Recent advances in the global effort to eradicate trachoma.
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Blindness↗
Biomedical subjects
Michael S Singer
Publications and source records attributed to Michael S Singer.
Structural activation pathways from dynamic olfactory receptor-odorant interactions.
We have simulated an odor ligand's dynamic behavior in the binding region of an olfactory receptor (OR). Our short timescale computational studies (up to 200 ps) have helped identify unprecedented postdocking ligand behavior of ligands. From in vacuo molecular dynamics simulations of interactions between models of rat OR I7 and 10 aldehyde ligands, we have identified a dissociative pathway along which the ligand exits and enters the OR-binding pocket--a transit event. The ligand's transit through the receptor's binding region may mark the beginning of a signal transduction cascade leading to odor recognition. We have graphically traced the rotameric changes in key OR amino acid side chains during the transit. Our results have helped substantiate or refute previously held notions of amino acid contribution to ligand stability in the binding pocket. Our observations of ligand activity when compared to those of experimental (electroolfactogram response) OR-activation studies provide a view to predicting the stability of ligands in the binding pocket as a precursor to OR activation by the ligand.
Aldehydes↗
Insect defences: taste alteration and endoparasites.
Taste sensation and food selection by animals can change adaptively in response to experience, for example to redress specific nutrient deficiencies. We show here, in two species of caterpillar, that infection by lethal parasites alters the taste of specific phytochemicals for the larvae. Given that these compounds are toxic to the parasites and are found in plants eaten by the caterpillars, their changed taste may encourage parasitized caterpillars to increase consumption of plants that provide a biochemical defence against the invaders.
Adaptation, Physiological↗
Disentangling food quality from resistance against parasitoids: diet choice by a generalist caterpillar.
The relative importance of food quality and enemy-reduced space is a central but unresolved issue in the evolutionary ecology of host use by phytophagous insects. Indeed, a practical obstacle to experimentally disentangling the functional roles of these factors is the host specificity of insect herbivores, particularly toxic plant specialists. In this study, we employ a toxic plant generalist to uniquely disentangle these alternative explanations. We experimentally demonstrate that the value of enemy-reduced space supersedes that of food quality in determining the diet and host preference of the polyphagous woolly bear caterpillar Grammia geneura (Lepidoptera: Arctiidae). Caterpillars sacrificed superior growth efficiency in choosing a mixed diet that included toxic host plants and provided resistance against parasitoids. The resistance of individual caterpillars was associated with the relative amount of defensive plants eaten as well as with the sequestration of pyrrolizidine alkaloids from one such plant (Senecio longilobus).
Ambrosia↗
Risk factors for road traffic injury in Pakistani children.
Road traffic injury (RTI) is an important cause of disability and mortality in Pakistani children. To focus interventions more effectively, we wished to identify factors that would predict which children were most at risk. We studied inpatients at Children's Hospital of the Pakistan Institute of Medical Sciences in Islamabad. We compared three groups: children who sustained an RTI, those who sustained an injury unrelated to road traffic, and those admitted for reasons other than injury. Most RTIs in our sample involved pedestrians, and most children were unsupervised. Children from small homes, families with many children, or tents used as homes were at elevated risk for RTI compared to non-RTI injured children and non-injured controls. Children with uneducated mothers were at greater risk for RTI compared to non-injured controls. We recommend focusing injury prevention programs on children from small homes, large families, and squatter settlements. Beyond conventional strategies for injury prevention, studies should test the benefits of improved playgrounds, school enrollment, supervised after-school programs, housing assistance projects, and educational programs for mothers.
Accidents, Traffic↗
What determines host range in parasitoids? An analysis of a tachinid parasitoid community.
Despite the vast diversity of parasitic insects and their importance in natural and agricultural communities, our knowledge of what determines their patterns of association with hosts remains sparse. Unlike most parasites that tend to be specialized, parasitoid flies in the family Tachinidae exhibit a broad spectrum of host-specificity, with many species attacking a wide range of hosts. This variability in host-specificity makes them a useful model for examining the ecological and historical factors that determine host associations. We analyzed data collected from a 5-year rearing program of Lepidoptera in southern Arizona to investigate the factors that influence tachinid-host associations. After controlling for a strong effect of sample size, a significant portion of the remaining variance in host range was explained by differences among phylogenetic groups of tachinids and/or their correlated reproductive strategies. Relatively specialized tachinids tended to be associated with monophagous or narrowly oligophagous hosts and attacked them at relatively high frequencies, a pattern we suggest is related to host location efficiency. Cluster analysis indicated that host abundance, gregariousness, food-plant type, and morphology are all important determinants of tachinid host use. Little concordance was found between how tachinid species cluster according to characteristics of their hosts and their estimated phylogenetic relationships. Together, the results of this study suggest that ecological factors are important determinants of host use in these parasitoids and although phylogenetic history may influence the range of hosts used, its power to explain the ecological or taxonomic character of hosts used appears limited.
Analysis of Variance↗
Prediction of protein residue contacts with a PDB-derived likelihood matrix.
Proteins with similar folds often display common patterns of residue variability. A widely discussed question is how these patterns can be identified and deconvoluted to predict protein structure. In this respect, correlated mutation analysis (CMA) has shown considerable promise. CMA compares multiple members of a protein family and detects residues that remain constant or mutate in tandem. Often this behavior points to structural or functional interdependence between residues. CMA has been used to predict pairs of amino acids that are distant in the primary sequence but likely to form close contacts in the native three-dimensional structure. Until now these methods have used evolutionary or biophysical models to score the fit between residues. We wished to test whether empirical methods, derived from known protein structures, would provide useful predictive power for CMA. We analyzed 672 known protein structures, derived contact likelihood scores for all possible amino acid pairs, and used these scores to predict contacts. We then tested the method on 118 different protein families for which structures have been solved to atomic resolution. The mean performance was almost seven times better than random prediction. Used in concert with secondary structure prediction, the new CMA method could supply restraints for predicting still undetermined structures.
Amino Acid Sequence↗