@article{VinkenGrimmBaatoutetal.2025, author = {Vinken, Mathieu and Grimm, Daniela and Baatout, Sarah and Baselet, Bjorn and Beheshti, Afshin and Braun, Markus and Carstens, Anna Catharina and Casaletto, James A. and Cools, Ben and Costes, Sylvain V. and De Meulemeester, Phoebe and Doruk, Bartu and Eyal, Sara and Ferreira, Miguel J. S. and Miranda, Silvana and Hahn, Christiane and Akyuz, Sinem Helvacioglu and Herbert, Stefan and Krepkiy, Dmitriy and Lichterfeld, Yannik and Liemersdorf, Christian and Marcus, Kr{\"u}ger and Marchal, Shannon and Ritz, Jette and Schmakeit, Theresa and Stenuit, Hilde and Tabury, Kevin and Trittel, Torsten and Wehland, Markus and Zhang, Yu Shrike and Putt, Karson S. and Zhang, Zhong-Yin and Tagle, Danilo A.}, title = {Taking the 3Rs to a higher level: replacement and reduction of animal testing in life sciences in space research}, series = {Biotechnology advances}, volume = {81}, journal = {Biotechnology advances}, number = {7/8}, publisher = {Elsevier}, doi = {10.1016/j.biotechadv.2025.108574}, year = {2025}, abstract = {Human settlements on the Moon, crewed missions to Mars and space tourism will become a reality in the next few decades. Human presence in space, especially for extended periods of time, will therefore steeply increase. However, despite more than 60 years of spaceflight, the mechanisms underlying the effects of the space environment on human physiology are still not fully understood. Animals, ranging in complexity from flies to monkeys, have played a pioneering role in understanding the (patho)physiological outcome of critical environmental factors in space, in particular altered gravity and cosmic radiation. The use of animals in biomedical research is increasingly being criticized because of ethical reasons and limited human relevance. Driven by the 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, major efforts have been focused in the past decades on the development of alternative methods that fully bypass animal testing or so-called new approach methodologies. These new approach methodologies range from simple monolayer cultures of individual primary or stem cells all up to bioprinted 3D organoids and microfluidic chips that recapitulate the complex cellular architecture of organs. Other approaches applied in life sciences in space research contribute to the reduction of animal experimentation. These include methods to mimic space conditions on Earth, such as microgravity and radiation simulators, as well as tools to support the processing, analysis or application of testing results obtained in life sciences in space research, including systems biology, live-cell, high-content and real-time analysis, high-throughput analysis, artificial intelligence and digital twins. The present paper provides an in-depth overview of such methods to replace or reduce animal testing in life sciences in space research.}, language = {en} } @article{MushunuriAdesojiKrauseetal.2025, author = {Mushunuri, Ashwini and Adesoji, Oluyomi and Krause, Roland and May, Patrick and Lerche, Holger and Becker, Albert and Grimm, Daniela and Nothnagel, Michael and Schulz, Herbert}, title = {Genetic risk factor identification for common epilepsies guided by integrative omics data analysis}, series = {Epilepsia}, journal = {Epilepsia}, publisher = {Wiley}, doi = {10.1111/epi.70021}, pages = {15}, year = {2025}, abstract = {Objective Genetic generalized epilepsies (GGEs) comprise the most common genetically determined epilepsy syndromes, following a complex mode of inheritance. Although many important common and rare genetic factors causing or contributing to these epilepsies have been identified in the past decades, many features of the genetic architecture are still insufficiently understood. This study integrates genome-wide association study (GWAS) data from the International League Against Epilepsy Consortium on Complex Epilepsies with transcriptome-wide association studies to identify genes whose genetically regulated expression levels are associated with epilepsy. Methods To achieve this, we used multiple computational approaches, including MAGMA, a tool for gene analysis of GWAS data, and its derivatives E-MAGMA and H-MAGMA, to improve gene mapping accuracy by utilizing tissue-specific expression and chromatin interaction data. Furthermore, we developed ME-MAGMA to incorporate methylation quantitative trait loci data, providing insights into epigenetic factors. Results We identified a total of 897 false discovery rate-corrected (<.05) candidates. These include voltage-gated calcium channels, voltage-gated potassium channels, and other genes such as NPRL2, CACNB2, and KCNT1 associated with epilepsy pathogenesis that act as key players in neuronal communication and signaling in the brain. Significance In this study, we propose new candidate genes to expand the dataset of potential epilepsy-causing genes. Further research on these genes may enhance our understanding of the complex regulatory mechanisms underlying GGE and other types of epilepsy, potentially revealing targets for therapeutic intervention.}, language = {en} } @article{WehlandCorydonGonzalezTorresetal.2025, author = {Wehland, Markus and Corydon, Thomas J. and Gonz{\´a}lez-Torres, Luis Fernando and Abdelfattah, Fatima and Sahana, Jayashree and Schulz, Herbert and Mushunuri, Ashwini and Burenkova, Hanna and Wuest, Simon L. and Kr{\"u}ger, Marcus and Kraus, Armin and Grimm, Daniela}, title = {New Knowledge About Tissue Engineering Under Microgravity Conditions in Space and on Earth}, series = {International Journal of Molecular Sciences}, volume = {27}, journal = {International Journal of Molecular Sciences}, number = {1}, publisher = {MDPI}, doi = {10.3390/ijms27010341}, year = {2025}, abstract = {Microgravity (µg)-generated three-dimensional (3D) multicellular aggregates can serve as models of tissue and disease development. They are relevant in the fields of cancer and in vitro metastasis or regenerative medicine (tissue engineering). Driven by the 3R concept—replacement, reduction, and refinement of animal testing—µg-exposure of human cells represents a new alternative method that avoids animal experiments entirely. New Approach Methodologies (NAMs) are used in biomedical research, pharmacology, toxicology, cancer research, radiotherapy, and translational regenerative medicine. Various types of human cells grow as 3D spheroids or organoids when exposed to µg-conditions provided by µg simulating instruments on Earth. Examples for such µg-simulators are the Rotating Wall Vessel, the Random Positioning Machine, and the 2D or 3D clinostat. This review summarizes the most recent literature focusing on µg-engineered tissues. We are discussing all reports examining different tumor cell types from breast, lung, thyroid, prostate, and gastrointestinal cancers. Moreover, we are focusing on µg-generated spheroids and organoids derived from healthy cells like chondrocytes, stem cells, bone cells, endothelial cells, and cardiovascular cells. The obtained data from NAMs and µg-experiments clearly imply that they can support translational medicine on Earth.}, language = {en} }