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Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1α (HIF-1α) will be stabilized to activate the transcription of target genes that are responsible for the metabolism, proliferation, and metastasis of tumor cells. Targeting and inhibiting the transcriptional activity of HIF-1 may provide an interesting strategy for cancer therapy. In the present study, an immune library and a synthetic library were constructed for the phage display selection of Nbs against recombinant PAS B domain protein (rPasB) of HIF-1α. After panning and screening, seven different nanobodies (Nbs) were selected, of which five were confirmed via immunoprecipitation to target the native HIF-1α subunit. The inhibitory effect of the selected Nbs on HIF-1 induced activation of target genes has been evaluated after intracellular expression of these Nbs in HeLa cells. The dramatic inhibition of both intrabody formats on the expression of HIF-1-related target genes has been confirmed, which indicated the inhibitory efficacy of selected Nbs on the transcriptional activity of HIF-1. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Regional estimates of the effects of ozone pollution on forest growth depend on the availability of reliable injury functions that estimate a representative ecosystem response to ozone exposure. A number of such injury functions for forest tree species and forest functional types have recently been published and subsequently applied in terrestrial biosphere models to estimate regional or global effects of ozone on forest tree productivity and carbon storage in the living plant biomass. The resulting impacts estimated by these biosphere models show large uncertainty in the magnitude of ozone effects predicted. To understand the role that these injury functions play in determining the variability in estimated ozone impacts, we use the O-CN biosphere model to provide a standardised modelling framework. We test four published injury functions describing the leaf-level, photosynthetic response to ozone exposure (targeting the maximum carboxylation capacity of Rubisco (Vcmax) or net photosynthesis) in terms of their simulated whole-tree biomass responses against data from 23 ozone filtration/fumigation experiments conducted with young trees from European tree species at sites across Europe with a range of climatic conditions. Our results show that none of these previously published injury functions lead to simulated whole-tree biomass reductions in agreement with the observed dose–response relationships derived from these field experiments and instead lead to significant over- or underestimations of the ozone effect. By re-parameterising these photosynthetically based injury functions, we develop linear, plant-functional-type-specific dose–response relationships, which provide accurate simulations of the observed whole-tree biomass response across these 23 experiments.

Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2865] Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2858] Supplementary material for: [https://www.sciencedirect.com/science/article/pii/S0277538719301664?via%3Dihub]