Biology subjects

Buehler, M.

Publications and source records attributed to Buehler, M..

8 recordsLinked to original sources

bioRxiv2026

Heart rate variability as a candidate correlate of susceptibility to ASMR and music-induced frisson: an exploratory pilot study

BackgroundAutonomous sensory meridian response (ASMR) and music-induced frisson are sensory-affective phenomena characterized by tingling, chills, and pronounced emotional responses. Previous research has mainly focused on physiological changes during these experiences, whereas much less is known about whether baseline physiological state is associated with subsequent susceptibility. ObjectiveTo examine whether baseline autonomic flexibility, indexed primarily by heart rate variability (HRV), is associated with later ASMR/frisson responsiveness. Resting EEG measures were included as secondary exploratory markers. MethodsFifteen participants were recruited by convenience sampling; after artifact-based exclusion, 10 participants were included in the analyses. A 5-minute resting baseline EEG and ECG was recorded prior to stimulus presentation. Participants were then exposed to auditory and audiovisual ASMR stimuli, classical music excerpts, and a control stimulus, and reported whether they had experienced ASMR-typical sensations or frisson. Main analyses examined associations between baseline physiological parameters and a combined response-positive outcome. Exploratory analyses included participant-level correlations, comparisons between susceptible and non-susceptible participants, and stimulus-specific effect sizes. ResultsHRV-related measures showed the clearest and most consistent pattern of association with responsiveness. Higher baseline total HRV power was associated with a greater number of response-positive stimuli (r = 0.756, p = 0.011), with similar positive associations for high-frequency HRV (HF; r = 0.672, p = 0.033) and baseline heart rate slope (r = 0.751, p = 0.012). Stimulus-specific analyses likewise showed the most consistent positive baseline effects for total HRV power, with HF and heart rate slope pointing in the same direction. Frontal alpha asymmetry (FAA) was negatively associated with responsiveness ({rho} = -0.862, p = 0.001), but EEG findings overall were less consistent than the HRV-related pattern and are best interpreted as secondary exploratory observations. ConclusionsIn this exploratory pilot sample, baseline HRV, particularly total HRV power, showed the most coherent physiological association with susceptibility to ASMR and music-induced frisson. The findings are consistent with the possibility that these experiences depend not only on stimulus properties, but also on pre-existing physiological state. Given the small sample and exploratory design, the results should be interpreted as hypothesis-generating and require replication in larger confirmatory studies.

neuroscience↗

bioRxiv2026

The HMD domain of the PAF complex primes Rad6-Bre1 E3 ligase complexes for H2B ubiquitination

Mono-ubiquitination of histone H2B (H2Bub) is deposited by Bre1-type E3 ubiquitin ligase complexes during transcription elongation and is critical for chromatin organization, DNA repair, and transcription regulation. In S. pombe, this activity is carried out by HULC, a complex of the Bre1 homologs Brl1 and Brl2 with Rhp6 and Shf1. While H2Bub deposition depends on recruitment of HULC to RNA Pol II by the Paf1 complex (PAF1C), the molecular basis for how PAF1C activates HULC has remained unclear. Using AlphaFold modelling, biochemical reconstitution, and functional assays, we define the architecture of HULC as a flexible 1:1:1:1 assembly in which Shf1 stabilizes an elongated coiled-coil hairpin that brings the RING and Rad6-binding domains into proximity. However, for full stimulation of HULC activity, we find that the HMD domain of the PAF1C subunit Prf1 stimulates ubiquitin transfer through a RING-binding region (RBR) that repositions the RING domains adjacent to Rhp6 in a catalytically competent configuration. These findings reveal an activation mechanism in which transcription-associated Prf1 primes HULC for ubiquitin transfer through the Prf1RBR, revealing a critical regulatory interface for H2B ubiquitination.

molecular biology↗

bioRxiv2024

MHC heterozygosity may increase subordinate but not alpha male siring success in white-faced capuchin monkeys (Cebus imitator)

