Biology subjects

Eisenberg, T.

Publications and source records attributed to Eisenberg, T..

8 recordsLinked to original sources

bioRxiv2026

PFKFB3 inhibition restores β-cell responsiveness to acetylcholine in a 3xTg-AD pancreatic tissue-slice mode

The glycolytic regulator PFKFB3 supports dysfunctional {beta}-cell states, but its role in pancreatic Ca2+ signaling remains unclear. We examined responses to PFKFB3 inhibitors (AZ67, AZ26) in pancreatic tissue slices from aged 3xTg-AD mice, a model of Alzheimer's disease that develops impaired glucose tolerance and diabetes as comorbidity. Compared to wild-type controls, {beta}-cells showed weaker glucose-stimulated and acetylcholine-potentiated Ca2+ activity, accompanied by increased nuclear PFKFB3 positivity in insulin-defined islet-cell populations, used here as a PFKFB3-associated stress-state marker. During glucose and acetylcholine stimulation, AZ67 increased {beta}-cell Ca2+ event frequency while maintaining short events. In neighboring acinar cells, PFKFB3 inhibitor exposure was followed by renewed oscillations after acetylcholine-evoked activity had waned. {beta}-cell recruitment was preserved during adrenergic inhibition, and enhanced activity persisted after inhibitor withdrawal, although these recordings were exploratory and residual tissue drug exposure could not be excluded. An effect that survives both drug removal and adrenergic opposition identifies a Ca2+ signaling phenotype in 3xTg-AD {beta}-cells that is acutely inducible yet not transient, and establishes PFKFB3 as a regulator of muscarinic responsiveness in the stressed {beta}-cell.

physiology↗

bioRxiv2025

Presenilin-1 controls glucose metabolism and identity of pancreatic beta cells

AbstractPresenilin 1 is an endoplasmic reticulum protein, most known for its role in pathogenesis of familial Alzheimers Disease (AD). Presenilin 1 has been attributed roles in intracellular calcium homeostasis in the brain, as well as in the pancreatic beta cells, where it has been shown to be fundamental for glucose-induced insulin secretion. Functional similarity of presenilin 1 in regulation of intracellular calcium homeostasis in the brain and pancreas prompted us to investigate a prevalent assumption that associates AD and diabetes mellitus. By examining pancreatic islets from AD model mice, we have found deficits in initial phase of glucose-induced calcium signaling and insulin secretion. Furthermore, these transgenic mice showed a tendency towards reduced expression of mature beta cell markers, which was even more pronounced in islets and beta cell lines with a transient knock down of presenilin 1. We demonstrate here that presenilin 1 controls beta cell glycolysis by regulating sub-cellular calcium homeostasis and, in doing so, contributes to preservation of beta cell identity.

cell biology↗

bioRxiv2025

Up-to-date MALDI-TOF MS based identification of the complete Corynebacterium diphtheriae species complex for improved diagnostics

The Corynebacterium (C.) diphtheriae species complex (CdSC) comprises the closely related pathogenic species C. diphtheriae, C. belfantii, C. rouxii, C. ulcerans, C. silvaticum, C. ramonii and C. pseudotuberculosis according to the taxonomic revisions after 2018. Due to their close relationship, reliable species identification within the CdSC is also challenging using MALDI-TOF mass spectrometry (MS) for fast and reliable identification of bacteria. However, the most commonly used commercial databases for MALDI-TOF MS do not reflect the current CdSC taxonomy. Therefore, the objective of the present study is to expand the Bruker MALDI-Biotyper database version K (MBTK) in order to achieve reliable identification for all currently known Corynebacterium species within the CdSC. Furthermore, the database extensions were verified with a systematic formal validation procedure in accordance with the German guideline for species identification by MALDI- TOF MS. For this, 321 strains including all seven valid species of the CdSC were identified with a set of 328 spectra using the commercial MBTK database and a customer-supplemented modified MBTK. This custom database version included 33 reference spectra of the CdSC and representatives of all four recently described species. The results of the formal validations for both, the commercial and the extended database, combined partly with a single signal analysis, provide a substantiated basis for the identification of bacteria of the CdSC. A key element for a fast up-to-date identification has been the exchange of user-generated sets of MSPs on the open access MALDI-UP catalogue that includes reference spectra for all members of the CdSC. HighlightsO_LIUsing MALDI-TOF MS, all current species of the C. diphtheriae species complex are accurately identified according to the current taxonomy C_LIO_LIValidation was performed using spectra from different institutions and an approved gold standard protocol C_LIO_LIThe extension and exchange of user created reference spectra via the MALDI User Platform proved to be a key tool for precise identification of bacteria C_LI Importance StatementBacteria belonging to the Corynebacterium (C.) diphtheriae complex are important pathogens for humans and animals. Identification of the species of this complex described since 2018, i.e. C. belfantii, C. rouxii, C. ramonii, and C. silvaticum, using the widely approved MALDI-TOF mass spectrometry is possible. This has been achieved by improved identification using supplemented MALDI reference databases. Comprehensive validation meets the requirements for accurate pathogen identification in accordance with recognised guidelines. This approach of identification is certainly a model for other bacterial species of interest to react on current taxonomic revisions in a short time frame.

microbiology↗

bioRxiv2025

Evidence of a novel sublineage of Streptococcus agalactiae in elephants from zoo populations in Germany

