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Most theories used to explain the evolution of eusociality rest upon two key assumptions: mutations affecting the phenotype of sterile workers evolve by positive selection if the resulting traits benefit fertile kin, and that worker traits provide the primary mechanism allowing social insects to adapt to their environment. Despite the common view that positive selection drives phenotypic evolution of workers, we know very little about the prevalence of positive selection acting on the genomes of eusocial insects. We mapped the footprints of positive selection in Apis mellifera through analysis of 40 individual genomes, allowing us to identify thousands of genes and regulatory sequences with signatures of adaptive evolution over multiple timescales. We found Apoidea- and Apis- specific genes to be enriched for signatures of positive selection, indicating that novel genes play a disproportionately large role in adaptive evolution of eusocial insects. Worker-biased proteins have higher signatures of adaptive evolution relative to queen-biased proteins, supporting the view that worker traits are key to adaptation. We also found genes regulating worker division of labor to be enriched for signs of positive selection. Finally, genes associated with worker behavior based on analysis of brain gene expression were highly enriched for adaptive protein and cis -regulatory evolution. Our study highlights the significant contribution of worker phenotypes to adaptive evolution in social insects, and provides a wealth of knowledge on the loci that influence fitness in honey bees.

The rise of insect societies, marked by the formation of reproductive and sterile castes, represents a major unsolved mystery in evolution. Across several independent origins of sociality, the genomes of social hymenopterans share two peculiar attributes: high recombination and low but heterogeneous GC content. For example, the genome of the honey bee. Apis mellifera, represents a mosaic of GC-poor and GC-rich regions with rates of recombination an order of magnitude higher than in humans. However, it is unclear how heterogeneity in GC content arises, and how it relates to the expression and evolution of worker traits. Using population genetic analyses, we demonstrate a bias in the allele frequency and fixation rate of derived or G mutations in high-recombination regions, consistent with recombination's causal influence on GC-content evolution via biased gene conversion. We also show that recombination and biased gene conversion actively maintain the heterogeneous GC content of the honey bee genome despite an overall A/T mutation bias. Further, we found that GC-rich genes and intergenic regions have higher levels of genetic diversity and divergence relative to GC-poor regions, also consistent with recombination's causal influence on the rate of molecular evolution. Finally, we found that genes associated with behavior and those with worker-biased expression are found in GC-rich regions of the bee genome and also experience high rates of molecular evolution. Taken together, these findings suggest that recombination acts to maintain a genetically diverse and dynamic part of the genome where genes underlying worker behavior evolve more quickly.

Organizational members may be reluctant to express opinions or concerns because they feel that speaking out is futile. This phenomenon, named “acquiescent silence,” is examined in this paper through the lens of learned helplessness theory. We tested the learning effect generated by repeated failures to influence situations with voice over time. This learning could foster a state of acquiescent silence that mirrors learned helplessness. Both experimental studies ( N = 654) showed that individuals exposed to repetitive instances of low voice instrumentality were less likely to use new voice opportunities and felt increasingly helpless. These findings shed light on the impact of perceived voice ineffectiveness on employee future voice behaviors and propose a framework clarifying the development of acquiescent silence over time.

Fire severity is a key fire regime characteristic with high ecological and carbon cycle relevance. Prior studies on boreal forest fires primarily focused on mapping severity in North American boreal forests. However, the dominant tree species and their impacts on fire regimes are different between North American and Siberian boreal forests. Here, we used Sentinel-2 satellite imagery to test the potential for using the most common spectral index for assessing fire severity, the differenced Normalized Burn Ratio (dNBR), over two fire scars and 37 field plots in Northeast Siberian larch-dominated (Larix cajanderi) forests. These field plots were sampled into two different forest types: (1) dense young stands and (2) open mature stands. For this evaluation, the dNBR was compared to field measurements of the Geometrically structured Composite Burn Index (GeoCBI) and burn depth. We found a linear relationship between dNBR and GeoCBI using data from all forest types (R2 = 0.42, p < 0.001). The dNBR performed better to predict GeoCBI in open mature larch plots (R2 = 0.56, p < 0.001). The GeoCBI provides a holistic field assessment of fire severity yet is dominated by the effect of fire on vegetation. No significant relationships were found between GeoCBI components (overall and substrate stratum) and burn depth within our fires (p > 0.05 in all cases). However, the dNBR showed some potential as a predictor for burn depth, especially in the dense larch forests (R2 = 0.63, p < 0.001). In line with previous studies in boreal North America, the dNBR correlated reasonably well with field data of aboveground fire severity and showed some skills as a predictor of burn depth. More research is needed to refine spaceborne fire severity assessments in the larch forests of Northeast Siberia, including assessments of additional fire scars and integration of dNBR with other geospatial proxies of fire severity.

