Biology subjects

Kirschner, P.

Publications and source records attributed to Kirschner, P..

4 recordsLinked to original sources

bioRxiv2026

Enhancing pancreatic islet cell survival via NMDAR antagonist-driven ROR1 activation as revealed by phosphoproteomics

NMDA receptors (NMDARs) control function and survival not only of neurons, but also of insulin-producing pancreatic beta cells. Since insufficient insulin secretion and beta cell death are key events during diabetes development, targeting NMDARs offers a therapeutic approach. Specifically, the NMDAR antagonist dextrorphan (DXO) increases glucose-stimulated insulin secretion in clinical trials. Furthermore, treatment with DXO or optimized DXO derivatives prevents pancreatic islet cell death upon diabetogenic insults. Nonetheless, the signaling pathways induced by NMDAR inhibition are poorly understood. Here, we use complementary approaches, phosphoproteomics and tyrosine kinase profiling, to demonstrate that DXO and its derivatives rapidly regulate multiple intracellular signaling clusters, including mTOR and ERK signaling, in pancreatic islets. Notably, mTOR inhibition, but not ERK inhibition, is sufficient to negate DXO's protective effects. Further, we show that activation of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) is a universal event upon NMDAR inhibition in islets. Simultaneous knockdown of Ror1/ROR1 and its paralogue Ror2/ROR2 compromises the viability of both mouse and human islets, highlighting the ROR1/2 signaling axis as a promising avenue for enhancing beta cell survival.

molecular biology↗

bioRxiv2026

Piloting floral-visitor assemblages: Camera-based monitoring in Physoplexis comosa (Campanulaceae), a cliff-dwelling Eastern Alpine endemic Physoplexis comosa (Campanulaceae)

Understanding floral visitor dynamics along elevational gradients is essential for assessing potential implications for pollen limitation and population genetic processes in fragmented populations of cliff-dwelling alpine endemics. Physoplexis comosa (Campanulaceae) is a chasmophytic paleoendemic restricted to vertical rock faces on dolomitic and limestone bedrock from 200 to 2,800 m a.s.l. The species exhibits a specific floral morphology with fused corolla apices, basal openings for nectar access, and secondary pollen presentation, yet its functional floral visitor assemblage has remained poorly characterized across the species' elevational range. In this pilot study, we tested a two-tier camera-monitoring setup combining action cameras for diurnal monitoring with Raspberry Pi-based systems equipped with IR illumination for combined diurnal and nocturnal recording. We conducted monitoring across five elevational sites (1,480 to 2,400 m a.s.l.) in the Eastern Alps. Recorded video material was downsampled and annotated using the Addax platform alongside manual cross-validation to record physical contact events. Preliminary results confirm the technical feasibility of continuous monitoring in steep terrain and suggest possible elevational variation in diurnal visitors, alongside nocturnal activity by Geometridae moths. Camera-based observations provided higher functional resolution and revealed a different visitor assemblage than previous eDNA metabarcoding trials. This proof-of-concept establishes a methodological foundation for forthcoming multi-day monitoring campaigns and complements ongoing studies of the mating system and population-genetic analyses.

ecology↗

bioRxiv2025

Glacial Legacies - How refugial dynamics shaped the evolution of the Alpine endemic bush-cricket Anonconotus italoaustriacus

Mountain ranges like the European Alps harbor large endemic biodiversity shaped by Pleistocene climatic oscillations. The flightless bush-cricket Anonconotus italoaustriacus, endemic to the Southern Limestone Alps (SLA) and the eastern Central Alps (CA), provides an ideal model to study the evolutionary and refugial dynamics of endemic alpine arthropods. Using genomic SNP data, we employed phylogenetic analyses, Bayesian clustering, and demographic modeling to investigate the species evolutionary history and its refugial dynamics. Our results support a scenario of survival in multiple peripheral refugia during the Last Glacial Period (LGP; 115-11.7 ka), with populations in the southern SLA and eastern CA exhibiting the highest private allelic richness. Postglacial recolonization of interior alpine regions occurred exclusively from refugia on the southeastern margin of the SLA, most likely facilitated by open habitat corridors along transversal valleys. In contrast, populations in the southern SLA exhibited long-term isolation and distributional stasis, emphasizing the importance of small, stable refugia in preserving genetic diversity. We propose that polyandry, a reproductive strategy of A. italoaustriacus, contributed to its resilience by maintaining high genetic diversity despite repeated bottlenecks and habitat fragmentation. These findings highlight the importance of integrating evolutionary history into conservation strategies, particularly for alpine endemics with fragmented distributions. Protecting both long-term stable refugia and dynamic evolutionary hotspots is critical for the conservation of A. italoaustriacus and other high-altitude arthropods in the face of ongoing environmental change.

evolutionary biology↗

bioRxiv2025

Spatiotemporal diversification of forest understorey species reveals the existence of multiple Pleistocene forest refugia in Central Europe

During Pleistocene cold stages, European temperate forests were not only restricted to refugia in the southern European peninsulas. Rather, there is increasing evidence for survival of trees also in isolated patches further north, termed "northern refugia". While their existence is undisputed, based on what is known from a handful of tree species, there is very limited knowledge about forest understoreys. Here, we fill this gap by examining the evolutionary histories of three Central European forest understorey species (FUS; Aposeris foetida, Cardamine trifolia, Hacquetia epipactis). To do so, we use a set of exploratory and explicit analyses utilizing genomic data and ecological niche models, and interpret these data following an a priori defined framework. We identify the northwestern Balkan Peninsula as the primary diversification center for the three species but found additional northern refugia in the Alps, the Carpathians, and the Apennines. Divergence times indicated pre-Last Glacial Maximum (LGM) diversification within each FUS, suggesting persistence of forest islands in Central Europe during Pleistocene cold stages rather than exclusively post-LGM colonization. We conclude that FUS thrived in scattered northern refugia. This refines our understanding of past forest dynamics and further supports widespread long-term persistence of forest patches in Central Europe during Pleistocene cold stages.

evolutionary biology↗