Biology subjects

Brauer, J.

Publications and source records attributed to Brauer, J..

3 recordsLinked to original sources

bioRxiv2026

HDAC inhibition via suberoylanilide hydroxamic acid (SAHA) ameliorates Doxorubicin-induced cardiotoxicity

BackgroundAnthracycline-induced cardiotoxicity remains a major limitation of cancer therapy, and effective preventive strategies are lacking. Topoisomerase II{beta} (Topo IIb) has been implicated as a central driver of this toxicity, suggesting that epigenetic regulators may interfere with pathological cardiac response. Methods and ResultsHere, we show that doxorubicin promotes Topo IIb accumulation at cardiomyocyte gene promoters (e.g., Actc1, Myl2, and Myh7) overlapping myocyte enhancer factor 2 (MEF2) binding sites and enhances MEF2-dependent transcription. This response is attenuated by the pan-histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA). SAHA-mediated cardioprotection requires class IIa HDACs, as genetic loss of HDAC4 abolishes its effect. Mechanistically, SAHA induces acetylation of the chaperone 14-3-3, disrupting its interaction with HDAC4/5, promoting their nuclear accumulation, and repressing MEF2-driven transcription. In vivo, SAHA mitigates doxorubicin-induced cardiotoxicity. ConclusionThese findings identify HDAC inhibition as a cardioprotective repurposing strategy and reveal a mechanistic link between epigenetic regulation and anthracycline-associated cardiotoxicity.

molecular biology↗

bioRxiv2022

White Matter Brain Structure Predicts Language Performance and Learning Success

Individual differences in the ability to deal with language have long been discussed. The neural basis of these, however, is yet unknown. Here we investigated the relationship between long-range white matter connectivity of the brain, as revealed by diffusion tractography, and the ability to process syntactically complex sentences in the participants native language as well as the improvement thereof by multi-day training. We identified specific network motifs that indeed related white matter tractography to individual language processing performance. First, for two such motifs, one in the left and one in the right hemisphere, their individual prevalence significantly predicted the individual language performance suggesting a predisposition for the individual ability to process syntactically complex sentences, which manifests itself in the white matter brain structure. Both motifs comprise a number of cortical regions, but seem to be dominated by areas known for the involvement in working memory rather than the classical language network itself. Second, we identified another left hemispheric network motif, whose change of prevalence over the training period significantly correlated with the individual change in performance, thus reflecting training induced white matter plasticity. This motif comprises diverse cortical areas including regions known for their involvement in language processing, working memory and motor functions. The present findings suggest that individual differences in language processing and learning can be explained, in part, by individual differences in the brains white matter structure. Brain structure may be a crucial factor to be considered when discussing variations in human cognitive performance, more generally.

neuroscience↗

bioRxiv2021

Individual alpha power predicts language comprehension

Alpha power attenuation during cognitive task performing has been suggested to reflect a process of release of inhibition, increase of excitability, and thereby benefit the improvement of performance. Here, we hypothesized that changes in individual alpha power during the execution of a complex language comprehension task may correlate with the individual performance in that task. We tested this using magnetoencephalography (MEG) recorded during comprehension of German sentences of different syntactic complexity. Results showed that neither the frequency nor the power of the spontaneous oscillatory activity at rest were associated with the individual performance. However, during the execution of a sentences processing task, the individual alpha power attenuation did correlate with individual language comprehension performance. Source reconstruction localized effects in temporal-parietal regions of both hemispheres. While the effect of increased task difficulty is localized in the right hemisphere, the difference in power attenuation between tasks of different complexity exhibiting a correlation with performance was localized in left temporal-parietal brain regions known to be associated with language processing. From our results, we conclude that in-task attenuation of individual alpha power is related to the essential mechanisms of the underlying cognitive processes, rather than merely to general phenomena like attention or vigilance. HighlightsO_LIComprehension of structurally complexed embedded sentences is correlated with individual alpha power attenuation during task but not with alpha power at rest. C_LIO_LIThese effects were localized in temporal-parietal brain regions known to be associated with language processing. C_LI Data availability statementAnonymized raw data will be made available upon request via email to the corresponding author provided the requesting researchers sign a formal data sharing agreement and cite this paper as origin of the data.

neuroscience↗