionary dynamics at the population level play a central role in creating the diversity of life on our planet. In this study, we sought to understand the origins of such population-level variation in mating systems and defensive acylsugar chemistry in Solanum habrochaites—a wild tomato species found in diverse Andean habitats in Ecuador and Peru. Using Restriction-site-Associated-DNA-Sequencing (RAD-seq) of 50 S. habrochaites accessions, we identified eight population clusters generated via isolation and hybridization dynamics of 4–6 ancestral populations. Detailed characterization of mating systems of these clusters revealed emergence of multiple self-compatible (SC) groups from progenitor self-incompatible populations in the northern part of the species range. Emergence of these SC groups was also associated with fixation of deleterious alleles inactivating acylsugar acetylation. The Amotape-Huancabamba Zone—a geographical landmark in the Andes with high endemism and isolated microhabitats—was identified as a major driver of differentiation in the northern species range, whereas large geographical distances contributed to population structure and evolution of a novel SC group in the central and southern parts of the range, where the species was also inferred to have originated. Findings presented here highlight the role of the diverse ecogeography of Peru and Ecuador in generating population differentiation, and enhance our understanding of the microevolutionary processes that create biological diversity.     

Isocitrate dehydrogenase 1 R132C mutation occurs exclusively in microsatellite stable colorectal cancers with the CpG island methylator phenotype

The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.     

Mathematical and computational modeling in biology at multiple scales

A variety of topics are reviewed in the area of mathematical and computational modeling in biology, covering the range of scales from populations of organisms to electrons in atoms. The use of maximum entropy as an inference tool in the fields of biology and drug discovery is discussed. Mathematical and computational methods and models in the areas of epidemiology, cell physiology and cancer are surveyed. The technique of molecular dynamics is covered, with special attention to force fields for protein simulations and methods for the calculation of solvation free energies. The utility of quantum mechanical methods in biophysical and biochemical modeling is explored. The field of computational enzymology is examined.