Biology subjects

Weber, E.

Publications and source records attributed to Weber, E..

4 recordsLinked to original sources

bioRxiv2026

Interpretable Hierarchical RNNs for rs-fMRI: Promise and Limits of Individualized Brain Dynamics

Modeling individual brain dynamics from resting-state fMRI (rs-fMRI) remains challenging due to substantial inter-subject variability, noise, and limited data length per subject. Here, we systematically evaluate whether hierarchical shallow piecewise-linear recurrent neural networks (shPLRNNs), recently introduced as interpretable dynamical system reconstruction models, can generate individualized rs-fMRI time series while preserving subject-specific functional connectivity structure. We applied the framework to 1,423 rs-fMRI samples from healthy participants of the Marburg-Munster Affective Disorders Cohort Study (MACS). Simulated rs-fMRI data reproduced substantial empirical FC structure, with comparable reconstruction accuracy on the validation and held-out test sets. Generalization to unseen individuals was heterogeneous and strongly depended on how typical a subjects connectivity pattern was relative to the training cohort, with template similarity explaining 37% of variance in reconstruction accuracy. Learned subject-specific parameters exhibited significant test-retest stability and higher within-subject than between-subject similarity on longitudinal data from two different timepoints, supporting their interpretation as individualized dynamical markers. Associations between individual parameters and demographic or cognitive variables were statistically significant but modest in effect size, and predictive performance remained below that obtained using empirical rs-fMRI features directly. Empirical FC was used as a reference for static subject information rather than as a target to be outperformed. Together, these results suggest that hierarchical shPLRNNs can extract meaningful and partially stable individual-specific dynamical structure from rs-fMRI data. The findings delineate key trade-offs between model expressivity, generalization and subject specificity, and point to directions for future methodological refinement in individualized brain modeling. Graphical AbstractA hierarchical dynamical RNN captures substantial individual rs-fMRI functional connectivity structure using compact subject-specific parameters embedded in shared population dynamics. The resulting representations generalize to held-out subjects and show test-retest stability, but only modest associations with phenotypic variables. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/713153v3_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@1b029edorg.highwire.dtl.DTLVardef@90bdd6org.highwire.dtl.DTLVardef@9f6b77org.highwire.dtl.DTLVardef@486c9e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Rapid Assessment of Immune Effector Cell-mediated Cytotoxicity using mRNA Lipid Nanoparticles

Cellular immunotherapy has revolutionized cancer treatment by enabling more targeted and personalized disease management. As the field progresses, there is an increasing need for high-throughput in vitro assays to efficiently assess the cytotoxicity of therapeutic cells. Conventional cytotoxicity assays pose various limitations in the workflow and scalability. Here, we present an mRNA lipid nanoparticle (mRNA-LNP) approach to efficiently and robustly deliver reporter genes to target cells for assessing immune effector cell-mediated cytotoxicity. This approach enables the rapid, homogenous reporter expression without compromising the viability of target cells. The cytotoxicity results obtained using mRNA-LNP-transfected cells are highly consistent and comparable to those obtained using cell lines with stable reporter gene expression. Finally, we highlight the mRNA-LNP approachs compatibility across a diverse range of tumor models, including primary tumor-derived models, enabling rapid and high-throughput assessment of the potency of various cytotoxic therapeutic cells.

immunology↗

bioRxiv2022

Radiogenomics of C9orf72 expansion carriers reveals global transposable element de-repression and enables prediction of thalamic atrophy and clinical impairment

Hexanucleotide repeat expansion (HRE) within C9orf72 is the most common genetic cause of frontotemporal dementia (FTD). Thalamic atrophy occurs in both sporadic and familial FTD but is thought to distinctly affect HRE carriers. Separately, emerging evidence suggests widespread de-repression of transposable elements (TEs) in the brain in several neurodegenerative diseases, including C9orf72 HRE-mediated FTD (C9-FTD). Whether TE activation can be measured in peripheral blood and how the reduction in peripheral C9orf72 expression observed in HRE carriers relates to atrophy and clinical impairment remain unknown. We used the FreeSurfer pipeline and its extensions to assess the effects of C9orf72 HRE and clinical diagnosis (n = 78) on atrophy of thalamic nuclei. We also generated a novel, whole-blood RNA-seq dataset to determine the relationships between peripheral C9orf72 expression, TE activation, thalamic atrophy, and clinical severity (n = 114). We confirmed global thalamic atrophy and reduced C9orf72 expression in HRE carriers. Moreover, we identified disproportionate atrophy of the right mediodorsal lateral nucleus in HRE carriers and showed that C9orf72 expression associated with clinical severity, independent of thalamic atrophy. Strikingly, we found global peripheral activation of TEs, including the human endogenous LINE-1 element, L1HS. L1HS levels were associated with atrophy of multiple pulvinar nuclei, a thalamic region implicated in C9-FTD. Integration of peripheral transcriptomic and neuroimaging data from HRE carriers revealed atrophy of specific thalamic nuclei; demonstrated that C9orf72 levels relate to clinical severity; and identified marked de-repression of TEs, including L1HS, which predicted atrophy of FTD-relevant thalamic nuclei. Significance StatementPathogenic repeat expansion in C9orf72 is the most frequent genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (C9-FTD/ALS). The clinical, neuroimaging, and pathological features of C9-FTD/ALS are well-characterized, whereas the intersections of transcriptomic dysregulation and brain structure remain largely unexplored. Herein, we utilized a novel radiogenomic approach to examine the relationship between peripheral blood transcriptomics and thalamic atrophy, a neuroimaging feature disproportionately impacted in C9-FTD/ALS. We confirmed reduction of C9orf72 in blood and found broad dysregulation of transposable elements--genetic elements typically repressed in the human genome--in symptomatic C9orf72 expansion carriers, which associated with atrophy of thalamic nuclei relevant to FTD. C9orf72 expression was also associated with clinical severity, suggesting that peripheral C9orf72 levels capture disease-relevant information.

neuroscience↗

bioRxiv2020

Effect of allelopathy on plant performance

Allelopathy (i.e. chemical interactions between plants) is known to affect individual performance, community structure and plant invasions. Yet, a quantitative synthesis is lacking. We performed a meta-analysis of 385 studies that measured allelopathic effects of one species (allelopathy plant) on another species or itself (test plant). Overall, allelopathy reduced plant performance by 25%, but the variation in allelopathy was high. Type of method affected allelopathic effect. Compared to leachates, allelopathy was more negative when residues of allelopathy plants were applied, and less negative when soil conditioned by allelopathy plants was applied. The negative effects of allelopathy diminished with study duration, and increased with concentrations of leachates or residues. Although allelopathy was not significantly related to life span, life form and domestication of the interacting plants, it became more negative with increasing phylogenetic distance. Moreover, native plants suffered more negative effects from leachates of naturalized alien plants than of other native plants. Our synthesis reveals that allelopathy could contribute to success of alien plants. The negative relationship between phylogenetic distance and allelopathy indicates that allelopathy might drive coexistence of close-related species (i.e. convergence) or dominance of single species.

ecology↗