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Biology subjects

Voelkl, B.

Publications and source records attributed to Voelkl, B..

5 recordsLinked to original sources

Population genetics of bumble bee species with diverging population dynamics

Pollinator populations are facing worldwide declines, underscoring conservation needs. Yet, conservation assessments still mostly rely on occurrence data, often derived from heterogeneous and opportunistic observations. While such data can inform on species presence and distribution, they may overlook important markers of population declines. This is particularly problematic for social species such as bumble bees, which typically exhibit low effective population sizes despite high abundance of workers observed in the field. Despite these putative pitfalls, the relationship between occurrence-based and genetic-based estimates remains largely unexplored in social bees. We here investigated spatio-temporal genetic patterns in five Swiss Bombus species representing contrasting population trajectories over the last century: B. humilis and B. sylvarum (stable), B. ruderatus (increasing), B. pomorum (regionally extinct), and B. veteranus (declining). Museum specimens collected between 1929 and 2023 were genotyped at 11 microsatellite loci to compare spatio-temporal fluctuations in genetic diversity and population structure with occurrence data. Overall, multilocus heterozygosity and allelic richness remained stable in all species during the time period investigated, indicating that the diverging population trends did not result in substantial variation of genetic diversity. In contrast, strong and significant shifts in allelic frequencies between time periods were detected in three species, suggesting recent immigration events. Isolation by distance was detected in the cold-adapted B. veteranus, while the extant warm-adapted species (B. humilis, B. sylvarum, B. ruderatus) showed high levels of gene flow between locations. In B. pomorum, increasing genetic homogenization was observed before extinction. Altogether, these findings show that genetic diversity indexes are not the most adapted tools to monitor conservation status of social bee populations, and that estimates of population structure such as allelic shifts may be more informative. Moreover, these results highlight the importance of monitoring metapopulation dynamics and ensuring connectivity among populations to facilitate gene flow and enable demographic rescue processes.

ecology↗

Evidence for HARKing in mouse behavioural tests of anxiety

Anxiety disorders are among the most common mental health conditions needing new and better treatments. Research and development of anxiolytic drugs using animal models heavily rely on behavioural tests, most of which measure anxiolytic effects by increased exploratory activity in potentially threatening environments. However, interpretation of such tests is ambiguous because reduced exploratory activity can reflect either anxiety or sedation by the compound. Based on a systematic review of the sensitivity of mouse behavioural tests of anxiety to anxiolytic drugs, we analysed outcomes of 206 studies testing the effect of diazepam in either the open-field test or the hole-board test, as outcomes of these tests showed substantial variation in both direction and strength of the drug effect. Surprisingly, we found that both the rationale given for using the test, whether to detect anxiolytic or sedative effects, and the predicted effect of diazepam, anxiolytic or sedative, strongly depended on the reported test results. The most likely explanation for such strong dependency is post-hoc reasoning, also called hypothesizing after the results are known (HARKing). HARKing can invalidate study outcomes and hampers evidence synthesis by inflating effect sizes. It may also lead researchers into blind alleys, put patients in clinical trials at risk, and waste animals, time, and resources for inconclusive research.

animal behavior and cognition↗

Rearing environment persistently modulates the phenotype of mice

The phenotype of an organism results from its genotype and the influence of the environment throughout development. Even when using animals of the same genotype, independent studies may test animals of different phenotypes, resulting in poor replicability due to genotype-by-environment interactions 1-4. Thus, genetically defined strains of mice may respond differently to experimental treatments depending on their rearing environment 5. However, the extent of such phenotypic plasticity and its implications for the replicability of research findings have remained unknown. Here, we examined the extent to which common environmental differences between rearing facilities modulate the phenotype of genetically homogeneous (inbred) mice. We conducted a comprehensive multi-center study, where inbred mice from the same breeding stock were reared in five different facilities throughout early life and adolescence, before being transported to a single test laboratory. We found persistent effects of rearing facility on the composition and heterogeneity of the gut microbial community. These effects were paralleled by persistent differences in body weight and in the behavioural phenotype of the mice. Furthermore, we show that common variation among rearing facilities is strong enough to influence epigenetic patterns in neurons at the level of chromatin organization. We detected changes in chromatin organization in the regulatory regions of genes involved in nucleosome assembly, neuronal differentiation, synaptic plasticity and regulation of behavior. Our findings demonstrate that common environmental differences between rearing facilities may produce facility-specific phenotypes, from the molecular to the behavioural level. We expect our findings to stimulate further research into the mechanisms and drivers of these epigenetic changes mediated by the laboratory environment. Furthermore, they highlight an important limitation of inferences from single-laboratory studies and a need to account for the animals environmental background in study design to produce robust and replicable findings.

neuroscience↗

Reliability of Mouse Behavioural Tests of Anxiety: a Systematic Review and Meta-Analysis on the Effects of Anxiolytics.

Animal research on anxiety and anxiety disorders relies on valid animal models of anxiety. However, the validity of widely used rodent behavioural tests of anxiety has repeatedly been questioned, as they often fail to produce consistent results across independent replicate studies using different study populations or different anxiolytic compounds. In this study, we assessed the sensitivity of behavioural tests of anxiety in mice to detect anxiolytic effects of drugs prescribed to treat anxiety in humans. To this end, we conducted a pre-registered systematic review of studies reporting tests of anxiolytic compounds against a control treatment using common behavioural tests of anxiety in mice. PubMed and EMBASE were searched on August 21st 2019 for studies published in English and 814 papers were identified for inclusion. Risk of bias was assessed based on Syrcles risk of bias tool and the Camarades study quality checklist on a randomly selected subsample of 180 papers. Meta-analyses on effect sizes of treatments using standardized mean differences (Hedges g) showed that only two of 17 test measures reliably detected effects of anxiolytic compounds other than diazepam. Further, we report considerable variation in both direction and size of effects of most anxiolytics on most outcome variables, indicating poor replicability of test results. This was corroborated by high heterogeneity in most test measures. Finally, we found an overall high risk of bias. Our findings indicate a general lack of sensitivity of common behavioural tests of anxiety in mice to anxiolytic compounds and cast serious doubt on both construct and predictive validity of most of those tests. The use of animals to model human conditions can be justified only if the expected results are informative, reproducible, and translatable. In view of scientifically valid and ethically responsible research, we call for a revision of behavioural tests of anxiety in mice and the development of more predictive tests.

neuroscience↗

A Reaction Norm Perspective on Reproducibility

Reproducibility in biomedical research, and more specifically in preclinical animal research, has been seriously questioned. Several cases of spectacular failures to replicate findings published in the primary scientific literature have led to a perceived reproducibility crisis. Diverse threats to reproducibility have been proposed, including lack of scientific rigour, low statistical power, publication bias, analytical flexibility and fraud. An important aspect that is generally overlooked is the lack of external validity caused by rigorous standardization of both the animals and the environment. Here, we argue that a reaction norm approach to phenotypic variation, acknowledging gene-by-environment interactions, can help us seeing reproducibility of animal experiments in a new light. We illustrate how dominating environmental effects can affect inference and effect size estimates of studies and how elimination of dominant factors through standardization affects the nature of the expected phenotype variation through the reaction norms of small effect. Finally, we discuss the consequences of reaction norms of small effect for statistical analysis, specifically for random effect latent variable models and the random lab model.

developmental biology↗