TY - JOUR A1 - Castillo, Ruth A1 - Wurdack, Mareike A1 - Pauli, Thomas A1 - Keller, Alexander A1 - Feldhaar, Heike A1 - Polidori, Carlo A1 - Niehuis, Oliver A1 - Schmitt, Thomas T1 - Evidence for a chemical arms race between cuckoo wasps of the genus Hedychrum and their distantly related host apoid wasps JF - BMC Ecology and Evolution N2 - Background Brood parasites can exert strong selection pressure on their hosts. Many brood parasites escape their detection by mimicking sensory cues of their hosts. However, there is little evidence whether or not the hosts are able to escape the parasites’ mimicry by changing these cues. We addressed this question by analyzing cuticular hydrocarbon (CHC) profiles of Cerceris and Philanthus wasps and their brood parasites, cuckoo wasps mimicking the CHC profiles of their hosts. Some of these hosts use hydrocarbons to preserve their prey against fungal infestation and thus, they cannot significantly change their CHC composition in response to chemical mimicry by Hedychrum brood parasites. Results We found that the CHC overlap between brood parasites and their hosts was lower in case of host wasps not preserving their prey than in case of prey-preserving host wasps, whose CHC evolution is constrained. Furthermore, the CHC profiles in non-preserving host wasps is more strongly diversified in females than in males, thus in the sex that is chemically mimicked by brood parasites. Conclusion Our results provide evidence for a chemical arms race between those hosts that are liberated from stabilizing selection on their chemical template and their parasites. KW - chemical mimicry KW - philanthidae KW - hymenoptera KW - evolutionary arms race KW - cuticular hydrocarbons KW - chrysididae Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301289 VL - 22 IS - 1 ER - TY - JOUR A1 - Maihoff, Fabienne A1 - Bohlke, Kyte A1 - Brockmann, Axel A1 - Schmitt, Thomas T1 - Increased complexity of worker CHC profiles in Apis dorsata correlates with nesting ecology JF - PLoS ONE N2 - Cuticular hydrocarbons (CHC) are known to serve as discrimination cues and will trigger defence behaviour in a plethora of eusocial insects. However, little is known how about nestmate recognition ability selects for CHC diversification. In this study we investigate differences in CHC composition of four major honey bee species with respect to the differences in their nesting behavior. In contrast to A. mellifera, A. cerana and A. florea, the giant honey bee A. dorsata prefers to build their nests in aggregations with very small spatial distances between nests, which increases the probability of intrusions. Thus, A. dorsata exhibits a particularly challenging nesting behavior which we hypothesize should be accompanied with an improved nestmate recognition system. Comparative analyses of the worker CHC profiles indicate that A. dorsata workers exhibit a unique and more complex CHC profile than the other three honey bee species. This increased complexity is likely based on a developmental process that retains the capability to synthesize methyl-branched hydrocarbons as adults. Furthermore, two sets of behavioral experiments provide evidence that A. dorsata shows an improved nestmate discrimination ability compared to the phylogenetically ancestral A. florea, which is also open-nesting but does not form nest aggregations. The results of our study suggest that ecological traits like nesting in aggregation might be able to drive CHC profile diversification even in closely related insect species. KW - Apis dorsata KW - cuticular hydrocarbons KW - nesting Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301353 VL - 17 IS - 7 ER - TY - JOUR A1 - Buellesbach, Jan A1 - Diao, Wenwen A1 - Schmitt, Thomas A1 - Beukeboom, Leo W. T1 - Micro‐climate correlations and conserved sexual dimorphism of cuticular hydrocarbons in European populations of the jewel wasp Nasonia vitripennis JF - Ecological Entomology N2 - 1. Protection against desiccation and chemical communication are two fundamental functions of cuticular hydrocarbons (CHCs) in insects. In the parasitoid jewel wasp Nasonia vitripennis (Walker), characterised by a cosmopolitan distribution through largely different environments, CHCs function as universally recognised female sex pheromones. However, CHC uniformity as basis for sexual recognition may conflict with the desiccation protection function, expected to display considerable flexibility through adaptation to different environmental conditions. 2. We compared male and female CHC profiles of N. vitripennis across a wide latitudinal gradient in Europe and correlated their CHC variation with climatic factors associated with desiccation. Additionally, we tested male mate discrimination behaviour between populations to detect potential variations in female sexual attractiveness. 3. Results did not conform to the general expectation that longer, straight‐chain CHCs occur in higher proportions in warmer and drier climates. Instead, unexpected environmental correlations of intermediate chain‐length CHCs (C31) were found exclusively in females, potentially reflecting the different life histories of the sexes in N. vitripennis. 