Schistosoma mansoni: Cytotoxicity of hemocytes from susceptible snail hosts for sporocysts in plasma from resistant Biomphalaria glabrata

Sporocysts of Schistosoma mansoni (PR1 strain) survive and grow in Biomphalaria glabrata PR albino strain snails, whereas they are encapsulated and die in B. glabrata 10R2 strain snails. These processes also occur in an in vitro system in which the only living cells are those of sporocysts and snail hemolymph. Hemocytes of the susceptible snail are normally not effective in damaging sporocysts. However, when the encounter occurred in the presence of cell-free plasma from resistant snails, previously impotent hemocytes severely damaged sporocysts in 24 hr. The cytotoxic capacity of resistant strain hemocytes was not altered by plasma from susceptible snails. Furthermore, it was retained even when plasma was replaced by culture medium free of snail components. The nature of the plasma factor(s) which facilitated damage by otherwise impotent hemocytes is discussed, and evidence is evaluated for the hypothesis that snail resistance is dependent upon the specificity of cytophilic factors present both in the plasma and on the hemocyte plasma membranes.     

Mitochondrial DNA Variants of Respiratory Complex I that Uniquely Characterize Haplogroup T2 Are Associated with Increased Risk of Age-Related Macular Degeneration

Background

Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been reported in large prospective cohorts.

Methodology/Prinicipal Findings

We examined the relationship of inherited mtDNA variants with advanced AMD in 1168 people using a three-stage design on samples from 12-year and 10-year prospective studies on the natural history of age-related eye disease. In Stage I we resequenced the entire genome in 99 elderly AMD-free controls and 215 people with advanced AMD from the 12-year study. A consistent association with AMD in 14 of 17 SNPs characterizing the mtDNA T haplogroup emerged. Further analysis revealed these associations were driven entirely by the T2 haplogroup, and characterized by two variants in Complex I genes (A11812G of MT-ND4 and A14233G of MT-ND6). We genotyped T haplogroups in an independent sample of 490 cases and 61 controls from the same study (Stage II) and in 56 cases and 246 controls from the 10-year study (Stage III). People in the T2 haplogroup were approximately 2.5 times more likely to have advanced AMD than their peers (odds ratio [OR] = 2.54, 95%CI 1.36–4.80, P≤0.004) after considering the totality of evidence. Findings persisted after considering the impact of AMD-associated variants A69S and Y402H (OR = 5.19, 95%CI 1.19–22.69, P≤0.029).

Conclusion

Loci defining the mtDNA T2 haplogroup and Complex I are reasonable targets for novel functional analyses and therapeutic research in AMD.     

Guidelines for a priori grouping of species in hierarchical community models

Recent methodological advances permit the estimation of species richness and occurrences for rare species by linking species‐level occurrence models at the community level. The value of such methods is underscored by the ability to examine the influence of landscape heterogeneity on species assemblages at large spatial scales. A salient advantage of community‐level approaches is that parameter estimates for data‐poor species are more precise as the estimation process “borrows” from data‐rich species. However, this analytical benefit raises a question about the degree to which inferences are dependent on the implicit assumption of relatedness among species. Here, we assess the sensitivity of community/group‐level metrics, and individual‐level species inferences given various classification schemes for grouping species assemblages using multispecies occurrence models. We explore the implications of these groupings on parameter estimates for avian communities in two ecosystems: tropical forests in Puerto Rico and temperate forests in northeastern United States. We report on the classification performance and extent of variability in occurrence probabilities and species richness estimates that can be observed depending on the classification scheme used. We found estimates of species richness to be most precise and to have the best predictive performance when all of the data were grouped at a single community level. Community/group‐level parameters appear to be heavily influenced by the grouping criteria, but were not driven strictly by total number of detections for species. We found different grouping schemes can provide an opportunity to identify unique assemblage responses that would not have been found if all of the species were analyzed together. We suggest three guidelines: (1) classification schemes should be determined based on study objectives; (2) model selection should be used to quantitatively compare different classification approaches; and (3) sensitivity of results to different classification approaches should be assessed. These guidelines should help researchers apply hierarchical community models in the most effective manner.     

