Biology subjects

Behrens, F.

Publications and source records attributed to Behrens, F..

5 recordsLinked to original sources

bioRxiv2026

Kidney disease reprograms microbiome-host signaling to promote heart failure

BackgroundHeart failure is prevalent in chronic kidney disease (CKD) and linked to chronic inflammation. CKD-typical gut microbiome dysbiosis may stimulate inflammation, as bacterial aromatic metabolites are highly abundant and engage transcriptional programs through the aryl hydrocarbon receptor (AhR). Whether this axis drives cardiac remodeling and is therapeutically targetable remains unknown. MethodsWe used the subtotal nephrectomy model (STNx) and microbiome depletion by oral antibiotics. We investigated cardiac and renal function, AhR activity, metabolite profiles, and immunophenotypes by flow cytometry and transcriptomics. Candidate metabolite indoxyl sulfate (IxS) was tested in experimental HFpEF. In vivo and in vitro AhR inhibition (AhRi) was performed using a clinically tested compound. Mechanistic studies were performed in primary human and murine cardiac fibroblasts and T cells, as well as translational validation using UK Biobank data. ResultsMicrobiome depletion lowered bacterial metabolites and attenuated cardiac fibrosis and diastolic dysfunction in STNx, identifying AhR-driven expansion of interleukin-17A (IL-17A)-producing T helper cells (TH17) as key effector. Plasma IL-17A was stage-dependently elevated in CKD patients, particularly in HFpEF, and associated with all-cause mortality. Bacterial metabolite IxS promoted TH17 polarization and exacerbated cardiac dysfunction in HFpEF. AhRi using a small molecule inhibitor reduced TH17 abundance and attenuated cardiac fibrosis in STNx. Mechanistically, AhR and IL-17A signaling synergistically induced a conserved pro-fibrotic phenotype in human and murine cardiac fibroblasts, and AhR inhibition blocked ECM production in response to CKD patient serum. ConclusionA microbiome-AhR-IL-17A axis drives CKD-associated cardiac fibrosis. AhRi prevents remodeling, highlighting a potential therapeutic avenue to prevent cardiorenal multimorbidity.

immunology↗

bioRxiv2022

Cardiac ventricular myosin and slow skeletal myosin exhibit dissimilar chemo-mechanical properties despite the same myosin heavy chain isoform.

The myosin II motors are ATP-powered, force-generating machines driving cardiac and muscle contraction. Myosin II heavy chain isoform-beta ({beta}-MyHC) is primarily expressed in the ventricular myocardium and slow-twitch muscle fibers, such as in M. soleus. M. soleus-derived myosin II (SolM-II) is often used as an alternative to the ventricular {beta}-cardiac myosin ({beta}M-II); however, the direct assessment of detailed biochemical and mechanical features of the native myosins is limited. By employing the optical trapping method, we examined the mechanochemical properties of the native myosins isolated from rabbit heart ventricle and M. soleus muscles at the single-molecule level. Contrary to previous reports, the purified motors from the two tissue sources, despite the same MyHC isoform, displayed distinct motile and ATPase kinetic properties. {beta}M-II was [~]threefold faster in the actin filament-gliding assay than SolM-II. The maximum acto-myosin (AM) detachment rate derived in single-molecule assays was [~]threefold higher in {beta}M-II. The stroke size for both myosins was comparable. The stiffness of the AM rigor cross-bridge was also similar for both the motor forms. The stiffness of {beta}M-II was found to be determined by the nucleotide state of the actin-bound myosin. Our analysis revealed distinct kinetic differences, i.e., a higher AM detachment rate for the {beta}M-II, corresponding to the ADP release rates from the cross-bridge, thus elucidating the observed differences in the motility driven by {beta}M-II and SolM-II. These studies have important implications for the future choice of tissue sources to gain insights into cardiomyopathies

biophysics↗

bioRxiv2020

Quantifying Physiological Synchrony through Windowed Cross-Correlation Analysis: Statistical and Theoretical Considerations

Interpersonal synchrony is a widely studied phenomenon. A great challenge is to statistically capture the dynamics of social interactions with fluctuating levels of synchrony and varying delays between responses of individuals. Windowed Cross-Correlation analysis accounts for both characteristics by segmenting the time series into smaller windows and shifting the segments of two interacting individuals away from each other up to a maximum lag. Despite evidence showing that these parameters affect the estimated synchrony level, there is a lack of guidelines on which parameter configurations to use. The current study aimed to close this knowledge gap by comparing the effect of different parameter configurations on two outcome criteria: i) the ability to distinguish synchrony from pseudosynchrony by means of surrogate data analyses and ii) the sensitivity to detect change in synchrony as measured by the difference between two within-subject conditions. Focusing on physiological synchrony, we performed these analyses on heartrate, skin conductance level, pupil size, and facial expressions data. Results revealed that a range of parameters were able to discriminate synchrony from pseudosynchrony. Window size was more influential than the maximum lag with smaller window sizes showing better discrimination. No clear patterns emerged for the second criterion. Integrating the statistical findings and theoretical considerations regarding the physiological characteristics and biological boundaries of the signals, we provide recommendations for optimizing the parameter settings to the signal of interest.

physiology↗

bioRxiv2019

Physiological synchrony promotes cooperative success in real-life interactions

Cooperation is pivotal for society to flourish and prosper. To ease cooperation, humans express and read emotions and intentions via explicit signals or subtle reflections of arousal visible in the face. Evidence is accumulating that humans synchronize these nonverbal expressions, as well as the physiological mechanisms underlying them, potentially promoting cooperative behavior. The current study is designed to verify the existence of this putative linkage between synchrony and cooperation. To that extent, 152 participants played multiple rounds of the Prisoners Dilemma game in a naturalistic dyadic interaction setting. During one round of games they could see each other, and during a second round they could not. The results showed that when peoples heart rate and skin conductance level aligned, they cooperated more successfully. Interestingly, for skin conductance level synchrony to boost cooperation, face to face contact was essential. The effect of heart rate synchrony on cooperation was context independent. Skin conductance level, but not heart rate, tended to closely correlate with changes in pupil size and we discuss how the pupil might provide a window to partners sympathetic arousal. These findings show how unconscious mechanisms guide social behavior and emphasize the importance of studying social processes between rather than within individuals in real-life interactions. Significance StatementHuman cooperation is remarkable in its scale, complexity, and efficiency. However, whereas people think of themselves as rational agents, they actually partly base their decision to cooperate with someone on gut feelings. These feelings are informed by non-verbal expressions that are picked up implicitly and that synchronize across interaction partners. For the first time, we show that the alignment of peoples arousal over multiple rounds of the Prisoners dilemma game predicts cooperative success. Through synchrony, partners converge emotionally, fostering understanding and bonding, which are key ingredients when it comes to successful cooperation. This suggests that successfully cooperating does not depend on individuals, but on the connection between individuals, emphasizing the importance of studying social decision-making processes in real-life settings.

physiology↗

bioRxiv2019

The choreography of human attraction: physiological synchrony in a blind date setting

Humans are social animals whose mental wellbeing is shaped by the ability to attract and connect with each other. In a dating world, in which success can be determined by brief interactions, apart from physical features, there is a whole choreography of movements, physical reactions and subtle expressions that drive humans sexual attraction. To determine what drives attraction, we measured nonverbal dynamics between people during real-life interactions outside the laboratory, where dating is most relevant. Participants wore eye-tracking glasses with embedded cameras, and devices to measure physiological signals including heart rate and skin conductance. Crucially, visible signals that can be controlled, such as facial expressions or gaze, did not predict attraction. Instead, attraction was predicted by synchrony in heart rate and skin conductance between partners, which are unconscious and difficult to regulate. Our findings suggest that shared emotionality is vital for mutual attraction. Moreover, physiological synchrony may provide a medium for translating visible expressions into embodied emotions, which can turn into intentions via somatosensory simulation. Significance StatementIn our modern world where millions of people meet online without interacting face-to-face, the question "what defines attraction" has become very relevant. In this study, we used modern technologies to lay down a foundation for the processes that drive human attraction during real-life interactions. Contrary to common belief, we found that attraction is not predicted by a frequency of expression or eye fixation duration, nor is linearly related to the participants autonomic nervous system activity. Importantly, we found that the more a participant synchronized their heart rate and skin conductance with their partner, the more they felt attracted toward that person. This study reveals a fundamental physiological process that plays a role in the formation of romantic relations.

physiology↗