Biology subjects

Koester, M.

Publications and source records attributed to Koester, M..

5 recordsLinked to original sources

bioRxiv2026

Expecting the unexpected: Great apes anticipate surprise in others

Humans adeptly navigate complex social environments by attempting to anticipate the actions and emotional responses of others. Although our closest ape relatives have sophisticated social cognitive abilities, we do not know whether they have a cognitive understanding of others' emotions. For the epistemic emotion surprise, a cognitive understanding would require sensitivity to an agent's belief, to reality, and to any misalignment between the two, allowing one to model the mental conditions that drive surprise. In a non-invasive eye tracking study with 31 chimpanzees and bonobos, apes showed evidence of a cognitive understanding of surprise: they detected the misalignment between an agent's belief and reality, exhibiting greater pupil dilation right before an agent encountered an unexpected outcome relative to an expected one. This suggests that apes and humans share a more complex understanding of others' mental lives than previously thought, capacities that likely evolved millions of years ago in a common ancestor.

animal behavior and cognition↗

bioRxiv2026

Synergistic anti-tumor activity of EGFR inhibition and C/EBPβ antagonism in GBM.

Glioblastoma (GBM) is the most prevalent primary brain cancer, with poor prognosis and limited therapeutic options available. The genetic and cellular heterogeneity characteristic of GBM contributes to poor response rates. Activating mutations of the epidermal growth factor receptor (EGFR) gene are among the most frequent alterations in GBM, occurring in roughly half of cases. Despite the prevalence of EGFR mutations, EGFR inhibition has shown limited success in GBM. The transcription factor C/EBP{beta} is a master regulator of the mesenchymal transformation in GBM, an aggressive state characterized by increased invasiveness and resistance to chemotherapy. Lucicebtide is a C/EBP{beta} antagonist peptide with demonstrated single agent activity in patients with recurrent GBM that is currently being evaluated in a clinical trial in combination with radiation and temozolomide in patients with newly-diagnosed GBM (NCT04478279), with emerging data supporting clinical activity in that setting. Here we show that in the TCGA-GBM dataset, patients with EGFR mutations display significant enrichment of a high C/EBP{beta} activity signature. Functionally, genetic inactivation of EGFR by CRISPR results in synthetic lethality in the presence of lucicebtide in GBM cell lines, and synergistic in vitro cytotoxicity and suppression of C/EBP{beta} target gene expression was observed in combination experiments with lucicebtide and EGFR inhibitors. Finally, enhanced anti-tumor activity was demonstrated in vivo in the combination setting, as combined subpharmacologic dose levels of lucicebtide and the EGFR inhibitor osimertinib potently suppressed GBM xenograft growth. These data identify EGFR and C/EBP{beta} dependencies in GBM and support lucicebtide combination with EGFR inhibitors as a potential therapeutic option for a sizable fraction of GBM patients.

cancer biology↗

bioRxiv2024

Infants and adults neurally represent the perspective of others like their own perception

Perspective taking is central to human cognition and interaction. Preverbal infants already seem to consider the perspective of others, and adults do so continually, in parallel with other cognitively demanding tasks. Yet, the representational format in which others perspectives are implemented in the mind and brain remains unclear. We addressed this question by using a neural marker that provides a precise index of visual object processing. We presented adults and 12-14-months-old infants with objects flickering at 4 Hz, evoking phase-locked rhythmic activity at the exact same frequency over visual cortex that is highly specific of visually processing the flickering object. The object then became occluded from the participants view. Critically, in one condition another person continued to see the object, whereas in control conditions the observers view was blocked or no observer was present. Remarkably, both in adults and infants, the frequency-tagged neural response specific of own visual object processing persisted when their own view was blocked and only the other person could see the object, but not in either control condition. These findings provide direct neural evidence that representing another persons perspective engages our own perceptual object processing and demonstrate that this representational format is already present in infancy. TeaserFrequency-tagging shows that objects seen only by others activate ones own object-specific perception in adults and infants.

neuroscience↗

bioRxiv2024

The fungal protein Jps1 facilitates unconventional protein secretion through a direct phosphoinositide interaction

Protein secretion is indispensable for essential cellular processes in eukaryotic cells, contributing significantly to nutrient acquisition, defense or communication. Alternative pathways bypassing the endomembrane system collectively referred to as unconventional secretion are gaining increasing attention. A number of important molecules such as cytokines, fibroblast growth factor or viral proteins are being exported through these mechanistically diverse pathways. In the fungal model Ustilago maydis, cytokinesis-dependent unconventional secretion mediates export of the chitinase Cts1 via the fragmentation zone. This membrane-rich compartment is formed during cytokinesis between mother and daughter cells. Recently, we identified Jps1, a previously uncharacterized protein, as a crucial factor for Cts1 localization and export. Combining biochemical experiments and in vivo studies, we here uncover two pivotal features of Jps1: dimerization and phosphoinositide (PIP) binding. Our findings reveal that a conserved structural core domain mediates homodimerization, while surrounding flexible variable regions suggest potential diversification in different basidiomycete species. Jps1 does not harbor a canonical PIP-binding domain but instead specificity of the interaction with the preferred PIP PI(4,5)P2 is determined by basic residues. Importantly, loss of PI(4,5)P2 binding specificity results in mis-localisation, morphological defects and reduced extracellular Cts1 activity, particularly at low cell densities. This discovery sheds light on previously unknown key features of Jps1, elucidating its role in supporting Cts1 secretion, and representing a crucial step towards understanding the broader implications of unconventional secretion in eukaryotic cells.

biochemistry↗

bioRxiv2021

Visual category representations in the infant brain

Visual categorization is a human core cognitive capacity 1,2 that depends on the development of visual category representations in the infant brain 3-7. However, the exact nature of infant visual category representations and their relationship to the corresponding adult form remains unknown 8. Our results clarify the nature of visual category representations from electroencephalography (EEG) data in 6- to 8-month-old infants and their developmental trajectory towards adult maturity in the key characteristics of temporal dynamics 2,9, representational format 10-12, and spectral properties 13,14. Temporal dynamics change from slowly emerging, developing representations in infants to quickly emerging, complex representations in adults. Despite those differences, infants and adults already partly share visual category representations. The format of infants representations is visual features of low to intermediate complexity, whereas adults representations also encode high complexity features. Theta band activity contributes to visual category representations in infants, and these representations are shifted to the alpha/beta band in adults. Together, we reveal the developmental neural basis of visual categorization in humans, show how information transmission channels change in development, and demonstrate the power of advanced multivariate analysis techniques in infant EEG research for theory building in developmental cognitive science.

neuroscience↗