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Abstract Targeting brain insulin resistance (BIR) has become an attractive alternative to traditional therapeutic treatments for Alzheimer’s disease (AD). Incretin receptor agonists (IRAs), targeting either or both of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, have proven to reverse BIR and improve cognition in mouse models of AD. We previously showed that many, but not all, IRAs can cross the blood-brain barrier (BBB) after intravenous (IV) delivery. Here we determined if widespread brain uptake of IRAs could be achieved by circumventing the BBB using intranasal (IN) delivery, which has the added advantage of minimizing adverse gastrointestinal effects of systemically delivered IRAs. Of the 5 radiolabeled IRAs tested (exenatide, dulaglutide, semaglutide, DA4-JC, and DA5-CH) in CD-1 mice, exenatide, dulaglutide, and DA4-JC were successfully distributed throughout the brain following IN delivery. We observed significant sex differences in uptake for DA4-JC. Dulaglutide and DA4-JC exhibited high uptake by the hippocampus and multiple neocortical areas. We further tested and found the presence of AD-associated Aβ pathology minimally affected uptake of dulaglutide and DA4-JC. Of the 5 tested IRAs, dulaglutide and DA4-JC are best capable of accessing brain regions most vulnerable in AD (neocortex and hippocampus) after IN administration. Future studies will need to be performed to determine if IN IRA delivery can reduce BIR in AD or animal models of that disorder.

European beech (Fagus sylvatica L.) is becoming one of the go-to species in reconstructing declining conifer stands in Europe under climate change. Assisted migration may be considered when looking for suitable beech seedlings. Knowledge about the photosynthetic performance of beech seedlings is fundamental to understanding an essential part of their growth and survival potential in different planting conditions. We investigated the within-provenance variation in photosynthetic performance driven by altitude in contrast to inter-provenance variation given by geographical distance. The experiment was conducted on seedlings replanted in a Danish common garden comprising a cluster of provenances with various altitudinal subgroups transplanted from the Calabria region (Italy) and two local Danish provenances. Provenance and within-provenance variation in chlorophyll fluorescence (ChlF) kinetics, gas exchange (GE), flushing, and senescence were assessed. ChlF measurements revealed within-provenance differences based on altitude of origin and could distinguish between the two Danish provenances. In contrast, GE parameters detected variation in the geographical distance among Italian provenances. High-elevation subgroups of Italian provenances showed the best leaf-level photosynthetic performance in Danish weather conditions with high precipitation levels. Altitude of origin can be a significant source of within-provenance variation. We demonstrated that assessing this variation in young trees may be instrumental in maximizing the potential of provenance variation across diverse planting sites.