The genes of the major histocompatibility complex (MHC) are vital to vertebrate immunity and may influence mate choice in several species. The extent to which the MHC influences female mate choice in primates remains poorly understood, and studies of MHC-based mate choice in platyrrhines are especially rare. White-faced capuchin monkeys (Cebus imitator) reside in multimale-multifemale groups where alpha males sire most of the offspring. In this study, we investigated the roles of social dominance, relatedness, and MHC genotypes in determining which mating pairs produced offspring in wild white-faced capuchins in the Sector Santa Rosa (SSR), Area de Conservacion Guanacaste, Costa Rica. We find that males in this population do not differ significantly in MHC metrics based on their social status or siring success. Using mixed conditional logit models and generalized linear models, we find that alpha males that are distantly related to reproducing females are significantly more likely to sire offspring while MHC metrics do not predict the probability of siring offspring, or becoming an alpha male. However, we do find some evidence that subordinate males heterozygous at MHC loci sire significantly more offspring than homozygous subordinates. Further, one-sided binomial simulations reveal that offspring are more frequently heterozygous at MHC loci than expected given the gene pool. We conclude that in this population with limited genomic variation, females may preferentially mate with MHC-diverse subordinate males when related to the alpha, leading to increased probabilities of MHC-diverse offspring.

evolutionary biology↗

bioRxiv2024

Evolutionary trajectories of IDH-mutant astrocytoma identify molecular grading markers related to cell cycling

1To study the evolutionary processes that drive malignant progression of IDH-mutant astrocytomas, we performed multi-omics on a large cohort of matched initial and recurrent tumor samples. The overlay of genetic, epigenetic, transcriptomic and proteomic data, combined with single-cell analysis, have identified overlapping features associated with malignant progression. These features are derived from three molecular mechanisms and provide a rationale of the underlying biology of tumor malignancy: cell-cycling, tumor cell (de-)differentiation and remodeling of the extracellular matrix. Specifically, DNA-methylation levels decreased over time, predominantly in tumors with malignant transformation and co-occurred with poor prognostic genetic events. DNA-methylation was lifted from specific loci associated with DNA replication and was associated with an increased RNA and protein expression of cell cycling associated genes. All results were validated on samples of newly diagnosed IDH-mutant astrocytoma patients included the CATNON randomized phase 3 clinical trial. Importantly, malignant progression was hardly affected by radio- or chemotherapy, indicating that treatment does not affect the course of disease. Our results culminate in a DNA-methylation based signature for objective tumor grading.

cancer biology↗

bioRxiv2023

Nitrogen signaling factor triggers a respiration-like gene expression program

Microbes have evolved intricate communication systems that enable individual cells of a population to send and receive signals in response to changes in their immediate environment. In the fission yeast Schizosaccharomyces pombe, the oxylipin Nitrogen Signaling Factor (NSF) is part of such communication system, which functions to regulate the usage of different nitrogen sources. Yet, the pathways and mechanisms by which NSF acts are poorly understood. Here, we show that NSF physically interacts with the mitochondrial sulfide:quinone oxidoreductase Hmt2 and that it prompts a change from a fermentation- to a respiration-like gene expression program independently of the carbon source. Our results suggest that NSF activity is not restricted to nitrogen metabolism alone and that it could function as a rheostat to prepare a population of S. pombe cells for an imminent shortage of their preferred nutrients.

microbiology↗

bioRxiv2022

Targeting tumour-intrinsic neural vulnerabilities of glioblastoma

Glioblastoma is the most common yet deadliest primary brain cancer1. The neural behavior of glioblastoma, including the formation of synaptic circuitry and tumour microtubes, is increasingly understood to be pivotal for disease manifestation2-9. Nonetheless, the few approved treatments for glioblastoma target its oncological nature, while its neural vulnerabilities remain incompletely mapped and clinically unexploited. Here, we systematically survey the neural molecular dependencies and cellular heterogeneity across glioblastoma patients and diverse model systems. In 27 surgical patient samples, we identify cancer cell morphologies indicative of poor prognosis, and discover repurposable neuroactive drugs with anti-glioblastoma efficacy by image-based drug screening. Glioblastoma cells exhibit functional dependencies on highly expressed neuroactive drug targets, while interpretable molecular machine learning (COSTAR) reveals their downstream convergence on AP-1-driven tumour suppression. This drug-target connectivity signature is confirmed by accurate in silico drug screening on >1 million compounds, as well as by multi-omic profiling of glioblastoma drug responses. Thus, Ca2+-driven AP-1 pathway induction represents a tumour-intrinsic vulnerability at the intersection of oncogenesis and neural activity-dependent signaling. Opportunities for clinical translation of this neural vulnerability are epitomized by the antidepressant Vortioxetine synergizing with current standard of care treatments in vivo. Together, the results presented here provide a mechanistic foundation and conceptual framework for the treatment of glioblastoma based on its neural origins.

