Differential Responses of Brain,Gonad and Muscle Steroid Levels to Changes in Social Status and Sex in a Sequential and Bidirectional Hermaphroditic Fish

Sex steroids can both modulate and be modulated by behavior, and their actions are mediated by complex interactions among multiple hormone sources and targets. While gonadal steroids delivered via circulation can affect behavior, changes in local brain steroid synthesis also can modulate behavior. The relative steroid load across different tissues and the association of these levels with rates of behavior have not been well studied. The bluebanded goby (Lythrypnus dalli) is a sex changing fish in which social status determines sexual phenotype. We examined changes in steroid levels in brain, gonad and body muscle at either 24 hours or 6 days after social induction of protogynous sex change, and from individuals in stable social groups not undergoing sex change. For each tissue, we measured levels of estradiol (E₂), testosterone (T) and 11-ketotestosterone (KT). Females had more T than males in the gonads, and more E₂ in all tissues but there was no sex difference in KT. For both sexes, E₂ was higher in the gonad than in other tissues while androgens were higher in the brain. During sex change, brain T levels dropped while brain KT increased, and brain E₂ levels did not change. We found a positive relationship between androgens and aggression in the most dominant females but only when the male was removed from the social group. The results demonstrate that steroid levels are responsive to changes in the social environment, and that their concentrations vary in different tissues. Also, we suggest that rapid changes in brain androgen levels might be important in inducing behavioral and/or morphological changes associated with protogynous sex change.     

Urogenital schistosomiasis infection prevalence targets to determine elimination as a public health problem based on microhematuria prevalence in school-age children

BackgroundRecent research suggests that schistosomiasis targets for morbidity control and elimination as a public health problem could benefit from a reanalysis. These analyses would define evidence-based targets that control programs could use to confidently assert that they had controlled or eliminated schistosomiasis as a public health problem. We estimated how low Schistosoma haematobium infection levels diagnosed by urine filtration in school-age children should be decreased so that microhematuria prevalence was at, or below, a “background” level of morbidity.MethodologyData obtained from school-age children in Burkina Faso, Mali, Niger, Tanzania, and Zambia who participated in schistosomiasis monitoring and evaluation cohorts were reanalyzed before and after initiation of preventive chemotherapy. Bayesian models estimated the infection level prevalence probabilities associated with microhematuria thresholds ≤10%, 13%, or 15%.Principal findingsAn infection prevalence of 5% could be a sensible target for urogenital schistosomiasis morbidity control in children as microhematuria prevalence was highly likely to be below 10% in all surveys. Targets of 8% and 11% infection prevalence were highly likely to result in microhematuria levels less than 13% and 15%, respectively. By contrast, measuring heavy-intensity infections only achieves these thresholds at impractically low prevalence levels.Conclusions/significanceA target of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children could be used to determine whether a geographic area has controlled or eliminated schistosomiasis as a public health problem depending on the local background threshold of microhematuria.     

Effect of sonication on paraffin-embedded tissue preparation for DNA flow cytometry

Since the publication of paraffin block extraction procedures, flow cytometric analysis of DNA ploidy and S-phase of tumor specimens has been widely applied. DNA aneuploidy, DNA tetraploid (elevated G2/M), and elevated S-phase are clinically significant in some tumor systems. True DNA tetraploid cell lines will contain a large 4c population and perhaps an 8c population; samples with cell aggregates will also contain a 6c population. Microscopic examination of samples having a 6c peak revealed nuclei with adhering debris and doublets, triplets, and larger nuclear aggregates. After sonication, a uniform suspension of single nuclei without adherent debris was seen. In addition to reducing the percent of G2/M cells, sonication also reduced S-phase percent such that it was closer to the bromodeoxyuridine labeling index. The DNA ploidy classification of specimens was also compared pre- and post-sonication. Four of 96 breast cancer samples changed classification; all were specimens in which the histogram became cleaner and a small DNA aneuploid peak became apparent after sonication.     

