Biology subjects

Schwarz, K.

Publications and source records attributed to Schwarz, K..

12 recordsLinked to original sources

bioRxiv2025

Degradation of rutin and genistein and the effect on human bacterial fecal populations of obese and non-obese

This study re-evaluates the microbial degradation of rutin and genistein, emphasizing health-related metabotypes and novel degradation and transformation products of these compounds. In silico predictions and calculations were made to determine the molecular formulae of metabolites derived from precursor molecules by methylation, sulfation, and dehydroxylation. To validate these, anaerobic, ex vivo experiments were conducted with pooled fecal samples of obese and non-obese test persons (n=7 per group) over 48 hours, followed by 16S rRNA gene sequencing and semi-targeted high-resolution mass spectrometry analysis. We identified 46 rutin and 23 genistein metabolites, including novel methylated and sulfated derivatives. Microbial analysis revealed that the plant compounds influenced 34 bacterial families and 83 genera. Rutin inhibited obesity-associated genera while promoting butyrate-producing bacteria in BMI >40 samples, but reduced health-associated bifidobacteria and increased enterobacteria. Both compounds stimulated Eggerthella. These findings highlight significant microbial and metabolic shifts induced by plant-derived compounds, suggesting potential health implications.

microbiology↗

bioRxiv2023

Neural speech tracking benefit of lip movements predicts behavioral deterioration when the speaker's mouth is occluded

Observing lip movements of a speaker is known to facilitate speech understanding, especially in challenging listening situations. Converging evidence from neuroscientific studies shows enhanced processing of audiovisual stimuli. However, the interindividual variability of this visual benefit and its consequences on behavior are unknown. Here, we analyzed source-localized magnetoencephalographic (MEG) responses from normal-hearing participants listening to audiovisual speech with or without an additional distractor speaker. Using temporal response functions (TRFs), we show that neural responses to lip movements are, in general, enhanced when speech is challenging. After conducting a crucial control for speech acoustics, we show that lip movements effectively contribute to higher neural speech tracking, particularly when a distractor speaker is present. However, the extent of this visual benefit varied greatly among participants. Probing the behavioral relevance, we show that individuals who benefit more from lip movement information in terms of neural speech tracking, show a stronger drop in performance and an increase in perceived difficulty when the mouth is occluded by a surgical face mask. By contrast, no effect was found when the mouth was not occluded. We provide novel insights on how the benefit of lip movements in terms of neural speech tracking varies among individuals. Furthermore, we reveal its behavioral relevance by demonstrating negative consequences for behavior when visual speech is absent. Our results also offer potential implications for future objective assessments of audiovisual speech perception.

neuroscience↗

bioRxiv2023

Eye movements track prioritized auditory features in selective attention to natural speech

Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention - one of the key principles of adaptive behavior. A strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech in simultaneously recorded eye tracking and magnetoencephalographic (MEG) data. Using temporal response functions (TRF), we show that eye gaze tracks acoustic features (envelope and acoustic onsets) of attended speech, a phenomenon we termed ocular speech tracking. Ocular speech envelope tracking even differentiates a target from a distractor in a multi speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition. Our results extend previous findings of a joint network of attention and eye movement control as well as motor theories of speech. They provide valuable new directions for research into the neurobiological mechanisms of the phenomenon, its dependence on learning and plasticity, and its functional implications in social communication.

