Biology subjects

Koch, U.

Publications and source records attributed to Koch, U..

4 recordsLinked to original sources

bioRxiv2025

Separation slang - Laboratory mice use low-frequency call repertoire during physical separation

The discovery of a diverse repertoire of ultrasonic vocalizations (USVs) sparked interest in understanding their role in mouse social behavior. Social communication in mice is not just vocal, but multimodal and occurs mostly in close proximity. Aiming to unravel the impact direct physical interaction has on the vocal communication of same-sex mouse dyads, we separated mice through a divider preventing direct physical interaction, but allowing visual, olfactory and some tactile interaction through holes. Separated dyads emitted a distinct call repertoire consisting mainly of calls in or just above the human audible range (but not squeaks) as well as Noisy calls, and only to a lesser degree of USVs. Increasing the possibility for direct interaction through larger holes in the divider led to an adaption of the call repertoire. The separation-induced call repertoire was neither affected by sex, nor was it mouse strain specific, even though differences in spectro-temporal parameters and call class proportion occurred. Lastly, buspirone treatment showed no observable effect, suggesting anxiety to not be the main driver underlying the separation-induced call repertoire. We show that separated same-sex mouse dyads predominantly emit a call repertoire that until now has only been observed in isolation or during aversive stimulation.

animal behavior and cognition↗

bioRxiv2025

Enabling antibiotic research: towards selective peptide deformylase inhibitors

Peptide deformylase plays a crucial role in prokaryotic translation and constitutes an antibiotic target previously addressed in clinical trials. In eukaryotes, mitochondrial translation also relies on peptide deformylase, necessitating antibiotic development to aim for selective inhibition of the bacterial enzymes. In the present study, we investigated two compound series: derivatives of actinonin and compounds containing a 5-bromoindole scaffold. Antibacterial activity was evaluated by microdilution-based minimal inhibitory concentration assay and selectivity investigated using human peripheral blood mononuclear cells. In vitro peptide deformylase inhibition was compared for the Escherichia coli and human enzyme. To validate peptide deformylase inhibition in vivo, a mass spectrometric analysis directly coupled to the minimal inhibitory concentration assay was developed for the model organism Bacillus subtilis. Two compounds originating from this work (ZHO-119, ZHO-197) showed antibacterial activity comparable to actinonin, and for the comparator compound BB-3497 superior anti-gram-negative and anti-tubercular activity was confirmed. The three compounds displayed no cytotoxicity and were equally selective in vitro for the bacterial enzyme. The mass spectrometry-based analysis indicates that in addition to peptide deformylase, ZHO-197 very effectively inhibits bacterial methionine aminopeptidase, the metallo-enzyme that removes the deformylated N-terminal methionine.

microbiology↗

bioRxiv2022

Absence of the fragile X mental retardation protein alters response patterns to sounds in the auditory midbrain

Among the different autism spectrum disorders, Fragile X Syndrome (FXS) is the most common inherited cause of mental retardation. Sensory and especially auditory hypersensitivity is a key symptom in patients, which is well mimicked in the Fmr1 -/- mouse model. However, the physiological mechanisms underlying FXSs acoustic hypersensitivity in particular remain poorly understood. Here, we categorized spike response patterns to pure tones of different frequencies and intensities from neurons in the Inferior Colliculus (IC), a central integrator in the ascending auditory pathway. Based on this categorization we analyzed differences in response patterns between IC neurons of WT and Fmr1 -/- mice. Our results report broadening of frequency tuning, an increased firing in response to monaural as well as binaural stimuli, an altered balance of excitation-inhibition, and reduced response latencies, all expected features of acoustic hypersensitivity. Furthermore, we were surprised to notice that all neuron response types in Fmr1 -/- mice displayed enhanced offset-rebound activity outside their excitatory frequency response area. These results provide evidence that the loss of Fmr1 not only increases spike responses in IC neurons similar to auditory brainstem neurons, but also changes response patterns such as offset spiking. One can speculate this to be an underlying aspect of the receptive language problems associated with Fragile X syndrome.

neuroscience↗

bioRxiv2019

Canonical NOTCH signaling controls the early progenitor state and emergence of the medullary epithelial lineage in fetal thymus development.

Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH-independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPC at the expense of cTEC differentiation. Finally, we uncover a direct interaction between NOTCH and FOXN1, the master regulator of TEC differentiation. These data establish NOTCH as a potent regulator of TEPC and mTEC fate during fetal thymus development and are thus of high relevance to strategies aimed at generating/regenerating functional thymic tissue in vitro and in vivo.

developmental biology↗