4. Furthermore, we found no indication of population‐specific male mate preference, confirming the stability of female sexual attractiveness, likely conveyed through their CHC profiles. C31 mono‐ and C33 di‐methyl‐branched alkanes were consistently and most strongly associated with sexual dimorphism, suggesting their potential role in encoding the female‐specific sexual signalling function. 5. Our study sheds light on how both adaptive flexibility and conserved sexual attractiveness can potentially be integrated and encoded in CHC profiles of N. vitripennis females across a wide distribution range in Europe. KW - chemical communication KW - climatic factors KW - desiccation resistance KW - sex pheromones KW - sexual dimorphism Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262770 VL - 47 IS - 1 SP - 38 EP - 51 ER - TY - JOUR A1 - Peindl, Matthias A1 - Göttlich, Claudia A1 - Crouch, Samantha A1 - Hoff, Niklas A1 - Lüttgens, Tamara A1 - Schmitt, Franziska A1 - Pereira, Jesús Guillermo Nieves A1 - May, Celina A1 - Schliermann, Anna A1 - Kronenthaler, Corinna A1 - Cheufou, Danjouma A1 - Reu-Hofer, Simone A1 - Rosenwald, Andreas A1 - Weigl, Elena A1 - Walles, Thorsten A1 - Schüler, Julia A1 - Dandekar, Thomas A1 - Nietzer, Sarah A1 - Dandekar, Gudrun T1 - EMT, stemness, and drug resistance in biological context: a 3D tumor tissue/in silico platform for analysis of combinatorial treatment in NSCLC with aggressive KRAS-biomarker signatures JF - Cancers N2 - Epithelial-to-mesenchymal transition (EMT) is discussed to be centrally involved in invasion, stemness, and drug resistance. Experimental models to evaluate this process in its biological complexity are limited. To shed light on EMT impact and test drug response more reliably, we use a lung tumor test system based on a decellularized intestinal matrix showing more in vivo-like proliferation levels and enhanced expression of clinical markers and carcinogenesis-related genes. In our models, we found evidence for a correlation of EMT with drug resistance in primary and secondary resistant cells harboring KRAS\(^{G12C}\) or EGFR mutations, which was simulated in silico based on an optimized signaling network topology. Notably, drug resistance did not correlate with EMT status in KRAS-mutated patient-derived xenograft (PDX) cell lines, and drug efficacy was not affected by EMT induction via TGF-β. To investigate further determinants of drug response, we tested several drugs in combination with a KRAS\(^{G12C}\) inhibitor in KRAS\(^{G12C}\) mutant HCC44 models, which, besides EMT, display mutations in P53, LKB1, KEAP1, and high c-MYC expression. We identified an aurora-kinase A (AURKA) inhibitor as the most promising candidate. In our network, AURKA is a centrally linked hub to EMT, proliferation, apoptosis, LKB1, and c-MYC. This exemplifies our systemic analysis approach for clinical translation of biomarker signatures. KW - EMT KW - drug resistance KW - invasion KW - stemness KW - 3D lung tumor tissue models KW - KRAS biomarker signatures KW - boolean in silico models KW - targeted combination therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270744 SN - 2072-6694 VL - 14 IS - 9 ER - TY - JOUR A1 - Schmitt, Andrea A1 - Tatsch, Laura A1 - Vollhardt, Alisa A1 - Schneider-Axmann, Thomas A1 - Raabe, Florian J. A1 - Roell, Lukas A1 - Heinsen, Helmut A1 - Hof, Patrick R. A1 - Falkai, Peter A1 - Schmitz, Christoph T1 - Decreased oligodendrocyte number in hippocampal subfield CA4 in schizophrenia: a replication study JF - Cells N2 - Hippocampus-related cognitive deficits in working and verbal memory are frequent in schizophrenia, and hippocampal volume loss, particularly in the cornu ammonis (CA) subregions, was shown by magnetic resonance imaging studies. However, the underlying cellular alterations remain elusive. By using unbiased design-based stereology, we reported a reduction in oligodendrocyte number in CA4 in schizophrenia and of granular neurons in the dentate gyrus (DG). Here, we aimed to replicate these findings in an independent sample. We used a stereological approach to investigate the numbers and densities of neurons, oligodendrocytes, and astrocytes in CA4 and of granular neurons in the DG of left and right hemispheres in 11 brains from men with schizophrenia and 11 brains from age- and sex-matched healthy controls. In schizophrenia, a decreased number and density of oligodendrocytes was detected in the left and right CA4, whereas mean volumes of CA4 and the DG and the numbers and density of neurons, astrocytes, and granular neurons were not different in patients and controls, even after adjustment of variables because of positive correlations with postmortem interval and age. Our results replicate the previously described decrease in oligodendrocytes bilaterally in CA4 in schizophrenia and point to a deficit in oligodendrocyte maturation or a loss of mature oligodendrocytes. These changes result in impaired myelination and neuronal decoupling, both of which are linked to altered functional connectivity and subsequent cognitive dysfunction in schizophrenia. KW - schizophrenia KW - hippocampus KW - CA4 KW - dentate gyrus KW - postmortem KW - stereology KW - oligodendrocyte KW - neuron Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290360 SN - 2073-4409 VL - 11 IS - 20 ER -