University of Wuerzburg

Circadian master clocks in the brain consist of multiple neurons that are organized into populations with different morphology, physiology, and neuromessenger content and presumably different functions. In most animals, these master clocks are distributed bilaterally, located in close proximity to the visual system, and synchronized by the eyes with the light-dark cycles of the environment. In mammals and cockroaches, each of the two master clocks consists of a core region that receives information from the eyes and a shell region from which most of the output projections originate, whereas in flies and several other insects, the master clocks are distributed in lateral and dorsal brain regions. In all cases, morning and evening clock neurons seem to exist, and the communication between them and other populations of clock neurons, as well as the connection across the two brain hemispheres, is a prerequisite for normal rhythmic function. Phenomena such as rhythm splitting, and internal desynchronization are caused by the "decoupling" of the master clocks in the two brain hemispheres or by the decoupling of certain clock neurons within the master clock of one brain hemisphere. Since the master clocks in flies contain relatively few neurons that are well characterized at the individual level, the fly is particularly well suited to study the communication between individual clock neurons. Here, we review the organization of the bilateral master clocks in the fly brain, with a focus on synaptic and paracrine connections between the multiple clock neurons, in comparison with other insects and mammals.

The dataset published in this work is derived from the ‘Corona Health’ app, developed in collaboration with the German Robert Koch Institute (RKI) during the early stages of the COVID-19 pandemic. The smartphone application aimed to monitor the mental and physical health of the public through real-time data collection. The dataset incorporates Ecological Momentary Assessments (EMA), Patient-reported Outcome Measures (PROMs), GPS data, and digital phenotyping from app users who consented. The data includes responses from 1805 mostly German users who completed baseline and follow-up questionnaires, capturing their physical health status over time. These questionnaires cover health-related topics, including medical history, cardiovascular risk factors, lifestyle habits, and the impact of the pandemic on health behaviors. The resulting dataset offers insights into health trajectories and behaviors during the pandemic and can be utilized for further research on physical health, user engagement, and the efficacy of EMA and digital phenotyping in health monitoring. The data is publicly available under a Creative Commons license on zenodo.org/records/11093394.

The benefit that antibiotics confer to the welfare of mankind is threatened by bacterial resistance. Resistance to daptomycin, a cyclic lipopeptide frequently used for the treatment of complicated bacteremia, is a prime example of this alarming situation. As the restricted number of antibacterial drug targets limits de novo development, chemical modification of existing compounds represents an alternative development option for future antimicrobials. This approach involves altering compounds to target bacteria through multiple mechanisms and/or to reinforce them against resistant strains. Herein, the conjugation of polycationic peptides to daptomycin enhances its effectiveness against a highly daptomycin‐resistant laboratory strain of Staphylococcus aureus and clinical isolates of Enterococcus faecium with reduced daptomycin sensitivity. Notably, unlike daptomycin, the activity of these conjugates does not necessarily depend on the calcium concentration. In addition to regaining bacteriolytic activity, the findings indicate the acquisition of an additional or amended mode of action as evidenced by pore formation and the disruption of membrane potential. The combination of enhanced in vitro potency, in vivo activity, and tolerability highlights the potential of this drug modification strategy in combating multidrug‐resistant bacteria.

Spatial omics enable the characterization of colocalized cell communities that coordinate specific functions within tissues. These communities, or niches, are shaped by interactions between neighboring cells, yet existing computational methods rarely leverage such interactions for their identification and characterization. To address this gap, here we introduce NicheCompass, a graph deep-learning method that models cellular communication to learn interpretable cell embeddings that encode signaling events, enabling the identification of niches and their underlying processes. Unlike existing methods, NicheCompass quantitatively characterizes niches based on communication pathways and consistently outperforms alternatives. We show its versatility by mapping tissue architecture during mouse embryonic development and delineating tumor niches in human cancers, including a spatial reference mapping application. Finally, we extend its capabilities to spatial multi-omics, demonstrate cross-technology integration with datasets from different sequencing platforms and construct a whole mouse brain spatial atlas comprising 8.4 million cells, highlighting NicheCompass’ scalability. Overall, NicheCompass provides a scalable framework for identifying and analyzing niches through signaling events.

A bstract The Fubini-Study metric is a central element of information geometry. We explore the role played by information geometry for determining the circuit complexity of Virasoro circuits and their deformations. To this effect, we study unitary quantum circuits generated by the Virasoro algebra and Fourier modes of a primary operator. Such primary-deformed Virasoro circuits can be realized in two-dimensional conformal field theories, where they provide models of inhomogeneous global quenches. We consider a cost function induced by the Fubini-Study metric and provide a universal expression for its time-evolution to quadratic order in the primary deformation for general source profiles. For circuits generated by the Virasoro zero mode and a primary, we obtain a non-zero cost only if spatial inhomogeneities are sufficiently large. In this case, we find that the cost saturates when the source becomes time-independent. The exact saturation value is determined by the history of the source profile. As a byproduct, returning to undeformed circuits, we relate the Fubini-Study metric to the Kähler metric on a coadjoint orbit of the Virasoro group.