In their classic experiments, Olds and Milner showed that rats learn to lever press to receive an electric stimulus in specific brain regions. This led to the identification of mammalian reward centers. Our interest in defining the neuronal substrates of reward perception in the fruit fly Drosophila melanogaster prompted us to develop a simpler experimental approach wherein flies could implement behavior that induces self-stimulation of specific neurons in their brains. The high-throughput assay employs optogenetic activation of neurons when the fly occupies a specific area of a behavioral chamber, and the flies’ preferential occupation of this area reflects their choosing to experience optogenetic stimulation. Flies in which neuropeptide F (NPF) neurons are activated display preference for the illuminated side of the chamber. We show that optogenetic activation of NPF neuron is rewarding in olfactory conditioning experiments and that the preference for NPF neuron activation is dependent on NPF signaling. Finally, we identify a small subset of NPF-expressing neurons located in the dorsomedial posterior brain that are sufficient to elicit preference in our assay. This assay provides the means for carrying out unbiased screens to map reward neurons in flies.

Developmental plasticity generates phenotypic variation, but how it contributes to evolutionary change is unclear. Phenotypes of individuals in caste-based (eusocial) societies are particularly sensitive to developmental processes, and the evolutionary origins of eusociality may be rooted in developmental plasticity of ancestral forms. We used an integrative genomics approach to evaluate the relationships among developmental plasticity, molecular evolution, and social behavior in a bee species (Megalopta genalis) that expresses flexible sociality, and thus provides a window into the factors that may have been important at the evolutionary origins of eusociality. We find that differences in social behavior are derived from genes that also regulate sex differentiation and metamorphosis. Positive selection on social traits is influenced by the function of these genes in development. We further identify evidence that social polyphenisms may become encoded in the genome via genetic changes in regulatory regions, specifically in transcription factor binding sites. Taken together, our results provide evidence that developmental plasticity provides the substrate for evolutionary novelty and shapes the selective landscape for molecular evolution in a major evolutionary innovation: Eusociality.

