Redundancy and recombination in the Echinococcus AgB multigene family: is there any similarity with protozoan contingency genes?

Numerous genetic variants of the Echinococcus antigen B (AgB) are encountered within a single metacestode. This could be a reflection of gene redundancy or the result of a somatic hypermutation process. We evaluate the complexity of the AgB multigene family by characterizing the upstream promoter regions of the 4 already known genes (EgAgB1-EgAgB4) and evaluating their redundancy in the genome of 3 Echinococcus species (E. granulosus, E. ortleppi and E. multilocularis) using PCR-based approaches. We have ascertained that the number of AgB gene copies is quite variable, both within and between species. The most repetitive gene seems to be AgB3, of which there are more than 110 copies in E. ortleppi. For E. granulosus, we have cloned and characterized 10 distinct upstream promoter regions of AgB3 from a single metacestode. Our sequences suggest that AgB1 and AgB3 are involved in gene conversion. These results are discussed in light of the role of gene redundancy and recombination in parasite evasion mechanisms of host immunity, which at present are known for protozoan organisms, but virtually unknown for multicellular parasites.

Morphological Diversity and the Roles of Contingency, Chance and Determinism in African Cichlid Radiations

Background: Deterministic evolution, phylogenetic contingency and evolutionary chance each can influence patterns of morphological diversification during adaptive radiation. In comparative studies of replicate radiations, convergence in a common morphospace implicates determinism, whereas non-convergence suggests the importance of contingency or chance. Methodology/Principal Findings: The endemic cichlid fish assemblages of the three African great lakes have evolved similar sets of ecomorphs but show evidence of non-convergence when compared in a common morphospace, suggesting the importance of contingency and/or chance. We then analyzed the morphological diversity of each assemblage independently and compared their axes of diversification in the unconstrained global morphospace. We find that despite differences in phylogenetic composition, invasion history, and ecological setting, the three assemblages are diversifying along parallel axes through morphospace and have nearly identical variance-covariance structures among morphological elements. Conclusions/Significance: By demonstrating that replicate adaptive radiations are diverging along parallel axes, we have shown that non-convergence in the common morphospace is associated with convergence in the global morphospace. Applying these complimentary analyses to future comparative studies will improve our understanding of the relationship between morphological convergence and non-convergence, and the roles of contingency, chance and determinism in driving morphological diversification.

Probabilistic contingency learning with limbic or prefrontal damage

AB A fundamental capacity of the human brain is to learn relations (contingencies) between environmental stimuli and the consequences of their occurrence. Some contingencies are probabilistic; that is, they predict an event in some situations but not in all. Animal studies suggest that damage to limbic structures or the prefrontal cortex may disturb probabilistic learning. The authors studied the learning of probabilistic contingencies in amnesic patients with limbic lesions, patients with prefrontal cortex damage, and healthy controls. Across 120 trials, participants learned contingent relations between spatial sequences and a button press. Amnesic patients had learning comparable to that of control subjects but failed to indicate what they had learned. Across the last 60 trials, amnesic patients and control subjects learned to avoid a noncontingent choice better than frontal patients. These results indicate that probabilistic learning does not depend on the brain structures supporting declarative memory.

Pretreatment Tables Predicting Pathologic Stage of Locally Advanced Prostate Cancer

BACKGROUND Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. OBJECTIVE To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. INTERVENTION Retropubic RP and pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. RESULTS AND LIMITATIONS In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. CONCLUSIONS These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. PATIENT SUMMARY Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment.