Biology subjects

Hartmann, H.

Publications and source records attributed to Hartmann, H..

14 recordsLinked to original sources

bioRxiv2026

Villin-SNAP25 interaction regulates insulin secretion downstream of ICA512 signaling

Pancreatic islet {beta}-cells step-up insulin production and secretion in response to the elevation of blood glucose levels. ICA512/PTPRN is a transmembrane cargo of the insulin secretory granules (SGs). Upon SG exocytosis, its Ca2+/calpain mediated cleavage at the plasma membrane generates an ICA512-cleaved cytosolic fragment (ICA512-CCF) which as a decoy phosphatase prolongs phospho-STAT5/3 activities, thereby enhancing the transcription of mRNAs for SG cargoes, including insulin and its own, to replenish SG stores. In addition, ICA512 positively regulates the expression of F-actin modifier villin. Villin, in turn, modulates the size of actin cages surrounding cortical SGs, hence regulating SG mobility and exocytosis. Here we show that villin controls the number of SG docking sites for exocytosis by directly interacting at low glucose with the t-SNARE SNAP-25, thus restricting in this condition SG access to fusion sites and insulin release. Replacement of ICA512-CCF N-terminal ubiquitin-acceptor lysine 609 (K609) with valine (V) stabilized ICA512-CCF in insulinoma cells and homozygous ICA512K609V mice and enhanced the levels of phospho-STAT5/3 and villin. In ICA512K609V female mice these molecular traits correlated with reduced body weight, improved insulin sensitivity, reduced basal insulin secretion and onset time for glucose stimulated insulin secretion. Taken together, these data demonstrates that SG exocytosis induced ICA512 retrograde signaling acts in concert with the novel SNARE complex regulator villin to plastically adapt {beta}-cell actin cytoskeleton and access to SG docking sites for optimal control of insulin secretion in response to variations in extracellular glucose levels. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/699220v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@37d835org.highwire.dtl.DTLVardef@5389f1org.highwire.dtl.DTLVardef@855d98org.highwire.dtl.DTLVardef@1c3c639_HPS_FORMAT_FIGEXP M_FIG Graphical abstract Model of ICA512 and STAT3/5-dependent regulation of -cell function. At basal conditions, villin limits secretory granule (SG) docking by interacting with SNAP-25, restricting insulin release (1). Increased metabolic load triggers hyperglycemia-induced ICA512 processing and growth factor-mediated STAT3/5 phosphorylation (2-4), enhancing ISG mRNAs, granule biogenesis, and villin expression (5,6). Villin modulates SNARE protein availability, controlling SG docking and secretion. Together, ICA512 retrograde signaling and villin-mediated SNARE regulation dynamically remodel the -cell actin cytoskeleton, adjusting SG docking site access to ensure appropriate insulin secretion in response to fluctuating glucose levels. C_FIG

cell biology↗

bioRxiv2025

Meta-analytic evidence for distinct neural correlates of conditioned vs. verbally induced placebo analgesia

Placebo analgesia demonstrates that belief and expectation can significantly alter pain, even without active treatment. Placebo analgesia can be induced through verbal suggestion, classical conditioning, or their combination, though the role of conditioned neural responses above and beyond effects of verbal instructions remains unclear. We conducted a systematic meta-analysis of individual participant data from 16 within-participant placebo neuroimaging studies (n = 409), employing univariate and multivariate analyses to identify shared and distinct mechanisms of placebo analgesia induced by suggestions alone versus suggestions combined with conditioning. Both techniques increased activity during pain in the dorsolateral prefrontal and inferior parietal cortices and decreased activation in the insula, putamen, and primary sensory areas. Adding conditioning enhanced engagement of regions associated with context representation and pain modulation (e.g., dorsolateral/dorsomedial prefrontal cortices) and decreases in nociceptive regions (e.g., primary sensory and insular areas). Conditioning also strengthened the association between analgesia and nociceptive activity, as reflected in the Neurologic Pain Signature. Combining conditioning with instructions yielded greater analgesia, mediated by increased ventromedial prefrontal and dorsal caudate activity, alongside decreased sensory-nociceptive and cerebellar activity. These findings suggest the two strategies rely on partially distinct mechanisms, which could be combined to optimize placebo analgesias clinical application.