BackgroundThe uptake of biosimilars has been suboptimal in North America. In response, in 2019, British Columbia (BC) became the first jurisdiction in North America to require patients with inflammatory arthritis to switch to a biosimilar version of infliximab and etanercept to maintain public coverage through the ‘Biosimilars Initiative’ policy. In 2021 this policy was extended to include adalimumab. The Biosimilars Initiative extended a previous policy which required people starting a biologic to use a biosimilar. Large commercial insurers which provide supplementary drug coverage also introduced biosimilars policies in line with the BC provincial government. Under both biosimilar switching policies, exceptional coverage to reference products was allowed if medically needed.ObjectivesTo quantify the impact of the Biosimilars Initiative and the initial policy requiring new initiators to a biologic to use a biosimilar on uptake and spending on biosimilar infliximab, etanercept, and adalimumab in British Columbia (BC).MethodsAdministrative claims data in BC from January 2013 through March2023 were analyzed using interrupted time series analysis, a quasi-experimental study design commonly used to evaluate policy changes. Two policy interventions were evaluated: (1) new starts, whereby individuals initiating infliximab, etanercept, or adalimumab for the first time were required to start the biosimilar (implemented between Feb 2016 and July 2017), and (2) mandatory switching, which required those already receiving infliximab or etanercept (implemented between May and Nov 2019), or adalimumab (implemented between April and October 2012) to switch to the biosimilar version in order to maintain coverage. A segmented linear regression was used to model the level and trend change in biosimilar etanercept and infliximab utilization and spending before and after the two policy interventions.ResultsWe identified 208,984 BC residents ≥18 years who qualified for public drug coverage, were treated with etanercept or infliximab, and were eligible for analysis between January 2013 and November 2020. After the new start policy, we detected a small gradual increase in the proportion of biosimilar etanercept prescriptions dispensed of 0.65% (95%CI 0.44, 0.85) per month. The monthly trend related to the proportion of total spending on biosimilar etanercept also increased (0.51, 95%CI 0.28, 0.73). After the mandatory switching policy (the Biosimilars Initiative), there was a sustained increase in the proportion of biosimilar etanercept and infliximab prescriptions dispensed of 76.98% (95%CI 75.56, 78.41) and 58.43% (95%CI 52.11, 64.75), respectively. Similarly, there was a persistent increase in spending on biosimilar etanercept and infliximab of 78.22% (95%CI 76.65, 79.79) and 71.23% (95%CI 66.82, 75.65), respectively. Similar results were seen for adalimumab which was switched later.Figure 1.Overall proportion of prescriptions dispensed that were biosimilar etanercept and infliximabConclusionOur study found new start policies resulted in small, gradual increases in biosimilar utilization. However, the mandatory switch policy, the Biosimilars Initiative, resulted in a marked immediate and sustained impact on uptake. Further analysis will examine changes in other health utilization, and long-term impact on prescribing patterns. These findings may be particularly relevant to areas with a more concentrated insurance system where mandatory switching policies could lead to greater savings.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers by repeatedly pairing them with hypoaggressive or hyperaggressive opponents, respectively. As described previously, we observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them. Olfactory conditioning experiments showed that winning is perceived as rewarding, while losing is perceived as aversive. Moreover, the effect of chronic fighting experience generalized to other behaviors, such as gap-crossing and courtship. We propose that in response to repeatedly winning or losing aggressive encounters, male flies form an internal state that displays persistence and generalization; fight outcomes can also have positive or negative valence. Furthermore, we show that the activities of the PPL1-γ1pedc dopaminergic neuron and the MBON-γ1pedc>α/β mushroom body output neuron are required for aversion to an olfactory cue associated with losing fights.

Nutrition is known to interact with genotype in human metabolic syndromes, obesity, and diabetes, and also in Drosophila metabolism. Plasticity in metabolic responses, such as changes in body fat or blood sugar in response to changes in dietary alterations, may also be affected by genotype. Here we show that variants of the foraging (for) gene in Drosophila melanogaster affect the response to food deprivation in a large suite of adult phenotypes by measuring gene by environment interactions (GEI) in a suite of food-related traits. for affects body fat, carbohydrates, food-leaving behavior, metabolite, and gene expression levels in response to food deprivation. This results in broad patterns of metabolic, genomic, and behavioral gene by environment interactions (GEI), in part by interaction with the insulin signaling pathway. Our results show that a single gene that varies in nature can have far reaching effects on behavior and metabolism by acting through multiple other genes and pathways.

Understanding the retinogeniculate pathway in vitro can offer insights into its development and potential for future therapeutic applications. This study presents a Polydimethylsiloxane-based two-chamber system with axon guidance channels, designed to replicate unidirectional retinogeniculate signal transmission in vitro . Using embryonic rat retinas, we developed a model where retinal spheroids innervate thalamic targets through up to 6 mm long microfluidic channels. Using a combination of electrical stimulation and functional calcium imaging we assessed how channel length and electrical stimulation frequency affects thalamic target response. In the presented model we integrated up to 20 identical functional retinothalamic neural networks aligned on a single transparent microelectrode array, enhancing the robustness and quality of recorded functional data. We found that network integrity depends on channel length, with 0.5–2 mm channels maintaining over 90% morphological and 50% functional integrity. A reduced network integrity was recorded in longer channels. The results indicate a notable reduction in forward spike propagation in channels longer than 4 mm. Additionally, spike conduction fidelity decreased with increasing channel length. Yet, stimulation-induced thalamic target activity remained unaffected by channel length. Finally, the study found that a sustained thalamic calcium response could be elicited with stimulation frequencies up to 31 Hz, with higher frequencies leading to transient responses. In conclusion, this study presents a high-throughput platform that demonstrates how channel length affects retina to brain network formation and signal transmission in vitro .