Biology subjects

Riedel, J.

Publications and source records attributed to Riedel, J..

5 recordsLinked to original sources

bioRxiv2026

Nonlinear regime transitions enable reservoir computation in activator-inhibitor cellular automata

Activator-inhibitor systems are usually studied as pattern-forming media, but the same local nonlinear interactions can also shape how information is stored and separated over time. Here we first introduce a reaction-diffusion-inspired cellular automaton as a tunable nonlinear medium with two activation families, a continuous sigmoid and a logistic-step relaxer. In each case, a single family-specific parameter changes the nonlinear response or relaxation dynamics while leaving the neighbourhood wiring fixed. This provides a controlled way to move the activator-inhibitor system between collapsed, structured, saturated, and overshooting regimes, and to relate these regimes to state-level diversity and pattern compressibility. We then use reservoir computing to test whether these tuned pattern-forming regimes support fading memory, input separability, and downstream readout learning. In this role, reservoir computing is not treated as an architecture to be optimised, but as a diagnostic of the computational properties of the untrained medium. Across parameter sweeps, stronger memory and separability are concentrated near transition regions rather than distributed uniformly across parameter space. These results identify activator-inhibitor cellular automata as interpretable unconventional reservoir substrates in which effective gain, threshold, and relaxation parameters tune the balance between pattern formation, memory, and separability. More broadly, they support the view that tissue-like or physical pattern-forming media may, in principle, shift between patterning and information-processing regimes by modulating local nonlinear dynamics.

systems biology↗

bioRxiv2023

Overactivated epithelial NF-κB disrupts lung development in human and nitrofen CDH

Background & ObjectiveAbnormal lung development is the main cause of morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH), a common birth defect (1:2500) of largely unknown pathobiology. Recent studies discovered that inflammatory processes, and specifically NF-{kappa}B associated pathways are enriched in human and experimental CDH. However, the molecular signaling of NF-{kappa}B in abnormal CDH lung development and its potential as a therapeutic target requires further investigation. Methods & ResultsUsing sections and hypoplastic lung explant cultures from the nitrofen rat model of CDH and human fetal CDH lungs, we demonstrate that NF-{kappa}B and its downstream transcriptional targets are hyperactive during abnormal lung formation in CDH. NF-{kappa}B activity was especially elevated in the airway epithelium of nitrofen and human CDH lungs at different developmental stages. Fetal rat lung explants had impaired pseudoglandular airway branching after exposure to nitrofen, together with increased phosphorylation and transcriptional activity of NF-{kappa}B. Dexamethasone, the broad and clinically applicable anti-inflammatory NF-{kappa}B antagonist, rescued lung branching and normalized NF-{kappa}B signaling in hypoplastic lung explants. Moreover, specific NF-{kappa}B inhibition with curcumenol similarly rescued ex vivo lung hypoplasia and restored NF-{kappa}B signaling. Lastly, we showed that prenatal intraperitoneal dexamethasone administration to pregnant rat dams carrying fetuses with hypoplastic lungs, significantly improves lung branching and normalizes NF-{kappa}B in vivo. Conclusions: Our results indicate that NF-{kappa}B is aberrantly activated in human and nitrofen CDH lungs. Anti-inflammatory treatment with dexamethasone and/ or specific NF-{kappa}B inhibition should be investigated further as a therapeutic avenue to target lung hypoplasia in CDH.

developmental biology↗

bioRxiv2022

Proteomic Profiling of Hypoplastic Lungs Suggests an Underlying Inflammatory Response in the Pathogenesis of Abnormal Lung Development in Congenital Diaphragmatic Hernia