cancer biology↗

bioRxiv2022

Mouse Nuclear RNAi-defective 2 Promotes Splicing of Weak 5' Splice Sites

Removal of introns during pre-mRNA splicing, which is central to gene expression, initiates by base pairing of U1 snRNA with a 5 splice site (5SS). In mammals, many introns contain weak 5SSs that are not efficiently recognized by the canonical U1 snRNP, suggesting alternative mechanisms exist. Here, we develop a cross-linking immunoprecipitation coupled to a high-throughput sequencing method, BCLIP-seq, to identify NRDE2 (Nuclear RNAi defective-2) and CCDC174 (Coiled-Coil Domain-Containing 174) as novel RNA-binding proteins in mouse ES cells that associate with U1 snRNA and unspliced 5SSs. Both proteins bind directly to U1 snRNA independently of canonical U1 snRNP specific proteins, and they are required for the selection and effective processing of weak 5SSs. Our results reveal that mammalian cells use non-canonical splicing factors bound directly to U1 snRNA to effectively select suboptimal 5SS sequences in hundreds of genes, promoting proper splice site choice and accurate pre-mRNA splicing.

molecular biology↗

bioRxiv2020

Wide awake at bedtime? The effects of caffeine on sleep and circadian timing in teenagers - a randomized crossover trial

BackgroundAdolescents frequently consume caffeine with unknown consequences on sleep and circadian rhythms. In adults, the evidence indicates that caffeine acutely reduces homeostatic sleep pressure and delays the circadian timing system. ObjectiveHere, we investigated the acute effects of caffeine intake on the developing sleep-wake regulatory system of teenagers. DesignIn a double-blind randomized crossover laboratory study, 18 teenagers (16.1 {+/-} 1 years old, pubertal development scale [PDS]: 2.76 {+/-} 0.35) ingested 80 mg caffeine (vs placebo) four hours prior to bedtime. Until bedtime, participants regularly filled in the Karolinska Sleepiness Scale and gave saliva samples to measure melatonin secretion. During nighttime, we quantified homeostatic sleep need by the electroencephalographically derived amount of slow wave sleep duration (SWS). After sleep, participants rated sleep quality by the Leeds Sleep Evaluation Questionnaire. ResultsWhile participants felt less sleepy after caffeine vs. placebo (P=0.038), their ratings of sleep quality were not strongly affected by the treatment. However, objectively, SWS was on average reduced by [~]20 min after caffeine vs. placebo (P=0.026). This caffeine-induced reduction was more pronounced in those individuals with more SWS under placebo (regression: P=0.042; standardized beta=0.622, P=0.011), even if controlling for habitual caffeine intake or pubertal stage (PDS). In melatonin onsets we observed both delays and advances in response to caffeine. This variance could partly be explained by differences in relative dose (i.e., mg caffeine/kg of bodyweight): the higher the relative dose, the more likely were delays (regression: P=0.01; standardized beta=0.592, P=0.01). ConclusionsIn teenagers, evening caffeine intake of already 80 mg (i.e. [~]8fl oz of common energy drinks) is sufficient to promote alertness at the costs of subsequent sleep. These costs might be more pronounced in adolescents with a higher need for SWS. Moreover, caffeine might disturb the circadian timing system, consequently hampering the balanced interplay of sleep-wake regulatory components. Sources of SupportMarie-Heim-Voegtlin Grant of the Swiss National Science Foundation (SNSF) PMPDP1_171364

neuroscience↗