neuroscience↗

bioRxiv2025

Fluorescence Lifetime Unmixing: A New Workflow for FLIM Live-Cell Imaging

Fluorescence lifetime imaging microscopy (FLIM) translates the duration of excited states of fluorophores into lifetime information as additional source of contrast in images of biological samples. This offers the possibility to separate fluorophores particularly beneficial in case of similar excitation spectra. Here, we demonstrate the distinction of fluorescent molecules based on FLIM phasor analysis, called lifetime unmixing, in live-cell imaging using open-source software for analysis. We showcase two applications using Caenorhabditis elegans as a model system. First, we unmixed the highly spectrally overlapping fluorophores mCherry and mKate2 to distinctively track tagged proteins in six-dimensional datasets to investigate cell division in the developing early embryo. Second, we unmixed fluorescence of tagged proteins of interest from masking natural autofluorescence in adult hermaphrodites. For FLIM data handling and workflow implementation, we developed the open-source plugin napari-FLIM-phasor-plotter to implement conversion, visualization, analysis and reuse of FLIM data of different formats. Our work thus advances technical applications and bioimage data management and analysis in FLIM microscopy for life science research.

cell biology↗

bioRxiv2024

Large-scale remote sensing reveals that tree mortality in Germany appears to be greater than previously expected

Global warming poses a major threat to forests and events of increased tree mortality are observed globally. Studying tree mortality often relies on local-level observations of dieback while large-scale analyses are lacking. Satellite remote sensing provides the spatial coverage and sufficiently high temporal and spatial resolution needed to investigate tree mortality at landscape-scale. However, adequate reference data for training satellite-based models are scarce. In this study, we employed the first maps of standing deadwood in Germany for the years 2018-2022 with 10 m spatial resolution that were created by using tree mortality observations spotted in hundreds of drone images as the reference. We use these maps to study spatial and temporal patterns of tree mortality in Germany and analyse their biotic and abiotic environmental drivers using random forest regression. In 2019, the second consecutive hotter drought year in a row, standing deadwood increased steeply to 334 {+/-} 189 kilohectar (kha) which corresponds to 2.5 {+/-} 1.4% of the total forested area in Germany. Picea abies, Pinus sylvestris, and Fagus sylvatica showed highest shares of standing deadwood. During 2018-2021 978 {+/-} 529 kha (7.9 {+/-} 4.4%) of standing dead trees accumulated. The higher mortality estimates that we report compared to other surveys (such as the ground-based forest condition survey) can be partially attributed to the fact that remote sensing captures mortality from a birds eye perspective and that the high spatial detail (10 m) in this study also captures scattered occurrences of tree mortality. Atmospheric drought (i.e., climatic water balance and vapor pressure deficit) and temperature extremes (i.e., number of hot days and frosts after vegetation onset) were the most important predictors of tree mortality. We found increased tree mortality for smaller and younger stands and also on less productive sites. Monospecific stands were generally not more affected by mortality, but only when interactions with damaging insects (e.g., bark beetles) occurred. Because excess tree mortality rates threaten many forests across the globe, similar analyses of tree mortality are warranted and technically feasible at the global scale. We encourage the international scientific community to share and compile local data on deadwood occurrences (see example: www.deadtrees.earth) as such a collaborative effort is required to help understand mortality events on a global scale.

ecology↗

bioRxiv2024

deadtrees.earth - An Open-Access and Interactive Database for Centimeter-Scale Aerial Imagery to Uncover Global Tree Mortality Dynamics

Excessive tree mortality is a global concern and remains poorly understood as it is a complex phenomenon. We lack global and temporally continuous coverage on tree mortality data. Ground-based observations on tree mortality, e.g., derived from national inventories, are very sparse, not standardized and not spatially explicit. Earth observation data, combined with supervised machine learning, offer a promising approach to map tree mortality over time. However, global-scale machine learning requires broad training data covering a wide range of environmental settings and forest types. Drones provide a cost-effective source of training data by capturing high-resolution orthophotos of tree mortality events at sub-centimeter resolution. Here, we introduce deadtrees.earth, an open-access platform hosting more than a thousand centimeter-resolution orthophotos, covering already more than 300,000 ha, of which more than 58,000 ha are fully annotated. This community-sourced and rigorously curated dataset shall serve as a foundation for a global initiative to gather comprehensive reference data. In concert with Earth observation data and machine learning it will serve to uncover tree mortality patterns from local to global scales. This will provide the foundation to attribute tree mortality patterns to environmental changes or project tree mortality dynamics to the future. Thus, the open and interactive nature of deadtrees.earth together with the collective effort of the community is meant to continuously increase our capacity to uncover and understand tree mortality patterns.

