Biology subjects

Reiss, J.

Publications and source records attributed to Reiss, J..

4 recordsLinked to original sources

bioRxiv2026

Sparse Machine Learning Pipeline with Stabl Identifies Cord Blood Multi-Omic Signatures of Bronchopulmonary Dysplasia

Background: Several omics studies have been completed in recent years, with the goal of identifying biomarkers of complex multifactorial diseases, such as bronchopulmonary dysplasia (BPD). Objective: To evaluate the performance of 3 distinct omics platforms, using a machine learning pipeline with integration of sparse, reliable and adaptive biomarker identification (Stabl). Methods: Using a well-characterized birth cohort, cord blood metabolomics, proteomics and adductomics data were integrated with Least Absolute Shrinkage and Selection Operator (LASSO) regression and Stabl, to evaluate predictive performance for BPD. Results: Sparse multivariable modeling of 45,000 features measured in 217 infants (52 term, 165 extremely preterm <28 weeks; 82 with BPD and 35 with severe BPD/death) identified a perfect signature for preterm birth with both LASSO and Stabl (AUROC=1.0; p<0.001). Analysis of the preterm group yielded excellent predictive power for severe BPD (AUROC=0.83; p=0.005). Stabl identified a set of 12 biomarkers (2 adducts, 3 proteins and 7 metabolites) with good performance for predicting grade III BPD (AUROC=0.76; P=0.03). Biomarkers across the 3 omics platforms revealed dysregulated pathways of innate/adaptive immune responses, metabolic programming and oxidative stress. Conclusions: The sparse machine learning pipeline is a complementary approach for identifying novel pathways and biomarkers of multifactorial BPD and its endotypes.

bioinformatics↗

bioRxiv2025

Habitat complexity reduces feeding strength of freshwater predators

1. The physical structure of an environment potentially influences feeding interactions among organisms, for instance, by providing refuge for prey. We examined how habitat complexity affects the functional feeding response of an ambush predator (damselfly larvae Ischnura elegans) and a pursuit predator (backswimmer Notonecta glauca) feeding on the isopod Asellus aquaticus. 2. We ran experiments in aquatic microcosms with an increasing number of structural elements (0, 2, or 3 rings of plastic plants in different spatial configurations), resulting in five habitat complexity levels. Across these levels, predators were presented with different prey densities to determine the functional response pattern. The experimental design and analysis allowed us to test for effects of structure presence, amount, and complexity level on functional response in one pass, without confounding predictors. 3. The feeding for both predators across all complexity levels was best described by a type II functional response model, and habitat drove feeding strength. Regarding the latter, the predators showed different responses to the complexity treatments. The overall feeding rate of I. elegans was mainly explained by the absence vs. presence of structure. Yet, in the case of N. glauca, feeding rate was strongly dependent on habitat complexity with the predator showing a unique maximum feeding rate (i.e. the inverse of the handling time) for each complexity level and a decreasing attack rate with increasing amount of habitat. 4. On average, prey consumption by both predators was reduced when complex structures were present, compared to the no habitat structure environment (e.g. consumption more than halved for some treatments). Our findings demonstrate that habitat complexity dampens feeding rates and therefore plays a key role in the stability of freshwater ecosystems.

ecology↗

bioRxiv2024

Inhibiting DPP4 activity protects hiPSC-derived steatotic HLCs by supporting fatty acid and purine metabolism and dampening inflammation

BackgroundMetabolic dysfunction-associated steatotic liver disease (MAFLD) has a high prevalence and high co-morbidity for other diseases. Due to the complexity of this multifactorial disease, therapy options are still rather limited. We employed an in vitro pluripotent stem cell-based model to decipher potential disease-associated molecular pathways and to study the mode of action of prospective drugs. Dipeptidyl peptidase 4 (DPP4) or Cluster of differentiation 26 (CD26) is involved in inflammation, infections, immune disorders, type 2 diabetes, kidney disease and cancer. MethodsWe induced the steatosis phenotype in human induced pluripotent stem cell (iPSC) derived hepatocyte-like cells (HLCs) by oleic acid (OA)-feeding and confirmed regulation of clinically relevant pathways by NGS-based global transcriptomic analyses. Analysis of the secretome of steatotic HLCs revealed DPP4 as a potential key mediator of the disease. To further elucidate its role in the development of MAFLD, we inhibited DPP4 activity with Vildagliptin (VILDA) and analyzed the global transcriptome changes as well as specific gene and protein expression of steatosis-associated genes with and without DPP4 inhibition. ResultsMAFLD-associated pathways such as PPAR- and TNF signaling were differentially regulated in hiPSC-derived steatotic HLCs. We found increased hepatic DPP4 activity and secretion upon OA. Gene expression of fatty acid and purine metabolism and inflammation-associated pathways were regulated upon DPP4 inhibition. ConclusionsOur HLC-model confirmed association of DPP4 with metabolism and inflammation which foster the development of MAFLD. Inhibiting DPP4 with VILDA partially relieved the steatotic phenotype on a global transcriptomic level. Impact and implicationsGiven the difficulties of identifying suitable anti-MAFLD drugs, novel model systems are urgently needed. Our in vitro HLC-model reproduced DPP4-dependent aspects of the disease and responded positively to Vildagliptin treatment. Further elucidation of the role of DPP4 in the etiology of MAFLD and other diseases is warranted.

cell biology↗

bioRxiv2019

Temporary anosmia in mice following nasal lavage with dilute detergent solution

Olfactory sensory deprivation induces anosmia and reduces tyrosine hydroxylase and dopamine levels in the olfactory bulb. The behavioral consequences specific to the loss of olfactory bulb dopamine are difficult to determine because sensory deprivation protocols are either confounded by side effects or leave the animal anosmic. A new method to both induce sensory deprivation and to measure the behavioral and circuit consequences is needed. We developed a novel, recoverable anosmia protocol utilizing nasal lavage with a dilute detergent solution. Detergent treatment did not damage the olfactory epithelium as measured by scanning electron microscopy, alcian blue histology, and acetylated tubulin immunohistochemistry. One treatment induced anosmia that lasted 24-48 hours. Lastly, five days of treatment reduced both olfactory bulb tyrosine hydroxylase and dopamine levels which indicates that anosmia persists between treatments. This is the first report of a sensory deprivation protocol that induces recoverable anosmia and can be paired with biochemical, histological, and behavioral investigations of olfaction.

neuroscience↗