Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune diseases: chronic activation, normal selection

Autoimmune diseases show high diversity in the affected organs, clinical manifestations and disease dynamics. Yet they all share common features, such as the ectopic germinal centers found in many affected tissues. Lineage trees depict the diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. We previously developed an algorithm for quantifying the graphical properties of IGV gene lineage trees, allowing evaluation of the dynamical interplay between SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we apply this method to ectopic GC B cell clones from patients with Myasthenia Gravis, Rheumatoid Arthritis, and Sj?gren's Syndrome, using data scaling to minimize the effects of the large variability due to methodological differences between groups. Autoimmune trees were found to be significantly larger relative to normal controls. In contrast, comparison of the measurements for tree branching indicated that similar selection pressure operates on autoimmune and normal control clones.     

The co-distribution of Plasmodium falciparum and hookworm among African schoolchildren

Background

On the island of Bioko (Equatorial Guinea), insecticide-treated nets (ITNs) have been the main tool used to control malaria over the last 13 years. In 2004, started an indoor residual spraying (IRS) campaign to control malaria. The purpose of this study is to asses the impact of the two control strategies on the island of Bioko (Equatorial Guinea), with regards to Plasmodium infection and anaemia in the children under five years of age.

Methods

Two transversal studies, the first one prior to the start of the IRS campaign and the second one year later. Sampling was carried out by stratified clusters. Malaria infection was measured by means of thick and thin film, and the packed cell volume (PCV) percentage. Data related to ITN use and information regarding IRS were collected. The Pearson's chi-square and logistic regression statistical tests were used to calculate odds ratios (OR)

Results

In the first survey, 168 children were sampled and 433 children in the second one. The prevalence of infection was 40% in 2004, and significantly lower at 21.7% in 2005. PCV was 41% and 39%, respectively. 58% of the children surveyed in 2004 and 44.3% in 2005 had slept under an ITN. 78% of the dwellings studied in 2005 had been sprayed. In the 2005 survey, sleeping without a mosquito net meant a risk of infection 3 times greater than sleeping protected with a net hanged correctly and with no holes (p < 0.05).

Conclusion

IRS and ITNs have proven to be effective control strategies on the island of Bioko. The choice of one or other strategy is, above all, a question of operational feasibility and availability of local resources.     

Two Randomized Trials Provide No Consistent Evidence for Nonmusical Cognitive Benefits of Brief Preschool Music Enrichment

Young children regularly engage in musical activities, but the effects of early music education on children''s cognitive development are unknown. While some studies have found associations between musical training in childhood and later nonmusical cognitive outcomes, few randomized controlled trials (RCTs) have been employed to assess causal effects of music lessons on child cognition and no clear pattern of results has emerged. We conducted two RCTs with preschool children investigating the cognitive effects of a brief series of music classes, as compared to a similar but non-musical form of arts instruction (visual arts classes, Experiment 1) or to a no-treatment control (Experiment 2). Consistent with typical preschool arts enrichment programs, parents attended classes with their children, participating in a variety of developmentally appropriate arts activities. After six weeks of class, we assessed children''s skills in four distinct cognitive areas in which older arts-trained students have been reported to excel: spatial-navigational reasoning, visual form analysis, numerical discrimination, and receptive vocabulary. We initially found that children from the music class showed greater spatial-navigational ability than did children from the visual arts class, while children from the visual arts class showed greater visual form analysis ability than children from the music class (Experiment 1). However, a partial replication attempt comparing music training to a no-treatment control failed to confirm these findings (Experiment 2), and the combined results of the two experiments were negative: overall, children provided with music classes performed no better than those with visual arts or no classes on any assessment. Our findings underscore the need for replication in RCTs, and suggest caution in interpreting the positive findings from past studies of cognitive effects of music instruction.     

Plasma IP-10, apoptotic and angiogenic factors associated with fatal cerebral malaria in India

Background

Knowledge on insecticide resistance in target species is a basic requirement to guide insecticide use in malaria control programmes. Malaria transmission in the Mekong region is mainly concentrated in forested areas along the country borders, so that decisions on insecticide use should ideally be made at regional level. Consequently, cross-country monitoring of insecticide resistance is indispensable to acquire comparable baseline data on insecticide resistance.

Methods

A network for the monitoring of insecticide resistance, MALVECASIA, was set up in the Mekong region in order to assess the insecticide resistance status of the major malaria vectors in Cambodia, Laos, Thailand, and Vietnam. From 2003 till 2005, bioassays were performed on adult mosquitoes using the standard WHO susceptibility test with diagnostic concentrations of permethrin 0.75% and DDT 4%. Additional tests were done with pyrethroid insecticides applied by the different national malaria control programmes.

Results

Anopheles dirus s.s., the main vector in forested malaria foci, was susceptible to permethrin. However, in central Vietnam, it showed possible resistance to type II pyrethroids. In the Mekong delta, Anopheles epiroticus was highly resistant to all pyrethroid insecticides tested. It was susceptible to DDT, except near Ho Chi Minh City where it showed possible DDT resistance. In Vietnam, pyrethroid susceptible and tolerant Anopheles minimus s.l. populations were found, whereas An. minimus s.l. from Cambodia, Laos and Thailand were susceptible. Only two An. minimus s.l. populations showed DDT tolerance. Anopheles vagus was found resistant to DDT and to several pyrethroids in Vietnam and Cambodia.