ecology↗

bioRxiv2023

Restoration of Cone Circuit Functionality in the Regenerating Adult Zebrafish Retina

Unlike humans, teleosts like zebrafish exhibit robust retinal regeneration after injury from endogenous stem cells. However, understanding the functional recovery of the regenerated retina remains a challenge. In particular, it is unclear if regenerating cone-photoreceptors can regain physiological function and integrate correctly into post-synaptic circuits. To bridge this gap, we employed two-photon calcium imaging of living retina, focusing on photoreceptor responses before and after an intense light-induced lesion in the adult zebrafish retina. To assess the functional recovery of cones and their downstream circuits, we exploited the colour opponency in adult zebrafish cones. We find that UV cones exhibit an intrinsic Off-response to short-wavelength blue light, but an On-response to longer-wavelength green light, which depends on feedback signals from outer retinal circuits. Accordingly, we examined the presence and quality of Off-versus On-responses, to assess the functional recovery of cones and their correct integration into outer retinal circuits. We find that regenerated UV cones regain both Off-responses to short-wavelength and On-responses to long-wavelength within 3 months after light lesion. Hence, physiological circuit functionality is restored in regenerated cone photoreceptors, suggesting that inducing endogenous regeneration is a promising strategy for human retinal repair. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/566441v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@c9f038org.highwire.dtl.DTLVardef@1ba255borg.highwire.dtl.DTLVardef@1ea7f60org.highwire.dtl.DTLVardef@50adf3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Impaired updating of working memory representations in individuals with high BMI: evidence for dopaminergic mechanisms

Everyday life requires an adaptive balance between distraction-resistant maintenance of information and the flexibility to update this information when needed. These opposing mechanisms are proposed to be balanced through a working memory gating mechanism. Prior research indicates that obesity may elevate the risk of working memory deficits, yet the underlying mechanisms remain elusive. Dopaminergic alterations have emerged as a potential mediator. However, current models suggest these alterations should only shift the balance in working memory tasks, not produce overall deficits. The empirical support for this notion is currently lacking, however. To address this gap, we pooled data from three studies (N = 320) where participants performed a working memory gating task. Higher BMI was associated with overall poorer working memory, irrespective of whether there was a need to maintain or update information. However, when participants, in addition to BMI level, were categorized based on certain putative dopamine-signaling characteristics (Single Nucleotide Polymorphisms; specifically, Taq1A and DARPP-32), distinct working memory gating effects emerged. These SNPs, primarily associated with striatal dopamine transmission, appear to be linked with differences in updating, specifically, among high-BMI individuals. Moreover, blood amino acid ratio, which indicates central dopamine synthesis capacity, combined with BMI, shifted the balance between distractor-resistant maintenance and updating. These findings suggest that both dopamine-dependent and dopamine-independent cognitive effects exist in obesity. Understanding these effects is crucial if we aim to modify maladaptive cognitive profiles in individuals with obesity.

neuroscience↗

bioRxiv2022

Real-time monitoring of endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation

Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitored Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging platforms with single-molecule Fluorescence Correlation Spectroscopy (FCS), we demonstrate that Fgf8a, produced at the embryonic margin, propagates by free diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a mediated patterning. Manipulation of the Fgf8a input alters the signaling outcome, thereby establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, using diffusion-hindered versions of Fgf8a, we demonstrate that extracellular diffusion of the protein from the source is critical for it to achieve its morphogenic potential.

developmental biology↗

bioRxiv2021

Emotional ego- and altercentric biases in high-functioning autism spectrum disorder: Behavioral and neurophysiological evidence

Self-other distinction is a crucial aspect of social cognition, as it allows us to differentiate our own mental and emotional states from those of others. Research suggests that this ability might be impaired in individuals with autism spectrum disorder (ASD), but convincing evidence of self-other distinction deficits in the emotional domain is lacking. Here we aimed at evaluating emotional self-other distinction abilities in adults with and without ASD, in two behavioral pilot studies and one fMRI study. By using a newly developed virtual ball-tossing game that induced simultaneous positive and negative emotional states in each participant and another person, we were able to measure emotional egocentric and altercentric biases (namely the tendency to ascribe self-/other-related emotions to others/ourselves, respectively). Despite no behavioral differences, individuals with ASD showed decreased activation 1) in the right temporoparietal junction (rTPJ) during active overcoming of the emotional egocentric bias vs. passive game viewing, and 2) in the right supramarginal gyrus (rSMG) during ego-vs. altercentric biases, compared to neurotypical participants. These results suggest a different recruitment of these two regions in ASD when dealing with conflicting emotional states of oneself and another person. Furthermore, they highlight the importance of considering different control conditions when interpreting the involvement of rTPJ and rSMG during self-other distinction processes.