neuroscience↗

bioRxiv2022

A new type of transcriptional reprogramming by an IRF4 mutation in lymphoma

SUMMARY PARAGRAPHDisease-causing mutations in genes encoding transcription factors (TFs) are a recurrent finding in hematopoietic malignancies and might involve key regulators of lineage adherence and cellular differentiation1-3. Such mutations can affect TF-interactions with their cognate DNA-binding motifs4, 5. Whether and how TF-mutations impact upon the nature of binding to TF composite elements (CE) and influence their interaction with other TFs is unclear. Here, we report a new mechanism of TF alteration in human lymphomas with perturbed B cell identity. It is caused by a recurrent somatic missense mutation c.295T>C (p.Cys99Arg; p.C99R) targeting the center of the DNA-binding domain of Interferon Regulatory Factor 4 (IRF4), a key TF in immune cell-differentiation and -activation6, 7. IRF4-C99R fundamentally alters IRF4 DNA-binding, with loss-of-binding to canonical IRF motifs and neomorphic gain-of-binding to canonical and non-canonical IRF composite elements (CEs). Furthermore, IRF4-C99R thoroughly modifies IRF4 function, by blocking IRF4-dependent plasma cell induction, and up-regulating disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single arginine mutation creates a complex switch of TF specificity and gene regulation. These data open the possibility of designing specific inhibitors to block the neomorphic, disease-causing DNA-binding activities of a mutant transcription factor.

cancer biology↗

bioRxiv2022

A metabolomic view on local climate adaptation: Latitudinal divergence of heat and drought responses in a coastal plant

Studying natural variation in multi-stress resistance is central for predicting and managing the population dynamics of wild plant species under rapid global change. Yet, it remains a challenging goal in this field to integrate knowledge on the complex biochemical underpinnings for the targeted non-model species. Here, we studied latitudinal divergence in combined drought and heat stress resistance in European populations of the dune plant Cakile maritima, by combining comprehensive plant phenotyping with metabolic profiling via FT-ICR-MS and UPLC-TQ-MS/MS. We observed pronounced constitutive divergence in growth phenology, leaf functional traits and defence chemistry (glucosinolates, alkaloids) among population origins. Most importantly, the magnitude of growth reduction under stress was partly weaker in southern plants and associated with divergence in plastic growth responses (root expansion, leaf abscission) and the stress-induced modulation of primary and specialized metabolites with known central functions not only in plant abiotic but also biotic stress resistance. Our study supports that divergent selection has shaped the constitutive and stress-induced expression of numerous morphological and biochemical functional traits to mediate higher abiotic stress resistance in southern Cakile populations, and highlights that metabolomics is a powerful tool to explore the mechanistic underpinnings of local stress adaptation in non-model species. HighlightPlant defence chemistry and its modulation by abiotic stress exhibits latitudinal clines across natural populations of a coastal plant.

ecology↗

bioRxiv2021

Tumour mutations in long noncoding RNAs that enhance cell fitness

Long noncoding RNAs (lncRNAs) can act as tumour suppressors or oncogenes to repress/promote tumour cell proliferation via RNA-dependent mechanisms. Recently, genome sequencing has identified elevated densities of tumour somatic single nucleotide variants (SNVs) in lncRNA genes. However, this has been attributed to phenotypically-neutral "passenger" processes, and the existence of positively-selected fitness-altering "driver" SNVs acting via lncRNAs has not been addressed. We developed and used ExInAtor2, an improved driver-discovery pipeline, to map pancancer and cancer-specific mutated lncRNAs across an extensive cohort of 2583 primary and 3527 metastatic tumours. The 54 resulting lncRNAs are mostly linked to cancer for the first time. Their significance is supported by a range of clinical and genomic evidence, and display oncogenic potential when experimentally expressed in matched tumour models. Our results revealed a striking SNV hotspot in the iconic NEAT1 oncogene, which was ascribed by previous studies to passenger processes. To directly evaluate the functional significance of NEAT1 SNVs, we used in cellulo mutagenesis to introduce tumour-like mutations in the gene and observed a consequent increase in cell proliferation in both transformed and normal backgrounds. Mechanistic analyses revealed that SNVs alter NEAT1 ribonucleoprotein assembly and boost subnuclear paraspeckles. This is the first experimental evidence that mutated lncRNAs can contribute to the pathological fitness of tumour cells.

genomics↗

bioRxiv2021

Fungal Mineral Weathering Mechanisms Revealed Through Direct Molecular Visualization