The Map Problem: A Comparison of Genetic and Sequence-Based Physical Maps

The genetic order of autosomal genome-scan markers from Marshfield panels 9 and 10 were compared with their physical order, on the basis of the assembled nonredundant human genome sequence from the Human Genome Project-Santa Cruz (HGP-sc; October 2000 and April 2001 releases) and Celera (CEL; February 2001 release) databases. The genetic order of 96% of the markers on the Marshfield map for panel 10 is supported by a likelihood ratio of > or = 3 (odds ratio of 1,000:1). Inconsistencies with the genetic panel 10 map were found for 5% and 2% of the markers in the CEL and HGP-sc sequences, respectively. These inconsistencies consisted of both positional and chromosomal-assignment disagreements. For the majority of these inconsistent markers, the genetic order was supported by a likelihood ratio of > or = 3, and the physical order in the other assembly matched the genetic order. The majority of the inconsistencies between the physical- and genetic-map order point to errors in the physical-map order. A Web site is made available that displays inconsistencies for genetic markers from Marshfield panels 9 and 10 between their genetic-map positions and sequence-based physical-map positions, as well as inconsistencies between their sequence-based physical position. This Web site also contains genetic-map distances, physical-map positions from the Celera and Human Genome Project sequence, and likelihood-ratio support for the genetic maps.     

Methods for Inferring Health-Related Social Networks among Coworkers from Online Communication Patterns

Studies of social networks, mapped using self-reported contacts, have demonstrated the strong influence of social connections on the propensity for individuals to adopt or maintain healthy behaviors and on their likelihood to adopt health risks such as obesity. Social network analysis may prove useful for businesses and organizations that wish to improve the health of their populations by identifying key network positions. Health traits have been shown to correlate across friendship ties, but evaluating network effects in large coworker populations presents the challenge of obtaining sufficiently comprehensive network data. The purpose of this study was to evaluate methods for using online communication data to generate comprehensive network maps that reproduce the health-associated properties of an offline social network. In this study, we examined three techniques for inferring social relationships from email traffic data in an employee population using thresholds based on: (1) the absolute number of emails exchanged, (2) logistic regression probability of an offline relationship, and (3) the highest ranked email exchange partners. As a model of the offline social network in the same population, a network map was created using social ties reported in a survey instrument. The email networks were evaluated based on the proportion of survey ties captured, comparisons of common network metrics, and autocorrelation of body mass index (BMI) across social ties. Results demonstrated that logistic regression predicted the greatest proportion of offline social ties, thresholding on number of emails exchanged produced the best match to offline network metrics, and ranked email partners demonstrated the strongest autocorrelation of BMI. Since each method had unique strengths, researchers should choose a method based on the aspects of offline behavior of interest. Ranked email partners may be particularly useful for purposes related to health traits in a social network.     

Schistosome sporocyst-killing Amoebae isolated from Biomphalaria glabrata.

Explants and swabs from the pericardium and mantle of three strains of Biomphalaria glabrata, two of them resistant to infection with Schistosoma mansoni, have yielded small amoebae, 3–5μm in diameter, in culture. These amoebae have been grown axenically through > 50 passages to date. The amoebae form cysts in dense cultures. When mixed with S. mansoni mother sporocysts in vitro, the amoebae adhere to and kill the trematodes within several hours. For 1–2 days thereafter, the amoebae proliferate rapidly at a generation time of about 5 hr, then return to normal growth. Sonically disrupted sporocysts also induce proliferation. Live sporocysts do not attract the amoebae or emit soluble substances which influence amoebal growth. Amoebae also adhered to and killed S. mansoni daughter sporocysts and cells derived from B. glabrata embryos; however, they did not harm S. mansoni cercariae or rediae of other trematode species. The proportion of mantle explants yielding amoebae was significantly higher (P<0.05) in one of the resistant snail strains than in the susceptible strain; however, whether amoebae contribute to snail resistance is unknown. Exposure of snails to S. mansoni miracidia did not influence the proportion of snails yielding amoebae.