neuroscience↗

bioRxiv2021

Bark beetles locate fungal symbionts by detecting volatile fungal metabolites of host tree resin monoterpenes

Outbreaks of the Eurasian spruce bark beetle (Ips typographus) have decimated millions of hectares of conifer forests in Europe in recent years. The ability of these 3-6 mm long insects to kill mature trees over a short period has been ascribed to two main factors: (1) mass attacks on the host tree to overcome tree defenses and (2) the presence of fungal symbionts that support successful beetle development in the tree. While the role of pheromones in coordinating mass attacks has been well studied, the role of chemical communication in maintaining the fungal symbiosis is poorly understood. We previously demonstrated that I. typographus can recognize beneficial fungal symbionts of the genera Grosmannia, Endoconidiophora and Ophiostoma by their de novo synthesized volatile compounds. Here, we hypothesize that the fungal symbionts of the bark beetles might metabolize spruce resin monoterpenes of the beetles host tree, Norway spruce (Picea abies), and that the volatile products could be used as cues by beetles for locating breeding sites with beneficial symbionts. We show that Grosmannia penicillata and other fungal symbionts altered the profile of spruce bark volatiles by converting the major monoterpenes into an attractive blend of oxygenated derivatives. Bornyl acetate was metabolized to camphor, and - and {beta}-pinene to trans-4-thujanol and other oxygenated products. Other co-occurring non-beneficial fungi (Trichoderma sp.) also produce oxygenated monoterpenes, but in non-attractive ratios. Extensive electrophysiological measurements showed that the bark beetle possesses dedicated olfactory sensory neurons for oxygenated metabolites. Compounds such as camphor and trans-4-thujanol attracted beetles at specific doses in olfactory experiments, and the presence of symbiotic fungi enhanced attraction of females to pheromones. Finally, we show that colonization of fungal symbionts on spruce bark diet stimulated beetles to make tunnels into the diet. Collectively, our study suggests that the blends of oxygenated metabolites of conifer monoterpenes produced by fungal symbionts are used by bark beetles as attractive cues to find breeding or feeding sites containing their essential microbial symbionts. The oxygenated metabolites may aid beetles in assessing the presence of the fungus, the defense status of the host tree and the density of conspecifics at potential feeding and breeding sites.

ecology↗

bioRxiv2020

Placebo analgesia does not reduce empathy for naturalistic depictions of others' pain in a somatosensory specific way

Empathy for pain involves the affective-motivational and sensory-discriminative pain network. The shared representations account postulates that sharing anothers pain recruits underlying brain functions also engaged during first-hand pain. Critically, causal evidence for this has only been shown for affective pain processing, while the specific contribution of ones own somatosensory system to empathy remains controversial. Experimental paradigms used in previous studies did not a) direct attention towards a specific body part or b) employed naturalistic depictions of others pain, which could explain the absence of somatosensory effects. In this preregistered fMRI study, we thus aimed to test whether a causal manipulation of first-hand pain affects processing of empathy in a somatotopically- matched manner. Forty-five participants underwent a placebo analgesia induction in the right hand and observed pictures of right vs. left hands in pain. We found neither behavioral nor neural evidence for laterality-specific modulation of empathy for pain. However, exploratory analyses revealed a general effect of the placebo on empathy, and higher brain activity in bilateral anterior insula when viewing others hands in pain corresponding to ones own placebo hand. These results refine our knowledge regarding the mechanisms underlying empathy for pain by specifying the influence of first-hand pain on empathic responding.

neuroscience↗

bioRxiv2020

Neural correlates of interpersonal space permeability and flexibility in autism spectrum disorder

