Comparing life histories across taxonomic groups in multiple dimensions: how mammal-like are insects?

Explaining variation in life histories remains a major challenge because they are multi-dimensional and there are many competing explanatory theories and paradigms. An influential concept in life history theory is the ’fast-slow continuum’, exemplified by mammals. Determining the utility of such concepts across taxonomic groups requires comparison of the groups’ life histories in multidimensional space. Insects display enormous species richness and phenotypic diversity, but testing hypotheses like the ’fast-slow continuum’ has been inhibited by incomplete trait data. We use phylogenetic imputation to generate complete datasets of seven life history traits in orthopterans (grasshoppers and crickets) and examine the robustness of these imputations for our findings. Three phylogenetic principal components explain 83-96% of variation in these data. We find consistent evidence of an axis mostly following expectations of a ’fast-slow continuum’, except that ’slow’ species produce larger, not smaller, clutches of eggs. We show that the principal axes of variation in orthopterans and reptiles are mutually explanatory, as are those of mammals and birds. Essentially, trait covariation in Orthoptera, with ’slow’ species producing larger clutches, is more reptile-like than mammal-or-bird-like. We conclude that the ’fast-slow continuum’ is less pronounced in Orthoptera than in birds and mammals, reducing the universal relevance of this pattern, and the theories that predict it

Stabilized Polymer Micelles for the Development of IT-147, an Epothilone D Drug-Loaded Formulation

Epothilones have demonstrated promising potential for oncology applications but suffer from a narrow therapeutic window. Epothilone D stabilizes microtubules leading to apoptosis, is active against multidrug-resistant cells, and is efficacious in animal tumor models despite lack of stability in rodent plasma. Clinical development was terminated in phase II due to dose limiting toxicities near the efficacious dose. Taken together, this made epothilone D attractive for encapsulation in a stabilized polymer micelle for improved safety and efficacy. We have designed a library of triblock copolymers to develop IT-147, a lead formulation of epothilone D that extends plasma circulation for accumulation in the tumor environment, and potentially decrease systemic exposure to reduce dose limiting toxicities. The drug loading efficiency for IT-147 exceeds 90%, is 75 nm in diameter, and demonstrates pH-dependent release of epothilone D without chemical conjugation or enzymatic activation. Administration of IT-147 at 20 mg/kg increases exposure of epothilone D to the plasma compartment over 6-fold compared to free drug. At the same dose, 20 mg/kg epothilone D from IT-147 is considered the no observed adverse effect level (NOAEL) but is the maximum tolerated dose for free drug. Consequently, IT-147 is positioned to be a safer, more effective means to deliver epothilone D

The diversity, intercorrelation, and macroevolutionary consequences of insect life histories

The life history of an organism describes its pattern of growth, reproduction, and survival, and thus is closely linked to fitness. Between species, life history traits vary widely and one of the major goals of life history theory is to explain how natural selection gives rise to this variation. However, there has been a lack of comparative life history studies focussing on insects, which comprise over half of the currently described macroscopic species. I conduct a class-level analysis of insect life history traits, and explore the associations between life history strategies, ecology, metamorphosis, and macroevolutionary processes. In Orthoptera (grasshoppers, crickets and kin), I identify mostly ‘fast-slow’ variation in life history traits, except that larger (and otherwise ‘slower’) species have smaller, not larger, clutches of eggs. I find that this type of variation is closer to that of reptiles than that of either mammals or birds and discuss potential reasons for this similarity. Across the whole of the insects, I find that the primary axes of life history variation are related to a) amount of reproductive investment, and b) how this investment is divided into clutches. Further orthogonal axes contain variables related to development time, then adult lifespan. I show associations between life histories and diet (parasitoids and ecto-parasitoids are particularly fast-lived), metamorphosis (ametabolous species have longer lifespans), but not habitat (no difference between aquatic and terrestrial species). Finally, I find links between life history traits and diversification. Species richness is higher in orders and families with fast development times, and higher in families with high fecundity. Diversification rates are higher in families with high fecundity and those with short egg stages. Together, my work raises questions about the generality of widely invoked patterns of life history covariation and highlights the need to test these patterns in a taxonomically broad sense