Soil fungi facilitate the translocation of inorganic nutrients from soil minerals to other microorganisms and plants. This ability is particularly advantageous in impoverished soils, because fungal mycelial networks can bridge otherwise spatially disconnected and inaccessible nutrient hotspots. However, the molecular mechanisms underlying fungal mineral weathering and transport through soil remains poorly understood. Here, we addressed this knowledge gap by directly visualizing nutrient acquisition and transport through fungal hyphae in a mineral doped soil micromodel using a multimodal imaging approach. We observed that Fusarium sp. DS 682, a representative of common saprotrophic soil fungi, exhibited a mechanosensory response (thigmotropism) around obstacles and through pore spaces ([~]12 {micro}m) in the presence of minerals. The fungus incorporated and translocated potassium (K) from K-rich mineral interfaces, as evidenced by visualization of mineral derived nutrient transport and unique K chemical moieties following fungal induced mineral weathering. Specific membrane transport proteins were expressed in the presence of minerals, including those involved in oxidative phosphorylation pathways and transmembrane transport of small molecular weight organic acids. This study establishes the significance of fungal biology and nutrient translocation mechanisms in maintaining fungal growth under water and nutrient limitations in a soil-like microenvironment.

microbiology↗

bioRxiv2021

Direct cochlear recordings show human hearing nerve activity is modulated by selective attention

The architecture of the efferent auditory system enables prioritization of strongly overlapping spatiotemporal cochlear activation patterns elicited by relevant and irrelevant inputs. So far, attempts at finding such attentional modulations of cochlear activity delivered indirect insights in humans or required direct recordings in animals. The extent to which spiral ganglion cells forming the human auditory nerve are sensitive to selective attention remains largely unknown. We investigated this question by testing the effects of attending to either the auditory or visual modality in human cochlear implant (CI) users (3 female, 13 male). Auditory nerve activity was directly recorded with standard CIs during a silent (anticipatory) cue-target interval. When attending the upcoming auditory input, ongoing auditory nerve activity within the theta range (5-8 Hz) was enhanced. Crucially, using the broadband signal (4-25 Hz), a classifier was even able to decode the attended modality from single-trial data. Follow-up analysis showed that the effect was not driven by a narrow frequency in particular. Using direct cochlear recordings from deaf individuals, our findings suggest that cochlear spiral ganglion cells are sensitive to top-down attentional modulations. Given the putatively broad hair-cell degeneration of these individuals, the effects are likely mediated by alternative efferent pathways as compared to previous studies using otoacoustic emissions. Successful classification of single-trial data could additionally have a significant impact on future closed-loop CI developments that incorporate real-time optimization of CI parameters based on the current mental state of the user. Significance StatementThe efferent auditory system in principle allows top-down modulation of auditory nerve activity, however evidence for this is lacking in humans. Using cochlear recordings in participants performing an audiovisual attention task, we show that ongoing auditory nerve activity in the silent cue-target period is directly modulated by selective attention. Specifically, ongoing auditory nerve activity is enhanced within the theta range when attending upcoming auditory input. Furthermore, over a broader frequency range, the attended modality can be decoded from single-trial data. Demonstrating this direct top-down influence on auditory nerve activity substantially extends previous works that focus on outer hair cell activity. Generally, our work could promote the use of standard cochlear implant electrodes to study cognitive neuroscientific questions.

neuroscience↗

bioRxiv2019

Hemibiotrophic fungal pathogen induces systemic susceptibility and systemic shifts in wheat metabolome and microbiome composition

