Biology subjects

Hermann, S.

Publications and source records attributed to Hermann, S..

3 recordsLinked to original sources

bioRxiv2024

Positron emission tomography (PET) tracer enables imaging of high CD73 expression in cancer

Ecto-5-nucleotidase (CD73) is a potential new drug target for cancer immunotherapy. Its overexpression is associated with various aggressive cancers, including triple-negative breast cancer (TNBC) and pancreatic cancer, making it a promising target for diagnostic imaging. Besides antibodies, small molecule CD73 inhibitors have been developed and are currently in clinical trials. This study aimed to develop and evaluate fluorine-18 labeled high-affinity CD73 inhibitors as tracers for the non-invasive positron emission tomography (PET) imaging of CD73 expression in cancer. Two CD73 inhibitors were selected for radiolabeling based on their high potency (Ki values of ca. 1 nM), and favorable pharmacokinetic properties providing [18F]PSB-19427 ([18F]1) and [18F]MRS-4648 ([18F]2). Ex vivo imaging studies on human breast cancer tissues indicated specific binding of both radiotracers. Subsequent in vivo studies proved [18F]1 to be superior due to its long elimination half-life and its accumulation in TNBC and pancreatic cancer tissues, suggesting its potential as a versatile PET tracer for imaging various solid tumors. [18F]1 significantly outperformed [18F]FDG in visualizing triple-negative breast cancer, offering potential advantages over [18F]FDG in terms of specificity and diagnostic accuracy. Thus, [18F]1 is a PET tracer with outstanding properties suitable for broad application in cancer diagnosis and potentially in therapy control. Based on these results, further clinical development of PET tracers targeting CD73 is warranted. One Sentence SummaryA PET tracer for imaging CD73 expression was developed, enabling cancer diagnosis.

cancer biology↗

bioRxiv2022

Species-conserved mechanisms of cognitive flexibility in complex environments

Rapid learning in complex and changing environments is a hallmark of intelligent behavior. Humans achieve this in part through abstract concepts applicable to multiple, related situations. It is unclear, however, whether some of the underlying computational mechanisms also exist in other species. We combined behavioral, computational and electrophysiological analyses of a multidimensional rule-learning paradigm in rats and humans. We report that both species infer task rules by sequentially testing different hypotheses, rather than learning the correct action for all possible combinations of task-related cues. Neural substrates of hypothetical rules were detected in prefrontal network activity of both species. This species-conserved mechanism reduces task dimensionality and explains key experimental observations: sudden behavioral transitions and facilitated learning after prior experience. Our findings open the black box of hypothesis testing in rodents and provide a foundation for the translational investigation of impaired cognitive flexibility.

neuroscience↗

bioRxiv2021

Both consumptive and non-consumptive effects of predators impact mosquito populations and have implications for disease transmission

Predator-prey interactions influence prey traits through both consumptive and non-consumptive effects, and variation in these traits can shape vector-borne disease dynamics. Meta-analysis methods were employed to generate predation effect sizes by different categories of predators and mosquito prey. This analysis showed that multiple families of aquatic predators are effective in consumptively reducing mosquito survival, and that the survival of Aedes, Anopheles, and Culex mosquitoes is negatively impacted by consumptive effects of predators. Mosquito larval size was found to play a more important role in explaining the heterogeneity of consumptive effects from predators than mosquito genus. Mosquito survival and body size were reduced by non-consumptive effects of predators, but development time was not significantly impacted. In addition, Culex vectors demonstrated predator avoidance behavior during oviposition. The results of this meta-analysis suggest that predators limit disease transmission by reducing both vector survival and vector size, and that associations between drought and human West Nile virus cases could be driven by the vector behavior of predator avoidance during oviposition. These findings are likely to be useful to infectious disease modelers who rely on vector traits as predictors of transmission.

ecology↗