Biology subjects

Deutsch, J.

Publications and source records attributed to Deutsch, J..

4 recordsLinked to original sources

bioRxiv2025

Goats who stare at wolves - identifying natural response stimuli for an affect-driven attention bias test in small ruminants

Reliable and non-invasive assessment of affective states is crucial in animal welfare research. Linking affective states to cognitive processes, such as cognitive biases, provides a promising approach. An affect-driven attention bias - the tendency to focus more on threatening than on neutral or positive stimuli when in a negative affective state - has been observed in humans and non-human animal species. However, implementation is often hampered because ecologically relevant test setups need to be adapted to species-specific differences in the perception and processing of information from different modalities. As an initial step towards developing and validating an affect-driven attention bias test for goats, we aimed to identify visual stimuli perceived as potentially threatening using a looking-time paradigm. In a within-subject design, 30 adult female dwarf goats (Capra hircus) were presented with photographs of 12 animal species (six natural predators and six non-predators) from three taxa (mammals, reptiles, birds). Each image was shown for 10 seconds on one of two video screens, while the opposite screen remained white. Each goat completed four sessions (one per day) of six trials each: two sessions showing full-body and two sessions showing face/head-only images, resulting in 24 trials per subject. Analysis of relative looking duration revealed a significant interaction between animal taxon and predator category. Goats looked longer at predatory than non-predatory reptiles, while the opposite pattern was found for mammals. No difference was observed for birds. The presented body part (full body vs. face/head only) did not influence looking behaviour. These results suggest that photographs of predatory reptiles, particularly snakes, might be perceived as potentially threatening by goats, indicating their suitability as negative stimuli in future affect-driven attention bias tests. Further validation is needed to confirm their negative valence.

animal behavior and cognition↗

bioRxiv2025

Ligand-dependent G protein dynamics underlying opioid signaling efficacy

Activation of heterotrimeric G proteins by G protein-coupled receptors (GPCRs) requires large-scale opening of the G -helical domain (AHD) to expose the nucleotide-binding site and facilitate GDP-GTP exchange. While orthosteric ligands are known to modulate GPCR conformation and signaling efficacy, how these effects propagate to the G protein itself remains unclear. Using single-molecule fluorescence resonance energy transfer (smFRET) imaging, we monitored AHD motions in Gi proteins coupled to the -opioid receptor (OR) across a spectrum of ligand- and nucleotide-bound states. We find that receptor ligands differentially modulate these dynamics from over 70 [A] away, with higher-efficacy agonists more effectively promoting transitions to an open, low-nucleotide-affinity conformation. These data also capture transient OR-Gi intermediates during nucleotide binding and suggest that -opioid ligand efficacy arises in part from allosteric control over G protein conformational equilibria that kinetically gate activation.

biophysics↗

bioRxiv2025

Membrane phosphoinositides allosterically tune β-arrestin dynamics to facilitate GPCR core engagement

Arrestin proteins bind active G protein-coupled receptors (GPCRs) through coordinated protein-protein, protein-phosphate, and protein-lipid interactions to attenuate G protein signaling and promote GPCR internalization and trafficking. While there are hundreds of diverse GPCRs, only two {beta}-arrestin isoforms ({beta}arrs) must recognize and engage this wide range of receptors with varied phosphorylation patterns. Traditional models suggest that {beta}arr activation requires displacement of its autoinhibitory C-tail by a phosphorylated GPCR C-terminus; however, this paradigm fails to explain how minimally phosphorylated GPCRs still complex with {beta}arrs. Using single-molecule Forster resonance energy transfer imaging and hydrogen-deuterium exchange mass spectrometry, we observe basal dynamics in which the {beta}arr1 C-tail spontaneously releases from the N-domain, transiently adopting an active conformation that can facilitate binding of the phosphorylated GPCR C-terminus. We further demonstrate the importance of an intermediate state of {beta}arr1 arising from spontaneous C-tail release stabilized by the membrane phosphoinositide PI(4,5)P2. Both PI(4,5)P2 and mutations in the proximal or middle regions of the C-tail shift {beta}arr1 towards a partially released state, revealing an allosteric connection that informs a refined model for {beta}arr activation. In this model, membrane engagement conformationally primes {beta}arrs prior to receptor binding, thereby explaining how {beta}arrs are recruited by diverse GPCRs, even those with limited C-terminal phosphorylation.

biophysics↗

bioRxiv2021

SARS-CoV-2 triggers DNA damage response in Vero E6 cells

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the current COVID-19 pandemic and has now infected more than 200 million people with more than 4 million deaths globally. Recent data suggest that symptoms and general malaise may continue long after the infection has ended in recovered patients, suggesting that SARS-CoV-2 infection has profound consequences in the host cells. Here we report that SARS-CoV-2 infection can trigger a DNA damage response (DDR) in African green monkey kidney cells (Vero E6). We observed a transcriptional upregulation of the Ataxia telangiectasia and Rad3 related protein (ATR) in infected cells. In addition, we observed enhanced phosphorylation of CHK1, a downstream effector of the ATR DNA damage response, as well as H2AX. Strikingly, SARS-CoV-2 infection lowered the expression of TRF2 shelterin-protein complex, and reduced telomere lengths in infected Vero E6 cells. Thus, our observations suggest SARS-CoV-2 may have pathological consequences to host cells beyond evoking an immunopathogenic immune response.

cancer biology↗