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Fischbach, A.

Publications and source records attributed to Fischbach, A..

3 recordsLinked to original sources

PRISME: A MATLAB Toolbox For Large Data-Driven Multimodal Power Benchmarking

Low statistical power in neuroimaging often undermines research in the field, leading to missed effects, wasted resources, and reduced reproducibility. Performing power analyses during the study design phase is extremely important, but often prohibitively difficult due to a lack of analytical solutions and high computational costs. We present PRISME (Power Resampling Infrastructure for Statistical Method Evaluation), a MATLAB toolbox for neuroimaging power benchmarking. PRISME provides a computational framework for empirical power analysis independent of inference methods, enabling large scale power benchmarking and method comparison. The toolbox supports diverse neuroimaging data types, including both voxel-based activation and functional connectivity analyses, with a non-parametric, flexible algorithm and unified data representations. Furthermore, unlike previous empirical power approaches, PRISME supports multiple test types, such as association and difference tests with behavioral and clinical measures. Finally, PRISMEs 25x speedup from algorithmic optimizations enables larger-scale power benchmarking, including the first power analysis for the ABCD dataset. Overall, PRISME is the first method- and data-type-agnostic power benchmarking tool for neuroimaging, providing a single solution for power analysis across diverse study designs.

neuroscience↗

Highly polygenic control of photosynthetic responses to nighttime temperature in Arabidopsis studied by genomic prediction

O_LIRising nighttime temperature (Tnight) can reduce crop yields, while low Tnight may restrict plant growth and development. Despite these quantifiable effects of Tnight, the genetic basis underlying plant responses to Tnight remains unclear. We investigated natural variation in long-term response of effective photosynthetic efficiency (Fq/Fm) to Tnight among Arabidopsis accessions. C_LIO_LIGenome-wide association study (GWAS) was conducted for Fq/Fm of the accessions grown under 15{degrees}C or 20{degrees}C Tnight. The associated single nucleotide polymorphisms (SNPs) were identified and incorporated in genomic prediction (GP) models to assess the improvement of prediction accuracy. The predictions were experimentally validated in an independent, genetically diverse population. C_LIO_LIGWAS revealed highly polygenic architecture of Fq/Fm, with associated SNPs varying across Tnight conditions and measurement days. Notably, 15{degrees}C Tnight stabilized the contributions of a subset of associated SNPs, whereas 20{degrees}C Tnight enhanced day-to-day variations in SNP-trait associations. The GWAS-derived SNPs significantly improved the prediction accuracy of GP models, indicating their collective influence. The validation experiment confirmed the identification of low-Fq/Fm accessions in 15{degrees}C Tnight. C_LIO_LIThe results uncover the genetic underpinnings of long-term Fq/Fm response to cool vs warm nights and establish a framework for leveraging GWAS and GP to explore complex traits, such as photosynthesis, toward breeding climate-resilient crops. C_LI

plant biology↗

Artificial Hsp100-mediated systems for re-localizing protein aggregates

Spatial Protein Quality Control (sPQC) sequesters misfolded proteins into specific, organelle-associated inclusions within the cell to harness their toxicity. To approach the role of sPQC in cellular fitness, neurodegenerative diseases and aging, we report on the construction of Hsp100-based systems in yeast cells, which can artificially target protein aggregates to non-canonical locations. We demonstrated that aggregates of mutant Huntingtin (mHtt), the disease-causing agent of Huntingtons disease can be artificially targeted to daughter cells as well as to eisosomes and endosomes with this approach. Removing aggregates from mother cells did not significantly affect their lifespan and targeting mHtt to multiple smaller aggregates rather than one large inclusion did not alter its toxicity. We demonstrated that this approach is able to manipulate mHtt inclusion formation also in human cells and has the potential to be a useful complementation to present therapeutic approaches aimed at alleviating age-related neurodegenerative diseases.

cell biology↗