Correlated mutations via regularized multinomial regression

Background In addition to sequence conservation, protein multiple sequence alignments contain evolutionary signal in the form of correlated variation among amino acid positions. This signal indicates positions in the sequence that influence each other, and can be applied for the prediction of intra- or intermolecular contacts. Although various approaches exist for the detection of such correlated mutations, in general these methods utilize only pairwise correlations. Hence, they tend to conflate direct and indirect dependencies. Results We propose RMRCM, a method for Regularized Multinomial Regression in order to obtain Correlated Mutations from protein multiple sequence alignments. Importantly, our method is not restricted to pairwise (column-column) comparisons only, but takes into account the network nature of relationships between protein residues in order to predict residue-residue contacts. The use of regularization ensures that the number of predicted links between columns in the multiple sequence alignment remains limited, preventing overprediction. Using simulated datasets we analyzed the performance of our approach in predicting residue-residue contacts, and studied how it is influenced by various types of noise. For various biological datasets, validation with protein structure data indicates a good performance of the proposed algorithm for the prediction of residue-residue contacts, in comparison to previous results. RMRCM can also be applied to predict interactions (in addition to only predicting interaction sites or contact sites), as demonstrated by predicting PDZ-peptide interactions. Conclusions A novel method is presented, which uses regularized multinomial regression in order to obtain correlated mutations from protein multiple sequence alignments

Field Evaluation of Traditionally Used Plant-Based Insect Repellents and Fumigants Against the Malaria Vector Anopheles darlingi in Riberalta, Bolivian Amazon

Inexpensive insect repellents may be needed to supplement the use of impregnated bed-nets in the Amazon region, where the primary malaria vector, Anopheles darlingi (Root), is exophilic and feeds in the early evening. Three plants that are traditionally used to repel mosquitoes in Riberalta, Bolivian Amazon, were identified by focus group, and then they were tested against An. darlingi as well as Mansonia indubitans (Dyar & Shannon)/Mansonia titillans (Walker). Cymbopogon citratus (Staph), Guatemalan lemongrass, essential oil at 25% was used as a skin repellent, and it provided 74% protection for 2.5 h against predominantly An. darlingi and 95% protection for 2.5 h against Mansonia spp. Attalea princeps (name not verified) husks, burned on charcoal in the traditional way provided 35 and 51% protection against An. darlingi and Mansonia spp., respectively. Kerosene lamps, often used to light rural homes, were used as a heat source to volatilize 100% Mentha arvensis (Malinv ex. Bailey) essential oil, and they reduced biting by 41% inside traditional homes against Mansonia spp., although they were ineffective outdoors against An. darlingi. All three plant-based repellents provided significant protection compared with controls. Plant-based repellents, although less effective than synthetic alternatives, were shown by focus groups to be more culturally acceptable in this setting, in particular para-menthane-3, 8, idol derived from lemon eucalyptus, Corymbia citriodora (Hook). Plant-based repellents have the potential to be produced locally and therefore sold more cheaply than synthetic commercial repellents. Importantly, their low cost may encourage user compliance among indigenous and marginalized populations

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

Differential responses of zooplankton assemblages to environmental variation in temporary and permanent ponds

Permanent and temporary wetlands in Mediterranean shrublands represent unique repositories of biodiversity, which are increasingly threatened by human-induced habitat loss. The zooplankton of a permanent (P1) and a temporary pond (T35) in the Natural Reserve of Castelporziano, a rare residual stretch of such a shrubland in Central Italy (Latium), was investigated to: (1) expand and deepen knowledge of these endangered freshwater habitats, which represent a crucial component of Mediterranean biodiversity; (2) identify environmental controls regulating the development of zooplankton communities of each environment; and (3) highlight differences in the adaptive responses of the zooplankton community in relation to the different ecological conditions experienced by permanent and temporary habitats. Despite summer desiccation in T35, the two ponds exhibited a relative homogeneity in hydrological and physico-chemical dynamics. Zooplankton assemblages contained 41 total taxa, of which 32 were found in P1 and 28 in T35. Out of the 41 taxa identified, 22 (> 50%) were exclusively present in one of the two ponds. On a yearly basis, the community dynamics of P1 seemed to be conditioned by physical and chemical factors and by hydrological cycle characteristics, while the community of T35 responded to algal blooms, food competition and predator/prey equilibria rather than correlating to abiotic factors. The main differences amongst zooplankton assemblages were observed over short time scales and occurred both within and between seasons, highlighting the role of some structural taxa that dominated the average composition of the community throughout the year, and the importance of "quick-response" taxa in determining the short-term composition and structure variation of pond zooplankton. A year-round cyclic community succession peculiar to each pond is described

Interspecific competition delays recovery of Daphnia spp. populations from pesticide stress

Xenobiotics alter the balance of competition between species and induce shifts in community composition. However, little is known about how these alterations affect the recovery of sensitive taxa. We exposed zooplankton communities to esfenvalerate (0.03, 0.3, and 3 μg/L) in outdoor microcosms and investigated the long-term effects on populations of Daphnia spp. To cover a broad and realistic range of environmental conditions, we established 96 microcosms with different treatments of shading and periodic harvesting. Populations of Daphnia spp. decreased in abundance for more than 8 weeks after contamination at 0.3 and 3 μg/L esfenvalerate. The period required for recovery at 0.3 and 3 μg/L was more than eight and three times longer, respectively, than the recovery period that was predicted on the basis of the life cycle of Daphnia spp. without considering the environmental context. We found that the recovery of sensitive Daphnia spp. populations depended on the initial pesticide survival and the related increase of less sensitive, competing taxa. We assert that this increase in the abundance of competing species, as well as sub-lethal effects of esfenvalerate, caused the unexpectedly prolonged effects of esfenvalerate on populations of Daphnia spp. We conclude that assessing biotic interactions is essential to understand and hence predict the effects and recovery from toxicant stress in communities

The Microbiome of Brazilian Mangrove Sediments as Revealed by Metagenomics

Here we embark in a deep metagenomic survey that revealed the taxonomic and potential metabolic pathways aspects of mangrove sediment microbiology. The extraction of DNA from sediment samples and the direct application of pyrosequencing resulted in approximately 215 Mb of data from four distinct mangrove areas (BrMgv01 to 04) in Brazil. The taxonomic approaches applied revealed the dominance of Deltaproteobacteria and Gammaproteobacteria in the samples. Paired statistical analysis showed higher proportions of specific taxonomic groups in each dataset. The metabolic reconstruction indicated the possible occurrence of processes modulated by the prevailing conditions found in mangrove sediments. In terms of carbon cycling, the sequences indicated the prevalence of genes involved in the metabolism of methane, formaldehyde, and carbon dioxide. With respect to the nitrogen cycle, evidence for sequences associated with dissimilatory reduction of nitrate, nitrogen immobilization, and denitrification was detected. Sequences related to the production of adenylsulfate, sulfite, and H2S were relevant to the sulphur cycle. These data indicate that the microbial core involved in methane, nitrogen, and sulphur metabolism consists mainly of Burkholderiaceae, Planctomycetaceae, Rhodobacteraceae, and Desulfobacteraceae. Comparison of our data to datasets from soil and sea samples resulted in the allotment of the mangrove sediments between those samples. The results of this study add valuable data about the composition of microbial communities in mangroves and also shed light on possible transformations promoted by microbial organisms in mangrove sediments