Water Pollution Increases the Risk of Chytridiomycosis in Mexican Amphibians.

Chytridiomycosis is affecting amphibians worldwide, causing the decline and extinction of several amphibian populations. The disease is caused by the fungus Batrachochytrium dendrobatidis (Bd), a multihost pathogen living in freshwater habitats. While several environmental factors have been associated with the prevalence of Bd and its virulence, the effects of water quality on the pathogen are not clear yet. Some evidence suggests that water pollution may reduce amphibians' immune response and increase prevalence of Bd. To explore this hypothesis, we analyzed the relationship between water quality and the presence of Bd by using spatial data mining of 150 geolocations of Bd in amphibians from 9 families where Bd positive specimens have been previously reported, and water quality in 4,202 lentic and lotic water bodies in Mexico from 2010 to 2021. Our model showed that in the 3 main families where Bd was recorded, its presence is high in locations with low water quality, i.e., water polluted likely contaminated with urban and industrial waste. Using this model, we inferred areas suitable for Bd in Mexico; mainly in poorly studied areas along the gulf and on the pacific slope. We further argue that actions to reduce water pollution should become an integral part of public policies to prevent the spread of Bd and protect amphibians from this deadly pathogen.

Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: implications for xenograft models of human prostate cancer.

BACKGROUND: Ephrin-B2 is the sole physiologically-relevant ligand of the receptor tyrosine kinase EphB4, which is over-expressed in many epithelial cancers, including 66% of prostate cancers, and contributes to cancer cell survival, invasion and migration. Crucially, however, the cancer-promoting EphB4 signalling pathways are independent of interaction with its ligand ephrin-B2, as activation of ligand-dependent signalling causes tumour suppression. Ephrin-B2, however, is often found on the surface of endothelial cells of the tumour vasculature, where it can regulate angiogenesis to support tumour growth. Proteolytic cleavage of endothelial cell ephrin-B2 has previously been suggested as one mechanism whereby the interaction between tumour cell-expressed EphB4 and endothelial cell ephrin-B2 is regulated to support both cancer promotion and angiogenesis. METHODS: An in silico approach was used to search accessible surfaces of 3D protein models for cleavage sites for the key prostate cancer serine protease, KLK4, and this identified murine ephrin-B2 as a potential KLK4 substrate. Mouse ephrin-B2 was then confirmed as a KLK4 substrate by in vitro incubation of recombinant mouse ephrin-B2 with active recombinant human KLK4. Cleavage products were visualised by SDS-PAGE, silver staining and Western blot and confirmed by N-terminal sequencing. RESULTS: At low molar ratios, KLK4 cleaved murine ephrin-B2 but other prostate-specific KLK family members (KLK2 and KLK3/PSA) were less efficient, suggesting cleavage was KLK4-selective. The primary KLK4 cleavage site in murine ephrin-B2 was verified and shown to correspond to one of the in silico predicted sites between extracellular domain residues arginine 178 and asparagine 179. Surprisingly, the highly homologous human ephrin-B2 was poorly cleaved by KLK4 at these low molar ratios, likely due to the 3 amino acid differences at this primary cleavage site. CONCLUSION: These data suggest that in in vivo mouse xenograft models, endogenous mouse ephrin-B2, but not human tumour ephrin-B2, may be a downstream target of cancer cell secreted human KLK4. This is a critical consideration when interpreting data from murine explants of human EphB4+/KLK4+ cancer cells, such as prostate cancer cells, where differential effects may be seen in mouse models as opposed to human clinical situations.

Constructing ecological networks: a tool to infer risk of transmission and dispersal of leishmaniasis.

We extend a recently developed method for constructing ecological networks to infer potential biotic interactions between species and to also include environmental factors, in particular land cover, thus permitting a simultaneous analysis of the interaction between environment and species distribution as well as inter-species interactions. We apply the method to the transmission and dispersal of leishmaniasis in Mexico. We find that the most important potential vectors and reservoirs can be classified into assemblages associated with different types of habitat. This in turn can be used to understand and map potential transmission risk, as well as to construct risk scenarios for the dispersal of disease from one geographical region to another.

Wing shape as an indicator of larval rearing conditions for Aedes albopictus and Aedes aegypti (Diptera: Culicidae).

Estimating a mosquito's vector competence, or likelihood of transmitting disease, if it takes an infectious bloodmeal, is an important aspect of predicting when and where outbreaks of infectious diseases will occur. Vector competence can be affected by rearing temperature and inter- and intraspecific competition experienced by the individual mosquito during its larval development. This research investigates whether a new morphological indicator of larval rearing conditions, wing shape, can be used to distinguish reliably temperature and competitive conditions experienced during larval stages. Aedes albopictus (Skuse) and Aedes aegypti (L.) (Diptera: Culicidae) larvae were reared in low intraspecific, high intraspecific, or high interspecific competition treatments at either 22 or 32 degrees C. The right wing of each dried female was removed and photographed. Nineteen landmarks and 20 semilandmarks were digitized on each wing. Shape variables were calculated using geometric morphometric software. Canonical variate analysis, randomization multivariate analysis of variance, and visualization of landmark movement using deformation grids provided evidence that although semilandmark position was significantly affected by larval competition and temperature for both species, the differences in position did not translate into differences in wing shape, as shown in deformation grids. Two classification procedures yielded success rates of 26 - 49%. Accounting for wing size produced no increase in classification success. There seemed to be a significant relationship between shape and size. These results, particularly the low success rate of classification based on wing shape, show that shape is unlikely to be a reliable indicator of larval rearing competition and temperature conditions for Ae. albopictus and Ae. aegypti.