The species richness of vascular plants in forests can have contrasting effects on the occurrence of non‐native insects. The establishment of non‐native insect populations may be facilitated by low plant species richness, which reflects the availability of few but easily accessible resources, or hampered by high plant species richness due to spatial dilution of resources or biotic resistance (i.e., resistance against biological invasions). The relationship between the species richness of plants and non‐native insects is likely influenced by disturbance regimes, which, in European forests, mostly consists of timber harvesting. We investigated this relationship considering two major forest attributes: (i) species richness of non‐native vascular plants and (ii) forest management. From 1101 forest plots in Europe, we gathered occurrences of 1212 vascular plant species, including 160 non‐native species, and of 2404 beetle species, including 29 non‐native species. We tested the relationship between the species richness of non‐native beetles and plants using non‐linear quantile regressions. We disentangled the effect of non‐native plant species richness from that of management on the species richness of non‐native beetles, while accounting for forest structural variables, using structural equation models. We found clear evidence of a hump‐shaped relationship between non‐native beetle and plant species richness. The general shape of the relationship persisted when considering only woody or non‐woody plants, as well as only non‐native plants. The relationship was also similar between managed and unmanaged forests. However, the proportion of non‐native beetles in managed forests was higher than in unmanaged forests at the same plant species richness. Management had a direct negative effect on non‐native beetle species richness, whereas non‐native plant species richness had a direct positive effect. When considering all direct and indirect effects, management facilitated the occurrence of non‐native beetles indirectly via non‐native plants rather than directly. Synthesis and applications. Species richness of native and non‐native vascular plants modulates the species richness of non‐native beetles through relationships with opposite signs. The interplay with management regimes and forest structures determines whether non‐native beetles are promoted. Forest management aimed at reducing the intensity of disturbance while encouraging native plant species richness could promote the dominance of dilution effects and biotic resistance and could moderate the establishment of non‐native insects.

Clinical trials with antidepressants reveal significant improvements in placebo groups, with effects of up to 80% compared to real treatment. While it has been suggested that treatment expectations rely on cognitive control, direct evidence for affective placebo effects is sparse. Here, we investigated how cognitive resources at both the behavioral and neural levels influence the effects of positive expectations on emotional processing. Forty-nine healthy volunteers participated in a cross-over fMRI study where positive expectations were induced through an alleged oxytocin nasal spray and verbal instruction. Participants completed a spatial cueing task that manipulated attention to emotional face distractors while being scanned and were characterized regarding their general attention control ability. Placebo treatment improved mood and reduced distractibility from fearful compared to happy faces, particularly when more attentional resources were available for processing face distractors. This aligned with changes in activation and functional coupling within prefrontal-limbic networks, suggesting that expectations induce top-down regulation of aversive inputs. Additionally, neurobehavioral effects correlated with individual control ability. Our findings highlight the critical role of cognitive resources in verbally instructed placebo effects. This may be particularly relevant in patients with major depressive disorder, who often demonstrate enhanced negativity processing but have limited cognitive control capacity.

Background Separation anxiety disorder (SEPAD) is characterized by pronounced fear or anxiety concerning separation from attachment figures. Despite its high lifetime prevalence, adult SEPAD often remains undetected due to a lack of diagnostic tools in multiple languages. The Adult Separation Anxiety Questionnaire (ASA-27) is a key instrument for assessing symptoms of SEPAD in adults. However, no validated German version is available. Objectives This study addressed the translation and validation of the ASA-27 in a German-speaking population to introduce the first German questionnaire assessing SEPAD. Materials and methods A consecutive forward and backward translation was conducted. Reliability and validity of the German ASA-27 against several established anxiety-related psychometric scores were assessed in a large sample of 1520 healthy participants. Results Results revealed robust internal consistency (Cronbach’s α = 0.87) and a factor structure explaining 49.7% of variations in answers. Concurrent validity was confirmed through significant correlations with established anxiety measures. Younger age and female sex were positively correlated with ASA-27 scores. Conclusion The German ASA-27 constitutes a promising diagnostic tool for adult SEPAD with sound psychometric properties and a coherent factor structure, offering a structured and reliable assessment of SEPAD and its dimensional evaluation in German-speaking populations.

This paper investigates if and how self-similarity and having motor control impact sense of embodiment, self-identification, and body weight perception in Augmented Reality (AR). We conducted a 2x2 mixed design experiment involving 60 participants who interacted with either synchronously moving virtual humans or independently moving ones, each with self-similar or generic appearances, across two consecutive AR sessions. Participants evaluated their sense of embodiment, self-identification, and body weight perception of the virtual human. Our results show that self-similarity significantly enhanced sense of embodiment, self-identification, and the accuracy of body weight estimates with the virtual human. However, the effects of having motor control over the virtual human movements were notably weaker in these measures than in similar VR studies. Further analysis indicated that not only the virtual human itself but also the participants' body weight, self-esteem, and body shape concerns predict body weight estimates across all conditions. Our work advances the understanding of virtual human body weight perception in AR systems, emphasizing the importance of factors such as coherence with the real-world environment.

We report a new set of synthetically accessible lophine analogues for selective live-cell imaging of the endoplasmic reticulum (ER). The ER selectivity is achieved without employing state-of-the-art moieties used for the design of ER-targeting dyes.