Varga, O. | bioRxiv Science

bioRxiv2020

Trends in animal model preference for preclinical drug testing for type-2 diabetes and future directions

The importance of selecting accurate animal models of disease has become increasingly salient in recent years. This is particularly important for preclinical tests carried out to predict drug efficacy and safety for humans. We mapped past and current trends in animal model selection for type-2 Diabetes Mellitus (T2DM) antidiabetic drug research, and evaluate results in light of their implications for translational research. From data gathered from published studies on 41 orally administered antidiabetic drug classes from the MEDLINE Evaluator web service, we found animal model choice trends within - and across - drug classes to be substantially similar, with outbred rat strains being more prevalently used, since the 1990s. The observed consistency in choice of animal models in T2DM is advantageous for replicability and comparability of experiments, but prevalence of outbred strains raises a few concerns. In face of current criticism of the translational value of animal tests, predictive validity must be assessed on a case-by-case basis. We address some of the issues pertaining the most popular animal models in antidiabetic drug development and testing, including the lack of information on their predictive validity, and propose a back translation approach to estimate it retrospectively.

pharmacology and toxicology↗

bioRxiv2019

Completing Linnaeus’s Inventory of the Swedish Insect Fauna: Only 5000 Species Left

Despite more than 250 years of taxonomic research, we still have only a vague idea about the true size and composition of the faunas and floras of the planet. Many biodiversity inventories provide limited insight because they focus on a small taxonomic subsample or a tiny geographic area. Here, we report on the size and composition of the Swedish insect fauna, thought to represent roughly half of the diversity of multicellular life in one of the largest European countries. Our results are based on more than a decade of data from the Swedish Taxonomy Initiative and its massive inventory of the countrys insect fauna, the Swedish Malaise Trap Project The fauna is considered one of the best known in the world, but the initiative has nevertheless revealed a surprising amount of hidden diversity: more than 3,000 new species (301 new to science) have been documented so far. Here, we use three independent methods to analyze the true size and composition of the fauna at the family or subfamily level: (1) assessments by experts who have been working on the most poorly known groups in the fauna; (2) estimates based on the proportion of new species discovered in the Malaise trap inventory; and (3) extrapolations based on species abundance and incidence data from the inventory. For the last method, we develop a new estimator, the combined non-parametric estimator, which we show is less sensitive to poor coverage of the species pool than other popular estimators. The three methods converge on similar estimates of the size and composition of the fauna, suggesting that it comprises around 33,000 species. Of those, 8,600 (26%) were unknown at the start of the inventory and 5,000 (15%) still await discovery. We analyze the taxonomic and ecological composition of the estimated fauna, and show that most of the new species belong to Hymenoptera and Diptera groups that are decomposers or parasitoids. Thus, current knowledge of the Swedish insect fauna is strongly biased taxonomically and ecologically, and we show that similar but even stronger biases have distorted our understanding of the fauna in the past. We analyze latitudinal gradients in the size and composition of known European insect faunas and show that several of the patterns contradict the Swedish data, presumably due to similar knowledge biases. Addressing these biases is critical in understanding insect biomes and the ecosystem services they provide. Our results emphasize the need to broaden the taxonomic scope of current insect monitoring efforts, a task that is all the more urgent as recent studies indicate a possible worldwide decline in insect faunas.

ecology↗