The pathogenesis of lung hypoplasia in congenital diaphragmatic hernia (CDH), a common birth defect, is poorly understood. The diaphragmatic defect can be repaired surgically, but the abnormal lung development contributes to a high mortality in these patients. To better understand the underlying pathobiology, we used the nitrofen rat model of CDH and characterized the proteome of hypoplastic CDH lungs at the alveolar stage (E21). Amongst the 218 significantly altered proteins between CDH and control lungs were Tenascin C, CREBBP, LYN and STAT3. We showed that Tenascin C was decreased around the distal airway branches in nitrofen and human fetal CDH lungs. In contrast, STAT3 was significantly increased in the airway epithelium of nitrofen lungs at E21. STAT3 inhibition after direct nitrofen exposure to fetal rat lung explants (E14.5) partially reversed the hypoplastic lung phenotype ex vivo by increasing peripheral lung budding. Moreover, we demonstrated that several STAT3 associated cytokines (IL-15, IL-9, IL-2) are increased in fetal tracheal aspirates of CDH survivors compared to non-survivors after fetoscopic tracheal occlusion. Using pathway analysis for significantly altered proteins in our proteomic analysis, we observed an enrichment in inflammatory response associated with Epstein Barr Virus and cytokine signaling in nitrofen CDH lungs. However, we were unable to detect EBV mRNA via in-situ Hybridization in human CDH lungs. With our unbiased proteomics approach, we show for the first time that inflammatory processes are likely underlying the pathogenesis of abnormal lung development in CDH.

developmental biology↗

bioRxiv2020

Azole use in agriculture reduces Aspergillus fumigatus abundance but does not alter its population structure

Antibiotic resistance is an increasing threat to human health. In the case of Aspergillus fumigatus, which is both an environmental saprobe and an opportunistic human fungal pathogen, resistance is suggested to arise from fungicide use in agriculture, as the azoles used for plant protection are almost identical to the frontline antifungals used clinically. However, limiting azole fungicide use on crop fields to preserve their activity for clinical use could threaten the global food supply via a reduction in yield. In this study we clarify the link between fungicide use on crop fields and resistance in a prototypical human pathogen through systematic soil sampling on farms in Germany and surveying fields before and after azole application. We observed a reduction in the abundance of A. fumigatus on fields following fungicide treatment in 2017--a finding that was not observed on an organic control field applying only natural plant protection agents. However, this finding was less pronounced during our 2018 sampling, indicating that the impact of fungicides on A. fumigatus population size is variable and influenced by additional factors. The overall resistance frequency among agricultural isolates is low, with only 1-3% of isolates from 2016-2018 displaying resistance to medical azoles. Isolates collected after the growing season and azole exposure show a subtle, but consistent decrease in susceptibility to medical and agricultural azoles. Whole genome sequencing indicates that, despite the alterations in antifungal susceptibility, fungicide application does not significantly affect the population structure and genetic diversity of A. fumigatus in fields. Given the low observed resistance rate among agricultural isolates, as well the lack of genomic impact following azole application, we do not find evidence that azole use on crops is significantly driving resistance in A. fumigatus in this context. IMPORTANCEAntibiotic resistance is an increasing threat to human health. In the case of Aspergillus fumigatus, which is an environmental fungus that also causes life-threatening infections in humans, antimicrobial resistance is suggested to arise from fungicide use in agriculture, as the chemicals used for plant protection are almost identical to the antifungals used clinically. However, removing azole fungicides from crop fields threatens the global food supply via a reduction in yield. In this study, we survey crop fields before and after fungicide application. We find a low overall azole resistance rate among agricultural isolates, as well a lack of genomic and population impact following fungicide application, leading us to conclude azole use on crops does not significantly contribute to resistance in A. fumigatus.

microbiology↗

bioRxiv2020

Distance and Colour-based Scores for Blood Test Risk Stratification

We introduce a numerical and a colour-based risk stratification score to quantify abnormal blood analyte values. The score indicates how removed values of an individual are from considered healthy ranges from the literature or derived from empirical data such as medical surveys. The scores behaviour can be adjusted to incorporate medical knowledge by assigning multipliers or weights to individual components and is rooted on a numerical and a colour-based scheme. We test the score against real and synthetic data from medically relevant cases, extremes cases, and empirical blood cell count data from the CDC NHANES survey spanning 13 years, from 2003 to 2016. We find that both the numerical and colour-based scores are informative in distinguishing healthy individuals from those with diseases manifested with abnormal blood results.

bioinformatics↗