Streptococcus agalactiae research primarily centers on investigating human and bovine infections, although this pathogen also can be carried and cause infections in a wider range of animal species. Moreover, infections with S. agalactiae are posing significant health implications and, also, recent studies are highlighting a potential zoonotic risk. Despite the comparatively frequent isolation of S. agalactiae from elephants, only a few reports document infections in wild and zoo populations. We performed a comparative genomic analysis of 24 elephant isolates from three different zoos in Germany, to achieve a comprehensive characterization. Elephant isolates showed pronounced phylogenetic divergence from isolates of other host species, while also forming clusters based on their zoo of origin and their genotypes (MLST profiles). Capsular serotypes could not be identified for the majority of the isolates (n=20/24). Several genes, associated exclusively with the elephant host may underlie the pathogens capacity to improve its survival and virulence across varied ecological niches. This study not only deepens our understanding of S. agalactiae across diverse species and environments but also represents the first whole-genome sequencing characterization of S. agalactiae isolates from elephants, helping to expand our knowledge about infections in exotic animals.

bioinformatics↗

bioRxiv2024

Spermidine alleviates depression via control of the stress response

Depression is a stress-associated disorder, and it represents a major global health issue. Its pathophysiology is complex and remains insufficiently understood, with current medications often showing limited efficacy and undesirable side effects. Here, we identify imbalanced polyamine levels and dysregulated autophagy as key components of the acute stress response in humans, and as hallmarks of chronic stress and depressive disorders. Moreover, conventional antidepressant pharmacotherapy increases endogenous plasma concentrations of the polyamine spermidine exclusively in patients who respond to the treatment, suggesting a link between spermidine and successful outcomes. In a clinical trial, involving drug-naive depressed individuals, three weeks of spermidine supplementation increased autophagy and alleviated symptoms of depression. Behavioral and mechanistic findings of spermidine supplementation were validated in various mouse stress and depression models. In summary, spermidine supplementation mitigates polyamine dysregulation and stimulates autophagy under pathological stress conditions, offering a novel and well-tolerated treatment approach for stress-related depressive disorders.

neuroscience↗

bioRxiv2023

ReptiLearn: A Smart Home Cage for Behavioral Experiments in Reptiles

Understanding behavior and its evolutionary underpinnings is crucial for unraveling the complexities of brain function. Traditional approaches strive to reduce behavioral complexity by designing short-term, highly constrained behavioral tasks with dichotomous choices in which animals respond to defined external perturbation. In contrast, natural behaviors evolve over multiple time scales and under minimally constrained conditions in which actions are selected through bi-directional interactions with the environment and without human intervention. Recent technological advancements have opened up new possibilities for more natural experimental designs by replacing stringent experimental control with accurate multidimensional behavioral analysis. However, these approaches have been tailored to fit only a small number of species. This specificity limits the experimental opportunities offered by species diversity. Further, it hampers comparative analyses which are essential for extracting overarching behavioral principles and for examining behavior from an evolutionary perspective. To address this limitation, we developed ReptiLearn - a versatile, low-cost, Python-based solution, optimized for conducting automated long-term experiments in the home cage of reptiles, without human intervention. In addition, this system offers unique features such as precise temperature measurement and control, live prey reward dispensers, engagement with touch screens, and remote control through a user-friendly web interface. Finally, ReptiLearn incorporates low-latency closed-loop feedback allowing bi-directional interactions between animals and their environments. Thus, ReptiLearn provides a comprehensive solution for researchers studying behavior in ectotherms and beyond, bridging the gap between constrained laboratory settings and natural behavior in non-conventional model systems. We demonstrate the capabilities of ReptiLearn by automatically training the lizard Pogona vitticeps on a complex spatial learning task requiring association learning, displaced reward learning and reversal learning.

animal behavior and cognition↗

bioRxiv2021

Global analysis of protein arginine methylation

Quantitative information about the levels and dynamics of post-translational modifications (PTMs) is critical for an understanding of cellular functions. Protein arginine methylation (ArgMet) is an important subclass of PTMs and is involved in a plethora of (patho)physiological processes. However, due to the lack of methods for global analysis of ArgMet, the link between ArgMet levels, dynamics and (patho)physiology remains largely unknown. We utilized the high sensitivity and robustness of Nuclear Magnetic Resonance (NMR) spectroscopy to develop a general method for the quantification of global protein ArgMet. Our NMR-based approach enables the detection of protein ArgMet in purified proteins, cells, organoids, and mouse tissues. We demonstrate that the process of ArgMet is a highly prevalent PTM and can be modulated by small-molecule inhibitors and metabolites and changes in cancer and during ageing. Thus, our approach enables to address a wide range of biological questions related to ArgMet in health and disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/428036v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@37a0f1org.highwire.dtl.DTLVardef@273ebdorg.highwire.dtl.DTLVardef@87fcd6org.highwire.dtl.DTLVardef@1e84c07_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2020

Toxigenic and zoonotic Corynebacterium ulcerans emerges from widespread hedgehog disease

Toxin-producing Corynebacterium ulcerans, causing diphtheria in humans, were isolated from 53 diseased hedgehogs during spring 2020 in Belgium. Isolates showed low levels of acquired antimicrobial resistance. Pronounced strain diversity suggests emergence from an endemic situation. These findings stress the need for raising public awareness and improved wildlife disease surveillance.

microbiology↗