Yield losses caused by fungal pathogens represent a major threat to global food production. One of the most devastating fungal wheat pathogens is Zymoseptoria tritici. Despite the importance of this fungus and wheat as main staple food crop the underlying mechanisms of plant-pathogen interactions are poorly understood. Here we present a conceptual framework based on coinfection assays, comparative metabolomics, and microbiome profiling to study the interaction of Z. tritici in susceptible and resistant wheat. We demonstrate that Z. tritici suppresses the production of immune-related metabolites in a susceptible cultivar. Remarkably, this fungus-induced immune suppression spreads within the leaf and even to other leaves, a previously undescribed phenomenon that we term \"systemic induced susceptibility\". Using a comparative metabolomics approach, we identified defense-related biosynthetic pathways that are suppressed and induced in susceptible and resistant cultivars, respectively. We show that these fungus-induced changes also dramatically affect the wheat leaf microbiome. Our findings emphasize that immune suppression by this hemibiotrophic pathogen impacts specialized plant metabolism, alters its associated microbial communities, and renders wheat vulnerable to further infections.

plant biology↗

bioRxiv2019

Brain state stability during working memory is explained by network control theory, modulated by dopamine D1/D2 receptor function, and diminished in schizophrenia

Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory entails brain-wide switching between activity states. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Schizophrenia patients show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations.

neuroscience↗

bioRxiv2019

Generative network models identify biological mechanisms of altered structural brain connectivity in schizophrenia

BackgroundAlterations in the structural connectome of schizophrenia patients have been widely characterized, but the mechanisms leading to those alterations remain largely unknown. Generative network models have recently been introduced as a tool to test the biological underpinnings of the formation of altered structural brain networks.\n\nMethodsWe evaluated different generative network models to investigate the formation of structural brain networks in healthy controls (n=152), schizophrenia patients (n=66) and their unaffected first-degree relatives (n=32), and we identified spatial and topological factors contributing to network formation. We further investigated the association of these factors to cognition and to polygenic risk for schizophrenia.\n\nResultsStructural brain networks can be best accounted for by a two-factor model combining spatial constraints and topological neighborhood structure. The same wiring model explained brain network formation for all groups analyzed. However, relatives and schizophrenia patients exhibited significantly lower spatial constraints and lower topological facilitation compared to healthy controls. The model parameter for spatial constraint was correlated with the polygenic risk for schizophrenia and predicted reduced cognitive performance.\n\nConclusionsOur results identify spatial constraints and local topological structure as two interrelated mechanisms contributing to normal brain development as well as altered connectomes in schizophrenia. Spatial constraints were linked to the genetic risk for schizophrenia and general cognitive functioning, thereby providing insights into their biological basis and behavioral relevance.

neuroscience↗

bioRxiv2017

RNPP-type quorum sensing regulates solvent formation and sporulation in Clostridium acetobutylicum

The strictly anaerobic bacterium Clostridium acetobutylicum is well known for its ability to convert sugars into organic acids and solvents, most notably the potential biofuel butanol. However, the regulation of its fermentation metabolism, in particular the shift from acid to solvent production, remains poorly understood. The aim of this study was to investigate whether cell-cell communication plays a role in controlling the timing of this shift or the extent of solvent formation. Analysis of the available C. acetobutylicum genome sequences revealed the presence of eight putative RNPP-type quorum sensing systems, here designated qssA to qssH, each consisting of RNPP-type regulator gene followed by a small open reading frame encoding a putative signalling peptide precursor. The identified regulator and signal peptide precursor genes were designated qsrA to qsrH and qspA to qspH, respectively. Triplicate regulator mutants were generated in strain ATCC 824 for each of the eight systems and screened for phenotypic changes. The qsrB mutants showed increased solvent formation during early solventogenesis and hence the QssB system was selected for further characterisation. Overexpression of qsrB severely reduced solvent and endospore formation and this effect could be overcome by adding short synthetic peptides to the culture medium representing a specific region of the QspB signalling peptide precursor. In addition, overexpression of qspB increased the production of acetone and butanol and the initial (48-hour) titre of heat-resistant endospores. Together, these findings establish a role for QssB quorum sensing in the regulation of early solventogenesis and sporulation in C. acetobutylicum.

microbiology↗