Symmetry breaking and adaptation: evidence from a 'toy model' of a virus.

We argue that an induced breaking of the genetic synonym symmetry due to the action of genetic operators such as mutation can enhance the adaptability of a species to changes in the environment. In the case of a virus, the claim is that the codon bias in the neutralization epitope improves the virus' ability to generate mutants that evade the induced immune response. We support our claim with a simple 'toy model' of a viral epitope evolving in competition with the immune system. The effective selective advantage of a higher mutability leads to a dominance of codons that favor non-synonymous mutations. As further evidence we present a simple model for a genetic regulatory network that leads to adaptive evolution in a population of giraffes by means of an induced symmetry breaking rather than through any direct selective advantage.

Codon bias and mutability in HIV sequences.

A survey of the patterns of synonymous codon preference in the HIV env gene reveals a correlation between the codon bias and the mutability requirements of different regions of the protein. At hypervariable regions in gp120 one finds a greater proportion of codons that tend to mutate nonsynonymously, but to a target that is similar in hydrophobicity and volume. We argue that this strategy results from a compromise between the selective pressure placed on the virus by the induced immune response, which favors amino acid substitutions in the complementarity determining regions, and the negative selection against missense mutations that violate structural constraints of the env protein.

Self-adaptation in evolving systems.

A theoretical and experimental analysis is made of the effects of self-adaptation in a simple evolving system. Specifically, we consider the effects of coding the mutation and crossover probabilities of a genetic algorithm evolving in certain model fitness landscapes. The resultant genotype-phenotype mapping is degenerate in fitness space, there being no direct selective advantage for one probability versus another. Thus there is a "symmetry" between various genotypes that all correspond to the same phenotype. We show that the action of mutation and crossover lifts this degeneracy, that is, the genetic operators induce a breaking of the genotype-phenotype symmetry, thus leading to a preference for those genotypes that propagate most successfully into future generations. We demonstrate that this induced symmetry breaking allows the system to self-adapt in a time-dependent environment.

Emergence of algorithmic language in genetic systems.

In genetic systems there is a non-trivial interface between the sequence of symbols which constitutes the chromosome, or 'genotype', and the products which this sequence encodes--the 'phenotype'. This interface can be thought of as a 'computer'. In this case the chromosome is viewed as an algorithm and the phenotype as the result of the computation. In general, only a small fraction of all possible sequences of symbols makes any sense for a given computer. The difficulty of finding meaningful algorithms by random mutation is known as the brittleness problem. In this paper we show that mutation and crossover favor the emergence of an algorithmic language which facilitates the production of meaningful sequences following random mutations of the genotype. We base our conclusions on an analysis of the population dynamics of a variant of Kitano's neurogenetic model wherein the chromosome encodes the rules for cellular division and the phenotype is a 16-cell organism interpreted as a connectivity matrix for a feed-forward neural network. We show that an algorithmic language emerges, describe this language in extenso, and show how it helps to solve the brittleness problem.

Diabetes in pregnancy: maternal and infant outcome.

Previous studies have shown that diabetic women more commonly have complications of pregnancy and adverse infant outcomes than do other women. However, most of the studies have not evaluated women with gestational diabetes separately. The purpose of this study was to evaluate pregnancy complications and infant morbidity and mortality among births to women with gestational diabetes and women with established diabetes. Birth certificate data from 1984 in Washington State linked with death certificate data provided information on complications of pregnancy and infant outcome for 422 gestational diabetics and 144 established diabetics. A comparison group of 856 non-diabetic women who delivered a child was selected at random. Both established and gestational diabetic women were more likely to be reported to develop pre-eclampsia (relative risk (RR) = 4.0 and 9.6). Established and gestational diabetic women were also at increased risk of delivery by Caesarean section (RR = 2.1 and 5.0). Infants of established diabetics had a higher risk of congenital anomalies (RR = 7.6) than infants of non-diabetics and were at increased risk of death in the first 4 weeks (RR = 7.9) and the first year of life (RR = 5.0). Gestational diabetics were more likely to have high birthweight babies (greater than 4000 g) (RR = 2.1) while established diabetics were more likely to have babies at either extreme of birthweight (greater than 4000 g, RR = 1.7; less than 2500 g, RR = 3.2). We conclude that both gestational and established diabetes are associated with important increases in risk of pregnancy complications and adverse infant outcomes.