Previous research indicates that the size of interpersonal space at which the other is perceived as intrusive (permeability) and the ability to adapt interpersonal distance based on contextual factors (flexibility) are altered in Autism Spectrum Disorder (ASD). However, the neurophysiological basis of these alterations remains poorly understood. To fill this gap, we used fMRI and assessed interpersonal space preferences of individuals with ASD before and after engaging in cooperative and non-cooperative social interactions. Compared to matched controls, ASDs showed lower comfort in response to an approaching confederate, indicating preference for larger interpersonal space in autism (altered permeability). This preference was accompanied by reduced activity in bilateral dorsal intraparietal sulcus (dIPS) and left fusiform face area (FFA), regions previously shown to be involved in interpersonal space regulation. Furthermore, we observed differences in effective connectivity among dIPS, FFA, and amygdala in ASDs compared to controls, depending on the level of experienced comfort. No differences between groups were observed in interpersonal space regulation after an experienced social interaction (flexibility). Taken together, the present findings suggest that a dysregulation of the activity and connectivity of brain areas involved in interpersonal space processing may contribute to avoidance of physical proximity and social impairments in ASD.

neuroscience↗

bioRxiv2020

Another's pain in my brain: No evidence that placebo analgesia affects the sensory-discriminative component in empathy for pain

The shared representations account of empathy suggests that sharing other peoples emotions relies on neural processes similar to those engaged when directly experiencing such emotions. Recent research corroborated this by showing that placebo analgesia resulted in reduced pain empathy and decreased activation in shared neural networks. However, those studies did not report any placebo-related variation of somatosensory engagement during pain empathy. The experimental paradigms used in these studies did not direct attention towards a specific body part in pain, which may explain the absence of effects for somatosensation. The main objective of this preregistered study was to implement a paradigm overcoming this limitation, and to investigate whether placebo analgesia may also modulate the sensory-discriminative component of empathy for pain. We induced a localized, first-hand placebo analgesia effect in the right hand of 45 participants by means of a placebo gel and conditioning techniques, and compared this to the left hand as a control condition. Participants underwent a pain task in the MRI scanner, receiving painful or non-painful electrical stimulation on their left or right hand, or witnessing another person receiving such stimulation. In contrast to a robust localized placebo analgesia effect for self-experienced pain, the empathy condition showed no differences between the two hands, neither for behavioral nor neural responses. We thus report no evidence for somatosensory sharing in empathy, while replicating previous studies showing overlapping brain activity in the affective-motivational component for first-hand and empathy for pain. Hence, in a more rigorous test aiming to overcome limitations of previous work, we again find no causal evidence for the engagement of somatosensory sharing in empathy. Our study refines the understanding of the neural underpinnings of empathy for pain, and the use of placebo analgesia in investigating such models. HighlightsO_LIInvestigated placebo modulation of somatosensory and affective components of pain C_LIO_LILocalized placebo analgesia effects for self-report and fMRI of first-hand pain C_LIO_LINo evidence for such effects in empathy for pain C_LIO_LISuggests that somatosensory sharing does not play a critical role in pain empathy C_LI

neuroscience↗

bioRxiv2019

Differences in intake of high-fat high-sugar diet are related to variations in central dopamine in humans.

Obesity is associated with alterations in dopaminergic transmission and cognitive function. Recent findings from rodent studies suggest that diets rich in saturated fat and refined sugars (HFS) induce changes in the dopamine system independent of excessive body weight. However, so far the impact of HFS on the human brain has not been investigated. Here, we compared the effect of dietary dopamine depletion on dopamine dependent cognitive tasks between two groups that differ in habitual intake of dietary fat and sugar. Specifically, we used a double-blind within-subject crossover design to compare the effect of acute phenylalanine/tyrosine depletion (APTD) on a reinforcement learning and a working memory task, in two groups that are on opposite ends of the spectrum of self-reported HFS intake (low vs. high intake: LFS vs. HFS group). We tested 31 healthy young women, who were matched for BMI (mostly normal weight to overweight) and IQ. Depletion of central dopamine reduced the working memory specific performance on the operation span task (OSPAN) in the LFS, but not in the HFS group (p = 0.023, r = 0.210). Learning from positive and negative reinforcement (probabilistic selection task: PST) was increased in both diet groups after dopamine depletion (p = 0.048, r = 0.144). As secondary exploratory research question we measured peripheral dopamine precursor availability (pDAP) at baseline as an estimate for central dopamine levels. The HFS group had a significantly higher pDAP at baseline compared to the LFS group (p = .048, r = -0.355). Our data provides first evidence that the intake of HFS is associated with changes in indirect measures of central dopamine levels in humans. The observed associations are independent of body weight status, suggesting that consumption of HFS might be associated with maladaptive behaviors contributing to the development of obesity.

neuroscience↗