Biology subjects

Mehler, J.

Publications and source records attributed to Mehler, J..

3 recordsLinked to original sources

bioRxiv2026

Deciphering underground decarboxylase activity towards Nε-modified lysine derivatives in enterobacteria.

Thermal food processing generates diverse compounds interacting with the gut microbiota. Despite their abundance, the microbial turnover of diet-borne N{varepsilon}-modified lysine derivatives remains largely unexplored. We demonstrate that the enterobacterial ornithine decarboxylase SpeC degrades the prevalent advanced glycation end product N{varepsilon}-carboxymethyllysine (CML) to carboxymethylcadaverine via an underground activity ([~]4 molecules/enzyme/min). This promiscuity extends to additional N{varepsilon}-modified lysine derivatives - namely fomylated (FmL), monomethylated (MML) and dimethylated (DML) lysine - yielding previously unknown biogenic amines (mono- and dimethylcadaverine, formylcadaverine). Functionally, SpeC enables Escherichia coli to utilize CML as a sole nitrogen source. In specific strains, this metabolism reinforces pH-stress responses, supporting survival under mild acidic conditions typical for the colon. Furthermore, SpeC orthologs are widespread across human gut genomes, correlating with geography, diet, and disease. Together, these findings suggest a potential diet-microbiome communication axis, linking the intake of modified dietary chemicals to microbial physiology and hypothesized host impacts.

microbiology↗

bioRxiv2020

PCMD-1 bridges the centrioles and the PCM scaffold in C. elegans

Correct cell division relies on the formation of a bipolar spindle. In animal cells, microtubule nucleation at the spindle poles is facilitated by the pericentriolar material (PCM), which assembles around a pair of centrioles. Although centrioles are essential for PCM assembly, proteins that anchor the PCM to the centrioles are less known. Here we investigate the molecular function of PCMD-1 in bridging the PCM and the centrioles in Caenorhabditis elegans. We demonstrate that centrosomal recruitment of PCMD-1 is dependent on the outer centriolar protein SAS-7. While the most C-terminal part of PCMD-1 is sufficient to target it to the centrosome, the coiled-coil domain promotes its accumulation by facilitating self-interaction. We reveal that PCMD-1 is bridging the centrioles and PCM scaffold through protein-protein interactions with the PCM scaffold protein SPD-5, the mitotic kinase PLK-1 and the centriolar protein SAS-4. Using an ectopic translocation assay, we show that PCMD-1 is able to selectively recruit downstream PCM scaffold components to an ectopic location in the cell, indicating that PCMD-1 is sufficient to anchor the PCM scaffold proteins to the centrioles. Our work suggests that PCMD-1 is an essential functional bridge between the centrioles and the PCM.

cell biology↗

bioRxiv2019

Predictive Coding beyond simple tone-based oddball designs

As the evidence of predictive processes playing a role in a wide variety of cognitive domains increases, the brain as a predictive machine becomes a central idea in neuroscience. In auditory processing a considerable amount of progress has been made using variations of the Oddball design, but most of the existing work seems restricted to predictions based on physical features or conditional rules linking successive stimuli. To characterise the predictive capacity of the brain to abstract rules, we present here two experiments that use speech-like stimuli to overcome limitations and avoid common confounds. Pseudowords were presented in isolation, intermixed with infrequent deviants that contained unexpected phoneme sequences. As hypothesized, the occurrence of unexpected sequences of phonemes reliably elicited an early prediction error signal. These prediction error signals do not seemed to be modulated by attentional manipulations due to different task instructions, suggesting that the predictions are deployed even when the task at hand does not volitionally involve error detection. In contrast, the amount of syllables congruent with a standard pseudoword presented before the point of deviance exerted a strong modulation. Prediction errors amplitude doubled when two congruent syllables were presented instead of one, despite keeping local transitional probabilities constant. This suggest that auditory predictions can be built integrating information beyond the immediate past. In sum, the results presented here further contribute to the understanding of the predictive capabilities of the human auditory system when facing complex stimuli and abstract rules.\n\nSignificance StatementThe generation of predictions seem to be a prevalent brain computation. In the case of auditory processing this information is intrinsically temporal. The study of auditory predictions has been largely circumscribed to unexpected physical stimuli features or rules connecting consecutive stimuli. In contrast, our everyday experience suggest that the human auditory system is capable of more sophisticated predictions. This becomes evident in the case of speech processing, where abstract rules with long range dependencies are universal. In this article, we present two electroencephalography experiments that use speech-like stimuli to explore the predictive capabilities of the human auditory system. The results presented here increase the understanding of the ability of our auditory system to implement predictions using information beyond the immediate past.

neuroscience↗