Conclusion

This is the first large scale, cross-country survey of insecticide resistance in Anopheles species in the Mekong Region. A unique baseline data on insecticide resistance for the Mekong region is now available, which enables the follow-up of trends in susceptibility status in the region and which will serve as the basis for further resistance management. Large differences in insecticide resistance status were observed among species and countries. In Vietnam, insecticide resistance was mainly observed in low or transmission-free areas, hence an immediate change of malaria vector control strategy is not required. Though, resistance management is important because the risk of migration of mosquitoes carrying resistance genes from non-endemic to endemic areas. Moreover, trends in resistance status should be carefully monitored and the impact of existing vector control tools on resistant populations should be assessed.     

Streamlining genomes: toward the generation of simplified and stabilized microbial systems

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Highlights? Top-down and bottom-up approaches to genome streamlining. ? Computational support for constructing and refactoring streamlined genomes. ? From genome engineering to metabolic reprogramming. ? Perspectives in applied genome engineering.     

The effect of bark beetle infestation and salvage logging on bat activity in a national park

Salvage logging—the removal of dead trees in disturbed forest stands—has been controversially discussed. We investigated the impact of bark beetle attacks and subsequent salvage logging on insectivorous bats in a temperate mountain forest. We quantified bat activity (25,373?min counts; 32 plots) using batcorders during 221 all-night surveys in stands killed by bark beetles, with dead trees removed or not, and in vital, single- or multi-layered mature forest stands. We analysed the differences in activity of all bats in general and of bats of foraging guilds (open habitat, forest edge, closed habitat) in these habitats using a generalized linear Poisson mixed model, with plot and observation as random factors, and temperature and habitat as fixed factors. Only open-habitat foragers were slightly more active in salvage-logged stands than in bark-beetle-affected stands; they generally benefited from an open forest canopy, whereas closed-habitat foragers did not. Our results indicated that: (1) bats are less affected by salvage logging after a disturbance of a magnitude typical for European forests, probably because enough roosts are present in surrounding areas, (2) habitats for open foragers are improved by bark beetle infestation and (3) bats are poor bioindicators of negative impacts of salvage logging after natural disturbance in forests with a composition typical for Central Europe.     

Conservation of Dcm-mediated cytosine DNA methylation in Escherichia coli

In Escherichia coli, cytosine DNA methylation is catalyzed by the DNA cytosine methyltransferase (Dcm) protein and occurs at the second cytosine in the sequence 5'CCWGG3'. Although the presence of cytosine DNA methylation was reported over 35?years ago, the biological role of 5-methylcytosine in E.?coli remains unclear. To gain insight into the role of cytosine DNA methylation in E.?coli, we (1) screened the 72 strains of the ECOR collection and 90 recently isolated environmental samples for the presence of the full-length dcm gene using the polymerase chain reaction; (2) examined the same strains for the presence of 5-methylcytosine at 5'CCWGG3' sites using a restriction enzyme isoschizomer digestion assay; and (3) quantified the levels of 5-methyl-2'-deoxycytidine in selected strains using liquid chromatography tandem mass spectrometry. Dcm-mediated cytosine DNA methylation is conserved in all 162 strains examined, and the level of 5-methylcytosine ranges from 0.86% to 1.30% of the cytosines. We also demonstrate that Dcm reduces the expression of ribosomal protein genes during stationary phase, and this may explain the highly conserved nature of this DNA modification pathway.     

Microbial stratification in low pH oxic and suboxic macroscopic growths along an acid mine drainage

Macroscopic growths at geographically separated acid mine drainages (AMDs) exhibit distinct populations. Yet, local heterogeneities are poorly understood. To gain novel mechanistic insights into this, we used OMICs tools to profile microbial populations coexisting in a single pyrite gallery AMD (pH ∼2) in three distinct compartments: two from a stratified streamer (uppermost oxic and lowermost anoxic sediment-attached strata) and one from a submerged anoxic non-stratified mat biofilm. The communities colonising pyrite and those in the mature formations appear to be populated by the greatest diversity of bacteria and archaea (including ‘ARMAN'' (archaeal Richmond Mine acidophilic nano-organisms)-related), as compared with the known AMD, with ∼44.9% unclassified sequences. We propose that the thick polymeric matrix may provide a safety shield against the prevailing extreme condition and also a massive carbon source, enabling non-typical acidophiles to develop more easily. Only 1 of 39 species were shared, suggesting a high metabolic heterogeneity in local microenvironments, defined by the O₂ concentration, spatial location and biofilm architecture. The suboxic mats, compositionally most similar to each other, are more diverse and active for S, CO₂, CH₄, fatty acid and lipopolysaccharide metabolism. The oxic stratum of the streamer, displaying a higher diversity of the so-called ‘ARMAN''-related Euryarchaeota, shows a higher expression level of proteins involved in signal transduction, cell growth and N, H₂, Fe, aromatic amino acids, sphingolipid and peptidoglycan metabolism. Our study is the first to highlight profound taxonomic and functional shifts in single AMD formations, as well as new microbial species and the importance of H₂ in acidic suboxic macroscopic growths.