Caffeine Junkie: an Unprecedented Glutathione S-Transferase-Dependent Oxygenase Required for Caffeine Degradation by Pseudomonas putida CBB5

Caffeine and other N-methylated xanthines are natural products found in many foods, beverages, and pharmaceuticals. Therefore, it is not surprising that bacteria have evolved to live on caffeine as a sole carbon and nitrogen source. The caffeine degradation pathway of Pseudomonas putida CBB5 utilizes an unprecedented glutathione-S-transferase-dependent Rieske oxygenase for demethylation of 7-methylxanthine to xanthine, the final step in caffeine N-demethylation. The gene coding this function is unusual, in that the iron-sulfur and non-heme iron domains that compose the normally functional Rieske oxygenase (RO) are encoded by separate proteins. The non-heme iron domain is located in the monooxygenase, ndmC, while the Rieske [2Fe-2S] domain is fused to the RO reductase gene, ndmD. This fusion, however, does not interfere with the interaction of the reductase with N₁- and N₃-demethylase RO oxygenases, which are involved in the initial reactions of caffeine degradation. We demonstrate that the N₇-demethylation reaction absolutely requires a unique, tightly bound protein complex composed of NdmC, NdmD, and NdmE, a novel glutathione-S-transferase (GST). NdmE is proposed to function as a noncatalytic subunit that serves a structural role in the complexation of the oxygenase (NdmC) and Rieske domains (NdmD). Genome analyses found this gene organization of a split RO and GST gene cluster to occur more broadly, implying a larger function for RO-GST protein partners.     

Fast to Forgive,Slow to Retaliate: Intuitive Responses in the Ultimatum Game Depend on the Degree of Unfairness

Evolutionary accounts have difficulty explaining why people cooperate with anonymous strangers they will never meet. Recently models, focusing on emotional processing, have been proposed as a potential explanation, with attention focusing on a dual systems approach based on system 1 (fast, intuitive, automatic, effortless, and emotional) and system 2 (slow, reflective, effortful, proactive and unemotional). Evidence shows that when cooperation is salient, people are fast (system 1) to cooperate, but with longer delays (system 2) they show greed. This is interpreted within the framework of the social heuristic hypothesis (SHH), whereby people overgeneralize potentially advantageous intuitively learnt and internalization social norms to ‘atypical’ situations. We extend this to explore intuitive reactions to unfairness by integrating the SHH with the ‘fast to forgive, slow to anger’ (FFSA) heuristic. This suggests that it is advantageous to be prosocial when facing uncertainty. We propose that whether or not someone intuitively shows prosociality (cooperation) or retaliation is moderated by the degree (certainty) of unfairness. People should intuitively cooperate when facing mild levels of unfairness (fast to forgive) but when given longer to decide about another''s mild level of unfairness should retaliate (slow to anger). However, when facing severe levels of unfairness, the intuitive response is always retaliation. We test this using a series of one-shot ultimatum games and manipulate level of offer unfairness (50:50 60:40, 70:30, 80:20, 90:10) and enforced time delays prior to responding (1s, 2s, 8s, 15s). We also measure decision times to make responses after the time delays. The results show that when facing mildly unfair offers (60:40) people are fast (intuitive) to cooperate but with longer delays reject these mildly unfair offers: ‘fast to forgive, and slow to retaliate’. However, for severely unfair offers (90:10) the intuitive and fast response is to always reject.     

Mapping Interdisciplinary Fields: Efficiencies,Gaps and Redundancies in HIV/AIDS Research

While interdisciplinarity continues to increase in popularity among funders and other scientific organizations, its potential to promote scientific advances remains under-examined. For HIV/AIDS research, we examine the dynamics of disciplinary integration (or lack thereof) providing insight into a field''s knowledge base and those questions that remain unresolved. Drawing on the complete histories of two interdisciplinary journals, we construct bibliographic coupling networks based on overlapping citations to identify segregation into research clusters and estimate topic models of research content. We then compare how readily those bibliographic coupling clusters account for the structuring of topics covered within the field as it evolves over two decades. These comparisons challenge one-dimensional and/or cross-sectional approaches to interdisciplinarity. Some topics are increasingly coordinated across disciplinary boundaries (e.g., vaccine development); others remain relatively segmented into disconnected disciplinary domains for the full period (e.g., drug resistance). This divergence indicates heterogeneity in interdisciplinarity and emphasizes the need for critical approaches to studying the organization of science.